December 8, 2005
COUNCIL MEMBERS PRESENT
Edmund Pellegrino, M.D., Chairman
Rebecca S. Dresser, J.D.
Washington University School of Law
P. George, D.Phil., J.D.
William B. Hurlbut, M.D.
Leon R. Kass, M.D., Ph.D.,
American Enterprise Institute
Charles Krauthammer, M.D.
Peter A. Lawler, Ph.D.
Johns Hopkins University School of Medicine
Gilbert C. Meilaender,
Janet D. Rowley, M.D., D.Sc.
The University of Chicago
WELCOME AND ANNNOUNCEMENTS
CHAIRMAN PELLEGRINO: Good morning, and I welcome the
Council members to the 22nd Public Meeting of the President's
Council on Bioethics.
I want to recognize the presence of Dick Roblin, the
Designated Federal Officer — Dick is over here — in whose presence
this is a legally constituted meeting.
I think it most fitting to begin this session by expressing
my personal gratitude, as well as the gratitude of the Council and the
public, to Dr. Leon Kass, who is the outgoing Chairman of this
Council. He has been Chairman since the Council's beginning. We
are all indebted to him for the intellectual setting, the wisdom, and
the practical good sense he has brought to his assignment.
Together with the Council he has produced a series of
adamantly clear, helpful, and practical reports on some of the most
significant ethical problems and issues facing us as individuals and as
members of American and world society.
It is with diffidence, therefore, that I have accepted the
invitation to succeed Dr. Kass as Chairman. My hope and my intention
is, with the participation of the Council members, to maintain as
closely as possible the high standards set by Dr. Kass and, thus, to
serve the purposes of this Council as an instrument for the systematic
and orderly inquiry and debate into the complex issues facing humanity
in the field of bioethics today.
I hope that we can maintain the high standard of intellectual inquiry,
public responsibility, and prudent judgment that the intersections
of science and wisdom and ethics demand in our time.
SESSION 1: BIOETHICS AND AMERICAN
In today's discussion, we enter a new field of inquiry
for the Council — the ethical and bioethical issues involved in the
care of infants, children, and young adults. They are, as has so often
been said, the future of our nation and the world. They will confront
the problems and the promise of biotechnology and social change.
We can scarcely imagine today what the nature of those problems
and challenges and potentialities will be. Certainly, they will
involve such things as the uses of psychotrophic agents in children,
questions of human experimentation and clinical trials, issues of
consent, assent, and surrogate decisionmaking, as well as end-of-life
decisions, attitudes and values toward the disabled and the handicapped,
the questions of priority and the allocation of resources on the
basis of age and development, decisions of the utmost significance
during intrauterine and neonatal life, epidemic obesity, universal
vaccination, genetic testing. The list goes far beyond anything
we can fully envision at this time.
We have invited speakers whose expertise includes many of
the areas that I've mentioned, and many others they will bring to
our attention. We have asked them to be free to look at the issues as
individuals, from their own point of view, from their expertise, and
from their experience.
The second item, which we will discuss tomorrow, is a staff
paper on the subject of human dignity, a concept which is much used and
much abused in the bioethics literature today. It has been used
repeatedly by the Council itself, and we thought it wise perhaps to
reflect on some of the dimensions of this concept.
Before we begin, let me ask if you will express your
appreciation to Dr. Kass. He happily will be with us as a member of
the Council, and we will have continued access to his wisdom and his
Leon, thank you very, very much.
Our first speaker this morning will be Dr. Norman Fost, who
hardly needs any introduction in the field of pediatric ethics. You
have a summarization of his career and curriculum vitae, and I will ask
him to address us — Norm, there you are. And I have asked him very
clearly to tell us what he thinks over the many, many years of his
cogitations on this subject we should be addressing and the nation
should be addressing.
DR.FOST: Thanks very much, Ed, for inviting me to this
Dr. Pellegrino's invitation reminded me of the famous
exam question, "Discuss the universe and give two examples."
I've decided instead to give three examples to be unduly ambitious,
and to talk about the three issues of the many that we could talk about
that seem to me most pressing.
Through the lens of someone who has been engaged in these
issues for 40 years — not as long as Dr. Pellegrino but I'm
gaining on you — as a pediatrician, as an investigator, as a human
subject, as Chair of an IRB for 28 years, Chair of the Hospital Ethics
Committee, someone who has written and taught about these issues and
had the opportunity to be involved in federal policy.
And let me say that I think ethics does matter, that
Councils and Commissions like this have had a — that there's been
a dramatic change. I'm going to try to make the point that there
have been dramatic changes in the well being of children as a result of
committees and councils and commissions like this, and I think there is
the opportunity to have more influence.
I'm going to talk about three issues, two of which will
seemingly overlap with other speakers, namely end-of-life decisions,
research issues, and issues about genetic screening. But I've
talked with all of them, and I think there will be minimal overlap and
what they say will sort of pick up where I leave off.
But before I do that, I want to just say a few words about
two overriding issues that seem to me to dwarf traditional bioethics
concerns with regard to children.
First is the continuing problem of 40-plus million
Americans without insurance, a third of them children, somewhere
between eight and ten million children without third party coverage,
not eligible for Medicaid, who die at a higher rate than others, who
suffer, who come into life with burdens, who leave the starting gate
with a 200-pound gorilla on their back, whether due to prematurity or
single mothers on drugs or lack of access to care.
And this is always mentioned as the most important problem
involving children and Americans, but not enough is done about it.
It's a big issue, and I'm not going to say any more about it,
because it is so complicated. But I hope the Council will take some
cognizance of it in a larger context.
Second, I want to just say a few words about child abuse,
which is a special interest of mine. I've been director of a child
protection team for 35 years, and, here again, it's a problem that
affects millions of children.
I mean, there are over a million reports of child abuse in
the United States, and we know that that is the tip of the iceberg.
Underreporting is somewhere in the five to ten to one range. That is
only five to — only 10 to 20 percent of cases get reported.
And in the area of physical abuse alone, we have known for
30 years how to prevent this. Dr. Henry Kempe did a landmark study 35
years ago, showed that we can predict 80 percent of cases of physical
child abuse in the delivery room. We know before they go home who
these children are.
And in a randomized, controlled study, showed that the
simple intervention of lay home visitors, lay people asked to spend an
average of five hours a week with these usually single mothers, had
dramatic effects in reducing the incidence of physical abuse, permanent
disability, and, in some cases, even death.
We are the only country in the world that I know of,
certainly one of the few, that does not have routine home visitors.
It's considered bizarre in other countries that we allow these
children to be born and go home, and nobody checks in, nobody offers to
help. It is extraordinary.
But Dr. Kempe's studies have been repeated many times,
the effectiveness of home visitors, professional or lay visitors, has
been shown in — when done correctly, to have very dramatic effects.
In fact, I would say the most important professional thing I've
ever done is to have the chance to be involved in starting a nonprofit
agency in Madison whose sole purpose is to recruit lay volunteers for
home visitors. It has been copied elsewhere around the country, and it
has been immensely gratifying.
So, again, it's a huge issue. It affects,
logarithmically, more children than the issues that we're going to
be talking about. And I hope the Council at some point can take that
up. I'd be happy to talk more about it when the occasion arises.
But I will concentrate on the three traditional issues.
From a historical perspective, what I'd like to do is say something
about how it was when I started out in this field, how it is now, and,
in my view, how it should be, because I think things were terrible. I
think there have been dramatic changes. But I think there is still
work to be done, and I'll suggest what that might be.
So first some comments about withholding and withdrawing
life-sustaining treatment, end-of-life decisions in children who are
ill and handicapped and in need of medical care. My entre into
bioethics was facilitated by a single patient, a child who has come to
be known as the Hopkins Mongol case, in the language of the day, a
newborn with Down's Syndrome and duodenal atresia, intestinal
obstruction of a kind that's very easily fixed in a simple
operation that has virtually 100 percent success rate.
This was in 1971 when I was in my second year as Chief
Resident at Hopkins. The parents typically did not want surgery done.
It was withheld, an NPO signed, "Nothing by Mouth" was put on
the child's crib, and he was put into a room by himself and allowed
to die of dehydration over a 15-day period.
With the help of the Kennedy Foundation, we made a movie of
that case. That has been seen by more than a million people, and
became the centerpiece of a symposium at the Kennedy Center in
Washington. That was one of the first cases to bring bioethics into
the public sphere. It was one of the first widely-publicized cases
that attracted, appropriately, public scrutiny and discussion.
I went to the record room at Hopkins at the time and found
six other cases of the identical situation — that is, children with
Down's Syndrome and duodenal atresia who had been allowed to die.
In fact, a case just about three years before that had been taken to
court by Dr. Robert E. Cooke, the Chair of Pediatrics, to try to get
court intervention, without success. The court said that the parents
had the right to make that decision.
Shortly after that case and the publicity surrounding it, a
national survey was done of pediatricians and pediatric surgeons, and
70 percent of them agreed with what was done in that case. That is, 70
percent of American pediatricians polled said that, if confronted with
the same case, they would defer to the parents' wishes. They would
not go to court. They would not seek to override the parents.
A similar survey was done in Massachusetts and produced the
identical result; 70 percent of pediatricians in Massachusetts said
they thought it was — what the parents had asked for was okay, and
they would go along with it.
An article was published in The New England Journal by
one of my teachers at Yale, Dr. Raymond Duff, reporting that one
in five deaths at the Yale New Haven nursery over a two-year period
was due to withholding of standard medical treatment. This included
children with Down's Syndrome and other relatively modest handicaps
or disabilities, and children with profound disabilities who had
little prospects for a long or meaningful life.
And in the last paragraph of that article Dr. Duff said,
"If what we did is illegal, then that shows that the law needs to
The world 30 years later is dramatically different, I think
in part as a result of the work of a prior Presidential Commission on
Bioethics, work by the American Academy of Pediatrics, scholars in the
field, and so on. There has been a complete reversal of this
The turning point came in the mid-1980s when President
Reagan implemented so-called Baby Doe regulations that prohibited
discrimination on the basis of handicap. And to the best of my
knowledge, since 1985, there has not been a single case of a child who
has — with Down's Syndrome or spina bifida, the other common
malformation, who has died due to withholding of standard care simply
on the basis of having Down's Syndrome or spina bifida.
Needless to say, such children sometimes die, and sometimes
due to withholding of treatment, but because of some profound, often
untreatable, illness, not because they have Down's Syndrome.
So it has been a dramatic change. The status of children
with disabilities and the medical treatment that they receive is 180
degrees different from what it was 30 years ago, and even 20 years
ago. But this long history of undertreatment, of inappropriate, and I
think what is now widely agreed to be inappropriate withholding of
treatment in such children, has been replaced by what many of us
That is, there was a rebound effect from the Baby Doe
regulations. Dr. Kopelman, one of the later speakers, has written
eloquently about this, and what we have now is a country in which
children receive treatment regardless of whether it serves any interest
of theirs, children who have little or no prospects for a meaningful or
long life, but suffer in intensive care units or in intensive care
units in their homes, in part as a result of fear of legal
repercussions, in part due to what I consider misinterpretation of the
famous or infamous Baby Doe regulations.
Dr. Nelson I know will be saying a lot more about this
subject, but I think work is needed, and I hope the Council will
contribute to this discussion about finding a middle ground. One of
the causes of the transformation in this area is not just the Baby Doe
regulations, but the growth of hospital ethics committees, infant care
review committees as they were called at the time, which introduced for
the first time almost obligatory multidisciplinary/multidimensional
discussions in end-of-life decisions, not just for children but for all
As you know, these committees are now required by the Joint
Commission on Accreditation of Hospitals, and it's my view there
has been a dramatic change in just the process by which these
end-of-life decisions are made. So the debate is over a much narrower
ground of cases, a much narrower band of cases.
But in my view, there still is undue overtreatment, and it
is now very difficult in many parts of our country for a child to die
when there's widespread agreement that that would be in that
child's interest. Dr. Nelson will be saying much more about that.
Second, I'd like to say something about research, and
start again with personal experience. In the 1960s, a local reporter
at WABC in New York, WABC TV in New York named Gerald Rivers lurched
into national prominence with a sensational series of reports of
alleged abuses of profoundly retarded children at the Willowbrook
Hospital in Long Island, a state institution for the profoundly
Newly-admitted children to Willowbrook, he discovered, were
deliberately infected with the Hepatitis virus using fecal extracts
from other children in the institution. The reporter soon acquired a
new name to better fit his celebrity status. Gerald Rivers became
Geraldo Rivera, which is perhaps the most serious legacy of
It's beside the point that Willowbrook, in my view, has
been badly and consistently misreported over the decades, and was
framed by Geraldo Rivera and everybody since as a non-therapeutic
research study to learn about the epidemiology of Hepatitis. It was,
in fact, intended as an early vaccine study. That is, Dr. Krugman
thought what he was doing was trying to prevent the infection of
Hepatitis in these children, where it was endemic.
Dr. Krugman was vilified for what were called coercive
recruitment techniques and disregard for minimum standards of informed
consent. My own view is that the consent procedures used by Dr.
Krugman exceeded any in any study I've known since, and this, mind
you, was before IRBs existed, before there was any — there were any
requirements for research involving human subjects.
One last point in the category of personal disclosures. My
senior thesis at Yale involved a study of chromosome breaks in children
who had had viral infections, and my source of my patient material were
the children at Willowbrook. That is, I found a nurse there who would
call me when there was a new outbreak of some viral disease — measles,
rubella, or hepatitis.
I would drive down with my little bag, go into the main
ward there. The nurse would find an appropriate patient, yank his or
her arm through the crib rails, I would draw blood and go back to New
Haven and do my studies. No committees, no parents, no consent, no
review, no nothing.
Well, I'm not here today to discuss the pros and cons
of the Willowbrook studies, Dr. Krugman's or mine. The point is
that it was typical of the day — that is, research involving children
and most everyone else — was a free for all with no regulations, no
oversight, no committees, no review, and usually no standards for
consent from everybody — from anybody.
This was standard practice. One of my heroes at Yale, Dr.
Robert Cooke, elucidated with his mentor, Daniel Darrow, most of what
we know about the role of potassium in the body, in part by taking
infants out of orphanages in New Haven, bringing them into a clinical
research unit where they were exposed to heat stress.
Meticulous balance studies were done. These studies
resulted in what ultimately became WHO electrolyte solution, and Dr.
Cooke conservatively estimates he saved several billion lives through
this research on a very small number of children, but is just
astonished at what he did, looks back with sort of horror that he was
able to do that, and has said many times, "If there was just some
committee that I had — just any group of people that I had to check
this out with, it never would have happened. I could have done the
studies on sick patients with very minimal risk."
When I was an intern at Hopkins, one of my fellow interns
did a landmark study on hernias in children by taking infants who had
been admitted to the hospital for an elective herniorrhaphy the next
day. He was interested in the question of whether children with a
hernia at one side were at risk for a hernia on the other.
So at midnight when he was done with his regular intern duties, he would
pick these children out of their cribs, take them down to the emergency
department, inject their abdomens with high opaque, radio-opaque
dye, jiggle them around, put on a lead apron on himself, sweet talk
an emergency room X-ray tech to take a flat plate of the abdomen,
including the gonads, and published a landmark study showing a high
incidence of inguinal hernia.
To this day, those parents have no idea who their — that
their children had their gonads irradiated with very primitive X-ray
And, finally, these examples are by the dozens. But just
to make the point, Dr. Gross at the Boston Children's Hospital, the
Chief of Cardiovascular Surgery there in the 1970s, was interested in
the role of the thymus — an immunology poorly understood at the time
— and took children who were brought to the OR from elective surgery
for congenital heart disease, took out the thymus on some and not
others, and did heterologous skin transplants to see what the role of
the thymus was in rejection.
The children would come back to the ward with these funny
patches on their arms. The nurses didn't know what it was,
couldn't answer the parents' questions. Again, no permission
from anybody. So we've come a long way.
Three weeks ago Dr. Nelson and I spent a day and a half
discussing whether an investigator at the University of Chicago could
admit children to a hospital overnight to give them a single injection
of a probably harmless drug, and collect a few blood samples. It took
one year for this investigator to get permission from his local
institution and still required the permission of the Secretary of
Health and Human Services. And Dr. Nelson and I were part of a
committee to advise the Secretary on that.
So the kinds of egregiously unethical research involving
children and everybody else that was done in the 1960s, like starving
mongols to death, is ancient history. But just as the undertreatment
of handicapped infants has been replaced by overtreatment, in my view
the underregulation of research has been replaced by overregulation and
disregulation, with severe sanctions against institutions for failure
to document compliance with rules, many of which have little or no
relationship to protection of human subjects.
Let me just give one example, again, of dozens in the
discussion. We could expand on this if you like.
As you all know, Duke University some years ago was shut
down by the Office of Human Research Protections for alleged violations
in protection of human subjects. There were 25 different categories
cited by the Office of Human Research Protection. I'm just going
to mention one.
One was the failure to document a quorum in the conduct of
the IRB's business. The Chair of the IRB, whom I know well, showed
that they had documented a quorum at the beginning of the meetings and
used Roberts Rules, which state that a quorum is presumed to exist
unless it's challenged by somebody during the meeting.
The leader of the site visit from OHRP said, "No, sir,
the common rule — the federal regulations require that all business
conducted at the meeting must be approved by a quorum of those of the
committee. You had over 100 action items at each committee, and you
did not document a quorum, we know that there's a lot of Brownian
motion at these committee meetings, people leave to take pages, to go
to the bathroom, and what not, and so we have suspended all 2,200
protocols because you have no documentation that a quorum existed.
As a result of that suspension, Duke, and now everybody
else, documents a quorum 100 times during a meeting. The minutes from
— I'm Chair of our IRB. The minutes of our meetings are 150
single-spaced pages for a three-hour meeting. This is — the quorum
rule, of course, is only one of the many things we have to document.
One last anecdote about the quorum rule. OHRP went on to
shut down eight consecutive academic medical centers. The University
of Wisconsin was ninth on the list. We fully assumed that we would be
shut down because we were guilty of all the transgressions, virtually
all, that have happened at Duke.
And while we had taken steps to correct them to be in
compliance, we knew that if our records were examined that they could
show that our 2,000 active protocols also had been approved without
documentation of a quorum and many other things for each one.
Miraculously, we were not shut down. We received a
commendation letter. And as a result of this, when accreditation of
IRBs started, one of the new accreditation agencies asked us to become
their beta site, their testing site, since we were held in such high
esteem by the federal agency.
We were glad to do this. It gave us a chance at
essentially a free look at accreditation. It was literally cost-free.
If we flunked, it would be confidential. If we passed, we would be
accredited, so it seemed like a no-brainer.
The accreditation manual had 270 items. We had six months
to prepare. There was a four-day site visit. We flunked 70 percent of
those items, 70 percent of 270 items. This was an IRB that had
received a commendation from the federal authorities.
Let me just mention the quorum rule as an anecdote. We, of
course, as a result of the Duke experience had learned to document a
quorum 100 times at each meeting for each action item. But the site
visitor said, "You haven't documented whether a non-scientific
member of the IRB was in the room. The federal rules require that each
IRB must have a non-scientific member, somebody whose major expertise
is in non-scientific areas."
Well, we had several such members, and so we were quite
confident that there always was at least one such person in the room.
But the site visitor said, "You haven't documented it. All
you've said is that you have a quorum, but how do we know if the
quorum included a non-scientific member?"
Well, virtually all our votes are unanimous or unanimous minus
one. We just keep talking until we reach consensus. And I asked,
"Has there ever in the history of the world been a study which
involved humans, a research study, in which the vote was tipped
due to the vote of the non-scientific member? Do you know of any
Well, of course, nobody knew of such an instance, but that
was beside the point. A rule is a rule. As a result of that
requirement by that agency, Hopkins, I was told, in one of their IRBs
began passing a clipboard around at their IRB meetings where all 24
members signed the clipboard for each of 100 items at the committee —
2,400 signatures at one meeting — to make sure that the non-scientific
member and other IRB requirements were met.
This is silly, of course, but if it were just the only
example I wouldn't bother you with it. In my view, there are a
dozen similar kinds of rules, and the problem is that research which
used to be too easy is now too hard. That it is now very difficult to
get senior faculty to participate in IRBs.
We had a very valued member storm out of a meeting and quit
permanently because of discussions like this, saying, "This is not
what I'm here for. I'm happy to donate 150 hours a year of my
time at no reimbursement to protect human subjects, but not for this
kind of nonsense."
It is harder for investigators, of course. Clinical research
is dying in my view, as a field of inquiry. That is, there is a
dramatic decline in the number of young American physicians going
into this area. If you look at the lead author of New England
Journal articles over the last decade, less than 50 percent
are now American authors.
If you look at the number of M.D. principal investigators
of NIH funding, it is also in almost a straight line decline. Children
are the most serious victims of this decline in clinical research.
That is, children, unlike adults, are almost always treated with what
is euphemistically called innovative therapy.
My colleague Paul Lietman at Hopkins says innovative
therapy means if you don't want to learn any — if you promise not
to learn anything from what you're doing, you don't have to go
through an IRB. Eighty percent of all drugs prescribed for children in
America have never been approved or tested for safety or efficacy in
And as we know, children are not little adults. History is littered
with examples of large numbers of children who have died or suffered
because of treatments that were quite okay in adults, but turned
out to be toxic and even lethal in children — chlorenphenicol,
sulfonamides, oxygen given indiscriminately to children for 80 years
before anyone asked the question whether there might be a dose-response
Even simple bicarbonate, used as a buffer for patients with
acidosis, shown by Dr. Michael Simmons to cause death and profound
brain damage in infants with hyaline membrane disease. And on and on.
That is, children need research more than adults. The
problem is not that there's too much research in children, or too
much unregulated research as went on 30 years ago, but not enough. The
problem is that children are now "experimented on" but
without — and no systematic way and without any collection of data.
That said, the regulations for research need some
refining. Sara Goldkind will say more about this. I just want to
mention briefly a couple of elements of the regulations that seem to be
problematic and possibly an example of persistent underregulation. Dr.
Goldkind will say much more about this.
In my view, the justification for non-therapeutic research
on children has never been made. The brilliant work of the National
Commission for the Protection of Human Subjects never really, in my
view, made the case for allowing non-therapeutic intrusions into
children without children who were incapable of consent.
The argument that was made was a utilitarian one, namely
that it's good for children as a class. We wouldn't want to
live in a world in which no non-therapeutic research is done on
children. And it's good for them to have such studies done with
One of the restrictions was it's okay as long as the
research is of minimal risk. Realize, of course, that there is no such
exception for adults. That is, the utilitarian argument is equally
true. We could — knowledge could advance much more efficiently with
adults, if it weren't for this pesky consent problem.
If we could do more non-therapeutic research on adults
without their consent, we could learn a lot more a lot faster, but this
is absolutely taboo and appropriately so, but yet the argument is
allowed for children.
The minimal risk rule, defined in the federal rules as the
probability and severity of harm, comparable to what would happen on a
routine visit to the doctor, is interpreted widely — in a widely and
wildly variable way. Published studies have shown that IRB chairs and
IRB members interpret this to include everything from venapunctures to
non-therapeutic bronchoscopies and small bowel biopsies.
Investigators make the claim either that this is minimal
risk in my hands or this is what happens on a routine visit to my
office. I do a bronchoscopy on everybody I see. And the variation in
IRB acceptance of this kind of argument is quite remarkable.
So more work is needed in this area. Dr. Goldkind may say
some more about it, but I think we do not have enough conceptual work
or even practical, pragmatic definitions of the minimal risk rule.
The other area that, in my view, needs much more work is
the notion of assent. Legally valid informed consent is not possible
with young children, and so this term "assent" was invented
as a surrogate — the requirement that children at least be told in
language that's meaningful to them what is proposed, and
essentially that they don't need to do it if they don't want
I don't think this is taken seriously. I think if it were,
it's hard to imagine why any seven-year-old would let himself
or herself be stuck with a needle if it had no relationship to his
or her health care, and they didn't want to do it. Moreover,
there has never been an adequate discussion as to why the age of
seven is used as a boundary for this requirement.
Three-year-olds know perfectly well what a needle stick is all
about. They know perfectly well that they don't want it, for
the same reason that adults don't want it, because it's
annoying, because it hurts, and they would just rather not do it.
But there is no respect for three-year-olds or infants for such
Well, I don't want to have non-therapeutic research on
children stopped, but I think, as I say, conceptual work is needed, and
this Council is very qualified to either do that work or facilitate it.
Finally, let me just say a few words about genetic testing,
which Dr. Pellegrino referred to, which in my view is the most serious
of these three areas that is affecting the most number of children.
And, again, I'd like to start with a historical example and a
personal experience, and then express my concern about where we are
today, and then I'll close.
In 1960, PKU, Phenylketonuria, was known to be an
admittedly rare, but a well understood, cause of profound mental
retardation. It affects approximately 1 in 10,000 live-born children.
The biochemistry of it was fairly well understood. It's due to
inability to metabolize an amino acid named phenylalanine, which is
ubiquitous in proteins.
It was known that if you could diagnose this early enough
and get a child started on a restricted diet that you could ameliorate,
and in some cases prevent completely, the profound brain damage that
But the test that was available at the time, a urine test,
was inconvenient to get. It was obtained at the first well baby visit
after the child had been on a normal diet for a while and the horse was
out of the barn. That is, by the time children were diagnosed, brain
damage had already occurred.
The diet was expensive and unpalatable. Parents had an
awful time getting children to cooperate with it.
There were three breakthroughs in 1960 — the discovery by
Dr. Robert Guthrie of a simple test, making it cheap and efficient to
diagnose this condition on all newborns on a single drop of blood;
second, the development by Mead Johnson of Lofenalac, a low
phenylalanine milk that was reasonably affordable and palatable; and,
three, the election of John Kennedy.
President Kennedy, because of his profound interest in
mental retardation, his family's interest, with Dr. Guthrie formed
a so-called PKU lobby and arranged for laws to be passed in all states
requiring PKU testing, realizing correctly that doctors in offices
would be unlikely to adopt a test for a disease that affected 1 in
10,000 children — something that a pediatrician might never see in his
or her entire career. So mandatory newborn screening for PKU became
the national policy.
In 1973, I was invited by Dr. Barton Childs to be part of a
commission — a committee at the Institute of Medicine to look into the
PKU story. This was my first exposure to national policy.
The problem was, it turned out, that the PKU test was the
worst test in the history of the world. It had a sensitivity and
specificity that have not been matched to the best of my knowledge.
That is, the test had a five percent true positive rate. It had a 95
percent false positive rate. That is, a child with a positive test,
confirmed by a whole blood assay, had a 20 to 1 chance of being normal.
This was not appreciated for many years. So many normal
children, we now know, were started on a restricted diet, and it turned
out that a phenylalanine-restricted diet was as harmful, or more
harmful, as a diet with excess of phenylalanine. That is, this
essential amino acid, when withheld from normal children, resulted in
brain damage due to starving of brain cells, and every other cell in
the body, because phenylalanine is a part of so many proteins.
So many children — we don't know how many — were
made retarded by this program. Some were killed. In fact, kwashiorkor
developed in America in the PKU program in children who had profound
protein malnutrition because of the restricted diet.
Well, if that happened to a child with PKU, you might say
nothing ventured, nothing gained, these children had little to lose.
They were — had terrible prognoses anyway. But when this happened in
a normal child, it's obviously a major tragedy.
In 1965, the American Academy of Pediatrics sent a letter
to the Secretary of DHHS urging that the mandatory PKU screening
programs be stopped, because we didn't understand the significance
of the test, and we didn't know how to regulate the diet.
This letter was suppressed. People were called Luddites
who were against newborn screening. The PKU lobbying was very
powerful, and testing went on until 1971 when a political scientist
named Joseph Cooper uncovered this story through the Freedom of
Information Act and led to the appointment of the IOM Committee, whose
report was published in 1975 articulating principles for ethically
responsible newborn screening, particularly genetic screening or
screening for genetic disorders.
These guidelines published by the Institute of Medicine in
1975 have been essentially photocopied by a dozen committees,
commissions, councils, professional groups, lay groups. There is
virtual unanimity on the principles of responsible genetic screening,
and newborn screening in particular.
It is not a controversy, and it represents another
marvelous example of the good work of ethics, of thoughtful people and
ethics, law, public policy, patients, parents, and so on, agreeing on
guidelines. The only problem is that the guidelines are systematically
ignored. That is, newborn screening has expanded like topsy, with the
same mistakes that beleaguered the PKU program happening over and over
That is, numerous screening and treatment programs have
been implemented without testing, evaluation of the tests, without any
systematic study of the sensitivity, specificity, or predictive value
of the test, or of the interventions.
This happens in part because genetic testing and treatment
falls outside of the regulations of the FDA. That is, there is no toll
gate through which an investigator or an innovator has to go to get
these kinds of programs approved. He or she only needs to persuade
existing committees and state health departments to simply add another
test onto the drop of blood or the drops of blood that now exist for
virtually every newborn in America.
I won't take time to rehearse for you other examples of
newborn screening gone awry, and the large number of children in my
view who have been killed, normal children in some cases, by screening
and treatment programs that have never been adequately evaluated. Not
The new technologies, such as tandem mass spectrometry, now
make it possible to test for hundreds of conditions on this single drop
of blood. And, indeed, a committee of the American College of Medical
Genetics has persuaded the Secretary's Advisory Committee on
Genetic Testing to recommend to the Secretary national implementation
of a uniform standard for testing of newborns using tandem mass
These recommendations include over 50 conditions, half of
which have no known association with human disease. That is,
approximately half of the tests on the committee's recommended list
are abnormalities that have been observed whose relationship to
clinical manifestations are unknown or uncertain, and the other half
roughly involve serious diseases but diseases for which the sensitivity
and specificity and predictive value of the test is unknown, and in
which the interventions have never been systematically tested.
It is telling, in my view, that the UK equivalent of the
FDA has recommended implementation of only one of these 50 conditions.
Even worse, multi-array DNA testing — that is, the ability to test for
a thousand genetic variations using recombinant DNA techniques on a
single drop of blood is also now upon us, and work is proceeding
rapidly to add multi-array genetic testing to the newborn PKU spots.
So we now already have many states, including Wisconsin,
that does routine testing without consent, without prior research, for
dozens of conditions using tandem mass spectrometry. And I predict,
unless there is some dramatic change in the way we think about these
things, the way we do these things, that multi-array DNA testing will
occur within the next few years, as soon as the cost comes down to make
it efficient to do it.
This, to me, is a calamity involving every child in
America, the amount of mischief. The amount of harm, psychosocial harm
that will occur to families and children, not to mention medical harm,
is, in my view, going to be quite extensive.
And, worse, 20 years from now we won't know what harm
has been done, because in the absence of systematic studies we
won't know which children were helped and which were harmed,
because we won't know whether like — in the PKU program, we
won't know if a positive test meant that that was a child who was
destined to become brain damaged or dead, or whether it was a false
positive test that had poor predictive value.
In summary, where have we been? Where are we? Where are
we going? In the area of end-of-life decisions, there has been a
transformation from egregiously unethical undertreatment, withholding
of simple treatment from children with excellent prospects for long,
happy lives, to serious overtreatment.
A thoughtful kind of undertreatment has been replaced, in
my view, by a thoughtless kind of overtreatment. In the area of
research, egregiously unethical research with no oversight or
regulation has been replaced by too little research, with excessive and
inappropriate regulation. The result has been an expansion of
innovative therapy, a decline in physician investigators or funds to
And, finally, in the area of genetic screening, the mistakes of
the PKU program has resulted in guidelines about which there is
little dispute, but practices which have not changed at all and
which arguably may become much worse due to the advent of multi-array
I could tell many other stories in all these categories,
and there are, of course, other issues that we haven't talked
about. But these seem to me worthy of Council's attention.
Thank you for the opportunity to present to you.
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Fost. Dr.
Fost is going on 35 years in bioethics. Bioethics itself was invented
or baptized in 1972, according to some people. You were there at
the beginning. And thank you very, very much for your reflections
on pediatrics and pediatric ethics since then.
I'd like to open to Dr. Fost's paper. The members of the
Council put on their red light, indicating that they'd like
to talk, to save me from being a traffic cop.
DR. KASS: Thank you very much for a really lucid and
illuminating paper. I have I guess — and I appreciate and feel the
force of each of these issues. But if I could draw you out on sort of
the — some of the tacit ethical suggestions that you made along the
First, the second point on the research issues, you begin
by saying the case for non-therapeutic research on children hasn't
been made. You concluded by saying you don't want this to be shut
down, and, therefore, I assume you think the case can be made. And I
wonder — on non-utilitarian grounds, I assume, and I wonder if you
would — if you have any sort of beginning inklings as to how you could
Our mutual friend Paul Ramsey thought it was impossible to
make such a case, and I'm not sure I agree with you that the case
hasn't been made. But if you think that there is a way to make it,
I would be interested to hear at least the outline.
And, second, I wonder whether, if we follow your suggestion
that there is egregious — well, you didn't say egregious
overtreatment, but that there has been an excess — that there has been
a turn in the direction of excess treatment, and I'm not exactly
sure how you describe what constitutes the excess.
At one point, you talked about cases in which it would be
in the child's interest to die, and I wonder whether we might, 10
or 15 years from now, if such a formulation were made the standard of
care, whether we would say the case — we regret the way in which that
case was made. In other words, could — are you able to articulate,
for yourself at least, and suggest how we might articulate the
principles for deciding that this kind of treatment is really
The Council has dealt with this with respect to end-of-life
issues in the adults, and we've, in a way, affirmed the old
standards where the treatment is excessively burdensome or where
I take it you might think that there are some treatments
that would be efficacious and not excessively burdensome, but that
might still be excessive under the present circumstances. I don't
know that you mean that, but if you could say a little bit more on the
ethical side of what you think constitutes too much, or how we would
DR.FOST: Thanks, Leon. First, I'm glad you mentioned
Paul Ramsey, who was maybe more than anyone else responsible for my
entering this field as an undergraduate at Princeton. He was immensely
influential in getting me interested in these issues and stimulating me
to get involved, and an important mentor to me throughout my life, a
really wonderful man.
Paul Ramsey did not quite say "impossible." In
his famous debates with Richard McCormick, he said for a number of
years it was impossible to find an ethically coherent justification for
non-therapeutic research in children. But I'm sure, as you
remember, Leon, near the end he said that perhaps we had to sin
bravely, as he put it. That is, we have to do this kind of research.
We have to admit that it's wrong, but we have to do it.
What's the ethical rationale for that? In my view, a
better rationale than the simple utilitarian one would be what some
have called a constructive consent. That is, to have a reasonable
inquiry as to what a child in that circumstance would do if he or she
understood all the ramifications.
That is, if an infant had a moment of lucidity and could
understand everything that we understood, might he or she agree to
allow a mere venipuncture in the interest of the class to which he
belongs, the class of children or children with a certain disease, and
That seems to me at least a more plausible basis. I think
the bottom line is that, like Paul Ramsey, I don't want to see this
— to see a shutdown, a prohibition of non-therapeutic research. I
think that the minimal risk rules and the assent rules are useful
boundaries, but need to be, in the case of minimal risk, better
I think that it has gotten way out of control. I was part
of the National Commission deliberations, not as a member but as a
consultant. And I know that what was meant by that rule was things
that happen on a visit to a general pediatrician for a routine well
baby visit, and that has gotten way out of hand. So I think that needs
to be reined in, and I think if it were reined in I'd be
comfortable with it.
And I just think assent needs to be taken more seriously.
That is, children really — somebody really needs to say to them, and
we need to have more monitoring of it, "Junior, let me make
something clear. We want to stick a needle and get some blood from
you. You don't have to do this if you don't want to."
Now, would everybody say no? I don't think so. As
Will Gaylin famously said, "A parent has a right to decide that
their children are not going to grow up to be a selfish little
bastard." So that is some parents, and many parents in fact,
would persuade their children that they want them to volunteer for this
kind of research, because they think it's good for them to be a
volunteer, and it's important to be altruistic.
That does happen, and I think it's appropriate. I
don't think it's abusive. Parents do more serious things in
the name of altruism for their children.
So it's a long-winded way of saying I think the common
rule is adequate to protect children in this regard, if minimal risk
were defined more rigorously and if assent were taken more seriously.
That would still leave the problem of infants and children who
can't speak at all a little bit out there, but I invite you and the
others on this Council to help us. I think with some more work we
might be able to come up with an appropriate rationale.
With regard to your second question, I think if — the
problem is that even for children who meet the parameters that you
describe for adults, that it's treatment that is excessively
burdensome. And without compensating benefit, it is difficult in many
settings to allow these children to die a dignified death.
The Schiavo case is an adult case, of course, but there are
many children similar to Terri Schiavo, or not quite in a persistent
vegetative state which is harder to diagnose in infants and children,
but with profound brain damage in which there is unanimity among the
medical people that this child has little prospect for any kind of
social interaction, any opportunity to experience any of the pleasures
of life, even those of a profoundly retarded person, and in which
hospital attorneys or neonatologists, fearing legal consequences, or
the kind of public maelstrom that surrounded the Schiavo case, even the
involvement of the United States Senate, are reluctant to pull the plug
or to stop treatment.
Skip Nelson will be saying much more about this later, and
I don't want to intrude on his territory and where he has a lot of
clinical experience. But I think it is very difficult to let children
die in many settings, because of a very defensive attitude by lawyers,
In fact, Loretta Kopelman is the co-author of a famous study in
The New England Journal with her husband Arthur, a neonatologist,
showing that after the Baby Doe regulations large numbers of neonatologists
in America stopped using their judgment about what was in the interests
of their patients — that is, shifted towards overtreatment,
which was defined as treating children who they thought had no interest
in being children, as a result of the Baby Doe regulations, as a
result of, in my view, a false fear that the Baby Doe regulations
prohibited them from acting in the interests of their children.
So, in summary, again, a complicated area and a long-winded
answer, but I think the sorts of guidelines that apply to adults are
applicable to children. We can't even — it has become
increasingly difficult to even apply those. I think the use of ethics
committees provides a really reasonable procedural safeguard against
the kind of egregiously unethical withholding and withdrawing that
occurred 30 years ago.
I think it's hard to find cases of really what we would
call egregiously unethical withholding of treatment that has been
processed through an appropriately-constituted ethics committee. And,
as always, the courts are, and should be, available to people who
disagree with ethics committees or with decisions that are being made
in that way.
I hope that's responsive.
CHAIRMAN PELLEGRINO: Any other questions? Gil, and then
PROF. MEILAENDER: Yes. I want to raise several questions,
several areas. I'm going to pass on the end-of-life questions for
the moment, not because I think they're unimportant, but just to
try to get at a few deeper issues in some of the other areas.
First, with respect to the research, just as an aside,
there is probably no way we could settle this without getting out the
text, but I don't think Ramsey changed his mind, by the way. The
sin boldly stuff was, at least on my recollection, what Ramsey loved to
do. That is, play with possible justifications that one might come up
with for various things.
It was not, I think, his preferred proposal on the matter,
but we'd have to get the text to decide that one. But on the
research, I want to sort of get at a couple of what seem to me to be
deeper questions, and then also on the genetic testing.
The examples you gave were wonderful in a certain way of
the requirements, the hoops that you are forced to jump through, and
which do seem ridiculous to probably almost anybody sitting there
listening. Raise a deeper question, though, exactly what — what's
the larger concern here? The larger concern is, whom shall we trust?
And how do we structure circumstances in such a way that we think, you
know, trustworthy people are making decisions that are wise.
And we find ourselves in a circumstance, not just here but
in many areas of our life, where the only way we can seem to find to do
it is regulation/overregulation to the point of absurdity. But one of
the reasons we find ourselves in that circumstance has to do precisely
with the history you recounted, in a way.
So I'd be interested if you could say just a little
more about that kind of question about exactly how we satisfy ourselves
if there are people whom we can trust.
And then, one — second question on the research. This
follows up on Leon's question. On the one hand, you don't want
to shut down non-therapeutic research on children. On the other hand,
you don't think a moral justification for it, up until now,
that's satisfactory has been provided.
Would you be willing to say that to take up the question in
a non-frivolous manner would require leaving open the possibility, as
one possible answer, that it should stop? That is to say, your answer
to Leon was simply you're confident that an appropriate rationale
can be found if we work on it.
Well, and that may be true, but wouldn't — if
we're really serious and not frivolous in taking up the question,
wouldn't we, from the start, have to have at least as one
possibility the idea that maybe there wasn't any justification, and
we just couldn't say that?
And then, on the genetic testing, if I can just put one
more question before you, there must be deeper impulses or urges at
work that lead us to want to know, with respect to these newborns, not
just about PKU but about a couple hundred or a thousand possible
abnormalities, even if, as in many cases you've said, not for now
at least directly connected to any known disease.
What's going on there? In other words, is there some
larger cultural power or impulse at work about what we want from a baby
or our need to know something if we can know it. In other words, are
we going to solve these problems just by a recommendation, or are there
some sort of deeper issues at work that push us in certain directions?
And that may be very much harder to get a hand on than just a
I'd be interested if you could say something about
DR.FOST: Thanks. Those are all great questions.
First, with regard to who to trust in the research area,
it's my view that IRBs have worked extraordinary well. That is,
that's — that's the main thing that has changed since the
'60s and the '70s, the common rule and local IRBs to implement
It's very difficult to find, in the last 20 years —
and there have been several studies to support this — an example of
the kind of egregiously unethical research that was common and
ubiquitous in the '70s. There is a lot of conceptual basis for
IRBs. I myself am very enamored of what's called ideal observer
theory. Put in simple language — many heads are better than one.
And I think it's so hard to find an example of, really, the
kind of research that was common back then that whenever something
happens that's controversial it becomes a cause celebre. So
the death of Ellen Roche at Hopkins, the death of Jesse Gelsinger,
stay with us for years and years and years, probably decades, and
in my view don't even themselves constitute egregiously unethical
That is, I think it's very difficult. I think there is
a case to be made, both sides of those cases, and yet they've
acquired — they've become poster children as research gone wild.
Research has not gone wild. The Roche case and the
Gelsinger case are remarkable, because they are exceptionally uncommon,
and even those cases I think have been — there has been demagoguery
about them, and they've been overstated. So in my view IRBs have
done an amazing job.
Have they produced a zero-risk situation, a situation in
which no human subject ever gets mistreated? No, of course not.
Nothing can. But it's remarkably rare for — to have unanticipated
complications of those sort, but, more importantly, to have research
that would attract widespread condemnation.
So can you trust them? No, I wouldn't trust
investigators. I think investigators, left to their own devices, will
run through the stop signs for all the reasons that they did 30 years
ago, not because they are evil or mercenary, but because they — their
eye is on curing cancer in our lifetime and advancing science and
So, no, you need committees. I don't think we need the
kind of micromanagement at the federal level. I think the local IRBs
have generally done a good job. I think the sanctions are way too
punitive, and for all the wrong reasons. So that's my response to
With regard to non-therapeutic research, is it possible
that a serious inquiry will lead to the conclusion that there's no
justification for it? Sure. Where would that lead? Would that lead
to — lead me to recommend the policy of no more non-therapeutic
research involving children? No, I'd come out somewhere where Paul
Ramsey came at, and we — I'd be happy to dig out the text with
By the way, it was sin bravely, I think, not sin boldly.
But, obviously, national policy should not hinge on what
Paul Ramsey thought. It should hinge on what a consensus of people in
America think today.
So it may be that there is no — it may be one of these
unresolvable issues in which there is no real compelling moral argument
for it, but there is not a horrendous argument against it either, if we
keep it — if we keep the noise level down and keep it to truly minimal
And your last issue, what drives this mania for testing? I
had notes on that, and I'm glad you gave me a chance to expand. I
didn't want to use up too much of the air time.
There are several factors that are quite common in these —
in this repetition compulsion. One is that the PKU lobby has been
duplicated over and over again. That is, there almost always is a very
zealous lobby that forms, consisting of parents of children who have
died or have become profoundly — you know, if your child died of a
rare disease, you understandably don't want to see this happen
again to anybody ever.
And so — but you're not a scientist, and so you say
it's just unimaginable to me that every child in America isn't
tested for this very rare disorder, and so that something can be done
about it. So parents are very much out in front of this.
Second, they are put out in front by the testers, some of
whom have, frankly, commercial interests, so there is serious financial
conflicts of interest in some cases. That wasn't the case in PKU,
and it's not the case in all screening programs.
But there are commercial testing laboratories who would
love to have this happen, and are funding publicity campaigns, as
happens in other areas of medicine. So there is just frank commercial
conflicts of interest.
Third, there are empires that don't make people rich,
but that make people more powerful or influential. Let me tell you a
personal story there. I've been interested in newborn screening
for cystic fibrosis. I was co-investigator of what is I think the
largest clinical trial ever done. Dr. Farrell at University of
Wisconsin randomized over 600,000 infants over a 10-year period, to see
if early diagnosis and treatment for cystic fibrosis was helpful.
Fifteen years ago, before that trial was even done, was
even started, I was invited by WHO to attend a technical assistance
conference to help other countries begin cystic fibrosis newborn
screening. There were 25 countries there — Bahrain, the Soviet Union,
Argentina. They all wanted to start newborn CF screening, and my
thought was, why? I don't know of any evidence that it's
I know of lots of reasons why it might be harmful. Our
study explicated and documented many of these harms, medical as well as
psychosocial. You have far more serious problems in your country than
cystic fibrosis. You don't even know what the incidence of cystic
fibrosis is in your countries.
My sense of what was going on is that the people at the
meeting were the equivalent of state lab directors who, you know, it
was another machine. It was another couple of people on their staff
whose expanded budget — it was getting more information, possibly some
research interest. I don't think they were getting rich off of it,
but they — technicians like to do things. Doctors like to do things.
Testers like to test. So that's part of it also.
And part of it is very poorly thought out moral claims of
justice and unfairness. If Wisconsin is screening for 30 conditions,
it's unfair that a child in Iowa — and this has been the argument
used driving the Secretary's Advisory Committee as far as I can
tell. We need a uniform policy.
Well, if it's a bad policy, there's no virtue in it
being uniform. There is no unfairness in not distributing something
that has no known value or whose harms may exceed the benefits.
So those are some of the factors that have driven this, and
they have been repetitive.
CHAIRMAN PELLEGRINO: Dr. Lawler?
PROF. LAWLER: Yes. Thanks for the great presentation. Just
one point of clarification. The Baby Doe regulations were a great
advance in terms of protection of the rights of people with Down's
Syndrome. And that protection is more urgent than ever as there are
fewer and fewer people with Down's Syndrome around.
Now, you said that has led to a regime of overregulation,
over — of overtreatment — overtreatment, right. Now, the only thing
I didn't understand fully is whether that overtreatment is based
upon a misinterpretation of — a fearful misinterpretation of the
existing regulations, or if the regulations, as now exist, need to be
mended in some way, need to be changed in some way. What's the
bottom line on that?
DR.FOST: Thank you, again. I mean, it's as if
I've planted these questions. First, I agree with you completely
that the Baby Doe regulations were absolutely essential, or something
like them. That is, I hope I've conveyed my personal view that it
— I think I used the word "egregiously unethical"
withholding of treatment from children with Down's Syndrome, spina
bifida, and many other children, with excellent prospects for
meaningful, happy lives.
The overreaction, in my view — and Dr. Kopelman and Dr.
Nelson may disagree with this — my view is that overtreatment
that's based on Baby Doe regulations is based on a false
understanding of them. That is, I think the Baby Doe regulations have
been widely misinterpreted and misapplied.
For example, to whom do the regulations apply? Any
regulation has to say who it applies to. It applies to state health
departments. It's a regulation requiring state health departments
to respond in a certain way if there's a report of medical neglect,
of refusal to provide medically necessary treatment.
Absent a report, the state has no duties. And, in fact,
the Inspector General under President Reagan found all 50 states to be
in compliance, even though thousands of babies were still being allowed
to die in seeming violation of the substance of the rules.
The rules do not apply to doctors, hospitals, or parents.
So they don't, in my view, impose a single requirement on
physicians, families, and hospitals making local decisions.
They're as free as they ever were at — I mean, they are subject to
tort law and criminal law and all of the other laws that always did
exist, but in my view the Baby Doe regulations have actually no legal
implications for treatment decisions.
So the overtreatment that has been predicated on them is
misstated and is a misinterpretation of them. Is that responsive to
PROF. LAWLER: Exactly.
DR. ROWLEY: Thank you very much, Norman, and it's nice
to see you again.
I have a different question, because you really raised
three issues, of which you dealt with only one. Our Council meets
every few months, and I think I've been a proponent of dealing with
ethical issues related to children. We have actually in the past had
several people come and speak with us about children, particularly
early childhood development and brain development in young infants and
children, which were very helpful for me.
I think that, in fact, we are going to have to make a
choice, because we can't deal with the three issues that you
raised. And you made a point that the issue you were actually going to
discuss affected far fewer children than the two that you did not
And so from your perspective of the Council and where —
I hate to use the term "where it could have most effect,"
because I'm all in favor of tilting at windmills if only —
if that's the major thing we should be doing. But I would appreciate
your opinion as to whether — which of the issues that you
raised, such as our dreadful neglect of children born into poverty,
infants born into poverty, or child abuse, as compared with those
that you spent the time discussing.
DR.FOST: Janet, thank you for bringing me back to what
really matters, as you always do. Yes. I didn't talk at length
about the problems of poverty or the solutions to it or the problem of
the uninsured out of sheer diffidence. I mean, because I don't
have any particular expertise, certainly compared to other members of
the panel or other experts who you could bring in.
I mean, I have an ordinary person's notion of what
needs to be done. But those are overwhelmingly the problems that
oppress and afflict American children — being born into poverty, into
situations in which access to health care are constrained.
And child abuse I would put third on the list, because that
only — but that only involves a few million children as compared with
the tens of millions — I mean, these numbers are just absurd — who
start off life with no fair opportunity to really succeed.
So those are the overwhelming problems. And, yes, if this
Council could have an influence on the President's policies or the
country's policies on something that really affected children, I
would much rather you spent all your time on doing something about
problems of poverty and access to health care and child abuse than
these other three angels on the head of a pin issue, which in the final
analysis affect very few children.
So, and part of it, I talked about things. There's a
story Robert Morley, the great British comic actor, tells that — if
you'll indulge me — he was explaining why he quit school at age
12, and he said it was an exam question. The exam question was,
"Describe and discuss the Cape of Good Hope." "And I
wrote in my exam booklet, "I don't have the foggiest idea
where or what the Cape of Good Hope is, but I do know the 12
And he wrote the names of the 12 apostles and said
something about each. And he said, "They flunked me," and it
showed me once and for all they weren't interested in what I did
know but only in what I didn't know.
So I talked about what I do know, because it's
comfortable, and it seemed to me overreaching to go into any more
detail about things that I really am not very expert in.
DR. ROWLEY: No. But I — that was not the purpose. The
purpose was really to say if we as a group have to make a decision,
which will be in a sense a group decision, what kind of advice can you,
as a consultant, give us on that? So that was the purpose of the
DR.FOST: My advice would be that you spend what time and
resources you have in making recommendations that affect children who
were born into poverty and children who are born without reasonable
access to health care. If you can make some recommendations that might
influence national policy in those areas, it would be time well spent.
PROF. DRESSER: I have a related question, perhaps to push
you in this area, because I think one of the reasons we haven't
done as much as we should in bioethics on these issues is because we
don't know how to approach it. It seems so overwhelming. And I
know that some of us on the Council do want to get into these social
So I guess one way I think about it is with limited
resources, how would you allocate them differently from the way they
are allocated now? And I'd be interested in what thoughts you
might have, not just about allocation of health care resources and how
that might better affect children, but also research resources.
So if you were thinking about taking the NIH budget and
making it more child friendly, how would you spend your money?
DR.FOST: You've caught me off guard, Rebecca, which
is good. So I don't have well thought out responses to that
question. So I'll think aloud.
First, let me just say with regard to resources in health
care, I've gotten into big trouble with the American Academy of
Pediatrics for suggesting that the way we deliver pediatric health care
should be dismantled. That is, having a pediatrician for every child
is an extremely expensive way of providing mega hours of service that
has no known relationship to health.
Roughly half of a pediatrician's time is spent doing
health supervision, which has no known relationship to the health of
children. And these are — everything that's done on those visits
could be done far more cheaply and efficiently by a nurse or someone
with even less training. I mean, all of the immunizations, all of the
weighing and the measuring and the eye checks, and all of that, you
don't need a doctor to do that. The doctor spends almost no time
doing anything that you need a medical degree or training for.
So we could expand access of children if it were — if they
didn't have to be funneled through pediatric offices, if we had
more of a public health program with well baby stations as occurred 50
and 75 years ago, where immunizations were given and/or even acute
illnesses were managed by a non-M.D. So I would change that, if I
I would change the allocation of health resources away from
acute illness towards more preventive services, of which child abuse is
simply the most important example I know of. That is, prevention
through home visitor programs rather than the $5 million treatment of
every kid who gets whacked in the head and then we take care of him or
her the rest of their life.
With regard to research, I would greatly shift the emphasis
away from biomedical research into more epidemiologic and public health
research. My M.P.H., my one year getting a master's in public
health, showed me just how much more powerful epidemiologic approach is
to health care, both in research and implementation. I could give
dozens of examples that are probably familiar to you of how — I'll
just give one just to make — make the point.
My colleague Murray Katcher, a pediatrician in Madison, discovered
that were 100,000 patients admitted to hospitals each year for severe
scald burns, almost all infants and the elderly. If the hot water
heaters were set at 130 instead of 140 — at 140 it takes two
seconds to get a third degree burn. At 130, it takes 45 seconds.
So you would end burns forever if the heaters were set at 130.
He set out to do that. And to make a long story short, he
did it. So there is an intervention that — all new water heaters in
America now are set at 130. You can't get people to turn the old
ones down. So it will be 40 years before they all expire.
There is a piece of research and implementation that cost
zero, didn't cost one cent, that is going to prevent hundreds of
thousands, millions of cases of suffering and death due to hot water
burns, child-resistant containers — another virtually free
intervention that has prevented tens of hundreds of thousands.
So I would shift the whole national research budget to more
public health epidemiologic study and interventions of that sort. And
I myself would spend less on hard science, assuming fixed dollars.
CHAIRMAN PELLEGRINO: Dr. Hurlbut?
PROF. HURLBUT: You mentioned the massive experimentation
that is being done through off-label use of drugs, and then you also
said that clinical research is dying, and that we're looking at a
whole new set of potential interventions that are quasi-therapeutic
related to genetic screening. And it seems by implication those could
go backwards, too, into fetal development eventually. In other words,
you might end up administering drugs to pregnant women to — to deal
with some things eventually.
Well, looking at it post-natally, is there a way we can
enter into this difficult arena through the current therapeutically
justified trials, research, therapeutically? In other words, given the
difficulty of defining and justifying non-therapeutic interventions,
can we get a better handle on some of the research that needs to be
done through the therapeutic trials?
DR.FOST: Yes, definitely. If the PKU program had been
subject to a — even a randomized clinical trial, which is sometimes
hard to justify for what you think is a uniformly horrendous disorder,
some children with PKU would have been lost — that is, would fail to
have been treated. But many hundreds — we don't know the number
— of normal children would have been saved. That is, we would have
found out in a year or two, instead of 10 or 15 years, what we were
So that's point number one is if these new technologies
were studied systematically, I think in the long run we're less
likely to harm and more likely to help.
Even for conditions in which it is hard to justify a
randomized trial, even a simple registry — I mean, we presently
don't have a requirement for states that are implementing all of
these programs to maintain a registry, a state or a national registry.
That alone would at least allow for some observational collection of
data, so that 10 years from now we know what the outcomes of all these
So, in my view, that's urgently needed — a national
registry for all children that are screened and treated as a result of
these new technologies.
Third, I think having the laboratories of the states that
— let me say that differently. Having variation among the states I
think is a good idea, not a bad idea. That is, right now some states
like Wisconsin are doing them. Others are holding off.
I hope it stays that way for a time, because it's not
quite a prospective randomized trial, but it's a reasonably
controlled trial. So that 10 years from now we'll be able to look
at children in Idaho and with — who have these conditions, and we can
always diagnose the conditions, and we can always get a sample of blood
and find out who has these chemical abnormalities and who doesn't.
So I think in the absence of better knowledge having some
variation in the way states approach this is a healthy thing. I worry
a lot about a national standard being implemented. I hope that's
CHAIRMAN PELLEGRINO: Other comments?
DR. KASS: Norm, I wonder — again, this may be to ask
something outside of your area of expertise. But none of the things
that you have spoken about deal with the question of the mental health
of children. And I wonder if — I mean, child abuse is one area, and
the consequences of poverty and deprivation imply that part of the cost
is in terms of mental well being broadly conceived.
But do you have any suggestions along these lines? And not
just concerning, let's say, the health of the identifiable abused
children, but more generally whether there are things for this Council
to be thinking about in that area.
DR.FOST: Yes. In fact, I've written a couple of
papers, which I'd be happy to provide to you, on essentially the
perils of innovative therapy in emotional and behavioral disorders of
children. That is, the inadequate amount of prospective randomized,
controlled trials, the difficulty in getting funding is a big part
there, but also in getting investigators and some fighting off what I
consider to be somewhat demagogic opposition or resistance to
experimenting on children, or using them as research subjects, in
treatment trials, in therapeutic trials.
So I think mental health is especially forlorn as an area
for systematic research for interventions, pharmacologic, behavioral,
and others. And there's way too much innovative therapy that is,
as you probably know and other members of the Council, millions — tens
of millions of American children get SSRIs prescribed for everything
from depression to behavior problems to anxiety to obsessive-compulsive
disorder, with almost no data. And we now know that these drugs have
serious adverse effects, that suicidal ideation is now — and suicidal
behavior has been unequivocally shown to be increased in children.
Well, that may be worth it if you're prescribing it for
something that's a real problem and for something for which
there's a real benefit, but we don't know that. And I could
cite more specific data, and I can send you the article that shows it.
So the general answer is there is a tremendous shortfall in
the amount of research that should be done on children with mental,
emotional, and behavioral disorders. There is way too much innovative
therapy going on, especially in that area.
DR. KASS: May I? This was welcomed, but let me — let me
just put it a little harder. I talked about mental health and well
being. The answer came back in terms of the medical treatment of
disorders. And this may be what Gil was hinting at when he was asking
about the drive toward testing.
Should we be concerned about what in previous discussions
— we've had a few discussions of this so-called problem of
medicalization, of the — the revision of the understanding of child
development and child-rearing in medical terms such that the turn is
immediately for some kind of medical testing, medical intervention.
Do we need — I mean, is this something that ought to
concern us? How one actually conceives normal child development,
child-rearing practices, and to what extent the desire to see these
increasingly either through neuropsychiatric terms or medical terms is
itself something to be worried about, or is it — are we going in the
right direction, but we just don't have enough of it?
DR.FOST: Okay. I think I understand your question
better. Well, let's take ADHD as an example. That often arises in
these discussions — attention deficit hyperactivity disorder.
Explosion in medical approach to that disorder, millions of
prescriptions a year for children — for treatment of a disorder which
has no gold standard test, for which diagnosis is uncertain, and
criticism by many people who think that whatever problem a child has is
something that would be better if it were understood as an
environmental problem, behavioral problem, a parenting problem, a
school problem, and so on.
I think there's truth on both sides of that debate.
That is, I think there's no reason to be phobic about
medicalization of a problem, if medicine helps — if it's safe and
effective, and if we're sure it's getting to the right
children, and if we have systematic studies and have reasonable
So the fact that ten million children are getting a drug
that may help them perform better in school, if it's a safe drug
and if it does help them perform better in school and makes their lives
better for that reason — I mean, hypothetically, if the drug had no
side effects and were free, I don't see any reason, just because
it's a drug, that we should be against it. Nor would I see any
reason to be against better schools with better teacher-child ratios or
better parenting or environmental or behavioral approaches or nurturing
that would produce the same result.
But the problem, as you know, is it's easier and
cheaper to find a drug that will solve the problem than to figure out
how to get the teacher-student ratio down from 30 to 1 to 10 to 1. So
I don't see any a priori reason to be for or against any of these
Obviously, we should be doing research on all of these
fronts, and we should be looking for the most effective, most
efficient, safest, best way to help children. I don't see any
reason to be for or against drugs just because they're drugs.
CHAIRMAN PELLEGRINO: Dr. Meilaender?
PROF. MEILAENDER: This is a question that's related in
a way, though coming from a very different angle. And I can only come
at it — I mean, I'm not a practitioner, so I just have to go on my
own tiny little experience.
But it was interesting to me before, in an answer to an
earlier question, when you said that — I think you were talking about
allocation of resources or something and you said that — that
pediatricians spend a great deal of their time doing things that you
don't need medical training for. I mean, you could have other
people do them.
But that's connected to the medicalization question,
because I would have said — again, now just off — just off my own
personal experience, that pediatrics is the one area of medicine where
there is still a good bit of talk that goes on between doctors and
Now, that's not something maybe that you need certain
kinds of medical training for, but I wouldn't want to call it an
unimportant part of medical care. And, indeed, I think from the lay
person's perspective one of the problems with — I mean, a lot of
the jokes that people make about doctors — there's no talk that
goes on. You've got to kind of yank him back in the door sort of.
So it just — the question that interests me is sort of how
we ought to try to think about these questions, and whether we need to
think about them in — well, I was going to say larger, but that
prejudges the question — just what the right frame of reference is to
think about these.
You see, I would say that it's good that pediatricians
spend a lot of time just talking, even if it doesn't require some
sort of hyperspecialized training. And I wonder if you could just
think about that a little bit.
DR.FOST: I think it would be good if pediatricians spent
a lot of time talking, but they don't. No, there are numerous
studies that show —
PROF. MEILAENDER: Mine do, but —
DR.FOST: Yes. Well, it has been studied. Maybe it's
not the same everywhere. I'm sure it's not the same everywhere.
But the studies that have been done show — first of all, I
think what — the main thing that parents want out of that
well baby visit is — is talk.
And to talk about the long list of concerns about
child-rearing and child behavior and what to do about drugs and
alcohol, and all of the other things that beset parents and children
these days, the problem is empirically that the amount of time that a
typical pediatrician spends talking about those things in a well child
visit is about 90 seconds. That's the average.
Second, those things could all be very well done, as good
or better, by a qualified and trained nurse, nurse's aid, social
worker, somebody who could be equally knowledgeable. You don't
need to go to medical school and take — in fact, there is very little
in medical school or in residency training on those issues.
Pediatricians get remarkable little training in all of
that, in some programs better than others. But the point is you
don't need a pediatrician to do it.
So if I just had access to the dollars that go into
pediatric care in America, defined as care that children get in
pediatrician's offices, I could get a much bigger bang for that
buck, including much more talk — and I don't mean to belittle talk
at all. I agree with you, I could get much more talk by reallocating
it to less expensive, equally qualified practitioners.
PROF. MEILAENDER: Yes. I don't really know exactly
what got me to this, or how we come to it from where you started us.
But I don't think it's just the amount of talk. It's a
question of who you're talking to. See, I mean, I want to — when
I'm sick, there are certain people I want to talk to.
Get out of the medical realm entirely, the large
congregation, of which I'm a member, sends all sorts of people to
the hospital to talk to members of the congregation. And as I once
told my pastor a while back, "When I'm in there, you'd
better be there to talk to me."
It's not just a question of amount of talk. It's
the question of to whom you're speaking. And, once again,
that's got something to do with the way we conceive of what's
important in medicine. I just — I don't want to lose that in the
focus on specific specialized technical details.
DR.FOST: You're referring or suggesting that the
authority of the doctor may have some added value that would not accrue
to a less prestigious person?
PROF. MEILAENDER: Well, that may be true. And it's —
you know, I take — I spent a lot of time and money going to see this
person, and I expect something other than just technical expertise.
DR.FOST: Right. I mean, I think when you're sick or
when your child is sick there's a lot of truth to what you say, and
validity to it. But if your child is bed-wetting, I don't know
that the kind of advice that you need, and the kind of remedies that
are available, and where do I start, and what do I do about this, I
don't know that there's much added value in having somebody
with an M.D. after his or her name as compared with somebody who knows
the field, knows what's available, knows what to do, can get you
started on the right track in an empathic way.
CHAIRMAN PELLEGRINO: Alfonso?
DR.GÓMEZ-LOBO: This is just a brief reflection from
someone looking at all of these things completely from the outside.
And I'm very much impressed by the — your reference to poverty and
to the deprivation of access to health of young children, because of
the social condition.
And it seems to me that that seems to be sort of a
grounding reality, and my reflection is simply this. As a Council, we
should consider that surely as part of bioethics, as part of social
justice issues. And I just hope that in the final report on issues
relating to childhood we go into that as deeply as we can.
Now, I think that there's an intersection with politics
and social policy that it's very hard for us to tackle. But,
still, it seems to me it — it seems to be so central, so deeply rooted
in virtually everything that happens afterwards that we should really
as a Council consider it, I think.
DR.FOST: Yes. Let me just give you one fact that ties
some of this together, some of my comments together. One-third of all
abused children in America are ex-prematures. One-third of all abused
children in America are ex-premature children.
Prematurity accounts for about six percent of American
births. It accounts for about 33 percent of child abuse in America.
Who gets born — the reasons for that are multiple. Prematures are
born, many of them, to teenage mothers. They are children who are
notoriously difficult to take care of. They have disabilities and
handicaps. There's a lack of bonding. In the newborn period
they're in an intensive care unit for weeks or months, and the
parents take this stranger home, and so on.
Who has premature children? Teenage mothers, poor mothers,
mothers without prenatal care, mothers who have health and drug
problems of their own. That is, poverty, lack of prenatal care,
prematurity, child abuse, if you could just reduce the incidence of
premature — our problems of prematurity dwarf. I mean, you know,
it's one of those many areas of American health where we're
near the bottom of the list of industrialized countries.
If something could be done to reduce that, there would be
reduced child abuse.
CHAIRMAN PELLEGRINO: Dr. McHugh? We have time for one
DR. McHUGH: Just one question. I enjoyed your
presentation, Dr. Fost, and I particularly appreciated some of those
old stories that I remember about how, really, the doctors lost the
trust of families who had given their children into hospitals and
discovered that — some of them discovered directly, others indirectly,
that the doctors and even the nurses themselves had lost some interest
in the loved one that they had submitted there.
And the loss of trust or the betrayed trust has produced
what it always does — namely, this increase in regulation, the
regulations that are completely out of control now and are interfering
with our capacity to work it.
But, you know, the blame does fall back upon us. We did
it, and now we are paying a terrible price. And to win back the trust
of the American people of this sort requires not only the presence of
IRBs but the particular demonstrations, as you've demonstrated
today, of the — of what we are losing.
Now, I'd just like you to look ahead now, since, you
know, we have — this world we're in now and we ourselves
aren't perfect — what kinds of things do you think we are going to
think in 10 or 15 years from now represent egregious betrayals of trust
in hospitals and places of that sort, to the families, that bring our
children — their children to them?
I wonder whether, for example, you might think in terms of
whether managed care in the great shortage of time now presented to —
in-hospital to patients and families that might lead — mean longer
time, or investments of more resources for the care of them, even with
chronic illnesses like the AIDS epidemic in young children, and whether
we are prepared to carry the concerns and services that those kids
And you have mentioned in this little discussion with Dr. Meilaender
how little talk gets done. And maybe little talk gets done by pediatricians
and other M.D.'s because they don't know any psychology, and
we don't teach psychology in most — to most medical students.
It's the only basic science they don't know anything about.
And, eventually, even empirical psychology would help them
in this, and this neglect might be something that people will come to
regret and ultimately find, once again, imposed upon them. Do you have
any predictions from what we're doing now?
DR.FOST: Well, I'll accept your invitation to wax
political for a moment. If I — if you asked me to guess what will
most embarrass us, or make us ashamed of ourselves 25 years from now,
it would be the massive reallocation of funds from the lower and middle
classes to the upper classes.
That is, in a country that has these problems that
we've been talking about, the continuing widening of the gap
between the rich and the poor and the reallocation of funds in the —
from those who are least well off to those who are best off. That, to
me, should be an embarrassment, and I think will be. And the effect
that that will have on our children will become clearer as time goes
DR. McHUGH: Are we doctors contributing to that? Are we
— in the way we run our hospitals and insist on the lengths of stay
and things? Is that really — by the way, the care of the poor is
certainly something we all agree on, and those of us who live and work
in hospitals of — in the inner city see this all the time.
But the pressure is not simply in relationship to whether
the government is going to take a concern for the poor, but whether the
hospitals themselves are contributing to the abuse of the poor and the
kind of regulations that they are prepared to enforce upon their young
In our hospital, the doctors are told that they have to
have a certain short length of stay to be darn sure that they get the
money from — and these are for the poor.
DR.FOST: Well, you know, Justice Cardozo said laws
aren't written until they're first broken. So I think things
like managed care and length of stay rules, and so on, were necessary.
That is, I think the waste in the American health care system was, and
still is, prodigious, the inefficiency.
And given the finitude of funds that are available, I think
squeezing inefficiency out of that was unavoidable and necessary. And
doctors weren't doing it on their own, so payers had to hire
managed care companies to do it for them.
So I think that was unavoidable, necessary, and the studies
that I read — not all that bad in the final analysis. That is, there
are efficient managed care systems, like Kaiser Permanente, where
satisfaction rates are as high or higher in fee-for-service systems and
where patients are actually quite pleased with the care they get, even
though there has been a great squeezing down, and so on.
I think another thing that we at least should be
embarrassed about 25 years from now — whether we will be or not,
obviously, I don't know — is this constant ability to find new
technologies to spend our money on when we — we just — we're just
out of money when it comes to solving problems like the uninsured.
So it seems to me remarkable that the State of California
has $3 billion to spend on stem cell research. Forget the ethics of
stem cell research, about which you've dealt in great depth. But
that the citizens of that state could decide that they have $3 billion
for a technology that has as yet no known payoff, and even when it does
the number of people who it's likely to help are going to be
measured in a state that has prodigious problems with education, with
access to health care, with poverty, and so on.
We always can come up with a billion here and a billion
there for some new technical thing that is fun and fascinating. But
we're just out of money. We just can't afford to have basic
access to simple, ordinary, primary health care for 40 million people.
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Fost.
I'm afraid the schedule requires that we intervene at this point
and have our break. I'll take the Chairman's prerogative of
extending it beyond the time in the agenda, which is supposed to be at
10:45. And if you'll return at 10:50, we'll start promptly.
Thank you very much, Norman, for drawing on your extensive
And let me thank the Council members for their close
questioning on a very important topic.
(Whereupon, the proceedings in the foregoing
matter went off the record at 10:39 a.m. and went back on the record
at 10:59 a.m.)
SESSION 2: ETHICAL ISSUES IN NEONATAL
AND PEDIATRIC INTENSIVE CARE
CHAIRMAN PELLEGRINO: Our next speaker is Dr. Robert
Nelson. Dr. Nelson is Associate Professor of Anesthesiology and
Clinical Care at Children's Hospital of Philadelphia, and a Senior
Fellow, Center for Bioethics, the University of Pennsylvania.
He has his bachelor's degree from Wesleyan in chemistry
— he and I share that — an M.D. and M.Div. from Yale, and I had the
good pleasure of knowing Skip when he was a medical student at Yale,
pursuing a double degree in the School of Religious Studies as well.
He is occupied now, and moved very, very fast in the field of bioethics,
particularly in intensive care, but still ranging over a whole series
of issues of the kind we'll be looking at.
I've asked him, as I've asked the other speakers, to feel
free to range over the problems of pediatrics, but to try to concentrate
as closely as possible on his area of expertise.
Skip, welcome to the Council, and it's all yours.
DR. NELSON: Thank you, Ed. And in case people haven't
figured out, Skip is my nickname.
Which I've had since a little child. And, actually, an
anecdote on that — when I was a medical student, was asked what to put
on my name tag, I wrote down "Skip Nelson." And the Dean of
Students at the time vetoed it, because he didn't think that was
Immediate identity crisis, nevertheless. And I've kept
it. So I went into pediatrics, so I don't have to apologize for
the fact that that's my nickname.
I'm certainly honored by the privilege to speak here,
and certainly by the task of speaking and even using some of his own
work in front of one of my mentors, Dr. Pellegrino, with whom I took a
reading course back in 1976, the summer of 1976 when he was President
of Yale New Haven.
And then, the daunting task as well to follow Norm Fost,
who sets a tough mark when it comes to remarks, as far as in the field
Before I start my presentation, I can't help resist but
make two comments from the previous discussion, briefly. The first is,
to the extent that you decide to get into things like prematurity or
research, there have been committees — for example, the Institute of
Medicine, there is a current committee working on problems of
prematurity, and there is a report from the Institute of Medicine on
pediatric research that came out last year — March 2004.
And I would certainly hope and commend those reports to you
to build on if — if the desire is to begin to get into some of those
The second is a comment on Paul Ramsey and the non-therapeutic research.
Two things. In 1978, he wrote a chapter where he agreed with Bill
Bartholome that perhaps the parents' responsibility, or, if
you will, authority to nurture the moral growth of their child around
assent to non-therapeutic research might be a sufficient benefit
that he would admit that that would be inconsistent with what he
would call the parental covenant.
In a recent article that Lainie Ross and I wrote in Journal of
Pediatrics we suggest the concept of scrupulous parent as a way
to try and understand the risk exposure in non-therapeutic research,
and would invite the possibility of exploring more broadly what
that might mean, and perhaps Paul Ramsey may have had a narrow view
of parental covenant, and then perhaps a discussion of parental
authority might be a way to begin to ground decisionmaking in non-therapeutic
And I see that notion of scrupulous parent functioning the
same way as a reasonable patient might in the law surrounding issues of
informed consent. But just as a suggestion.
Now, more directly on my topic — let me just move this
closer, so I'm not leaning — I think you'll find that Norm and
I disagree about the impact of the Baby Doe regulations, not so much in
the importance of what they did at the time but in how they're now
playing out in the law.
And I do have Powerpoint. You have the slides before you,
so there is not even — you can choose to look at the screen, or you
can look at the printed text before you.
But let me start first with some introductory remarks, and
here's the outline of what I'll cover. Over the last 40 years,
there have been dramatic benefits in technology. I mean, an example
for you to consider, the ventilation of newborns with hyaline membrane
disease started in the late 1960s. It wasn't until 1969 that even
the use of continuous positive airway pressure for the treatment of
hyaline membrane disease was started.
We've come a long way through that time to the 1990s
when we developed artificial surfactant, which is now administered
routinely, to where the window, if you will, and the discussion of the
transition of pre-viable to viable has narrowed to where we're
really debating, at least in neonatology, the difference between 23
versus 24 weeks' gestation.
So there has been — whereas if you went back into the
'60s, we'd be thinking about the 30-weeker or the 32-weeker.
At what point is neonatal intensive care not worth doing? The window,
because of the technology we have, is exceedingly small as we begin to
debate that issue.
The field of pediatric critical care medicine is also even
younger. I was in fellowship training in neonatology, which I did in
addition to my critical care, when the pediatric critical care boards
were even founded. When I was a resident at Mass General, Boston
Children's didn't have a pediatric intensive care unit. They
started it in 1981, with some areas starting it earlier.
So the field of pediatric critical care medicine is even younger than
neonatology. And there have been dramatic advances to the improvement
of child health. I mean, to give you an example, the morbidity
— I should say the mortality of a pediatric intensive care
unit ranges four to five percent. That's it — four to
five percent. Ninety-five percent of the children that enter survive,
and the majority of those survive well and survive in a condition
that they entered the ICU.
So the statistics, when we talk about issues of limiting or
withholding support, we are talking a narrow group of children. I
would agree with Norm about the priorities and the importance of
priorities. What I'm going to be talking with you about is a small
group of children.
There are important issues surrounding when we start
technology, the device and drug development you hear about, which
normally the two — off-label use of medications, provisions of needed
resources, and so forth.
But what I'd like to focus on as much because I think
it's an area that could use your help is the area of decisions
around when to either not apply or to stop our technology, issues
surrounding either the withholding, not starting, or the
withdrawing/stopping life-sustaining medical treatment in pediatrics.
And that's what I'd like to focus on as we move through this
Now, thinking about how to go about this, I often like to
start with cases. But I thought I'd start a little bit with a
framework for decisionmaking, and then a brief discussion of two
ethical principles, as much so when we get to the cases that I'm
choosing to discuss you have an idea of where I'm coming from, as
opposed to getting into the cases, you're kind of wondering what I
think and what my ethical stance is, etcetera. I'm just going to
lay that out at the start, so through the cases there won't be any
confusion, if you will, about my own particular approach.
And with apologies to Dr. Pellegrino, if I have modified
how he initially presented this, let me show you how I tend to think of
our interactions. I mean, in medicine we establish a diagnosis.
What's the importance of that?
It allows us to be able to predict an outcome, and then,
for that reason, make some kind of intervention or treatment that would
hopefully impact on the probability and the assessment — the benefit
of harm of that particular outcome. That's what we do as
physicians — make a diagnosis in order to establish an intervention.
Now, as I think about it, the interventions that we have
are structured around what could be called the "technical
good." In other words, we make an intervention to reverse a
physiologic state, an abnormality of some kind, that we hope, in
consultation with the family, is in fact for that child's benefit.
Now, most of the time — as I said, 9 times out of 10, or
19 times out of 20, it's straightforward. I mean, our technical
interventions do, in fact, support the good of the patient to the
extent that we then don't need to make explicit that relationship,
because, in fact, it works.
So we don't need to make explicit the value that rests
behind that technical good in establishing the prognosis, if you will,
or the outcome. It just is implicit and doesn't need to be made
The problem is when that isn't the case. When
there's no immediate relationship between the technical
intervention that I can make in an intensive care unit and what might
be, then, for the good of that particular patient. I can bring my
expertise surrounding, if you will, the kinds of outcomes I can produce
— again, if you will, structured within the probability of those kinds
of outcomes and within the information that we may or may not have
based on research.
The parent, or the child if they're old enough, may
bring, in fact, an important perspective on what they believe is good
for them. And it's out of — that particular discussion becomes a
sort of negotiated model in a setting where it's not readily
apparent that the technical good, the skills that I can bring as a
physician, in fact serve the good of the patient.
Now, I'm not saying I'm only talking technical talk
with them. I'm engaged in this discussion, but I'm engaged out
of my own particular expertise. I'm not limited in that
discussion. Hopefully, I can understand the good, and they can talk
about it. In fact, not talking about it and assuming that the
technical good is always right for the patient leads to problems, which
we'll get into.
So briefly, on two of the ethical principles that I think
are important as I struggle, if you will, with decisions around
limiting or withdrawing life-sustaining treatment in both the neonatal
and pediatric intensive care unit. The first is the classic teaching
of the symmetry, if you will, between withholding and withdrawing.
This was stated by the President's Commission on
Bioethics in the early 1980s, and the standard view is that, in fact,
if a treatment is or is not medically indicated, that there is no moral
or legal difference between withholding it or withdrawing it. If
you've decided not to give it, that's fine. If you give it,
you can take it away, depending upon whether it's medically
That those individuals, whether physicians or parents, who
struggle with taking something away that has already been started, if
it's not medically indicated, it is just a psychological issue.
It's not a moral or a legal difference.
Now, although I generally agree with that, I think there
are exceptions, and so I do not think that this principle stands on
ethical grounds as always being true. Why is that? It assumes that
the technology itself is value neutral; that, in fact, when you've
applied it there are no values that come with it.
It ignores the social and organizational context of that technology,
the values that have, in fact, shaped it, and the impact of any
change over time. What's different then, in the future that
might be different now? And it reduces technology to an essential
physiologic function. In other words — and let me give you
The palliative surgical procedures — in other words,
gastrostomy. A gastrostomy is not the same as a nasogastric tube when
it comes to issues of withdrawal. To argue it is I think ignores
important moral differences in the application of that technology.
Neither is a tracheostomy. Now, that itself would be a
broader discussion, and I may be laying out something. I'll get
into that a little bit later as well. But I personally don't think
in certain circumstances that this symmetry holds.
Now, the doctrine of double effect — this may be familiar
to some. It's certainly not familiar to clinicians, even though we
talk a lot about double effect when we use medications in the intensive
care unit. Let me just make a few points here.
The object of action must be right or indifferent in itself
and cannot be intrinsically wrong. I think that's fairly
straightforward. The wrong effect, though foreseen, cannot be
Now, what happens here is often when clinicians, say, give
a narcotic to relieve pain, if you look at studies there will be
reports that a third to a half may have the intention to hasten death,
although those same studies actually show — the ones done in the
United States, putting aside The Netherlands for the moment, that the
use of those medications in fact did not hasten death.
My suspicion is that those individuals are struggling with
their ambivalence, and our thinking about intentionality in a
psychological sense, not in the sense it was originally intended, which
is the structure of the Act itself — in other words, you can interpret
the intention of the actor by looking at the Act, not by what they say
they think they're doing when they do it.
So if you're giving an appropriate dose of medication
for that context, I don't care what you're thinking. And if
you're not giving an appropriate dose for that context, I don't
care what you're thinking. The act is how you interpret the
Now, the wrong effect cannot be the means to the right
effect, and this comes into the discussion of hastening death to
relieve suffering, which I'll talk a little bit about towards the
end of my remarks. And then, finally, there must be a proportionate
reason for allowing the wrong effect to occur, which gets to this
balance of benefit and burden of treatment.
Personally, I think this is a very important principle
behind the provision of either withholding or withdrawing
life-sustaining treatment, or the provision of palliative care in the
intensive care unit. And one reason I believe that is I personally do
not believe that I should ever intend, nor cause, the death of my
And for me, then, to be able to provide care under that
circumstance, given that belief, I need this doctrine. And I know
there's a number of criticisms that this doctrine has had in the
literature, but I still find it both useful and defensible.
So I'm going to spend a fair amount of my time telling the
stories of Baby Doe, Sidney Miller, and Emanuel Villa, to give you,
I guess, a different take on what Norm gave you about the Baby Doe
Now, this states the regulations. The regulations are now
part of the Child Abuse Protection and Treatment Act, and they
basically require medically-indicated treatment unless five — one of
five conditions hold — the infant is chronically and irreversibly
comatose, and I'll mention the definition of "infant" in
Of course, setting aside there are no professional
standards for determining chronic and irreversible coma in a neonate,
treatment would merely prolong dying, treatment is not effective in
ameliorating or correcting all of the infant's life-threatening
conditions, treatment would otherwise be futile in terms of survival,
and treatment would be virtually futile in terms of the survival of the
infant, and the treatment itself under such circumstances would be
Now, let me just at this point say I agree with Norm's
assessment of the impact of the Baby Doe regulations in the 1980s. I
also agree with him that it was very important to stop behavior that I
would consider unethical.
But any time you then try to write a general principle that
covers the specific cases that gave rise to that general principle, and
it gets divorced from those cases, it then, given the language, runs
the risk of being applied in a way that was either not intended or
extends it into arenas that were not foreseen.
And that's, in fact, the story that we will then be
discussing is: where has it gone, and where might it go? Not
necessarily where has it been, and what was the importance of it at the
Now, one note is that the interpretation of these
regulations, first, is that appropriate nutrition, hydration, and
medication, without specifying what that medication was, must always be
provided. That was an exclusion in the regulations. Nutrition and
hydration, medically provided, is a controversial topic, and this takes
a particular position on that topic for disabled newborns.
Another interpretation is the phrase, "It is clear
that Congress did not intend to sanction considerations of the future
quality of life of an infant likely to survive if the treatment is
provided." So the intent of the Baby Doe regulations, as stated,
was to sanction any consideration of quality of life.
And I think one challenge, if, in fact, we think that has
gone too far, is to say, "Do we want to recapture that
language?" which I think has difficulties with it, admittedly, or
do we want to somehow figure out other ways to speak about the value of
interventions for critically ill newborns and children. That may avoid
some of the problems surrounding quality of life language.
And then, just to show you that this may seem to be just a
neonatal issue. But, frankly, since the majority of children, if not
the — if not at least a plurality of children in the pediatric
intensive care unit, are graduates of neonatal intensive care units, it
applies in that arena as well. An infant was defined as less than one
year of age.
However, if an infant is older than a year of age, and has
either been hospitalized since birth, was born extremely prematurely,
or has a long-term disability, these are also meant to apply by that
definition. So there is potentially an arena beyond simply neonatal
decisions where this could be a player.
So I'd like to tell you a tale of two cases, with
apologies to Dickens. The first is Sidney Miller. The date, 2003, was
the Texas Supreme Court decision. Sidney was born in 1990 at 23
weeks' gestation, either at 614 or 629 grams. For those
knowledgeable people, that's a bit heavier than you'd expect a
23-week infant to be.
There was some discussion, at least as I could tell from the literature,
since I don't know the case directly, of whether the child was
— there was some in utero infection that may have resulted
in some edema, etcetera. But this was the case, and the claim was
that she was resuscitated against parental wishes, which is fairly
The second case is Emanuel Villa, also known as Montalvo, from a Wisconsin
case who was born in 1996 at 23-3/7 days — weeks' gestation
at either 615 or 679, depending upon what document you look at,
who was resuscitated with inadequate information. And then, both
parents claimed failure of the physicians to obtain informed consent
for those resuscitations.
Now, here are the words of Mark Miller from an article in
The Hastings Center report. "We opted for compassionate care
based on the neonatologist's recommendation that the alternative
aggressive treatments would almost certainly cause painful lifelong
illness and disability.
What happened, then, as that decision circulated out into
the general neonatal intensive care unit, and other areas of the
hospital, is that an administrator ordered a neonatologist into the
delivery room without the consent of the parents to treat. That
basically was a claim that there was a hospital policy that all infants
about 500 grams required resuscitation, and it was also based on an
interpretation, if you will, of the Baby Doe regulations as applied in
the State of Texas.
So those two factual claims are not in dispute. It turns
out, interestingly enough, it was a neonatal fellow who was the one
that went in there, not the neonatologist. Talk about issues of
staffing and seniority, etcetera.
Now, the bottom line is the Texas Court of Appeals, and
then the Texas Supreme Court, though both for slightly different
reasons, said that there is no duty to obtain informed consent for
resuscitation prior to the birth of a premature infant. The Texas
Court of Appeals based this on an argument that the child's medical
condition was not terminal, which is language taken from the Texas
Natural Death Act.
And the Texas Supreme Court based this on the fact that
there's no requirement for informed consent, since the child born
then at 23 weeks' gestation — under those emergent circumstances,
the physician needed to make an independent decision about what was
required. And that was the argument of the Texas Supreme Court.
Now, George Annas wrote an article in New England Journal
of Medicine with his assessment, and just let me point some
of those comments out and then editorialize on them. First of all,
he commented that an informed decision about resuscitating an extremely
premature infant can be made only by actually examining the infant
at birth — is good medical practice.
Now, there's a debate about that. There is some
literature to suggest that if you have good early dates, which would
exclude a number of mothers who present with premature birth, but if
you had good early dates, and a first trimester ultrasound, that
that's actually more accurate in predicting gestational age and
then linking that with outcome, than an examination by a neonatologist
at the time of birth.
So that's a debatable point. But by and large, I think
it is true that clinicians would maintain, if you will, the right to
have discretion surrounding that resuscitation.
Now, he also makes a second point which I think is true,
that it didn't require the physician necessarily to resuscitate.
It just requires the physician to evaluate, although we'll go a
little bit further when we get to the Montalvo case.
The third point is he claimed that it would be unlikely
that anybody would question a decision to cease aggressive care.
Sidney Miller suffered complications in the neonatal intensive care
unit that many would argue was a basis for considering limitation or
withdrawal of support.
The parents, in fact, did not make that decision. They
didn't feel morally they could. It's a debatable point whether
or not everyone would agree. And then, finally, he makes the argument
that parental consent is legally required in the NICU. Well, that
would be, of course, true unless the parent had no right to withhold
treatments that were mandated for other reasons.
Now, let's go to Wisconsin and talk about — I'll
refer to the case as Montalvo. Born in 1996, 23-3/7 weeks'
gestational age, 615 or 679 grams. Again, resuscitated without — with
inadequate information. So this case — the parents agreed for
resuscitation at the time, but then, as they learned subsequent to that
the complications of prematurity, etcetera, they felt that that consent
was not fully informed.
So the parents made the argument that they should have had
the right to genuinely informed consent about the treatment of their
extremely premature infant. This quote is taken from a commentary that
was published by the mother and father. That's Nancy Montalvo, and
I think it's Brian Villa, in the Journal of Perinatology in 1999.
And as a personal note, this commentary was a publication
of a grand rounds that when I was still in Milwaukee I actually invited
them to give, and it was a discussion between the father and then a
mother of another infant who was born severely disabled who had I think
a very different view of disability, and then a discussion by a
neonatologist. And that grand rounds became this commentary.
I don't know at that time if they had brought suit or
not, but they subsequently did bring suit. And the Wisconsin Court of
Appeals made the following determination — informed consent comes into
play only when there is a choice of available viable alternatives.
Apparently, that is an interpretation of Wisconsin state law.
And they gave two reasons after the cesarean, which was the
mechanism of birth, why there were no available alternatives existed to
give rise to the obligation to engage in the informed consent process.
So the first reason is absent being in a persistent
vegetative state, in the State of Wisconsin there is no right to
withhold life-sustaining medical treatment. So requiring informed
consent presumes that the right to decide not to resuscitate the
newly-born child, or to withhold life-sustaining medical treatment,
The Wisconsin Supreme Court, in a case in 1997 which
involved an adult who was in a persistent vegetative state — and I
believe on a ventilator was the issue of the life-sustaining medical
treatment — found that withholding or withdrawing life-sustaining
medical treatment is not in the best interest of any patient not in a
persistent vegetative state.
That's a double negative, but it's an important
double negative because they did not say that it is in the best
interest of any patient in a persistent vegetative state. They
specifically meant to exclude making that decision if you were not in a
persistent vegetative state. So the double negative there is
It basically means that absent — in the State of
Wisconsin, absent the diagnosis of a persistent vegetative state, the
Supreme Court of the state has ruled that there is, in fact, no right
to withhold life-sustaining medical treatment from a child — for that
matter, from an adult. That that right does not exist. And we're
not talking about food and nutrition here. Let's be clear.
We're talking about anything. Anything.
Second reason — CAPTA prohibits withholding
life-sustaining medical treatment. Now, the argument that Norm made,
which is an argument that has been made by many, including myself, up
to now is that Baby Doe, at the local level as you're making
individual decisions, didn't apply. That it applied to state
Well, what's interesting about the Montalvo case is
they basically said that because the State of Wisconsin fulfilled the
requirements for getting state/federal funding under CAPTA, that, in
fact, the federal language of Baby Doe applied to individual treatment
Now, whether or not that's a correct or incorrect legal
interpretation, the point is that's what the court did. And they
pointed out that, in fact, this bars the withholding of medically
indicated treatment, except for the indications that I showed you
And so, therefore, the choice of withholding treatment —
in this case, resuscitation of an extremely low birth weight infant at
delivery — is exactly what CAPTA prohibits, in spite of the fact that
there was nothing in there that was meant to apply to a 23-3/7
week's gestational age infant.
So the Wisconsin court applied it, even though there is no
enabling legislation in the State of Wisconsin that takes the Baby Doe
regulation language and applies it.
Now, to go one step further, there is even another case in
Wisconsin — Burks v. St. Joseph's Hospital — where the Wisconsin
Supreme Court allowed a Plaintiff's claim alleging a violation of
EMTALA, which is the anti-dumping legislation. If you come into an
emergency room, you have the right to be treated.
Allowed a claim to go forward under facts where physicians
did not resuscitate her 200-gram 22-week newborn. Now, I don't
know the results of this case. I hope it settled out of court.
I'd hate to see what any court would say about this case. I would
But the very fact that the court decided to allow the claim
to go forward I think illustrates the risk there is of applying these
federal regulations in this arena.
Here was a quote from the Wisconsin court, which I guess I would
agree with, given what they're doing. "If treating physicians
can be sued for failing to resuscitate a baby they feel is not viable
(Burks), and for resuscitating a viable baby (Montalvo), they are
placed in a continuing 'damned' status. The public policy of Wisconsin
does not tolerate such a 'lose-lose' enigma."
Now, lest we think this is just the State of Wisconsin,
here is a quote from the Secretary of HHS, April of this year.
"DHHS will investigate all circumstances where individuals and
entities are reported to be withholding medical care from an infant
born alive, in potential violation of federal statutes for which we are
responsible." Two of which are the ones I've just shown you
— CAPTA and EMTALA.
This Act, which has its intent I think to enforce, if you
will, appropriate care for infants born right at the limits of
viability, whether that's palliative care or otherwise, defines
"born alive" as an infant at any stage of development who
breathes or has a beating heart or movement of voluntary muscles, which
would, in fact, include a 22-week gestation, 200-gram fetus, because
they likely would emerge, if they emerge intact, from, say, a
miscarriage with a beating heartbeat.
Now, maybe the courts just could help us with this best
interest standard. This is a quote of two courts. One is the
Wisconsin court; the other is the Texas court. This notion of best
interest, which is problematic and I think would require a fair amount
of flushing out. Others have written about its interpretation,
particularly Loretta Kopelman, and pointed out difficulties in
But here is what two courts said. Wisconsin — there is a
presumption that continued life is in the best interest of a patient.
Absent proof of persistent vegetative state, our courts have never —
my emphasis — never decided it is in the best interest of a patient to
withhold or withdraw life-sustaining medical care. Again, any
life-sustaining medical care, not — we're just talking any.
And then, in Texas, it is impossible for the courts to
calculate the relative benefits of an impaired life versus no life at
all, reminding us of some of the debates around the wrongful life
Now, in preparation for this talk, I sent around some
e-mail requests to colleagues in different states who I knew who were
involved in either neonatology or critical care, to say, "Well,
what issues do you think are important to you? What should I" —
and this, by the way, was at the top of everyone's list, the issues
surrounding, if you will, value of outcomes or quality in a palliative
care setting and in intensive care.
But here's some quotes from the person who responded
back to me from Wisconsin. With the Montalvo case, and now an EMTALA
case, there is concern among hospital risk management that these rules
make it illegal to provide any form of palliative care to infants. Any
form of palliative care to infants.
We were once told by our district attorney that if we were
to withhold or withdraw a trach vent from an infant with quadriplegia
from an unknown C1-C8 brain stem lesion — essentially it liquified.
I'm not debating about the merits of this case, but I suspect it
would be extended to others — that based on Edna MF, the case I showed
you, we would be committing criminal homicide.
And for those physicians in the audience, you'll know
that your malpractice covers civil litigation, not criminal.
You're on your own if that happens.
So let me give some personal reflections on technology, and
this is where I'm going to be sort of leaving, if you will, the
sort of legal and political realm and getting into a bit more personal
reflections based on my experience in applying technology in the
intensive care setting.
So back to this notion that technology is not value neutral —
I think there is a bias or a moral blindspot that is created by
this assumption that technology is value neutral. First of all,
it emphasizes the functional aspects of technology and obscures
an understanding of social context.
The application of technology includes values and
presuppositions that shape that technology and reinforce professional
control. For example, by doing a tracheostomy and going onto a
ventilator, you become a patient in a long-term ventilator-tracheostomy
There are certain moral assumptions and values that take
place within that program, that if you don't go into it
knowledgeable about those values, you may find your choices highly
limited, or the only choice being to actually leave that culture or
environment if you feel that the values you have are emerging as
different from that particular care environment.
Now, this is taken from the work of Barbara Koenig, where
she pointed out that the technological imperative, if you will, to
apply this technology is transformed into a moral imperative. She is
talking about plasmapheresis through a social process where technology
becomes habitual or routine, even absent any evidence of therapeutic
Now, there currently has been studies about the therapeutic
benefit of plasmapheresis in some limited conditions. But long before
we had any of those studies, plasmapheresis was felt to be morally and
technically required for certain conditions, absent any data to support
efficacy in that context.
So what about technology and end-of-life care? The role of
value — and I picked this language of value and burden and benefit to
avoid the language of quality of life, which I think can be
controversial and often open for misinterpretation. So one issue is:
what are we choosing?
This is influenced by one of my mentors in my graduate
studies, Arthur Dyck, who wrote an article called "Bene
Mortasia," where he basically said that what you're choosing
is not death, but you're choosing of how to live while dying, even
if, in fact, the process of dying is quicker under that circumstance.
In the intensive care unit, technology often turns dying
from a recognizable transition to an indeterminate ordeal. There are
many patients who die in our intensive care unit where it's almost
impossible to say where that transition took place, even if — from the
moment of application of the technology to the moment of death can be
three months, where that transition takes place.
We can say when they're dead, and we can when
they're not, but where they transition into dying as opposed to
hopefully surviving on our technical care is a very difficult time,
very difficult perception.
The whole argument of removing technology if not medically indicated
— in other words, restricting it to that — it restricts
removal to narrow technical criteria. So, for example, a ventilator
corrects respiratory distress and physiologic dysfunction, if, in
fact — I mean, it's indicated if you need a ventilator,
independent of the quality of life or what you want from that ventilator.
So if you ask me, "Is it medically indicated?"
yes, it is always medically indicated if you have respiratory failure.
So if you're telling me I can only take it away for that reason,
then you're restricting me and the family I'm working with to
either removal under narrow technical criteria or you're asking me
to sort of hide, if you will, my assessment of quality of life behind a
sort of veil, if you will, of technical criteria, which Robert Veatch
back in the discussion of spina bifida called a technical criteria
In other words, this was in response to the Lorber selection criteria,
where quadriplegia — I'm sorry, paraplegia, a high thoraco-lumbar
lesion was in that list. And he said to hide your moral judgment
about life in a wheelchair behind these technical criteria is a
technical criteria fallacy.
That's potentially what we would be risking, if, in
fact, we limit it to medical indications. And so I would argue that
avoiding any explicit discussion of the value of an anticipated outcome
for a child's future life risks reinforcing professional power and
authority in the application of that technology and disempowers
So religion and technology — these are what I would call
broad sociological generalizations, just based on my own experience.
Generally, the practice of religion in the United States is
characterized by harnessing technology for religious purposes,
supported by notions such as dominion. We could have a long discussion
about notions of dominion and the harnessing of nature, if you will,
but Protestant ethics, spirit of capitalism, etcetera, but it —
that's a starting point.
I hesitate to lay that out in front of this audience,
knowing that that's sort of out there as a nice — it's got a
big bull's-eye right in the center of it. But we'll keep
Religious language has been incorporated into the technical
practice of medicine. For example, the Miracle Modern Medicine and
Children's Miracle Network is, in fact, the name for the agency
that does primarily a large amount of fund-raising for a group of
Children's Hospital. Very worthy fund-raising, but we are creating
Recently, I would argue there is a growing emphasis on
right belief or orthodoxy, rather than faith or engaged response. And
the question I then ask is: to what extent have the values and beliefs
of technical interventions supplanted the values of religious faith?
There has been a shift in 30 years from instrumental to
intrinsic good. What happened? Two quotes. 1957, Pope Pius XII was
asked by a group of Italian anesthesiologists, "Can we remove
someone from a ventilator?" His answer was, "Life, health,
all temporal activities are, in fact, subordinated to spiritual
There was an article published in Issues in Law and Medicine
in 1987 on the topic of withholding fluid and nutrition, and in
that was this particular quote. It was signed by a large number
of theologians and ethicists. "Human bodily life is a good
of the person, not merely for the person. Such life is inherently
good, not merely instrumental to other goods. Thus, remaining alive
is never rightly regarded as a burden."
So somehow we've come from what I would argue is an
instrumental view of the importance of, if you will, biological life,
to an intrinsic view of its value.
What happened? Well, that article needs to be set into the
context of the debate about the withholding of fluid and nutrition from
Nancy Beth Cruzan. That's what it was particularly written in.
You'll notice the dates there — it was 1987 when it was
published. I think the Supreme Court case was decided in 1986 or 1987,
around that time, but that's basically the context for this debate.
So I'd argue that what is happening here — and I
don't mean to get into issues of abortion, which is not really our
topic — but what has happened, and I would also agree with some
philosophers, whose justification for abortion would lead people to be
rightly concerned that they could justify infanticide.
Is a view of a transition and a continuum, if you will, among
all of these various issues — abortion, infanticide, and euthanasia.
I have just selected some dates — Roe v. Wade, 1973; Ronald
Reagan, Baby Doe, 1982, when Baby Doe was born; Baby Jane Doe, which
was another case that led to the Supreme Court affirming the right
of parents to make a decision in the particular case of Baby Jane
Doe in 1986; Cruzan in 1990 — there is the date of the Supreme
Court decision — and then, in 1994, Republican control of
Here is a quote taken from a blog around the time of the
discussion of Terri Schiavo. The point here is — that I want to make
is that about Terri Schiavo, but about the link between all of these
different cases. So when we get to a discussion of the limitation or
withdrawal of life-sustaining treatment in popular culture, all of the
various issues of abortion, infanticide, and euthanasia, are seen in a
One challenge is: how do we break that? Because I see
them as very different issues, very different issues indeed. How do we
break that? And what kind of language can we, as a society, capture to
break those links?
Now, let me make some final comments before my concluding remarks
on Groningen Protocol, published in the New England Journal
of Medicine. Here are the three categories of infants that
it was proposed that that would be applied to — those with
no chance of survival despite optimal care.
Here, although there are many infants that we might
support, many children we might support for a long time, I think anyone
would agree that if, in fact, that support becomes useless, that in
consultation with the family we would withdraw support. And they would
The second group — depending on ICU care with a poor or a
grim prognosis. Again, if there's a decision that the burden and
benefit of treatment, as mentioned before, you affirmed in adults, we,
of course, would decide to limit or withdraw that support in usual
practice. Open question whether in Wisconsin you could do that as a
legal question, but that's what we do, and they would die.
It's the third one that's I think particularly
controversial — those with a hopeless prognosis who experience
unbearable suffering. And it's that group that the Groningen Protocol I think was presented as applying to, where, in fact, they
sought what I would call a technical end to suffering — 22 cases where
Now, personally, two comments here. I think it's a
problem. I think it's seeking a technology to end something that
is not a technical issue. My conversations with parents, as much out
of my own beliefs, if appropriate, is that all of the children in my
ICU are suffering, even those that will recover, and that the issue is
suffering to what purpose, that I have a technology that I can, in
fact, treat pain. I have a technology that I can, in fact, treat
agitation. I don't have a drug for suffering.
So there is, you know — so the ability there is it allows
me, if things don't go well — in other words, if that purpose
becomes suspect, over time it allows me to transition to a discussion
of the purpose of that suffering without having a big sort of shift in
frame of reference. But that's my own sense.
And deciding to choose death or to hasten death to end
suffering is not something that I would support.
So let me make some concluding remarks. Somehow, we need
to bring what I would call life to the end of life. We need to
acknowledge the values that drive our medical technology. We need to
appreciate the relationship between these goods of medicine — the
technical good, the good of the patient, and the ultimate good.
We need to foster the good of the patient as the purpose
and goal of medicine, not reduce it to just technology, because we fear
that discussion, which is what's happening I think with the
extension into eschewing any discussion of quality of life in
end-of-life issues in pediatrics.
We need to help patients and families through their, and
our, experience of suffering, and the purpose such suffering may
serve. We should respect the diverse religious and cultural values
that inform the experience of illness, dying, and death. I have made
an argument, both locally and nationally, that we should respect, for
example, religious objections to brain death determinations, death on
The New Jersey law allows that. We often get patients from
New Jersey to Children's Hospital of Philadelphia, and we respect
that parental determination.
We should seek relief or detachment from suffering through
setting aside our attachment to medical technology. And we should
nourish the wisdom to use technology in a way that does not obscure our
vision of the ultimate good, which I would argue I think is happening
to the extent that I believe that technological values are actually
corrupting, in some way, spiritual values.
And then, finally, to hold children and their parents
hostage. My intent here is to be proactive — to hold children and
their parents hostage, condemned to a life of suffering for no apparent
purpose, because we feel obligated to fight a rear guard action against
the introduction of moral values above and beyond those of the mere
perpetuation of biological life is immoral, rather than respecting
life, such an unrestrained imposition of medical technology desecrates
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Nelson.
We can begin discussion of Dr. Nelson's paper. Anyone
want to begin? Thank you. Gil?
PROF. MEILAENDER: Yes. I don't know whether this is
the most important place to begin or not, but it would help me if you
could give a little more specificity on something you said very near
the end. You said that technological values are corrupting spiritual
What sort of spiritual values do you have in mind?
DR. NELSON: The place I would start I guess is to go back
to the balance between what I called an emphasis on right orthodoxy
versus faith. And this doesn't happen all the time, but my
impression is that there is both a social and cultural emphasis, a
religious emphasis, and in the minds of some parents, depending upon
how they're advised by their religious advisors, an emphasis on
what should we believe in this context, that somehow, you know, what is
God doing, what is God not doing, what can we learn from this,
etcetera, as opposed to, in my view, trying to appreciate the meaning
of that experience from a perspective of faith.
Now, that — I'm being somewhat obscure, I realize, but
I've occasionally tried to talk with families about, you know, if
the relationship justifies sort of going in this direction. It's
not all the time. I don't want you to think that I do this a lot.
But, for example, the differences between faith, hope, and
love — I mean, I'm — as I talk with families, I'm — I
encourage them to think more about how they should respond about the
treatment of their child out of love, and try to show them how that
parental love in some sense may guide them better than some notion of
what they ought to do as dictated by, I would view, a sort of misplaced
emphasis on orthodoxy, depending upon their religious perspectives.
So those — I mean, it's — I mean, I guess that's
part of the discussion that would have to take place. I don't —
you know, I've talked about that with individual families, but that
would be part of the discussion.
PROF. MEILAENDER: Well, if I may just press it a bit, wouldn't
you think there might be circumstances in which my sense of what
I ought to believe should appropriately temper various feelings
that I have, which I, at the moment, think may be loving?
I mean, there is no imprimatur placed on my feelings at any
given time, and it may be that they need guidance and discipline, and
so forth. It just seems to me that whole process is considerably more
complex than setting sort of right belief against right feeling. And
so I'm still a little confused. These seem to be both spiritual
values, which generally exist in some sort of complicated interaction.
DR. NELSON: Agreed. And the last thing I would want to be
— have happen is for you to misinterpret me to argue for a sort of
Joseph Fletcher approach against a Paul Ramsey approach. No, I'm
not going there. The problem is that this is just not a conversation
that we — I mean, if we tried to carry this conversation, you know,
outside of the bedside conversation, where it's a much more nuanced
and complex discussion into a more broader social conversation, my fear
is it would get polarized immediately into the kinds of issues that
have made it very difficult to approach — cases such as Terri Schiavo,
which was really not about her but about a lot of other issues.
So that's my fear. I mean, at the bedside, yes. You
know, personally, I mean, I — you know, I can respect, and we do
respect as a group, for example, a parent's objection for religious
reasons to declaration of death on neurological criteria. From other
people's perspective that's the ultimate futility in the
provision of treatment. I'm treating a dead person.
But, you know, I'm not arguing here that there is one
belief that needs to stand. In some sense, it's that we need to
appreciate the plurality of that belief and be able to foster that in a
context where there seems to be a single sort of orthodoxy now that is
coming through the court system.
PROF. MEILAENDER: Just once more, and I will stop then.
But you did not — you said that you did not think that it was
appropriate to deliberately intend to end someone's life simply in
order to relieve their suffering. And so I take it, then, that the
fact that in some hard circumstance I am drawn to that, and I feel that
that sort of would be the loving thing to do, doesn't trump for you
the right belief that that would be the wrong thing to do.
It just seems to me that — in other words, I — there is
probably some point at which belief shapes end gauged response, to use
your language, and so the issue isn't really one about whether, you
know, the right spiritual value is engaged faith versus orthodox
belief. The issue is under what circumstances is there a belief in
shape — in place that's sufficiently strong that it should govern
DR. NELSON: Let me complicate my position a little bit
further. My statement that I would not do that it isn't much
shaped in my role as physician. All right? We could get into a much
longer discussion about whether assisted suicide in other contexts is
or is not appropriate. So, personally, I think the last people that
should be doing that are physicians, given all of the discussion you
had about the importance of talk and the lack of talk.
But, so some of that is shaped by my view of professional
role, and that would have to sort of nuance that conversation.
PROF. DRESSER: Skip, I think you made a point that I
don't know if anybody would disagree with, which is that when you
try to write rules on these complicated issues, they are likely to be
misapplied. And, you know, we just went through some of these — the
process of trying to think about when it's appropriate to withhold
or withdraw in people with dementia.
And we ended up talking about a standard that we called
best care for the patient now here. And in terms of describing that,
there were some statements of "here's what this would mean in
the abstract." But we went through some cases, and we talked
about how one person might think that this is the best care for the
patient now here. Another person might think this is, but these are
all sort of analyzed and presented in a sort of a case-based reasoning
I wonder if you think there is a better way to do it, or do
you think that there is a way to write rules that would work in a
satisfactory way? If not, it seems we do have to rely on discretion at
And is that better, do you think, than trying to write a
rule? I'm just wondering, how would you apply your thinking in
this presentation to figuring out a way of approaching these cases as a
policy matter or as sort of putting forth some ethical principles?
I'm just not quite clear on that.
DR. NELSON: This is one of the difficulties is sort of
where we are now as opposed to where we've been. I think it's
important to protect discretion at the bedside. Do I think it's
important enough that I would then sanction unethical decisions? No.
And so the challenge is how you tease those apart.
The story I've told you, which is playing out in
Wisconsin, which is not playing out in other states, but I think
that's not because it couldn't, is where those rules are
basically intruding into an area of discretion, where I don't think
they need to intrude, nor were they intended initially perhaps, nor
I agree with Norm that a lot of the activities that have
taken place in hospitals around ethics committees I think sort of, by
and large, brought a lot of those decisions out into the sunshine, if
you will, at least locally, not broader. So it's unclear to me at
this point that we need more rules as opposed to sort of a rollback.
And the only way I could understand or begin to say,
"How could we have that happen?" would be to foster a
conversation, which I could see this group is trying to do, around the
very issues that we were just talking about. At this point, you cannot
meaningfully — you can talk with a parent about this.
I mean, you can conceive of how you could talk meaningfully
about the value of continuing the treatment we're doing, the burden
of that treatment, the benefit that we might achieve, the outcomes that
we may expect, the chances of those outcomes, etcetera. That we can do
at the bedside.
I don't see us having that meaningful conversation in a
broader society, which I mean includes the society that parents run
in. It happens in professional journals, but it's not happening in
a way that seems to be impacting on the interpretation, if you will, of
laws that exist at state and federal levels, etcetera, and the like.
I mean, I can't imagine that the Montalvos think the
result of that case is a good one. I would hope not. It's exactly
the opposite of what they had hoped.
I don't know if that's responsive, but I guess
it's more about conversation and less about regulation — how to
capture that kind of language, so we're not, then, back into a
debate about abortion and infanticide, but about how we can
meaningfully talk about reasonable decisions about the application of
CHAIRMAN PELLEGRINO: Dr. Lawler?
PROF. LAWLER: The questions remains, though, how much
rollback, assuming we need rollback. For example, in your slide on
page 10, I like Pope Pius XII, and I am guided by him in many ways.
Nonetheless, he can't guide American law, actually. And under
American law, spiritual values really don't trump the right to
life. The right to life stands as its own bottom, so to speak.
So the abuse that brought these Baby Doe regulations into
being was parents choosing to think that someone who has Down's
Syndrome has an unacceptably low quality of life. I think you and I
agree that that decision is not only unethical, it probably should be
illegal. Not unethical in some abstract sense, but it should be
against American law.
Now, if that decision is — should be against American law,
then how much discretion can be allowed to compromise life? I mean, I
— you know, surely some discretion I guess. But it's not — I
don't think it's enough to say all of this can be decided by
conversation, because conversation has to be bounded by law, and law
has to be based on respect for the right to life.
So how much discretion would you allow, given, in your
opinion, we need more?
DR. NELSON: Well, I certainly wouldn't end with
conversation, and ultimately there would have to be some way of
carrying that into legislation.
The Baby Jane Doe case in 1986, which the U.S. Supreme
Court actually affirmed the right of a parent to make a decision to
withhold in this case surgery. It turns out I think she survived; I
don't recall how long — but as sort of part of parental rights.
Now, you know, that's sort of a parallel history to some extent
from the regulations. One of the difficulties is Congress is not
supposed to practice medicine. I mean, if you look at the —
if you look at the proposed rule, there were a lot of cases in it.
The final rule, there were no cases.
And so you end up with these principles that are divorced,
where you and I might agree that it would be appropriate for a parent
not to decide to treat a newborn who would meet the disabled newborn
criteria by the Baby Doe regulations. But by the regulations
themselves, in applying them, that's not a readily apparent
interpretation. And that's the challenge.
Right now, they are divorced of cases. They stand in a way
that explicitly eschews any discussion of quality, which, in my view,
is precisely what we as physicians are about, not just biological
life. All right? But then, how do we get that in a way that is not
discriminatory I think is important.
And that's a conversation — you can say, no, I
don't want to end with conversation, but that's — right now,
it's polarizing. Right now, as soon as you bring up that topic,
it's polarizing, as opposed to trying to discuss the values that
allow us to say, well, you know, that's really not what we had in
I don't — you know, if I had a solution to that, I
guess I would have very quickly written it up and sent it somewhere to
publish. I don't have a solution for that. It just strikes me as
a problem that — that exists there at this point in a very polarized
society around these issues.
CHAIRMAN PELLEGRINO: Leon?
DR. KASS: Let me try, on the same — on this same subject
— I think I share your sense that a certain kind of rigidity leads to
decisions that everybody present would recognize as somehow wrong, at
least that's their common sense, and that one is imposing — one is
behaving in a kind of cruel or inhumane way, simply to uphold a certain
kind of principle.
I mean, I — let's at least stipulate, and I think that
could be part of your resistance to the rigid adherence to a certain
kind of never or always. And let's also agree that it's not
just scare tactics, but — and it's not just the polarization of a
society that would lead one to be concerned about how it is we actually
justify the withholding and withdrawing, because, I mean, Norman before
talked about it's in the best interest — sometimes it's in the
best interest of the child not to be here.
That's a funny thing to say without politics. I mean,
it's a strange thing to say, especially on behalf of a child, but
never mind. So you were groping for a way to articulate so that other
people could understand your reasoning or your justification, when it
is that it makes sense not to use life-sustaining treatment.
I'm not sure I understood exactly how operationally —
how you would make operational this very nice intuition about the
difference between choosing death versus choosing how to live while
dying — a distinction to which I am quite friendly. But as you so
point out, in the presence of devilish interventions, the transition to
being in the process irretrievably of dying is opaque.
You want to get away from talking about quality of life language, and
yet it seems to me you are stuck. Unless I've missed something
— and we've struggled with this at the adult end, and,
as Rebecca said, with patients with dementia. We all have a certain
sense this is — this is cruel — these interventions
are cruel and nonsensical.
And if you say, "Why?" can you give an answer
that says otherwise, says something other than that? This
patient's life is not worth living any longer.
It didn't come out all that well, Dr. Nelson, but
I'm — I'm looking for a way in which we could not simply go on
our gut instinct in these matters, but to try to articulate in
communicable form so that other people could say, "Yes, I see
that, even if I don't agree with you."
DR. NELSON: I think one of the reasons why I wanted to
initially sort of avoid quality of life language is I didn't want
to have what I was saying sort of immediately fall into the sort of
polarizing positions around quality of life.
DR. KASS: Right.
DR. NELSON: But that language is, in fact, the language
that you might use at the bedside, maybe not those words but things
such as the child would no longer be — certainly, in the pediatric ICU
will not be the child you knew.
DR. KASS: I'm sorry?
DR. NELSON: You know, the child — the child will not be
— it will no longer be the child you knew. I mean, those kinds of
language about transition, often in terms of neurological damage, even
if one is anticipating possible survival, and the like.
You know, if you look at limiting or withdrawing support in
the intensive care unit specifically, and to some extent in the
neonatal ICU, the bulk of it is around resuscitation. Literature
suggested anywhere from 40 percent to 70 percent or higher of children
who die in an intensive care unit die in association with some limiting
or withdrawal of support.
The bulk of that is simply deciding not to resuscitate, so
they die. Then, you've got not escalating. You've pushed the
envelope as far as you can push it. It can't be pushed any more.
Then, you've got the taking away of pressers and
extubation. That's actually less likely. So the kinds of
decisions we're doing we think of — and fluid and nutrition I
could think in my — you know, over the last 15 years count on one hand
the number I'm familiar with. And I've actually never
recommended that to a family.
So we talk about those cases, but the bulk of it is just
deciding not to apply fairly simple resuscitation technology. Quality
is part of the language, and the value of that life going forward, the
burden of the treatment to get there, that's what we do. I'm
perfectly happy with discussions of excessive burden for achieved
benefit, but I don't read any of the things that I showed you as
allowing that language unless we protect that discretion.
And so the issue is how to do — how to protect without
losing of ground. I agree that's a challenge, but that's I
think what has to be done, somehow protect that discretionary space.
One final anecdote — the interpretation of what's
going on in Wisconsin certainly is often the advice of general counsel
in other institutions and other hospitals where they will say,
"Well, if you do that, even if it's agreed to by the
physicians and the parents as reasonable, if you do that, you will be
in violation of these regulations, and you could go to jail."
Even if, in fact — I know Norm points this out when he
talks on this topic — there is no such case of anyone, if you will,
going to jail for violating what would be perceived as a strict
application of the Baby Doe regulations. There is no case, but legal
counsel in hospitals often gives that advice.
DR. KASS: May I just follow up? Leaving the law aside and
just sticking on the plane of ethics for a moment, are there — you
talked about resuscitation, and there you could I think easily speak
about the possible burden of the treatment itself.
Are there cases where you would make a decision not to
resuscitate, which would lead you also not to give antibiotics in the
presence of an infection? And if not, why not? In other words, if
you've made the determination that this is a life in its trajectory
to the end, how would you set about distinguishing those two cases?
DR. NELSON: I guess I would not start where you started.
The conversation I would have with a parent would be that what
we're interested here is in the — if you will, the quality of the
experience of that child for whatever period of time that child is with
And if the provision of oxygen helps, even if it — if it
helps the experience, even if it might delay death, or the provision of
antibiotics, depending upon what that may be for provision of fluid —
in other words, if the focus is comfort at that point, my general
approach — and by and large, I think most ICU docs — is to have sort
of a — it's an a la carte menu. It's not — you know,
it's not, oh, you're going to get it all or you're going to
get nothing. It's taken on a case-by-case basis.
And there would be instances where you would — may not
given antibiotics, and there would be instances where you would based
on that difficult judgment. But I think that would separate — we have
also had families who might for resuscitation perceive, for example,
intubation as being invasive. But they wouldn't feel that way
about chest compressions, because, you know, they've seen it on TV,
and it doesn't look so bad, etcetera.
We know, as professionals, that that can be a very invasive
thing to do to somebody. And by and large, my experience has been if
you have a parent available at the bedside, as they often are, in the
hospital, particularly in the pediatric intensive care unit, and they
see that, they will tell you stop immediately because they didn't
realize that, in fact, it is as invasive as you've said it was.
So the reality is what they see. So all of those kinds of
decisions I think are taken case by case and not sort of you get it all
or you get it none.
DR. ROWLEY: Well, I hesitate to enter into this discussion,
because much of it is in the area of ethics, where I don't feel
terribly confident. But we have discussed over time here at the
Council the issue of medicalization, and it's always in the
context of some living individual and that — like ADHD or
all of the things that may be behavioral in children, which may
be better left just to either letting the child grow out of it or
other kinds of professional discussions with the child rather than
But it seems to me that in the neonatal intensive care
unit, particularly as technology gets better, we're going to be
able to keep more and more premies of lower and lower birth weights
alive through medical technology, and then you have to ask, what really
is the cost to the child involved, the infant involved? What's the
cost to the parent? What's the cost to society?
And we were pushing — or I was pushing Norman to say, in
terms of issues, that we really should talk about what are —
are fundamental, broad, ethical issues regarding children —
the cost of neonatal intensive care unit is enormous. And you think
of what that could do for immunizations for children, for food for
children, for professional help for babies in premature —
in poor families, just to begin to get the minimum of care.
You know, I worry that what you're saying is that technologically
we can do things. Then, if you follow the Wisconsin law, you are
forced to use these costly technologies for children, and I think
there are data coming out of the likely quality of life that a preemie
of certain birth weights have in the future for mental retardation,
for cerebral palsy, for long-term requirements of very strenuous
So I can't formulate this very well, but it — I'm
on your side in terms of saying that the physician has to have some
ability to use his judgment and help educate parents to what the future
outcome of a child of — infant of 200 grams or 300 grams, even 5- or
600 grams, what is their long-term expectancy for really high-quality
DR. NELSON: A couple of comments. First, I think if we
want to look at the cost of intensive care, I think it's very
important to do that in an intergenerational way. What do I mean by
that? Sure. Neonatal intensive care is expensive.
But if you do it on the quality of adjusted life years, and
you look at what you get — you know, the bang you get for your buck,
you're talking about someone who survives. We'll get to
whether they survive well, but someone who survives productively for a
large number of years compared to, say, adult intensive care.
So I — I don't want us to think — I would hope we
don't think of the resources we put into pediatrics as a zero-sum
gain within pediatrics, because children are not getting what they need
now. And if that's the case, we're not — we're basically
robbing Peter to pay Paul. I mean, it just — that would be
And neonatal intensive care is highly effective, and
it's highly effective, even if expensive, for a lot of infants.
And so I would just ask you, then, to look more broadly
intergenerationally about that distribution.
In terms of prematurity, I mean, the window that we've
got now is that — neonatologists, if you look at surveys at least, and
then you look at the biology, generally are uniformly in agreement that
less than 23 weeks' gestational age, assuming accurate dates,
etcetera, you just don't have a lung. I mean, until we develop
artificial womb technology, that is not a fetus-born infant who will
survive. It just won't happen.
After 24 weeks, the impact of surfactant, it used to be
true that if you took, you know, 24 weeks, and then you took up at
about 28 weeks, you could draw sort of a straight line, and mortality
would just climb up that line.
Well, now, with surfactant, it basically goes skyrocketing
in the first week, and then levels off. And so, basically, the
survival of 24-, 25-, 26-week prematures at this point in time is
Now, can you predict which one of those will develop
cerebral palsy, which one of those will get a bleed, which one — you
know, the complicated — necrotizing enterocolitis, short gut, I mean,
all of those things are not something you can figure out in the first
24 hours. I mean, if it's in the first — as I say to families, if
it happens fast in an intensive care unit, it's bad.
All things that happen good in an intensive care unit
happen slowly. So if in the first 24 hours some — I mean, something
happens, yes, it's really bad. But, unfortunately, a lot of bad
things happen late. So predictability becomes a problem.
The issue of quality of life is complex, and from whose
perspective, how do you measure it. It's a very difficult life for
families. It's a very difficult life for the parents. It's a
very difficult life for the children. But you ask them, and it's
not that bad. In fact, it's often pretty good, depending on who
you ask. So it's a complex question in terms of quality of life.
So I guess it's — there was something else, but
I've forgotten. If it comes to me, I'll say it.
CHAIRMAN PELLEGRINO: Dr. Hurlbut?
PROF. HURLBUT: This is a vague, very broad question, but you
kind of introduced it. Just from your experience thinking about these
matters, if you project out 50, 100 years from now, you can imagine
technologies such as what you just mentioned, an artificial womb or
various interventions, maybe very early on in the womb.
Does there come a point where medicine is sort of out of
its realm? I mean, you — is there someplace where medicine is sort of
an invitation but not an obligation? You know what I'm asking
DR. NELSON: Well, I think — let me just see if I do. I
mean, there certainly is a point at which we ought to be circumspect in
our use and development of technology. But I think back to Norm's
response on ADHD and drugs, you know, medicine is fundamentally
If there's a problem that people address as a problem,
and you can discover something that fixes that problem that happens to
fall sociologically within the armamentarium of physicians, it becomes
a medical problem.
It could be done otherwise, I mean, if we so choose. We
could take some of the things that physicians control as technology and
let other people control them if we wanted to. That would be one of my
solutions to the issue — to the issue of assisted suicide. I
don't think physicians should control that technology. Whether
anybody should do it is a separate question.
Now, you know, we have, for example, a fetal surgical program.
Their patients — the mothers who come in with fetuses looking
for treatment. Occasionally, they'll elect termination, but
by and large they have decided that they're looking for treatment
for their child.
And, you know, so it's extending down into that area.
I can't imagine some of those technologies, but I suspect at this
point, you know, unless — you know, it's really up to us to decide
if it's a problem worth fixing. And once we do that and identify
it and get a technology that can, in fact, help, whether that's in
medicine or not, I mean, it's going to happen.
Medicine is fundamentally pragmatic. I don't think
you're going to see physicians doing that. I think it's — you
know, as a society, we certainly haven't shown any ability to
control our health care — sort of provision of health care in any
meaningful way, whether it's conceptually in the provision of
resources or whether it's economically. It's chaotic. I guess
it — so I hear what you're asking. I'm not sure what the
solution might be.
CHAIRMAN PELLEGRINO: Dr. McHugh?
DR. McHUGH: I found your comments very interesting, but
they often turned, again, on this issue of quality of life, the
ultimate issues of quality of life and how we doctors know about it.
I wanted to perhaps get you to — draw you out a little bit
more on the stakeholders that relate to quality of life, and ultimately
the individual who has the greatest stake in it is the person who is
going to live or die. And I was enriched by what you said about the
value of neonatal care services and how they do produce people who are
happy and content.
Perhaps put it this way. One of the real problems with us
doctors is whether the technology begins to shape our character to the
point where our character is no longer open to other people's
Now, my encounter with that, my personal encounter with
that, was the Hopkins program in sex change operations in infants, when
it was believed — for no good reason and without any data — that the
quality of life of a little boy born with calycle problems would be
best served if his gonads were removed from him and he was raised as a
little girl, and that human beings had such plasticity you could grow
them up in either sex and it wouldn't matter.
And it was only when we insisted that there was contact
from pediatricians to the young adolescent and adult girl/boy that we
discovered that, in point of fact, those people felt themselves quite
mistreated, and that they had been for the best of reasons, with the
quality of life issues in — in front of them, that they had been
fundamentally deprived of the opportunity themselves to decide what
they were and would be, and that the doctors, instead of simply
protecting them and making sure that they didn't have kidney
infections through this, had decided what kind of life they would lead,
and often on the basis of rather silly ideas about how an infant and
child — a young child might feel about his genital structure during
the time of development.
Now, are we — that's a long story, of course. But it
brings me back to this question. Are we in the formation of our
character, in the development of our care services, really consulting
with the people whom we did serve to find out whether they think the
quality of life they have, that might be different from the one that we
have, is one that makes them happy? That's a long enough question.
DR. NELSON: Well, I agree with your story, if you will,
about gender reassignment. And one way one could understand that story
is it really was an n of 1 that got it all started. And as we began to
appreciate the way that, if you will, bias prejudged the question of
what the outcomes might be, and understood over time the impact of
that, I mean, those biases are changing, but there is still a lot of
debate around that issue.
We do have certain I think biases about what works and
doesn't work, in terms of functionality, which you could also see
as a predilection towards technology. And by failing to sort of do the
kind of work in sorting out the impact of that in terms of outcomes,
the kind of research that is necessary, that is sophisticated.
When I think of neonatal intensive care unit, I was having
a conversation the other day with a neonatologist from Israel who was
at a meeting this past week in Washington. It's called Hot
Topics. It's the neonatal meeting that occurs every year.
And what he said — there was an exchange between a couple
of parents in the audience and a researcher who is presenting quality
of life data. And by and large, the quality of life data were things
like, you know, how many kids that are born premature go to college,
high school, I mean, those kinds of functionality things.
The comment of the parents was that there was a great
disconnect between that information and their own experience. Now,
granted, that is anecdotal to parents in the audience. I mean, it —
obviously, highly selected to be motivated to go to a meeting of
professional neonatologists, but that there was a disconnect.
But the important thing that I would take away from that is
it's not that research is unimportant, but the methods perhaps need
to be more sophisticated, and that the conversation needs to include
parents, of course, and ideally include children.
Another illustration I was asked — I did a project looking
at what parents would think about a waiver of emergency consent for
resuscitation research. I was asked the question as I was presenting
that research, which I realized I didn't even consider. Someone
asked me if we had — step back. That regulation requires community
consultation, so we had consulted with parents as the community that
would be involved.
Someone asked me, "Well, why didn't you ask
kids?" For some reason, it — for some reason, even as a
pediatrician who asks kids many other questions, it didn't occur to
me to do a focus group of, say, adolescents or eight-year olds around
what they would want if their heart stopped.
I don't know what the IRB would have done if I was
going to do that kind of thing, but I asked them other kinds of
questions. Maybe I could have asked that.
So, yes, who you go to — I mean, I think it's very
important that the perspective of parents and children be honored. In
many ways, my concern is that the — that we've driven, if you
will, such an overlay of the regulations that I've gone through,
and of the sort of debate to where at the bedside is a great risk of
being unable to honor the expressed wishes of parents, particularly
since children often don't have a voice, given how ill they are, in
the intensive care unit, because of fears of the regulatory and legal
That the desire of physicians is to, in fact, honor that,
appropriately so, not inappropriately so. And it's getting harder
and harder to do that, and I think there's plenty of data that
would support that shift. And I agree with Norm that it's a shift
from undertreatment to overtreatment, and somehow we need to get back
— you know, sort of recapture the ability to have that conversation.
DR. ROWLEY: Well, I would like to just follow up on this, and
then tie it into my earlier question, because it seems to me with
regard to the view of parents who had children who were premature,
and particularly those that were very early premature, there must
be more than anecdotal data on what kinds of stress, if any, those
Now, I was shocked by Norm's statement that in child
abuse one-third of the children who are abused are premature. And so I
think that it would be useful in this discussion to have some sense of
what the outcome is for those children, and I did bring up parents and
families and what the impact of prematurity and level of prematurity is
within the family.
DR. NELSON: Yes. There is data that exists, but I think
part of — I guess two comments. I think tackling the problem
Norm identified, which is an important problem in my mind, is tackling
the issue of preventing prematurity. It's not tackling the
issue of: should neonatologists have withdrawn or limited support
in a group of premature infants? Because I suspect, even if we
did that, the statistics would not change that he cited.
I'm reminded of a case that hit the press in
Philadelphia where a caregiver basically beat a child with spina bifida
because the child was not toilet-trained. You know, so the frustration
— a) that shows a fair degree of ignorance, but the point I'm
making is the frustration that parents who don't have the kinds of
home visitation programs that Norm mentioned, or the kinds of support
that we ought to provide, when you're dealing with a child as they
grow up who may have some limitations, whether visual or physical,
because of the — just because of the circumstances of being born
prematurely, even if those disabilities are not to the extent to which
they are unable to sort of live quality, productive lives from their
own perspective, that that kind of frustration I would suspect is a
large part of the etiology behind the kinds of abuse that Norm
So that I would not tackle that problem by tackling the
application of our technology. I would tackle it by tackling the
prevention of prematurity and the support that we give parents that are
— have babies born prematurely.
DR. ROWLEY: Well, but suppose the data say that the
children — infants born weighing less than 600 grams have a 99 percent
chance, or a 95 percent chance of severe cerebral palsy, severe mental
retardation, and will lead handicapped lives for their — for as long
as they live, and really severely handicapped lives.
Then, I wonder if neonatologists don't begin to wonder
whether just because they can do something, and keep the infant alive,
is this something that they should do?
DR. NELSON: I agree. But, unfortunately, the data is not
quite so convincing. If we had 99 percent, I think there would be no
disagreement, but the data — even with the sort of worst conditions,
say, a grade four intraventricular hemorrhage, is more in the 70 and 80
percent, and so you get into a very difficult discussion about the
statistics versus this infant. And it's a much more difficult
Unfortunately, the data is not — doesn't drive the
answer as clearly as that would. I don't think anybody would
CHAIRMAN PELLEGRINO: Unless there is an urgent question, I
think we have reached the point where we need to break for lunch.
Thank you, Dr. Nelson, for a stimulating discussion
covering some very, very difficult issues. I've been restraining
myself. I have lots of questions along those lines.
I want to thank the audience and — particularly the Council
members, and I think we'll return here at 2:00 to pick up other
facets of this same range of questions in a little different direction.
Thank you very much.
(Whereupon, at 12:34 p.m., the proceedings
in the foregoing matter recessed for lunch.)
CHAIRMAN PELLEGRINO: Dr. Kopelman is our next speaker.
I've known Dr. Kopelman for many, many years. Her involvement
with these issues is well-known to all of us in the field. We have
asked her to talk about additional aspects of pediatric ethics.
And, as with the other speakers, I say that so she can go off in
any direction that she thinks is important for the Council to consider,
to cogitate, to take under advisement. So, Loretta, will you take
us off into the wild blue or wherever you want to go?
DR. KOPELMAN: I hope it won't be too wild.
SESSION 3: TAKING CARE: ETHICAL
CAREGIVING FOR CHILDREN TOO
DR. KOPELMAN: It is certainly a pleasure to be here, and
it is an honor to be asked. It's particularly an honor to be
asked by Dr. Pellegrino, whom I consider the father of medical ethics
in this country.
I was asked to discuss issues of assent, consent, and
permission for therapy and to some extent for research as well. And
that is a huge topic. So I was trying to think of a way to limit the
And what I thought I would do is use your own recommendations
from Taking Care: Ethical Caregiving in our Aging
Society and apply it to minors; in particular, your strong
recommendation for individualized decision-making using the best
care and best interest standard. I think that would be a wonderful
standard to use for all minors in many of the same ways you recommended
using it for individuals lacking decision-making capacity.
So my goals today I'll put under two headings: to discuss
issues of consent, permission, and assent in making minors'
health care decisions; and in choosing policies that support individualized
choices using the best care or best interest standard, which is
what you recommend in Taking Care.
The first topic is issues of consent, permission, and
assent in making minors' health care decisions. Let me just say a
little bit about language and the use of language here. Increasingly,
the pediatric literature is talking about parents and guardians giving
permission and reserving informed consent for something the person does
on his or her own behalf. So you give informed consent for yourself,
permission to have therapy or research involving your child. And not
everybody uses that language, but it's getting more and more common
in the pediatric literature.
And assent means affirmative agreement for those who lack
decision-making capacity. It does not mean they passively go along.
It does not mean that they haven't objected. It means a positive
agreement. And that's how the word is generally used as well.
Now, in the case of health care decisions and decisions
involving research for children, the ideal is shared decision-making
and consensus. Where clinicians and parents and the children all agree
about what should be done, that is certainly where there is a
discussion and an agreement.
That is the ideal. Next best is where there is a
discussion and maybe it isn't everybody's first choice, but
everybody can go along with it. In many cases, that's okay, too.
There's a consensus about the plan.
Parents or guardians generally have wide authority to make
decisions based on being most committed to their child's best
interest; most knowledgeable about them; involved for the long term,
not the short term, not for one particular hospital stay but for all
their care; and also because parents are most influential in fostering
values and traditions that make us who we are, the kind of people we
are. And because we generally think that's important that we have
certain values and traditions that are a part of who we are and the
decisions we make, we give parents or guardians certain latitude in the
kind of decisions that they make.
Just to review the elements of informed consent or permission, disclosure
of all material information, and in a therapy setting that would
generally include diagnosis, prognosis, treatment options, and consequences,
likely hazards for benefits.
In addition, there's understanding of the information disclosed.
As the risk of the procedure or the research or the therapy increases,
the more the clinicians has a duty to check and make sure that people
actually understand that information, perhaps by asking them questions
or asking them to use the information. This can be, this checking
can be, important, particularly if it's a long-term therapy
or research project.
People ought to know they participate voluntarily,
they're not coerced, and that physicians have a duty to make sure
the person giving permission or consent is competent to agree or deny
participation, and that they actually agree or authorize the
intervention, in fact, procedure, or research.
In research, there are additional elements of informed
consent or permission. One is disclosure that it is research. As
Rebecca has written, there is sometimes a misconception that
therapeutic research is seen as therapy when, in fact, it is not of
benefit to the particular child who is involved. And it would be
important for people to address that therapeutic misconception on the
part of those giving consent.
You're obligated to talk about the hazards or potential
hazards or benefits of the study in and of itself, as opposed to what
may be involved in therapeutic research. They need to know that the
research is voluntary and that the alternatives to it are explained.
They need to know how confidentiality will be maintained,
what compensation is available should they be injured, and who to
contact to answer questions. And the institutional review board has
the duty to make sure that these are fulfilled in a reasonable way.
They may also add other issues, such as the cost of the study, if there
are issues relating to pregnancy, dangers, or what will happen in the
event of new findings.
As the risks increase, so should the safeguards for research involving
children and others. And in "no benefit" studies, studies
not designed to benefit the children, as the risk increases, there
is more and more duty to check that the study is appropriate and
within the rules.
Parents generally give consent or permission, both for
research and therapy. For studies not funded by the FDA, teams can
sometimes give consent for themselves for minimal risk studies without
their parents' knowledge or permission.
In therapy and in some therapeutic research protocols,
parental consent can be waived if, say, in an emergency situation.
Parental and guardian authority can be challenged if they neglect,
abuse, or otherwise endanger the child.
In the beginning of the Twentieth Century, children were
generally viewed as property. Children are no longer viewed as
property, as they were in the beginning of the Twentieth Century.
Parents and guardians could give permission for therapy or
not for their children, as they did for themselves. If they made a bad
decision, well, that was very unfortunate, but the parents owned the
child. So it was their choice to make. You could try to talk them out
of it, of course, but it was their decision.
In the course of the Twentieth Century, children obtained rights
to have a certain threshold of care, independent of what their parents
wanted. And guardians were seen to have duties to children if they
abused, neglected, or otherwise endangered their child.
The most frequently used standard for persons lacking
decision-making capacity, including children, is the best care or the
best interest standard. I note I have included your definition of best
interest. You have defined it as a legal standard. I would only say
it's also a moral standard of caregiving for incompetent persons.
You defined it in terms of what a reasonable person would consider
in the same situation. A consideration of the best interest generally
attempts to weigh the burdens and benefits of treatment to the patient
in his present condition when no clear preferences of the patient
can be determined.
I would only add to this. It presupposes some kind of
consensus about what choices are unacceptable. I think if it's
defined that way, we can leave some flexibility in the best interest
standard, rather than think of best as there's one and only, one
best thing to do, an ideal approach to take.
So it presupposes, I would say, a consensus about what is
acceptable and what is not acceptable. And I think it is very hard to
use without such a consensus.
Also, it's usually said in this way as a
consequentialist standard, but I would argue that it presupposes a
framework of rights and duties as well, in which to use the best
Sometimes it's not clear what is the best care or the best interest.
And I have incorporated in my talk three different cases, which
are not high-profile cases, like those that were discussed this
morning. These are all cases that house officers picked.
We have a monthly conference. We meet with the house
officers. And each one at some time over the course of their three
years as a pediatric house officer selects a case that he or she
regards as particularly challenging that the house officer was involved
This is one of those cases. This is a house officer. She
had been a house officer exactly three months when she encountered this
J. R. was a 14-year-old boy with a rapidly progressing lymphoma
and uncertain prognosis. The parents are from another culture,
where competent adults are rarely told such a diagnosis, and insist
they do not want the child told anything about the diagnosis or
prognosis. They want other explanations given for the therapy he
When his parents are not in the room, J. R. asks, "What's
wrong with me?" So what should this brand new house officer
in pediatrics do? Any information you would like about this case
before I move on?
DR. McHUGH: Well, I would like to know whether she
knows anything about this boy other than his medical diagnosis and
whether she has had conversations with him about his life and —
DR. KOPELMAN: Yes. This is her case. She has known him
since his hospitalization. She knows him well. She knows the lab
findings. She has met his parents. She identifies this patient as her
DR. McHUGH: I will go on a little bit more. When she
was told these things by the parents that this is what they want, what
did she say to them at that time?
DR. KOPELMAN: She didn't say much of anything.
DR. McHUGH: I see.
DR. KOPELMAN: Now, there's also an attending, who
is not around right now. This is in the early evening. I'd
say about, she said about, nine o'clock. And nobody is around,
just her, the nurses, and this 14-year-old.
I should say that there are some studies that suggest 14-year-olds,
particularly who have life experiences like this, are pretty good
decision-makers, almost as good as most adults. They have capacities.
And some studies find they have capacities similar to adults in
dealing with issues like this.
DR. ROWLEY: I guess I would temporize with the
patient and just say this is something that because she is in a
junior position, she can say, "Well, this is something that
Dr. so and so should really be talking with you about."
DR. KOPELMAN: Okay.
DR. ROWLEY: I think the other thing is that the parents
really have to be educated, that it's going to be in
everybody's interest in the long run, particularly if the patient
goes on some kind of experimental therapy that's going to make him
very sick, that the patient has to be involved in this. And
they've got to learn that this is in their best interest as well as
their son's best interest.
DR. McHUGH: Although I agree with that, ultimately,
this, having things like this sprung on you, is not an unusual
physician's experience. And most of the times, physicians answer
promptly to this, saying, "I'm very distressed to know that
this is on your mind. And we need to talk with your parents about why
you are still worried about this."
Just as if somebody says to you, "Where do babies come
from?" they're 14 years old and you can't tell you, you
don't immediately say, "Well, let me explain it to you.
There's this anatomy and this structure and the like" even
though they eventually have to know those things.
DR. KOPELMAN: Let me tell what happened. I mean, this
is a house officer who in that situation, she just froze. She said
she just froze. And the 14-year-old was good enough at reading
the signs of that. And he said, "You know, don't you?
Why don't you tell me?"
And so she probably should have said, "Well, I'll
get together with you tomorrow. I'll get the attending. We'll
talk with your parents." But she didn't. She blurted it
out. She felt very badly about it. She didn't feel very pleased
about her performance.
On the other hand, I should say that that 14-year-old bonded with
her forever because she had told him the truth. So the two of them
formed a bond, and that was really very important.
If she had said something like "I don't know," that,
of course, would have been a lie or,at best, a deception, and she
didn't want to go that route. So that's what happened in
that case. And she wondered whether she had done the best for this
Increasingly, in the last generation, last 25 years, assent from
minors has been considered more and more important in therapy and
research. It acknowledges their emerging self-determination and
acknowledges that competence is task-related.
A lot of this grows out of social science studies about
what children do understand, how they are pretty good at reading what
is going on, even if people aren't talking to them.
And there's one set of studies from Dr. Bluebond-Langner published
in 1978. This was her Ph.D. dissertation. She asked permission
to go to a cancer unit and be like a fly on the wall and not interact,
just be an observer.
What she found was an elaborate system of mutual pretense,
where the doctors talked to the parents and nobody talked to the
children but the children didn't want to make it worse for their
parents by telling them they knew. They were trying to protect their
parents. The parents were trying to protect the children by not
telling them. And it was not making good sense.
The children were still trying to gather information by
relatively ingenious means. They would post guards and steal the
chart, which, of course, then was a paper chart. And then they would
steal it and run back to their rooms and read it with flashlights under
the covers or they would put tape recorders in conference rooms and
have an elaborate strategy for how to turn them on while the
discussions were going on.
And then they would inform each other, "Well, yes, of
course, you've got cancer. This is a cancer unit" and what
everything meant, what the different — of course, it was all wrong.
So they figured, well, it's probably better if they
were talking among themselves that, actually, they get good
information, rather than bad information.
PROF. GEORGE: Dr. Kopelman?
DR. KOPELMAN: Yes?
PROF. GEORGE: How was this information gathered? She was
a fly on the wall, and she observed them with flashlights — —
DR. KOPELMAN: She just observed —
PROF. GEORGE: — under the covers and —
DR. KOPELMAN: Yes, or they told her about it.
PROF. GEORGE: — stealing charts and things? Okay. Has
this been replicated? I mean, why should we believe all of this?
DR. KOPELMAN: I think it certainly has been replicated
that children know a lot more than they let on, I mean, that they
can read people pretty well, when they're being truthful and
when they're not. They can read cancer, you know, if they get
over five or six years of age.
So there's a growing body that children do understand
quite a bit of what is going on and that they feel very isolated if
they can't talk about the things that trouble them.
PROF. GEORGE: Well, I understand that is what is being
reported, may very well be true, but I am interested in whether we
really have rigorous data. These kinds of things are put forward as
scientific studies. I would like to be able to assess their
DR. KOPELMAN: There is a review in the Institute of
Medicine research with children, quite a long chapter with a review,
all the evidence for what children understand, who gets assent, when we
should get assent. I don't know. They must talk about 50 or 60
studies in that chapter.
And some of them, the difficulty with children is that you need
to make the information age-appropriate. And what you're going
to tell a 14-year-old will be different from what you want to tell
a 6- or 7-year-old.
But the people who do these sorts of things — I'm a
philosopher. I'm not a social scientist — say that it does foster
trust and cooperation, and it makes them feel less isolated.
The American Academy of Pediatrics recommends gaining
assent from children when it's possible and prudent to do so. And
the greater the benefit, minors' views should carry weight but not
be decisive, as it would be for an adult.
And the greater the benefit to the child, the more
justification for overriding a minor's unreasonable refusal or
demands regarding therapy. Assent in research is generally required
when it's possible and when there are no direct benefits to the
Many people write in "no benefit" studies the child's
dissent should trump. And I would echo Norm Fost's skepticism
about how often that really happens. A five, six, seven, eight-year-old
isn't thrilled about getting stuck one more time or a spinal
tap one more time or any of the other things that are considered
minimal risk and no benefit research.
So, again, in this chapter on the Institute of Medicine, they review
just how many times IRBs do have a mechanism for looking at assent
and dissent. I don't think we get very high grades, but I think
we are probably doing better than we did when Bluebond-Langner first
started to do her studies.
Consent from older minors is sometimes permissible for
treatment of some conditions; for example, treatment of sexually
transmitted diseases, treatment for substance abuse. And also for some
minimal risk studies, the FDA doesn't permit waiving parental
consent, but HHS sometimes does.
This brings me to another case selected by one of the house
officers. It involves a possible conflict between what the parents
want to know and what the adolescent wants them to know.
K. L. is a 16-year-old female patient being seen in the
adolescent clinic. When her mother leaves the room, she tells her
doctor she has been having unprotected sexual intercourse and wants a
prescription for birth control medication.
For a variety of personal and religious reasons, she does
not want her mother told. Her mother, however, has told doctors she
wants all the information about her daughter.
Now, in this discussion of this case, everybody agreed this
was certainly a teachable moment for the clinician to talk to this
16-year-old about, you know, "What are you doing with your life?
Who is this person? You know, what is going on?"
But the question was, should they tell the mother? Should
they not tell the mother? Should they write the prescription? Should
they send her to the health department and kind of wash their hands of
it? That was the case presented for discussion. I think this was
about six months ago.
In the State of North Carolina, doctors may make these
prescriptions without — it varies between the states, but they are
permitted to do this without parental consent in North Carolina.
Any questions about this case?
PROF. DRESSER: Well, one of the things that I think
would be important to think about and often I've just noticed
in discussing cases like this about whether to impose certain things
on children in the medical setting is how will this affect their
long-term view of medical care and their trust in the medical system.
So I think that's one factor that makes cases like this very
DR. ROWLEY: Yes. Well, I guess I would make the
comment that this young girl is going to get pregnant sooner or later
if she continues this kind of activity.
And then she is going to be in the situation either of
having an abortion and trying to get that done without her parents'
knowledge — I don't know what the rules are in North Carolina, but
it's difficult in many states — or, alternatively, she then is
going to have to confess that not only has she had intercourse but now
And I think that at 16, she ought to be in a situation
where she understands this. Clearly she understands it to some extent
because she wants a prescription for birth control.
I think the other point that you raised in terms of trying
to educate her about how her behavior is going to influence her whole
life is something that really has to be hammered home.
I would agree with Rebecca that it seems to me difficult to
tell her mother without the agreement of the patient.
DR. KOPELMAN: So you would honor confidentiality, tend to
honor? See, I mean, we can all agree with the important values. The
question in all of these situations is, which one do you rank higher?
PROF. MEILAENDER: I have a question, and then I have a
comment. What would be a religious reason for not wanting her mother
to be told?
DR. KOPELMAN: Well, this is according to the resident.
The daughter said that her mother belonged to a religious community
where if someone had sexual relations outside of marriage or was
unfaithful to a husband or wife, that that person was shunned and if
her mother knew about her sexual activity and didn't tell the
elders, her mother would be shunned.
Now, according to the resident, the daughter did want to
separate herself from that community. On the other hand, she
wasn't keen on being shunned. And she didn't want to have her
mother be shunned either.
So she felt that that was yet another reason for honoring
PROF. MEILAENDER: Well, I understand that. I think that
would be very peculiar to call that a religious reason. It's a
reason having something to do with her relation with her mother and
that's affected by some religious commitments her mother has made,
but one wouldn't ordinarily call that a religious reason.
DR. KOPELMAN: Fair enough.
PROF. MEILAENDER: But my comment is that I think it's
just inadequate, finally, to take up a case like this simply in the
language of consent and trying to figure out and confidentiality and so
forth as if it's ever a purely individual matter with whom
we're having sexual intercourse as if it isn't important in a
society for us to know that this person is my wife and, therefore, not
eligible to be somebody else's wife. So that this is never a
purely individual matter, in fact.
And there's something about the way taking up this case
in this kind of context thins it out that loses considerations that are
at least as important as consent and confidentiality I think.
DR. KOPELMAN: Well, the discussion among the residents
centered on —
DR. McHUGH: Can I ask another question?
DR. KOPELMAN: Sure.
DR. McHUGH: To add to what Gil is saying, you mentioned
that this is a visit in an adolescent clinic. We heard from Norman
this morning that pediatricians talk for about 90 seconds to people.
Was this a situation in which 90 seconds of talk was provided and then,
after that, this decision was made or is this, once again, this
individual's natural concerns in life and the issues of her worries
and fears were going to be explored by this group in the adolescent
DR. KOPELMAN: The house officer — I can only tell you
what she said. I was not there. She said that it was an occasion
for a discussion, not a 90-second visit.
I asked her, "Well, who is this person she is having unprotected
sex with? You know, is it a 30-year-old neighbor or a 16-year-old
high school student or who are we talking about here?" And
she didn't ask that question.
So I can't answer that because this is a real case and
the resident didn't ask the question. So I can't tell you that
part of it.
I know she did try to talk to her. She took the issues to
be issues of confidentiality and also was this young woman functionally
competent to make this decision. I think Dr. Rowley has suggested that
if you're going to be sexually active at 16, it's probably a
pretty good idea to use birth control. I'm not sure the resident
was able to sway her, talk her out of this.
So here I picked this case. I didn't mean to spin
anything out. It is a real case. The resident has a choice. The
attending has a choice to make within the framework of the current
health care system, where you don't have a whole lot of time to
talk to patients and what value you're going to put forward.
It is the case this resident picked out. So it was a case
which troubled her. There were certainly people in the group who
thought that it was terrible that she was having this sexual
intercourse outside of marriage. And they were more sympathetic to
talking to the mom. But I think there were only one or 2 people who
expressed that view in a room of about 45 or 50.
PROF. GEORGE: Well, I agree with Dr. Rowley that if she
keeps doing what she is doing, she is going to get pregnant. If she is
given birth control devices or pills, she will be far less likely to
get pregnant, although she may, nevertheless, get pregnant because of
the failure rate. The only way she is not going to get pregnant is if
she stops doing it.
Now, was it assumed or, for some reason, believed that the
mother if armed with the information about what her daughter was not
herself competent to prevent her daughter from continuing to engage in
DR. KOPELMAN: I did not have that impression from what the
resident said. I had more of an impression that there was already some
tension between the daughter and the mom because the mom is saying,
"Now, you tell me what is going on with my daughter." That
was sort of that was my impression. And the house officer felt like
she was kind of trapped between the mom and the daughter.
PROF. GEORGE: But it wasn't out of the question that
the mother might very well be competent to handle her daughter if she
had the information.
DR. KOPELMAN: Maybe.
PROF. GEORGE: The second question I had is, would it
materially change the thinking of people confronted with something like
this if we had one additional fact, and that is the person with whom
she is having sexual intercourse is her mother's boyfriend?
DR. KOPELMAN: Well, that's why I asked at the
conference. I said, "Who is this person?" I mean, it would
certainly make a difference, as far as I'm concerned, if it was
someone who was, say, four or five years older.
PROF. GEORGE: Well, that was going to be another
DR. KOPELMAN: In North Carolina, that is grounds if
it's a minor for rape, not statutory, rape, if the —
PROF. GEORGE: And would the person who came into
possession of the information be required to report it to the
DR. KOPELMAN: Yes, if it's abuse and neglect.
PROF. GEORGE: And that would be —
DR. KOPELMAN: I'm not an attorney either.
PROF. GEORGE: No. I understand.
DR. KOPELMAN: I am not a social scientist. I'm not
PROF. GEORGE: I understand. And the same would be true
if it were incestuous so that it was not the boyfriend of the mother
but the father of the girl?
DR. KOPELMAN: Yes.
DR. McHUGH: It seems to us or at least to me that you
need to instruct the residents on how to interview patients so they get
the pertinent information. It would help them a lot in how they are
DR. KOPELMAN: I think that is true, but they're not my
residents. I'm medical humanities. But I think the value of these
cases is that all the residents, the 45 of them sitting in the room in
the faculty, say, maybe for next time they'll think to ask a
question, "Well, who is it that you're seeing? Is this
someone who is five or six years older than you?"
And frequently we don't — I mean, clinicians have to
make decisions with — they don't have the full story and they have
to make a decision based on what they have before them.
DR. McHUGH: Well, that is ridiculous. Physicians are
supposed to get the whole story before they do something that is
significant. You have to get a whole story about somebody's
abdominal pain before you take a knife to it and, similarly, to their
lives themselves in the process of really winning the trust that you
want people to have for the profession.
DR. KOPELMAN: I take your point. On the other hand, the
16-year-old may not tell the truth either. So you're not going to
get the whole story without winning her trust beforehand.
DR. McHUGH: That's a standard issue and a standard
problem that develops out of an interactive process done by sympathetic
DR. KOPELMAN: Right.
DR. McHUGH: — with individuals of this sort by making
it clear to them that there are issues in this matter that are
important for them that the doctor could perhaps help them with.
DR. KOPELMAN: I think something I should have said
earlier, of course, consent and assent are not an event, not a form.
It is an ongoing process where you win trust and you learn more
And if this house officer sees this young woman again,
maybe she will hear more of the story and will win her trust and
confidence. I think the point here is that the involvement of the
adolescent is important. Their capacities are emerging. Their point
of view is differing from their parents. I think that was the point of
this case. At least that's the point I was trying to make.
PROF. LAWLER: Let's say that our standard is the best
interest. Can we agree that the house officer here did not have nearly
enough information to make a judgment concerning the best interest of
this young person?
This is a very serious flaw if, in fact, she wouldn't
go ahead and give her information on birth control and so forth.
DR. KOPELMAN: I think that's at the heart of this problem,
not only in the case of the 14-year-old, what should he be told,
but in the case of the 16-year-old. How should she be treated when
she requests birth control medication? Is it in her best interest
to get it or not?
I think I hear a little bit of disagreement around the
table. And I think that's what makes this —
PROF. LAWLER: Let me ask you, what kind of standards do
you think should be in place for a case like this?
DR. KOPELMAN: I would want to check in this case who —
to me, very important information is who is she having sexual relations
with. If it is someone five years older than her, I think you have
a duty to report.
Now, you may lose trust. She may never come back. But
there is so much abuse, sexual abuse, of teenagers that, you know, I
think we need to work on that.
Okay. One more case. This is the last case. This is a child with
a very serious condition called holoprosencephaly. It is an anomaly
that develops very early in fetal development. And it is the failure
of the lobes of the brain, of the cerebral hemisphere, to divide
And there's this range. There's this spectrum here
from severe — the most severe die in utero — to the least severe,
which is there's an incomplete separation, but some of those
children with the least severe versions are near normal. They have
The case three is an infant who has a very severe form of
it. And the question here once again is, what is the best care? What
is in the best interest of this infant?
Since birth, ten-month-old K. D., who has a diagnosis of holoprosencephaly,
has reacted only to painful stimuli. K. D. is admitted to the hospital
with edema. He is found to have renal failure of unknown cause.
Doctors determine that his kidney disease can be managed
with renal dialysis but not cured. Is it required? Is it optional or
counter.indicated given his underlying condition? Who should decide
what is the best care for this child?
The residents who picked this case gave us some background about the
family. There were four children. There is an older brother who
has a milder version of holoprosencephaly. And the two boys with
this condition are being cared for by the mother and two teenage
So there are four children in the family. And the two
daughters and the mom are providing the care for these boys, one of
whom is severely retarded and one who is not. He's still mentally
retarded, but he doesn't have as severe a case as this one.
So K. D. can live for many, many years with the dialysis and will not
live very long without it. So the question is, is it obligated,
is it required or is it counter-indicated?
Are there any questions you would like to ask about this
DR. ROWLEY: Well, I suppose one question is, what is
the financial status of the family just because if this — and
everybody can fault me for saying that is not the ethical issue, and I
understand that. But I tend to look at these issues in terms of the
whole family and what would be the impact of having to take a child
presumably three times a week or so to a dialysis clinic for some
several hours each time for the dialysis.
And these treatments, though there is some federal support,
I believe, for this, can be very demanding. And though it should not
be the determining factor, I think as one looks at the family as a
whole, that is a consideration that one would like to know in making
DR. KOPELMAN: I don't have that information. I'm
sorry. It was not something the resident brought up.
PROF. DRESSER: I assume this point about only reacts to
painful stimuli means that the child — is it himself?
DR. KOPELMAN: Him.
PROF. DRESSER: — would not experience burdens from the
DR. KOPELMAN: Well, I don't know.
PROF. DRESSER: Maybe a little.
DR. KOPELMAN: They're restrained. Wouldn't they
have to be restrained? In Taking Care, you wrote that
a majority of patients don't think life is good on dialysis,
that sometimes they draw off too little fluid, sometimes too much,
the clot gets infected.
So I don't know for a fact that it would be pain-free. But
this child is minimally conscious. And the only thing he seems
to react to is painful stimuli.
PROF. DRESSER: Okay. So it's just that we would
perhaps want to know more about the experiential burdens that he would
DR. KOPELMAN: As far as the residents and the attendings
could tell, he only reacted to pain.
DR. GÓMEZ-LOBO: Would a child who is normal be given
the dialysis in this case? In other words, any failure to give
the dialysis would be based exclusively on the holoprosencephaly?
DR. KOPELMAN: I would think that is probably true.
DR. GÓMEZ-LOBO: Then it is parallel to the Baby Doe
case, isn't it?
DR. KOPELMAN: And I am going to actually talk about Baby
Doe in the next section. I think it's interesting that all three
of us were given whatever topic we wanted to talk about and all three
of us talked about the Baby Doe regulations. Whether this child would
meet the Baby Doe regulations or not, I can tell you what happened in
In this case, the physicians, just as in the case you talked about
in Taking Care, they decided it was optional and they would
leave it up to the family. And the family chose to have the dialysis.
That was the outcome of this case.
They all agreed that if the family had said, "No, we
do not want to have the dialysis for K. D.," that they would have
gone along with that as well.
PROF. MEILAENDER: May I still pursue that case for just a
DR. KOPELMAN: Yes. I am not sure I can get back. Well,
PROF. MEILAENDER: I am just curious what the answer to
the question would be if — I mean, Rebecca had said that we would
ultimately need more information about the way the dialysis was
experienced by the patient himself, but if the dialysis did not seem to
be burdensome to the patient, didn't seem to respond as he did to
some other painful stimuli, and if it was clearly useful in prolonging
his life and would have been done for a child who didn't have this
disability, then what would the answer to this question be? If
you're not going to dialyze the child, why not?
DR. KOPELMAN: What would be the reason for regarding it as
optional? Why did the doctors think it was optional? Is that what
PROF. MEILAENDER: I would prefer to sort of fill in the
blank, "I'm not going to dialyze this child because"?
DR. KOPELMAN: I think the one thing to consider is what
would you want for yourself in the similar setting. If you were
minimally conscious, could only react to pain and that's how it was
going to be forever, what would you want for yourself?
And if you think we should do unto others, if we should
apply the Golden Rule, then I think I could accept someone saying,
"I wouldn't want this for myself. Therefore, I shouldn't
inflict it on others" or someone saying, "This is what I
would want for myself. Therefore, I think it's the right thing to
do for others."
PROF. MEILAENDER: Well, see, I wouldn't put it quite
that way. I wouldn't think of it quite that way. I would say,
"Since I am a human being, I would not want any of my fellow human
beings to decide that they wouldn't do this so that I would die.
And, therefore, I should not make similar decisions about other human
beings." Do you see that?
The question is how you fill in that blank in the
sentence. If you fill it in by saying, "I'm not going to do
this so that he goes away, so that his life of minimal capacity
ends," then that is not whether I would want that done for me or
not. It's whether I think that should be done to any human being.
DR. KOPELMAN: Well, in making my choice, though, it seems
to me in some sense I am saying, "This is what I would not want
for myself because there would be burdens and no benefits," as far
as I can see, for myself or anyone else.
PROF. MEILAENDER: But by hypothesis, there aren't any
DR. KOPELMAN: Yes, there are.
PROF. MEILAENDER: Not to the patient.
DR. KOPELMAN: Yes, yes. He senses pain.
PROF. MEILAENDER: But I began by saying at least in
lacking other information, we have no evidence that he experiences the
dialysis as burdensome.
DR. KOPELMAN: Well, we know he experiences procedures
as painful. That's his whole life, is pain. And, as I understand
it, at least from reading Taking Care, it's burdensome.
PROF. GEORGE: I think it would help if we were clear on
what the "it" is that's burdensome and what the
"this" is when we say we wouldn't want "this,"
"I wouldn't want this for myself. Therefore, I wouldn't
want this for others."
Is the "this" and the "it" this life under
these conditions or is it this treatment, which in the version of
the hypothetical I think now on the table is painful? Is it the
latter or the former?
DR. ROWLEY: Well, I am the last person who should be
discussing this, and it's too bad Dan isn't here. But dialysis
does involve the circulation through a system of blood to reduce the
amount of ammonia and other — Ed, you probably know as well or Paul —
things that are toxins in the blood. And you remove these through the
So you do either have to have, I believe, some kind of an in-dwelling
line or each time you have to be stuck to be hitched up to the instrument.
And the child is almost certainly going to have to be restrained
for four or five hours three times a week to undergo this. So this
is not a trivial procedure.
PROF. GEORGE: So does that mean that the "this"
is the burdensome treatment, not the life?
DR. ROWLEY: Correct.
PROF. GEORGE: So that if we shift the hypothesis back to
where Professor Meilaender opened, had it in his opening comment, and
there were no particular burdens or he couldn't feel them or
experience them, then there would not be any reason not to go forward
with the dialysis?
DR. KOPELMAN: That is another case. The case I'm
talking about, there are painful burdens. But if it was an
intervention where there was no pain involved, then it would be far
less problematic, I would say.
DR. KASS: I probably should keep silent on this, and I
will probably regret it, but Gil and Robby could find some way to
administer sufficient anesthesia or some kind of narcotic to eliminate
the pain to make it a pure case to prove the principle, but I think
there is something finally weird and even cruel to treat a child who
has, as far as we know, nothing but a reaction to painful pressure as a
continuing biological preparation to uphold the principle.
And I don't see the compelling reason for saying the
condition here doesn't somehow count. It doesn't make sense to
put this baby on dialysis. If you then have to give the reason for not
doing so, you might be embarrassed. And I have owned up to my
embarrassment on this point multiple times.
But this is not what medicine is supposed to be doing. And unless
you want to say every conceivable intervention which could be rendered
non-burdensome to this little infant becomes morally obligatory
because not to make it morally obligatory is to wish them dead,
then we've got something wrong in our thinking.
PROF. LAWLER: All right. This, though, was not such a
great case because the case is about this. This little human being
experiences life as nothing but pain and will be subjected to a
procedure which will bring more pain.
I have to say this is very difficult. I understand what Leon
is saying about this. And I might even be sympathetic as long as
you wouldn't generalize from this case to any other case if
life is 98 percent pain and the danger is caving on this. If Robby
and Gil cave on this, then what about a 10-month-old baby who is
quadriplegic, a ten-month-old baby who is severely retarded, at
what point do we say, then, the quality of life is so low the dialysis
makes no sense?
I'm jumping to the extreme case and pulling Leon's
heartstrings that hard, you know, you can't help but feel sympathy
for a position. On the other hand, Robby and Gil might say,
"We're not going to cave on this one" because in caving
on this one, then, in fact, it becomes a part of drawing the line.
What percentage of life would have to be painful before you would say
dialysis would make no sense because this is a genuinely extreme case
where life is nothing but pain. How many cases like this are there?
DR. KOPELMAN: Well, I think we can ask the neonatologists
here. They're not that uncommon.
PROF. MEILAENDER: I just want to clarify. You have,
alas, walked into a longstanding discussion and just found yourself in
the middle of it. And I sympathize with you at this point, but that
doesn't mean I'm willing to stop exactly.
DR. KASS: I just didn't want their to be the
impression there was unanimity around the table in the way in which the
conversation had been going. So I kept silent.
PROF. MEILAENDER: I understand. But I think if doing
this to this child is — if we have some reason to think that it is
placing burdens on that poor little child's life, that is a
decisive factor, as far as I am concerned.
But it's not a question simply of sort of trying to uphold
a principle, Leon. The Taking Care report, from which
you have gone to the trouble actually to read and to quote, makes
clear that these individualized decisions take place within a framework
that is governed by certain nonnegotiable principles. And one of
those has to do with not just trying to make people's lives
go away finally.
So it's not that one makes one's decision about the
case in order to try to uphold the principle. It's that we have
certain principles that shape our whole understanding of how we think
about cases and what we are doing. If we didn't have them, we
would think about cases entirely differently.
So, I mean, I think it's wrong to describe this as just
an attempt to save a principle. It's an attempt to allow our
thinking to be shaped by ways of looking at cases that are not simply
ad hoc but that recognize our common humanity.
DR. KOPELMAN: As I read Taking Care, I was struck
with how much better off infants would be with the principles that
you enumerate there than the Baby Doe regulations. The Baby Doe
regulations are technically for infants under one, but they create
a certain mindset in pediatrics for a lot of intensive care, too.
PROF. LAWLER: In your opinion, the Baby Doe regulations,
then, would compel the doctor to put the kid through dialysis, even if
dialysis was very painful?
DR. KOPELMAN: I have the Baby Doe regulations. And we can
talk about that case when we have the Baby Doe regulations up on the
board. We could just postpone that a little bit.
PROF. GEORGE: I won't hold us up very long. I just
wanted to clarify one thing. I appreciated Dr. Lawler's comment,
not only this most recent one but the one before it, which is the one I
am referring to right now.
I understand it and agree with the point he was making, but
let me just ask you if he was accurate in his understanding of the case
you had in front of us. I thought you said that the baby in the case
only responded to painful stimuli.
DR. KOPELMAN: Correct.
PROF. GEORGE: I think perhaps Dr. Lawler interpreted that
as meaning that the baby experienced nothing but pain in the sense of
experienced pain all the time, was under constant unpalliated pain.
Now, that wasn't what was going on, right?
DR. KOPELMAN: No. As far as anybody knows, you can't
really ask the baby.
PROF. GEORGE: Sure.
DR. KOPELMAN: But, as far as anybody knows, heart rate
goes up, you know, have a reaction to pain like others do as far as
PROF. GEORGE: Yes. Those would be two different, —
DR. KOPELMAN: Right.
PROF. GEORGE: — interestingly different —
PROF. LAWLER: That's right. I mean, so it's long
periods of calm with break-ins of pain.
DR. KOPELMAN: Minimally conscious.
PROF. LAWLER: Yes.
DR. KOPELMAN: So that they come to consciousness only when
there is pain is as best as anyone can tell.
PROF. GEORGE: Okay.
DR. KOPELMAN: Well, I quoted from you because I did think
that the principles you enumerated would be very useful. The goal
of caregiving — is it a bore to quote you back to yourself?
I hope it's not. Anyway, "the goal of ethical caregiving
in the clinical setting is not to extend the length or purpose or
postpone the end of a patient's life as long as it is medically
possible but always to benefit the life the patient still has."
So you look in terms of burdens and benefits, which I agree with.
The clearest ethical grounds for foregoing life.sustaining
treatment are an obligation to avoid inflicting treatments that are
unduly burdensome to the patient being treated and an obligation to
avoid treatments that are not at all or not any longer efficacious in
obtaining a desired end.
So I come now to choosing policies that support flexible
and individualized choice using the best care or best interest
standard. The Child Abuse Prevention and Treatment Act had amendments
in 1984 that are widely regarded as the Baby Doe regulations. It
requires maximal treatment for infants under one year unless in the
reasonable medical judgment of a physician one of the following apply:
chronically and irreversible comatose.
As Dr. Nelson said, this is very difficult to determine in
the newborn period, as is persistent vegetative state. So as a
condition, as a criterion for discontinuing, this is going to largely
not be used very often.
Treatment would merely prolong dying, not be effective in ameliorating
or correcting all of the infants' life-threatening conditions,
or otherwise be futile in terms of the survival of the infant.
Now, I would say the case we just discussed does not meet
the first condition. He's not in a coma. He's not in a
persistent vegetative state. And the treatment would not prolong
dying. He could live for many, many years with the dialysis.
Third condition is the provision of such treatment would be
virtually futile in terms of survival. And, again, he could live many,
many years for this. And the treatment itself under such circumstances
would be inhumane. There is no separate consideration of what is
inhumane in itself, only in relation to whether it's virtually
futile in terms of survival.
Now, a survey that my husband and I and another colleague did
soon after the Baby Doe regulations went into effect, the neonatologists
from the American Academy of Pediatrics, all of them were sent the
survey and a sampling of pediatricians. Other kinds of pediatricians,
in the academy were sent the survey.
We had a pretty good response on one mailing, almost 50
percent. They argued that standards of care were immediately altered.
They thought it gave, these rules gave, too little weight to the
infants' pain and suffering, too little weight to parental views
and to clinical judgment, the ability to make flexible individualized
Now, there have been a lot of surveys of adults. Most
adults want individualized decision-making for themselves and the
opportunities for their families and doctors to give adequate pain
medication to fulfill palliative goals.
Most adults do not want to prolong minimally or permanently
unconscious lives for themselves. And the Baby Doe regulations are
really pretty strict in not allowing for discontinuation of treatments
unless the infant is in coma or is dying or very likely to be dying.
So the question is, do the Baby Doe rules set up a standard different
from the best care and best interest standard? I would argue they
do. In the survey — again, this is a 20-year-old survey,
but nobody has done one since. Maybe it's time to do it again.
Up to a third thought the Baby Doe rules and the best interest standard
were different in one of the cases. We had three vignettes. And
in one of the cases, a third of them thought that they were required
by the Baby Doe rules to treat that baby in a way that they did
not think was in the infant's best interest.
Do they unfairly single out one group for rules that others of
us do not want? It seems to me fair that if we're going to
have Baby Doe rules for babies under one, then we should all have
them. If you're not going to trust the families and the clinicians
for babies under one, why should you trust them for 50-year-olds,
60-year-old, 70-year-olds, or 80-year-olds?
So, I mean, I would argue it's not fair to have unless
somebody can make a case a set of rules for just one age group. Does
it ignore duties to prevent unnecessary suffering?
Most of the neonatologists and pediatricians, I think it was around
75 percent, thought it did, gave too little consideration to suffering.
Did it give too little attention to parental views? Again, most
of them thought it did.
Did it unduly restrict prudence, the ability to make a here
and now decision considering the facts of the case? Does it give too
little consideration to clinical judgments? And, again, most thought
Now, in the case we have just been talking about, one of
the residents suggested, "Well, you know, maybe we should give
this baby dialysis for three months. When they get out of the range of
the Baby Doe rules, then we'll quit, you know." And I would
suggest to you doing that is probably not making the right decision in
the right way for the right reasons, but anyway.
Here is my concluding slide. And I would suggest that to the
extent possible, the same goals and values apply to health care
for the elderly with diminished capacity that you enumerated in
Taking Care should also apply to minors. We should consider
the values of what is going to benefit and what is going to do no
harm and foster individualized decision-making by families and clinicians
using the best care or best interest standard.
And, as I said when I introduced this, I don't think
you can use the best care or the best interest standard without some
kind of social consensus about what kinds of choices are unacceptable.
It presupposes a consensus, and it also presupposes some frameworks of
rights for the individual and duties to those individuals that are
pretty well enumerated or understood.
We should also consider the value of autonomy in honoring
assent or refusals of minors if they're reasonable. And I think
that's a point you make as well with people who have diminished
capacity but have a point of view among the elderly.
As issues of justice, we should treat similar cases
similarly, different cases differently, and the differences and
similarities should be relevant. I suggest to you being under one is
not necessarily relevant in and of itself for a different set of rules.
Another point about justice, of course — that's a
formal condition of justice to treat similar cases similarly. Another
formal condition of justice, which Aristotle clarified for us, of
course, is that a just system creates the opportunities for justice to
thrive and encourages good people to act well and perform their duties.
I think you heard a lot of angst this morning from intensivists,
from neonatologists about the difficulty of not being able to do
what they consider to be in the best interest of children, provide
the best care, because of rules which they perceive as thwarting
in some cases the best interest standard.
This was really brought home to me in a case conference we
had about six months ago. A woman gave birth to very premature twins.
One of them did well, and one of them was doing extremely badly. And I
cannot remember the details of the case. I'm sorry.
But there was a case conference with about six or seven
family members. One of them was a nurse on a palliative care unit and
one who is a pulmonologist. They were very used to dealing with dying
adults. And they said, "Well, maximal treatment in this case is
not in the best interest of this infant."
The three neonatologists present agreed, "but"
they said, "We feel obligated to follow the Baby Doe regulations.
So we can't do anything." The family expressed shock that
there should be such a difference in the treatment of adults and the
treatment of infants.
So I think that's to me, in part, a justice issue, not
only treating similar cases similarly but are we encouraging good
people to do the right thing in the right way for the right reason with
this very inflexible rule?
And then I would just mention one other value of
generalizability or consistency. Are we treating others as you would
want to be treated if you were in the situation of that infant?
I'll be happy to take any further questions you have.
I'm sure there are some. Yes?
DR. GÓMEZ-LOBO: Well, I couldn't agree more on the
conception of justice that you set out, but it seems to me — and you
may correct me if I'm wrong here in the information; I'm new to
most of these topics — that precisely the Baby Doe case was a case of
severe injustice. In other words, this child was treated differently
from other children of the same age precisely because of the Down's
syndrome disease or disability.
And that's what prompted this idea, it seems to me, to
protect precisely the most weak among us and protect them, in part,
from decisions made by third parties on whatever grounds, which may be
right or wrong. So I would like to understand a little bit more the
The second reason for raising this question is because I
understood Dr. Fost to be in disagreement with regard to
interpretations. In other words, the interpretation of the rules,
because it seemed to me that according to him, these rules would leave
latitude for discretion in certain cases, but I would say it's the
protection of the weak that seems to be or, at least as I understand
it, the focus of these rules.
DR. KOPELMAN: You raise two good points. I'll try to
address them, first one and then the other. What happened with the
baby who came to be known as Baby Doe in Indiana, that was a terrible
thing. I think today there's no question that infant would be
In the early '80s, when that case occurred, there were
very few intensive care units. There were very few neonatal units.
And, I mean, I'm not defending that case, but we need to think of
it in the context of virtually no intensive care units, no pediatric
intensive care, no neonatal intensive.
Hopkins had one of the few. There weren't that many
around the country. And that's why the case that Norm Fost
mentioned where the baby with the duodenal atresia didn't get
treated was very shocking. Many times if we put it in context of what
wasn't happening to adults, we would be shocked there, too.
So we have moved way beyond that Baby Doe. And I don't
think you would find anybody who would not treat that case today and
not because of Baby Doe rules but because they would view this baby as
having a good opportunity to enjoy life and have pleasures and interact
with people. We know an awful lot more about that genetic condition
And I think that part of the problem in this is that when
people talk about non.treatment of infants, that case pops into the
mind of a lot of people, "Oh, you're not going to treat an
infant with Down's syndrome. I know all about that"; whereas,
that's not where the neonatal discussions are. It's really
with infants, as far as anybody can tell, life is just a burden and
nothing else. And that's really where the discussions I've
DR. GÓMEZ-LOBO: That is precisely the case. I think
that at that moment, people considered Down's syndrome just a
burden. So has there really been a shift in thinking or do people
still think of life as a burden and not the illness as a burden or the
DR. KOPELMAN: Well, I am not sure about that. As I
understand it, — maybe Professor Dresser would like to address that —
legal theory was who had the right to decide. And the court said,
"Oh, it's the parents who have the right to decide." And
that's what went up through the Indiana courts.
I think people are much more inclined now to overrule the
parents. And the courts also said, "hey, the doctors disagree
about what is best. Let the parents decide." That was what was
going on for Baby Doe.
Now, was it a mistake? Yes, I think it was a mistake.
PROF. DRESSER: Well, I do think that you have pushed us
into the corner, where it is very uncomfortable. And that is this
question of if we are to adopt a sort of standard of what is reasonable
to allow parents and doctors to decide for infants, what is reasonable
discretion, you know, on the one hand, you can talk about cases where
we would say, "That's unreasonable."
And then you can talk about a child with Down's
syndrome and we can say, you know, withholding treatment is clearly
unreasonable, but that's partly because we live now and there is a
different social understanding of the condition.
So I think we're very aware that to some extent our
judgments about reasonableness are affected by social norms and things
that will change over time. So we don't want to get it wrong. So
I don't know if you — I mean, to me that is the real struggle with
children and with older people with dementia.
Another ingredient with the newborns is uncertainty that I
know I've heard people talk about. With, say, a person with
Alzheimer's, there's a trajectory and you can be pretty certain
about what that person's future looks like; whereas, with the
preemies, as we have heard this morning, you know, there are these
So you can say, "Well, this child is in a group where,
you know, 20 percent will die, 20 percent will be about average in
mental and physical abilities, and then the rest of them will be
somewhere in between. But we can't tell you where your child will
end up." How does that affect this calculus?
DR. KOPELMAN: Well, yes. You raise a good point.
Sometimes it is clear what the trajectory will be for older persons and
you figure, "Well, if we make a mistake, it's going to be a
mistake of months, you know, not decades, as it might be for the
I think that uncertainty is a very good reason to start
maximal treatment and evaluate. And, as Dr. Nelson said, things
sometimes go wrong very quickly and you get more information. And you
can make a much better particular choice using particular data once you
have good information.
And so I would argue for certainly beginning maximal
treatment if there's any uncertainty and evaluating along the way.
But if we have to treat everybody, just because one percent might do
pretty well, then I would say let's adopt that for all of us, that
you don't have any choice.
If there's a one percent chance, you know, heaven
forbid, that we are incapacitated, no matter what, if there's just
a very small chance we have to do everything, your family has no
CHAIRMAN PELLEGRINO: Dr. McHugh, Dr. Meilaender, and then
DR. McHUGH: Once again, I think you are wonderful to
stand up to this where you come. I've enjoyed your conversation as
well as the meeting this morning.
But I wanted to pick up one theme that you mentioned in
your penultimate slide, where you said we might be unfairly singling
out one group for rules others don't want.
I think that maybe children are the most appropriate group
because, as we have seen historically from medicine, children are
individuals we have betrayed more than many others. And, after all,
there is also a man who holds a chair in ethics at Princeton who thinks
that we should not think of lives of children until they develop their
So I think it may well be that the American public,
including me, feels that the child is lacking in champions and that
maybe we should pick them out as a particular group of people because
they lack the kind of championship that adults get and develop as they
flower as members of a family and a citizen, that maybe there are
certain kinds of times when, you know, that we've just got to say,
"Okay. Here are some rules that we want you to obey. They're
burdensome," all of that, but, you know, that's what you get
when you betray a trust. You get very burdensome rules put on top of
you. And to regain the trust takes a heck of a lot longer than it does
to lose it.
Now, Dr. Fost is closer to the case than I am, but I know a
bit about the Hopkins case because I still talk to some of the nurses
who were there when that case was put in.
The doctors made the decision, but the people who had to be
there with that baby were these nurses. You know, nurses aren't
like doctors. They have other things, wonderful things, that they do.
And we betray them if we don't accept their vocational commitment
and their role in caring for things.
So I've listened to a lot of very good information
today, but there's been a bit of whining about how tough it's
become, not enough acceptance of the fact that, you know, we kind of
put this on ourselves.
So I come back to this idea. Do you think that children
have adequate champions today so that we can be really sure that we can
DR. KOPELMAN: You raised about four or five things. One,
does it unfairly single out one group for rules others don't want
for themselves? And it's I would say rules that others don't
want for themselves should they become incompetent. And there's
pretty good data they don't want to live a life where they're
minimally conscious and just feel pain. They don't want to live a
life where they're minimally conscious, period. There's pretty
good data on that. If we know that's what competent adults project
they want, then I think it also. That was the point of that bullet
Do children under one lack champions? This has been a
charge, I think, that the reason you need the Baby Doe rules is that
parents and clinicians can't be trusted to act in their best
interest and do the right thing for them. And that's why you need
a rule that only allows you to quit or if they're dying or
I don't find any evidence for that, for that sweeping
claim. If there is any evidence, I don't know data that shows that
parents don't care about their children and are not inclined to do
a better job than some rule which is one size fits all.
I am sorry about the whining if that's what I have been
doing. I don't know. But I do hear a lot of angst from neonatal
nurses and doctors, who feel they are hurting babies and for no good
reason that they can think of.
DR. McHUGH: Look, don't get me wrong. I was just
teasing a little bit there, and I do that too often. What I meant was
that, in point of fact, we got into this problem because the children
were betrayed. And we heard about the betrayals more today from Dr.
Fost, even others.
All I would like to say is that when people begin to say we
now have overdone it, they might say, "Well, we are overdoing it
now because of the things we, we doctors, neglected to do before. And
we're doing our best to make up for that out of the experience we
have. And what more can we do to help you?"
DR. KOPELMAN: Again — should I continue?
CHAIRMAN PELLEGRINO: We have overused our time.
DR. KOPELMAN: Oh, I'm sorry.
CHAIRMAN PELLEGRINO: And I want to get the last three
DR. KOPELMAN: Okay.
CHAIRMAN PELLEGRINO: Could I ask you to answer all three?
DR. KOPELMAN: Certainly.
CHAIRMAN PELLEGRINO: We have Meilaender, Kass, and Lawler,
in that order, with a plea for conciseness.
PROF. MEILAENDER: You have made a kind of comparison
between the Baby Doe regulations and our Taking Care document.
And I want to take that up, fully conscious that the next speaker
in the queue may offer a different interpretation of our document.
Whether the Baby Doe regulations are perfect or not, I don't
know, but they attempt to provide a structure that guides decision-making.
I would say that that is one of the things that we tried to do in
the Taking Care document. That is to say, we wanted to
think through individualized decision-making but within a certain
structure, governed, for instance, by principles such as no deliberate
killing, whether by action or omission, equal dignity of all human
beings, whatever their particular capacities or stage of life, and
that those structure and shape the individualized decisions.
Now, in the paper we had from you on the Baby Doe
regulations, you say, for instance, — I'll quote a passage from
it, a sentence — "Adults facing a choice between prolonging life
and preventing a life of minimal or no consciousness or of no pain and
suffering sometimes believe that there are worse things than
Now, it strikes me that that language of "preventing a
DR. KOPELMAN: Did I say "prevent"?
PROF. MEILAENDER: Yes. I just read it here.
DR. KOPELMAN: Okay. Yes.
PROF. MEILAENDER: Well, just let me make my point. You
can understand, then, why someone might be worried that a restructuring
would not, in fact, leave in place the sort of guidance that we
suggested might properly shape individualized decision-making.
And that's the worry, not some kind of drive me to the wall
commitment to the notion that the Baby Doe regulations are perfect
and should never be changed but a worry that the kinds of proposals
for reformulating actually wouldn't bear a structural similarity
to the sort of approach we took in the Taking Care document.
CHAIRMAN PELLEGRINO: Thank you.
DR. KASS: Yes. I'm not going to quarrel with Gil
about what we have said. It does seem to me that your plea not to
somehow single out children as a separate group raises an interesting
question for this group insofar as it means to take up the subject of
children. And it's kind of a larger question. I don't quite
know how to get a handle on it, though it's been lurking at the
boundaries of the discussions all day today.
I mean, kind of a dumb way to say it is, what exactly do
you mean by a "child," by which I don't mean what is the
chronological age or how do you recognize them but what is the
conception of them such that we single them out for special
From my way of thinking, Paul spoke partly to the point
where he talked about that these are amongst people in our society, the
most often abused or betrayed. And Norman Fost this morning spoke
about those horrible figures and that they might be lacking in
champions. But it seems to me it's not just children as members of
especially vulnerable populations, which is the way the bioethics
literature tends to group them, that I think makes them of special
And before I would be prepared to say children are human
persons and, therefore, they come under the general heading of how you
treat human persons, I think it's incumbent upon us to try to sort
out for ourselves what do we mean by taking a special interest in them.
And here is just one small point. Going back to the case
of the 16-year-old girl, some people are concerned as to whether there
is rape here and a question of with whom she is sexually active.
No one sort of I think focused on the question of the
integrity of the family as one of the considerations in the care of
children. Janet referred to it when she spoke about the next case,
where she doesn't want to see just this child in isolation but
wants to think about the well.being and the family.
Here one has to sort of say, "Look, there's a
familial context here, which is also on trial in the presentation of
that case and is one of the things that's to be considered."
If we consider children simply as individuals of a young
sort but not see them as somehow integrated into the natural context
into which they belong, we're missing something.
That's not so much a criticism of anything that you
have said. It's something that the presentation has helped me to
see as something I think we need to pay attention to, Mr. Chairman.
I don't think I need a comment in response.
CHAIRMAN PELLEGRINO: Thank you, Leon.
DR. KOPELMAN: Okay. A brief response. The framework I
have worked in here has been people with diminished capacity, either
because they are minors or because they have dementia.
In both cases, it emits of degree. To the extent possible,
I have argued for honoring their assent. I do think as we are
responsible citizens and look forward to a time when we may have very
diminished capacity, sometimes we do let our families know that we
think there are worse things than dying. And that was the context in
which I made that remark in the Baby Doe rules.
And if we do have strong feelings about that, then I also
think the same values, the same principles we should be prepared to
consider for minors, too.
CHAIRMAN PELLEGRINO: Thank you.
DR. ROWLEY: Can I just make just one small comment,
both to Paul and to Gil? Actually, what Loretta was asking us to do
was to individualize treatment. What she is complaining and others are
complaining about with the Baby Doe is that there is no room for
judgment. There is no room for individualization as the rules are
CHAIRMAN PELLEGRINO: Thank you, Dr. Kopelman. I'm
sorry we're a little pressed for time. Thank you for your patience
with this. Obviously the interest in your remarks is very, very
high. And I think it's very pertinent to what we are doing.
Thank you for all the clarifications.
Let's take a few more moments in the break so that we don't
exhaust you entirely before Dr. Goldkind comes on. Let's reassemble
at 5 of 4:00.
(Whereupon, the foregoing matter went off the
record at 3:41 p.m. and went back on the record at 3:58 p.m.)
CHAIRMAN PELLEGRINO: I think we can go ahead probably.
DR. GOLDKIND: I would also like to thank Dr. Pellegrino
and the Council for having me here.
CHAIRMAN PELLEGRINO: Well, I was going to say a word about
DR. GOLDKIND: Okay.
CHAIRMAN PELLEGRINO: Dr. Goldkind is the bioethicist in
the Office of Pediatric Therapeutics within the Office of the
Commissioner of the Food and Drug Administration.
I was surprised to learn that she was the bioethicist for
the FDA. And some of her compatriots, I guess, were surprised, too.
But her presentation was a very impressive one, particularly because of
some of the issues she raised, I thought it would be very important to
have her talk to the Council as we open up the issue of pediatric
ethics, one of them being experimentation with children and some of the
problems as seen from the FDA point of view.
I told Dr. Goldkind please not to limit herself to that perspective,
but to range over other areas.
Thank you for joining us.
DR. GOLDKIND: Thank you for having me.
SESSION 4: ETHICAL ISSUES IN PEDIATRIC
DR. GOLDKIND: I would like to shift the conversation from
the clinical arena to the area of pediatric research and particularly
to regulated research.
What I would like to do is first start with where we have
been, what the evolution is in pediatric clinical trials. And I'm
going to look at societal, legislative, and regulatory history to do
Then I would like to talk about where we are now and the importance
and findings of pediatric research, what I call a shift in paradigm
from the view that research was risk-laden to the notion that research
is actually hope-laden and look at medical and societal influences
on that view and discuss two specific topics which are very challenging
issues, some of which we have heard a little bit about from Norm
on risk levels.
And in order to do so, I'm going to look specifically
at the FDA regulations on subpart D, which are the additional
safeguards for children in clinical investigations.
I would also like to touch upon the issue of inclusion of
healthy children that has already been raised this morning and look at
some ethical documents and subpart D referrals that we have actually
had to the agency to see if we could flesh out a little bit more
information on the inclusion of healthy children.
To begin so, I thought that I would begin with actually the birth
of the FDA and take us through about a 100-year history of where
we were and where we are now. It's interesting that while the
FDA was formed in 1906 in reaction to muckraking journalists to
consumer activists to professional societies to documents such as
Upton Sinclair's novel The Jungle, which exposed cure-all claims
and misbranded products with the idea that we should try and keep
products away from consumers who are not wary of what they're
purchasing and also that there ought to be even regulations among
products that are transmitted via physician prescription.
Prior to the 1906 regulation, there was a 1902 Biologics Act,
which was stimulated because of children who died after receiving
tetanus-laced diphtheria antitoxin. In the next couple of slides,
I'm going to mention some of the untoward and catastrophic effects
that have occurred in children which influenced some of the fundamental
FDA regulations that are still in effect today.
So two landmark dates are 1938, when safety requirements for drugs
were initiated and legislated, and 1962, pre-market efficacy requirements
for drugs were legislated. Both legislative initiatives were stimulated,
in part, by catastrophic events in children. Yet, even at the
time, the ethical approach to children was thought to be exclusion
The 1938 Act, as I said, was passed, in part, in response
to the sulfanilamide disaster, where an elixir of sulfanilamide was
prepared with a poisonous solvent, which was actually antifreeze. And
100 out of 107 of the people who were killed were children. This led
to safety requirements that are still in effect today.
And the sponsors specifically must show before marketing
that a product is safe for the use under the conditions of prescribed,
recommended, or suggested in the proposed labelling.
I would like to point out that the FDA is very specifically
focused on what is written in the label. And you will see this for the
efficacy requirements, too.
So research is conducted. And the information from those
research protocols are found in the label. So the label is a very
important document and reflective of some of the clinical findings.
In 1962, the Kefauver-Harrison amendments were passed, in part, in response
to the thalidomide tragedy. That is what we call the efficacy requirements,
which, again, are still in effect today. And both these pieces
of legislation are actually quite complex. And I'm just giving
you a few of the highlights of these pieces of legislation.
It basically states that sponsors must show before marketing that, based
on substantial evidence, which is adequate and well.controlled clinical
trials, the drug will have the effect it is claimed to have under
the condition of use, prescribed, recommended, or suggested in the
It also required maintenance of strict distribution
records, which was part of the problem in the thalidomide
circumstance. Once it was already recognized that thalidomide caused
phocomelia or limb deformations, they couldn't retrace all the
pills that were distributed. And it required that investigators
supervise trials. It required informed consent from study subjects.
And it required that animal studies be done prior to human exposure.
I put these up because these are certainly significant for
the protection of children. They're significant for the protection
of all human subjects.
So now I would like to sort of trace what I think is the
beginning, if you will, of some of the history related to the inclusion
of demographic subgroups in clinical trials and specifically children.
And I would like you all to recognize that it's not a
dichotomous situation where one day we had no children in clinical
trials and then the next day we did include them. In the 1950s,
children were already being enrolled in multi.site oncology research,
which was the harbinger of what we have today, which is the
Children's Oncology Group, which is a national and at times
multinational research endeavor on behalf of pediatric oncology.
In 1966, of course, Henry Beecher published his famous New
England Journal article that described about 20 or a little
bit over 20 research infractions. And Dr. Fost described Willowbrook,
which was a different perspective on Willowbrook, but that was one
of the studies that was mentioned in Dr. Beecher's publication.
In 1972, of course, we have the Tuskegee atrocities that were
brought to full light, which stimulated the formation of the National
Research Act and the national commission.
So at that point, there was this general, although not
complete, orientation to restrict children's participation in
research and protect them accordingly.
In 1977, the commission issued its report and
recommendations on research involving children, which forms the ethical
basis of our current pediatric regulations. It was really a novel and
insightful and innovative and very thoughtful report. The subpart D
regulations that I am going to discuss later come directly from that
So already in the 1970s, the American Academy of
Pediatrics' Committee on Drugs called for new drugs to be studied
in children under controlled circumstances.
And at that time, the AAP said that it was unethical to
adhere to a system which forces physicians to use therapeutic agents in
an uncontrolled experimental situation virtually every time they
prescribe for children. Dr. Fost alluded to that today.
The figures are somewhere between 75 and 80 percent of drugs that
are used in children, prescribed for them, had not been rigorously,
systematically tested. And so that children, when they go to the
pediatricians' offices, are prescribed medication and basically,
in an unsystematic, uncontrolled manner are turned into subjects
of one. So that's what that piece of those guidelines was in
In 1979, the FDA added a pediatric section to the
labeling. So if you open the Physician's Desk Reference in the
1970s, it looks a lot different than it does now in that there was no
pediatric section at that time and there was no pregnancy section at
that time. So there have been marked changes in the way that we study
Now, I think one of the pivotal times in history for research
and the notion of this shift from risk-laden to hope-laden was the
1980s AIDS crisis, where clearly there was a devastating and life-threatening
illness with no known treatments. And the AIDS activists lobbied
very hard for research access, which is the only way to get any
hope at therapeutics.
In 1985, the FDA adopted a regulation which required
integrated summaries of safety and efficacy by gender, age, racial
subgroups for any new drug application.
And, actually, just to give you some perspective, children
were not the only ones who were recommended to be excluded from trials,
pregnant women or women of child.bearing potential were also.
In 1977, there was a guideline at the FDA that women of child-bearing
potential should not be enrolled in clinical trials. And that certainly
has also shifted dramatically to the point that in 2004, the FDA
issued guidance on how you do pharmacokinetic studies in pregnant
women because there's an understanding now that certainly many
medications are used and needed in pregnancy.
I would say and many would say that beginning in 1994
through to 2003 was the near decade of most significant advancements in
pediatric legislation and research endeavors and initiatives.
In 1994, there was a regulation that was published that
said that sponsors should review pediatric data to determine whether
existing data was adequate to support pediatric labeling. It basically
introduced the concept of extrapolation of efficacy from adults to
So, in other words, if you have a disease such as, let's say,
Crohn's disease, that could occur in adults as well as children,
sponsors were supposed to think about whether you could take the
information you know from adults and transfer that down to the pediatric
population. That's basically what part of that regulation says.
Now, it did not require that clinical studies be done. And that,
you'll see, will change later.
In 1995, again, the American Academy of Pediatrics'
Committee on Drugs issued a statement that there is a moral imperative
to formally study drugs in children so that they can enjoy equal access
to existing as well as new therapeutic agents. I think that their
statement was very much in line with what it was in the 1970s, although
they wanted to contemporize it. But they basically agreed with the
fact that there was this moral imperative, which was their earlier
statement as well.
FDAMA was an extremely important piece of legislation for pediatric
research. And that occurred in 1997 because it authorized what's
called "pediatric exclusivity incentives," that were designed
to address the need for improved pediatric information.
And what it did was say that if the FDA issued a request for pediatric
studies and if those studies were designed and approved by the FDA
and they were completed, then the sponsor could get an additional
six-month period of market protection, not only in the specific
drug that they tested in children but in the entire moiety, in any
preparation that used that particular chemical.
So sildenafil, for example, is now tested for pulmonary hypertension
in children, but it's the compound that's known as Viagra.
So if that company were to get six months of exclusivity, then it
would apply to all of the products and all the uses of that moiety.
So this was a very important incentive to encourage pediatric research.
And that was I guess commonly called "the carrot."
In 1998, there is the final pediatric rule, which is also called
"the stick." It requires the evaluation of pediatric
information and supporting pediatric evidence. However, that was
enjoined early after it was legislated by a federal court, stating
that the FDA had overstepped its regulatory authority.
In 2000, the Children's Health Act was mandated and
that all research on children conducted, supported, or regulated by HHS
comply with subpart D. And their Code of Federal Regulations is 45 CFR
In 2000, the ICH document, which is a document that's a
global document meant to harmonize amongst all the nations that
participated in it — and that was Japan, the European Union, and the
United States. They issued a document called "Clinical
Investigation of Medicinal Products in the Pediatric Population."
That gives nod to the recognition that pediatric research could be done
globally and that it would be important to try and harmonize the human
subjects protections across those participating nations. In 2001, the
FDA adopted the subpart D regulations, which we'll talk about in
much more detail later.
And then, finally, there are two more pieces of legislation
that I want to go over before we shift to today. In 2002, the Best
Pharmaceuticals for Children Act basically reauthorized FDAMA's
pediatrics section sunset, the pediatric exclusivity.
It also established not only the process of studying drugs
that were on patent but a process of studying them, the drugs, that
were off patent. And it mandated that FDA and NIH establish a
collaboration in the study of drugs.
It also mandated that there be public dissemination of
summary findings for those studies conducted under the provisions of
BPCA. So this is a significant change because it mandated that there
be a public dissemination of findings, whether they were positive or
negative, because there was this recognition that there was a dearth of
information about the pediatric population and that any information
would be very helpful information. So it did not necessarily have to
be positive findings.
BPCA also stated that the FDA written requests would ask
sponsors to provide information on the representation of children of
ethnic and racial minorities as appropriate, that neonates should be
considered as appropriate. And it established the Office of Pediatric
Therapeutics at the FDA, which I'm in. And it also required that
there be an ethicist in that office and a pediatrician.
It mandated the public review of safety reports so that the
Pediatric Advisory Committee would be a body that would hear the public
review of adverse event reports that were accumulated as drugs were
used. And it mandated the dissemination of pediatric information, as I
had said before, obtained under BPCA.
The pediatric rule, which I had mentioned had been
previously enjoined, was reinstated in 2003 through the Pediatric
Research Equity Act. And this required that studies be done of certain
drugs and biological products if certain conditions were met, such as
there was a new indication, dosage form, route of administration, et
cetera, or if there were meaningful therapeutic benefits to this
proposed new medication over existing therapies. And that could be in
the realm of treatment, diagnosis, or prevention.
And it amended BPCA to broaden the functions of the
Pediatric Advisory Committee. And I'll talk a little bit more
about that committee as we go through the slides.
So what is the result of all of these regulations and
legislations? Well, currently we have had 100 products reflect new
labeling changes based on these pediatric studies. And this labeling
includes new indications, safety warnings, dosing information, and
sometimes extension to lower age groups.
A hundred and twenty-five products have been studied. And those results
have been submitted to the FDA. Some are still under review, and
some did not lead to any labeling changes.
Here are some of the lessons learned from pediatric
trials. Not all drugs that work in adults actually work in children.
And I have included some examples. There is rosiglitazone, which is
for type II diabetes; and zolmitriptan for migraine headaches.
Some drugs may need different trial designs for children
than adults to demonstrate efficacy. So antidepressants are difficult
to study, even in adults, but in pediatrics, we have not been able to
demonstrate efficacy. And it's unclear whether it's the trial
design or the drug itself.
Weight-based extrapolation of dose from adult data may be incorrect.
So in the past, the way pediatricians would prescribe medications
is simply to alter the dosage based on body weight adjustments.
In many of the drugs that we have gotten data back on, we find that
this assumption is incorrect. And this can lead to overdosing,
as in Luvox for girls between the ages of 8 to 11 may require lower
doses, and Lodine for juvenile rheumatoid arthritis requires about
a two times higher dose per kilogram than is required in younger
children than adults.
Additional lessons that we have learned are that there are undefined
unique pediatric adverse events. Lotrisone for inflammatory dermatoses,
for example, demonstrated that a third of 3- to 12-year olds had
hypopituitary adrenal access suppression and decreased the amount
of corticosteroids that they produced.
Camptosar, which is for chemotherapy, had marked dehydration and hypokalemia
in children when compared to adults. And then a number of drugs
— I just picked two. A number of drugs have effects on growth
and behavior, many of which are reversible when the children come
off the drugs, Ribavirin for hepatitis C and budesonide for asthma.
And then, finally, additional lessons that we have learned are
that even within the pediatric population, which is quite a heterogeneous
population, — we have heard from Skip. He has talked about
premature infants and children who need tremendous care in the NICU.
That's a very different population than your healthy 17-year-old
There's tremendous heterogeneity within the pediatric
population itself. And the way that pharmacokinetics, the way that
drugs are metabolized is more variable within the pediatric population
than originally anticipated.
So, for example, Pepcid clearance values change with age. And
Sotalol or a beta blocker, in that particular trial, they found
that you couldn't even make weight-adjusted changes based on
pediatric information. Body surface area adjustments were needed
to avoid cardiac arrhythmias.
And then, additionally, I wanted to point out that new technology
now allows modifications that we can make to the risk-benefit ratio
when we do pediatric trials, such as seen in pharmacokinetic studies,
where it used to be that you had to do population pharmacokinetics
and draw a lot of blood samples from a small number of children
to generate a dose-response curve.
Now there has been the understanding that you can do sample
pharmacokinetic studies, where you draw less blood samples from each
individual child but you draw them from a greater number of children so
you can get an integrated curve. So technology is also informing what
we understand about pediatric trials.
I want to look further at the shift from risk-laden to hope-laden.
This is a simple schematic that discusses the ethics in the altered
paradigm; whereas, before there was paternalism and protectionism,
with the focus on non.maleficence. The thought was that children
should be excluded from unnecessary research risks. With research
inclusion, there is more an honoring of the freedom to participate,
accessibility, and beneficence.
So some of the societal and medical factors that have contributed
to this shift are — as I had said before, there's been
a lot of experience with children in oncology research, and it's
been an extremely positive experience overall— the AIDS epidemic,
in which research was the only setting where potentially lifesaving
treatments were available, and advocacy groups and professional
societies have been significant, Elizabeth Glaser Foundation and
the American Academy of Pediatrics.
It's not just societies limited to children's
interests, but even groups that have advocated on the parts of women,
minorities, and elderly have informed us about demographic subgroups.
There's been a growing sophistication, as I mentioned, in the understanding
of the heterogeneity of the pediatric population. And then, once
again, there's been a recognition that because of significant
off-label use, children have been exposed to treatment risks in
the interest of avoiding research risks.
So where are we today? Today I would say that there is a
general consensus about scientific and ethical necessity of including
children in research. But there still is a debate about how best to
protect children in the research environment, and I'd like to talk
a little bit more about two challenging areas: the risk levels found
in 21 CFR 50, subpart D; and the involvement of healthy children.
So what I would like to do now is to go over in very schematic,
simple fashion what subpart D is. Subpart D, our additional safeguards
for children in clinical investigations, basically says that an
institutional review board, an IRB, can authorize a pediatric protocol
outright in their own committee's deliberations if they determine
that that protocol falls into one of three categories. It can either
be a protocol that is deemed to be only minimal risk exposure for
kids, or it can be a protocol that has greater than minimal risk
but it presents the prospect of direct benefit to the individual
subjects enrolled in the trials, or it can involve a minor increase
over minimal risk that presents no prospect of direct benefit to
the individual subjects. However, it's likely to yield generalizable
knowledge about the subject's disorder or condition.
Now, this, as I said, came directly from the national
commission's report on children. At that time, they wanted to sort
of leave, if you will, an out. They wanted to protect children, but
they also wanted to allow an opportunity for important research to go
forward, even if it didn't fall under one of these first three
And so there is an additional category to subpart D. That
basically says that if the IRB feels that the research cannot fall in
one of the first three categories of subpart D but the RIB has
determined that the research presents an opportunity to understand,
prevent, or alleviate a serious problem affecting the health or welfare
of children, then it can send that protocol to the federal agency for
an expert panel review.
The way that works — and I'm going to show you towards
the end of the presentation a few protocols that have come to the FDA
and to OHRP under this provision. The way that works is the IRB will
contact the FDA if it's FDA.regulated protocol or OHRP if it's
research that's federally supported or conducted for federal
We convene an expert panel that draws off of ethicists,
physicians, lawyers, education specialists, patient advocates,
statisticians. We comprise a group that is varied and that we think
each person's expertise will be significant to helping the
deliberation of that protocol.
It's a public process, and it affords the opportunity,
not only for written public comment but also for personal appearances
on behalf of the public, any advocacy group that wishes to come. And
we'll discuss a little bit more about what the comments have been
like in relation to those referrals.
Once the expert panel has completed its deliberations, then
the Pediatric Ethics Subcommittee chair presents those deliberations to
the Pediatric Advisory Committee, which is the parent committee to the
The Pediatric Advisory Committee is chartered to make a
recommendation to the FDA commissioner and, for purposes of these
referrals, to the Secretary of HHS as well. So that we now have
because of the liberation of the Pediatric Advisory Committee charter
under the Pediatric Research Equity Act of 2003, which I mentioned, the
ability to have a single federal panel. So that a referral that came
to the FDA would not be reduplicated in its review by OHRP. That
definitely streamlines the process and makes it more efficient and
makes it more ethically and scientifically coherent.
So what I want to look at is in the first three categories,
I'm going to talk about the referral process a little later, but
now I want to talk about what does subpart D have to say about risk
levels that we can expose children to as part of research?
The federal regulations define minimal risk. And they
define minimal risk as the probability and magnitude of the harm or
discomfort anticipated in the research are not greater in and of
themselves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examinations or
So right off the bat, you can see that "daily life"
in this particular definition is not tethered to the daily life
of home. And the national commission had said in the daily life
of healthy children, over the years it's been discussed and
rediscussed and as recently as March of 2004, the Institute of Medicine
issued a report on pediatric research and interpreted the "daily
life" to mean in the normal average healthy child living in
a safe environment.
The other risk category that is found in subpart D is greater
than minimal risk. That has no regulatory definition. In 50.53
category, it talks about a minor increase over minimal risk, but
certainly there can be understood to be more than a minor increase
over minimal risk, particularly in the referrals sent under that
subpart D referral process.
So if we look at the regulations a little bit further,
I've picked out and you can see highlighted in green some terms
that might help us put risk into a little bit better focus.
50.52 refers to the notion of justifying the anticipated
benefit to the risks based upon the anticipated benefits to the
subjects. So there's a risk.benefit calculus that occurs when
you're looking at the direct benefit category of subpart D.
It also says under 50.52 that the relation of the
anticipated benefit to the risk should be at least as favorable as that
presented by available alternative approaches.
50.53, the category that looks at minor increase over
minimal risk, where you have the prospect of generalizable knowledge
but not to the direct subjects involved, talks about the interventions
or procedures present experiences to the subjects that are reasonably
commensurate with those inherent in their actual or expected medical,
dental, psychological, social, or educational situations.
And then, finally, 50.53, again, referring to the category
of minor increase over minimal risk, states that the anticipated
knowledge should be of vital importance to the understanding of
amelioration of the subject's disorder or condition.
So the preamble to the FDA regulations gave a series of
examples of what they thought might be minimal risk when the regulation
was published. You can see clean catch urinalysis, stool samples, and
electroencephalogram, minimal diet or daily routine changes, or
standard psychological tests. This puts the cap at a very low level.
And also one of the points that I wanted to make about the
subpart D regulations is if you look at them, 50.52 and 50.53 all refer
to subjects with disorders or conditions. So if you're trying to
categorize healthy children in a research protocol or healthy controls,
then they either have to fall into the category of 50.51, which is
minimal risk, which is described here in this slide, or they have to
fall into the category of 50.54, which requires a federal referral for
Now, what do we know about minor increase over minimal
risk? Well, the national commission and the IOM report both suggested
that minor increase over minimal risk be understood as slightly more
than minimal risk, which, again, still implicates a very low level of
risk that is acceptable for children as part of research.
This is a slide that sort of brings together a series of
different suggested factors that might help us understand risk. And
what you want to look at is not only the types of interventions but the
times that they're repeated and the cumulative nature of the
interventions in the protocol, whether there are special considerations
for special populations.
So if you have children who are anemic, blood drawing may
be more of a risk than it might be for a population of children who are
not anemic. You have to look at the magnitude probability and duration
of the risks and also the sense, as I had said before, that risk may be
age.graded based on the heterogeneity of the pediatric population.
Look at the equivalence to daily life in terms of
experiences and routine physical or psychological examinations or tests
and look at commensurability or comparability, which I think are
quantitative and qualitative comparisons to experiences already
familiar to children being studied.
David Wendler in a very recent article stated that they
were going to — this particular article was an attempt to try to
quantify what are the risks that children are exposed to as part of
daily life. And so they looked at what are the risks of the average
child dying from a car trip or having some kind of an injury from
The figures are up on the board. Basically, what Wendler
and Emanuel concluded after they looked at those figures is that more
empirical data is needed to quantify risk levels. They also suggested
that maybe based on the fact that those risk levels seem to be higher
than what some IRBs might interpret, that maybe IRBs are
overestimating. Well, wait a minute. I'll go back up and say this
Based on the fact that these seem to be higher risk levels
than one might imagine for children as part of daily life, they thought
that maybe some IRBs are actually overestimating minimal risk.
An example that they use is that allergy skin testing by 60
percent of IRBs that were polled thought it was more than minimal
risk. Some thought it was a minor increase over minimal risk and some
thought it was more than minimal risk, but only about a third of the
polled IRBs thought that allergy skin testing was actually minimal
They also suggested that if the current federal regulations
index risk to daily life and daily life seems to be more risky than we
think it is based on empirical data, maybe the current federal
standards are allowing excessive risk in some cases.
Basically they call for more empiric data on risk level.
And when they were asked to look at a definition for minor increase
over minimal risk, Wendler and Emanuel proposed that it be understood
as the level of risk in the lives of those children who face a greater,
yet socially acceptable, risk.
Friedman, Ross, and Nelson suggest that minimal risk should
be understood as the probability and magnitude of physical or
psychological harm is no more than that to which is appropriate for a
scrupulous parent to intentionally expose a child for educational
purposes in family life situations. And they suggest that there ought
to be a single standard of research for children with or without the
disorder or condition under study. What you see here is an attempt to
try and place pediatric research and our understanding of risk within a
social context, I think.
Now shifting over to healthy children, this is the second
topic that I would like to cover. Going back to the Pediatric Advisory
Committee, it is a committee of multiple specialists, including patient
advocates and consumer representatives, et cetera, that meets to
deliberate issues of clinical trials in pediatrics, ethical issues.
And it issued a consensus statement in 1999 on the topic of
when should healthy children be included in pediatric research. And
they stated that, in general, pediatric studies should be conducted in
subjects who may benefit from participation in the trial. Usually this
implies that the subject has or is susceptible to the disease under
Looking at the ICH document, E11, that I referred to
earlier, it states that pharmacokinetic studies should generally be
conducted in patients with the disease and if the disease process is
similar, consider extrapolating efficacy from older to younger
children. And information that can be obtained in a less vulnerable
consenting population should not be obtained in a more vulnerable
So what you see suggested is that there be perhaps a staged
approach to some pediatric research if it's scientifically valid to
ICH E6, which is the guidance on good clinical practice,
states that unless an exception is justified, research should be
conducted in patients having a disease or condition for which the
investigational product is intended.
And then the Council for International Organizations of
Medical Sciences in collaboration with the World Health Organization in
2002 issued 21 or 22 guidelines with a company in commentary. This is
also understood as an international document. In it, they have a
guideline specifically addressing research in children.
They state that before undertaking research involving
children, the investigator must ensure that the research might not
equally well be carried out with adults.
Now I would like to shift back to what our experience has
been with the subpart D referrals and talk about three referrals that
we have had since December of 2003, when the Pediatric Research Equity
Act reauthorized the Pediatric Advisory Committee, and go through a
little bit more before I do that of what a referral looks like.
So once an IRB goes through its own internal deliberations
on a protocol and they determine that they think that there is an
opportunity to understand, prevent, or alleviate a serious problem
affecting the health and welfare of children but they just cannot
approve this under one of the first three categories of subpart D, then
they make the referral to the pertinent or joint federal agencies.
We convene an expert panel, as I mentioned to you before,
and usually take about a day's worth of deliberations. And those
deliberations include any scientific expertise that we think needs to
be presented to the expert panel. It includes a presentation by the
principal investigator. And it includes a representative of the
institutional review board of record to flesh out what their applicable
concerns have been with this particular protocol.
Then the referral is presented to the Pediatric Advisory
Committee once a recommendation has been determined by the Pediatric
Ethics Subcommittee. And those recommendations have to include what
approval category the subcommittee recommends and whether or not there
are any required modifications to the protocol or parental permission
or assent documents or whether there are any recommended modifications.
That gets presented to the advisory committee, which
deliberates. And in two out of three cases, the advisory committee
added they didn't disagree with the actual recommendations of the
subcommittee, but they added some stipulations to the list of
Then our office writes a memorandum and transmits those
recommendations along with a memorandum to the commissioner and some
additional supporting documents. And the commissioner of the FDA makes
a determination on whether or not the protocol can go forward. The
commissioner could also decide the protocol can't go forward or
could make modifications in the recommendations.
If it involves federally supported or conducted research,
then the commissioner's findings are then transmitted to the Office
for Human Research Protections. And they submit a memorandum to the
Assistant Secretary for Health, who has been authorized to make these
decisions on behalf of the Secretary.
And once the Secretary or the ASH, I should say, makes the
final determination about whether or not that project can be funded or
supported, then the project can go forward.
So it has actually been a process that sounds rather long
and complex, and it is. But it has actually been a process that has
been greatly streamlined since prior subpart D referrals before the
initiation of the advisory committee.
So here are three examples of subpart D referrals. All
three of them were initiated because the IRBs felt that the healthy
children or the children who did not have the disorder or condition
under study (the control group) did not fall into the first category of
subpart D of minimal risk. And so, however, in each case, the IRBs
felt that the research was significant research. And so these were
In the first case, a single dose of dextroamphetamine — it
was a ten.milligram dose — was to be given to children with and
without attention deficit hyperactivity disorder. And then functional
magnetic resonance studies were going to be done on all the children to
see if there were differences in the neural anatomy of children with
ADHD and children without ADHD.
In the second case, precursors, phospholipid precursors,
were to be administered to neonates to try and determine preferential
use of these phospholipids in the synthesis of surfactant.
In that case, these were premature infants who had respiratory
distress syndrome, previously known as hyaline membrane disease.
And they wanted to look at the control group. In order to minimize
any risk that they exposed the control group to, they selected full-term
infants who were also intubated and had arterial access in the intensive
care unit, but they were there for purposes other than lung disease,
such as awaiting cardiac surgery, et cetera.
So, in actuality, in that case, the main research
intervention was the administration of the phospholipids, which can be
found in hyperalimentation. There were no additional blood draws, and
any of the tracheal aspirates that they were going to get were going to
be gotten when routine care was delivered. So that was the comparison
And then in a third case, gonadotropin-releasing hormone agonists
tests in disorders of puberty, there has been a commercial lack,
for various reasons, at this point in an adequate diagnostic test
to try and differentiate some disorders of puberty.
So in this case, the principal investigator wanted to administer Lupron,
which is a gonadotropin-releasing hormone agonist, to children who
both have disorders of puberty and to children who do not have disorders
of puberty, to try and establish some sense of whether this challenge
test could be used as an adequate means to make this differential
So it involved the administration of a single dose at the
levels that are currently approved for the treatment of precocious
puberty in children.
And I can expand on any of these descriptions, but the
point that I was trying to make in this slide is that these were still
fairly low levels of risk for the healthy children, but because of the
way our subpart D regulations are written, they required a subpart D
In the first case, the commissioner approved that the study
went forward, but the study was eventually withdrawn by the sponsoring
agency. In the second case, both the commissioner and the ASH approved
that the study go forward. And in both of those cases, those were with
stipulated and recommended modifications. And in the third case, that
was just heard in November of '05. So we don't have
determinations on that one yet.
I look upon these particular subpart D referrals as almost
case precedents because they help us advance our understanding of what
we think is acceptable or not acceptable in pediatric research.
So, in conclusion, there has been significant progress in
pediatric therapeutic research from both the ethical and scientific
perspectives. Federal legislative initiatives have proven to be
important and useful tools in obtaining pediatric information.
And, as a consequence of study in children, there is an
improved understanding of pharmacokinetics criteria for extrapolation,
unique safety concerns, and trial designs for children. And a public
dissemination of summaries of pediatric trial results is important
because of the limited numbers of these trials.
CHAIRMAN PELLEGRINO: Thank you very much.
PROF. DRESSER: At one point you were having a shifting
from risk-laden to hope-laden in research. And so it sounds as
though you think it's a happy ending and everything is great,
but I wonder if you still have some ethical concerns about what
has happened along with this shift.
DR. GOLDKIND: Well, as my slides have demonstrated, I do think
that pediatric research is extremely important. I don't think
that the willy-nilly inclusion of children in pediatric research
I think that the graded introduction of research into the
pediatric population is important. And I think that there are a lot of
considerations that have to go into whether or not children should be
in the research.
I think, first and foremost, there needs to be attention to
the scientific question and is this scientifically valid research, do
children have to be included to answer the question, is this necessary
research. Even if it's perhaps scientifically valid, it might not
be important research.
I think that once you get to the point — and then you, of
course, have to ask whether information can be extrapolated from
adults. Sometimes there are disease states where you can extrapolate
efficacy, but you still may have to do some supporting studies, such as
the pharmacokinetic studies or the safety studies, in children.
So you have to ask what studies do I absolutely have to do
in children, what studies can I use from adults. I think you always
have to ask what does the animal data show, the preclinical work, and
is this a risk that we can take with children.
I think that the subpart D regulations are an important
part of protecting children in research. I think that we do still have
to answer the second part of your question, which is, what are some of
the ethical issues in pediatric research?
One of them would be a better understanding of those risk
levels. Another would be understanding the ability to globalize those
risk levels as we look more and more towards globalization of research.
PROF. HURLBUT: Just a little clarification. You mentioned at
one point that some studies were acceptable if they serve to prevent
or alleviate serious problems in the health and welfare of children.
I wanted to understand what that would include, because some conditions
that you might want to study you could only study in children but
don't manifest themselves until later.
Why would you separate off children except for the fact
that if you can do it in a later group; therefore, more voluntary
subjects or with informed consent? The fact that it's benefitting
children, is that to the point of the regulation or is it that —
DR. GOLDKIND: Well, these regulations were specifically
adopted to protect children. They require the additional safeguards
for children in clinical investigations. So they do specifically
address pediatric research.
PROF. HURLBUT: Let's use a hypothetical example that
you wanted to study later effects of obesity and some circulating
element or something, diabetes or something like that, and you could
see a benefit to adults by studying children. Would that be
DR. GOLDKIND: Disorder or condition is one of the aspects that
I didn't discuss in this particular regulation. And disorder
or condition is, again, another one of those issues that requires
some further discussion, but it has elements of current illness
or potentially an at-risk component to it or a future element to
it. That's certainly at least the way the Institute of Medicine
has understood it and other bodies as well.
So if you can think that there is a condition in children that may put
them at risk for something in the future when they become adults,
then there's the understanding that you can go ahead and look
at the pediatric population and include them in research on that
particular issue, given all the caveats that I've already addressed.
The reverse, where you have a disease entity in adults, you
have to make the case for why it's scientifically valid and
necessary to study the pediatric population, rather than a consenting
adult population. And when you have to make that case, I mean, the
onus is upon the investigators, the researchers, the IRBs to understand
what it is about studying that pediatric population that warrants using
a population that cannot consent.
PROF. HURLBUT: Just to take it one more step, you're
saying, though, if you could justify that, you could do it. I'm
thinking kind of hypothetically here, but there are quite a few
conditions in adult life, like osteoporosis, for example, that you
might gain some interesting information by invasive studies, slightly
invasive studies and maybe very invasive studies.
I mean, this is hypothetical, but suppose by coring out a
little piece of bone marrow you could predict something that would
happen at age 50. I mean, could you theoretically justify that or age
processes in studies like this eventually?
DR. GOLDKIND: Well, you know, as they say, the devil is in
the details, but if you could in some way justify why you have to study
that pediatric population and why they may eventually become at risk as
adults and there were some meaningful invention or preventive mechanism
that you could learn from that research, I would imagine that you could
But there are a lot of caveats.
CHAIRMAN PELLEGRINO: Leon?
DR. KASS: Thank you very much. I learned a lot,
starting from a very low level of understanding. So I appreciate this.
My general impression is that people are being very, very
cautious, notwithstanding the shift of the paradigm if these are the
cases, if these are the sort of illustrative kinds of cases that come
for referral under the 50.54.
I'm trying to think ahead if we're told that
there's a huge mushrooming of pharmacological agents, especially
directed at children, and if the general rule is children are different
and you need to do special kinds of treatment.
I guess the question is, what is the magnitude, anticipated
magnitude, of the need for involving healthy children as research
subjects, not for, say, a single shot to find the rate of renal
clearance of a drug but for questions of toxicity or things where your
population of patients is small; to do meaningful studies, you need
larger groups. I'm thinking out loud.
I could see that once you begin to open the door to
recruitment of healthy children as control groups here, for one reason
or another, and we're talking about a greatly increased
pharmacopeia, that this could be a very large business.
Am I right in thinking about that? Are people sort of concerned
about the question of recruitment? Just to say, I mean, when the
question of imposing risks on children is raised and then Norman
Fost says, you know, venipuncture, well, I could persuade an eight
or ten-year-old I think to be a good sport for that. I would be
much more reluctant to persuade them to injections of medications,
the very hazard of which we're trying to study here.
So can you help me sort of think about that with respect to
the healthy children question?
DR. GOLDKIND: Well, I think there are a number of
components to your question. One is that I can hearken back to some of
the data that we have. We have had about 45,000 children enrolled in
clinical trials since the 1997 exclusivity regulations, legislation, so
45,000 children in about 8 years of trials that the FDA has requested.
That's not all pediatric trials for sure. Those are trials that
the FDA requested as part of their exclusivity arrangements.
Since FDA adopted its subpart D regulations in 1983, they
have had roughly 20 subpart D referrals. So that's about one per
year at the most, probably a little less than that.
And there are all kinds of factors that influence taking
this in to the practical settings to be able to answer your question.
There are all kinds of factors that influence pediatric research.
One of the reasons that the pediatric exclusivity
incentives were so important to being able to accumulate the
information that I've shown you today is because there were
financial incentives associated with them.
Children tend to be, generally speaking, thankfully,
healthy. The market for medications is smaller than it is for adults.
And certainly for devices as well. And that has actually been one of
the hindrances to pediatric device development. I've talked a lot
today about drugs and biologics, but devices is another whole spectrum
And sponsors are not always interested in pursuing that
market. So that is one component, one real component, one practical
component, to keeping a check, if you will, on how many kids are in
Now, I think that the subpart D regulations are protective
to children because of precisely the scenario that you described. And
that is that when you have a cap on the amount of risk that children
can be exposed to, the nice thing is there is this safety valve in
subpart D, which is the referral system.
So, even though there is a cap, there is a low level of
risk that they can be exposed to, there is a mechanism by which perhaps
that research can still be advanced if needed.
I think that that cap mitigates just sort of the free flow
of healthy children into research.
CHAIRMAN PELLEGRINO: Gil? Dr. Meilaender? And let me say
we have exceeded our time. So this may be the last question.
PROF. MEILAENDER: This is a related question in
some ways. It has to do with healthy children again. The shift
from the risk-laden to the hope-laden paradigm, I mean, I think
I understand what you mean by that and understand how it might be
appealing in certain circumstances, but just conceptually or theoretically,
it seems like the wrong paradigm to apply when thinking about healthy
I mean, in the hope-laden paradigm, what are they hoping for in
doing it, just theoretically? Can you explain why, if we're
thinking about inclusion of healthy children in research, we shouldn't
think in terms of the risk-laden, rather than the hope-laden?
I mean, I think the hope-laden paradigm emerged precisely in terms of
people with serious illnesses wanting to get early and better access
to care and so forth. And I can't make it fit the healthy children
model, but maybe I'm missing something.
DR. GOLDKIND: Well, you know, I think that perhaps we have
to think of that in a somewhat flexible sort of way. I think that if
you look at the figures that I presented and that Dr. Fost presented,
that up until very recently, 80 percent of children who went to the
pediatrician got medicines that were not tested in children.
So that meant that there were a lot of risks that children
were being exposed to in just the average course of going to their
pediatrician. This was not recognized by a lot of parents. This
wasn't recognized by children who were there getting their
And there were — I presented maybe ten or so changes in
the labeling just as illustrative changes, but there are over 100
changes. There are changes in over 100 labels.
So, I mean, I really think of the shift in paradigm really, as
you say, to more children who have disorders or conditions who are
trying to get some benefit out of the research, but I think that
you can, if you're flexible, understand this notion of hope
in a more general way if you're reducing the risks that kids
are exposed to in their average course of encounter with the medical
CHAIRMAN PELLEGRINO: Well, thank you very much, Dr.
DR. GOLDKIND: Thank you.
CHAIRMAN PELLEGRINO: A very, very complete review. Thank
(Whereupon, the foregoing matter was concluded
at 5:11 p.m.)