TRANSCRIPT: Meeting 5, Session 1

Federal Standards - Introduction

Date

May 18, 2011

Location

New York, N.Y.

Presenters

Christine Grady, R.N., Ph.D.
Commission Member

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Transcript

DR. GUTMANN:  We’re going to dive right into the part of the Commission’s work that the Commission Members themselves and the International Task Force are avidly working on, which is what concerns many people in the public. And that –
  MAN 1: I think you can take that out of here. You have several signs of a [L____?] because a few are not coming. I [UNINTEL – OFF MIC] in the front row. And now after spending hundreds of dollars coming from California, I’m being kicked out. What is this? You know you’ve got a bunch of people coming here and you had a small room. I’m going to leave with this bullshit.
  DR. GUTMANN:  Oh, please stay.
  MAN 1:  I’m being kicked out. I’ve got no choice.
  MAN 2:  No, we have some seats over here.
  MAN 1:  No, they told me I’m being kicked out.
  MAN 2:  Please, gentleman.
  DR. WAGNER:  I apologize for the disruption, but why don’t we move ahead with our agenda? And there is opportunities, we said, at the end of today for public comment, and we most certainly invite and want to listen to that. But, our next speaker is one of our own actually, Member of the Commission, Christine Grady. She is also the Deputy Chief of the Department of Bioethics of the National Institutes of Health Clinical Center. And she serves as the Head of the Department Section on Human Subjects Research. Christine’s research focuses on research subject recruitment, incentives, vulnerability, international research ethics. And she is also Senior Research Fellow at the Kennedy Institute of Ethics and was elected as a Fellow of both the American Academy of Nursing and the Hastings Center. You know, this may be a very civilized system that only allows one person to speak at a time, which is something Americans aren’t used to, so I’ll shut mine off and see if we can’t get Christine speaking. Welcome, Christine.
  DR. GRADY:  That’s what it is. First, I want to say, it’s an honor to be on this side of the table, speaking to my fellow Commissioners.
  Secondly, I want to say that I’ve been asked to talk about standards for protecting human subjects in research in 10 minutes. And therefore, it will be a quick and sort of quick ride through the terrain. To start with, I want to say that since the experiments that Susan Reverby uncovered in Guatemala in the 40’s, there has been a proliferation of guidance and regulations and rules about protecting human subjects in research. And this slide just lists some of them.
  I’m going to talk about some of them, and some of the other speakers today are going to speak to them as well. But for someone who is going to do research in the United States with federally sponsored research, this is the list of rules that they need to know about and need to follow. Also, people who are reviewing research need to know these rules and follow them.
  So, actually, what it ends up, unfortunately being, is a little bit overwhelming. And so, people who are trying to do research, there’s a sort of growing evidence that there’s frustration with the number of rules. There is some inconsistency because of the differences between rules and not knowing how to follow them all. And I think perhaps the most problematic outcome of the proliferation of rules is that investigators more and more are outsourcing the details of following the rules.
  So in other words, rather than figure out what all the rules say, they hire somebody to take care of following the – complying with the ethical rules and the protection rules. And that creates a culture of, you know, not understanding what they are and not thinking they’re important to the work that the investigators are doing.
  So, just to go through some of them, the U.S. Common Rule, very familiar to most everybody in this room is the Federal Policy for the Protection of Human Subjects. And it’s currently followed by 17 federal agencies. It’s found in the Code of Federal Regulations that’s in different places for each agency.
  So, for example, for DHHS, it’s a title 45 code of federal regulations, part 46 for the VA and title 38, part 16 and for the USAID in title 24 part 60. And then there are others for the other agencies.
  The Common Rule, the 45 CFR 46, which is the DHHS Common Rule has several subparts. Subpart A is the basic DHHS policy for protection of human research subjects. And then, there are subparts that B, C and D that were added to provide additional protections for certain special populations – pregnant women, human fetuses, neonates prisoners and children.  And more recently, a subpart E was added which requires registration of IRBs.
 The Common Rule subpart A is primarily procedural. It includes the description of what people refer to often as the two pillars of human subjects protections, but they are procedural pillars.
  So the first is independent review and the second is informed consent. And the Common Rule, very specifically lays out details about the composition and function of local institutional review boards and details about the requirements for informed consent both in terms of information that should be provided and documentation and the possibility of wavering.
  There are also substantive criteria in the Common Rule, and these are found, for example, in this section which describes the criteria that an IRB should use when they’re determining whether or not a particular proposal is acceptable and approvable. And they include a number of items, which you will see are based on the Belmont principles. The Belmont principles being respect for persons’ beneficence and justice.
  And this subset, this list from the Common Rule is very much based on those principles. And I won’t read them.
  The DHHS has an Office of Human Research Protections - we have Jerry with us today – that makes sure that institutions that receive federal funding for research comply with the Common Rule. And they do this through a process of compliance of assurance through a process of federal wide assurances.
  So an institution receiving support from the federal government files an assurance with the OHRP and this assurance documents the institutional commitment to extend or comply the common rule to the covered research that they conduct.
  Institutions actually have a choice when they file their FWA, whether they want to have all research that their institution is conducting fall under the Common Rule, or just federally funded research.
  In addition to the Common Rule, another important agency in terms of human subjects protections is the Food and Drug Administration. And the Food and Drug Administration is not under the Common Rule, but has its own set of regulations that anyone who is doing an investigation of an FDA regulated product needs to know about and needs to follow.
  Now, the human subjects protection regulations are found primarily in Title 21 of the CFR part 50 and 56, which respectively are protection of human subjects and details about informed consent and details about institutional review boards.
  Those are very similar to the details that are delineated in the Common Rule, but there are some very important differences that investigators and review groups need to know about.
  There are also a number of other FDA regulations, which actually serve to provide protection for human subjects in different ways. And so, the IND regulations and the IDE regulations as an example, are important regulations for investigators for doing studies of FDA regulated products.
  In the early 90’s, the International Conference on Harmonization was a process that involved the regulatory agencies, the FDA in the United States and the comparable regulatory agencies in Europe and Japan. And they came together in an effort to harmonize some of the rules.
  And the goal of the International Conference on Harmonization was to harmonize the second bullet there actually, harmonize technical procedures and standards, improve quality and speed time to market.
  Part of the luminous guidance that comes out of ICH is something called the Good Clinical Practice Guidelines. And it’s the consolidated guideline. It’s found at E6 of the ICH Volumes and it’s referred to affectionately as ICH GCP.
  And ICH GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.
  The FDA endorsed the ICH GCP in 1997. Many countries around the world have adopted ICH GCP as part of their law. In the United States, it’s part of the guidance that the FDA uses, but not part of the law.
  And some have written that ICH GCP has become, in recent years, the de facto global standard for protection of human subjects.
  In addition to the federal regulations that the FDA has and the Common Rule has, there are some other important regulations and rules that investigators need to know about. So, clinicaltrials.gov is a registration system. There was registration of clinical trials prior to 2007, but in 2007 the FDA Amendment Act expanded the requirements for registering clinical trials with the goal of transparency so that all clinical trials of certain types have to be registered in the clinicaltrials.gov so that the purpose of the trial, the methods of the trial are open to the public. And now, more recently, the results of trials also need to be posted on clinicaltrials.gov.
  In addition to those, agencies that fund research often have their own specific agency requirements. So for example, the NIH has a number of agency requirements that add to human subject protections, including the three on this slide. NIH requires inclusion of women and minorities in clinical research. NIH requires the inclusion of children. And NIH requires plans for data and safety monitoring in clinical trials.
  In addition to that, if you’re an investigator doing research, so you have to know the Common Rule, you need to know the FDA regs, you need to know clinicaltrials.gov, you need to know the agency specific requirements. But if you’re doing research, especially international research, more than likely it’s collaborative research, and therefore you need to be aware of and follow regulations and laws that pertain to the jurisdictions of your collaborators and your host communities.
  In addition, there are a number of international research ethics codes and guidelines, which many people do follow, which many countries actually have adopted as part of their regulatory framework, and which any investigator doing clinical research needs to be able to justify his or her methods and research against the principles that are enunciated in these various codes. And I know we’re going to hear more about those today.
  So you can see why an investigator trying to do international research with federally supported international research might feel somewhat frustrated. These are the sort of scope of guidances that they need to know and need to follow.
  So I wanted to just end with sort of putting on the table some challenges that I think this array of guidance poses for international research. And I’ve decided to group these challenges into four categories, and I’m going to talk very sort of globally about what these issues are, but I think that these are issues that everyone ought to be aware of, especially thinking about how the standards for protecting human subjects work.
  Harmonization burden, effectiveness and collaboration and respect. I realized the other day that the first two actually maybe speak to the need for rationalization and streamlining of guidance. And the second two actually speak to more opening of what the guidance actually says. So, I’ll try to make that clear as I go through.
  So what about harmonization? Well, unfortunately, with all this list of rules and regulations that people need to follow, there are differences. There are differences in content. And so, the investigator doing the research study needs to know which content applies to their research.
  So, for example, there are differences in terms of waiver of consent between the Common Rule and the FDA regulations. There are reasons for that, but they are different.
  Secondly, there are differences between most or many national regulations in other jurisdictions and the United States regulations with respect to requirements for compensation for research injury.
  Also, as I’ve already alluded to, the rules have different purviews. So, those who receive U.S. federal support for their research have to follow the Common Rule. Those who are investigating products that will be FDA regulated need to follow the FDA rules. And the other guidance documents that exist depends on what are the laws and the rules and the authority in the jurisdiction where you’re going. All of which, by the way, all of those guidances have moral authority even if they don’t have the rule of law.
  There are also important differences in interpretations. So, some very key concepts to understanding how to protect in the systems that we have, like minimal risk and undo inducement and even responsiveness are described differently in different sets of guidance, or not really defined at all in some respects. And so, the interpretation of how to apply them to particular studies is very broad and very different.
  What about burden? You know already there are just a large number of rules and guidelines. I think that the sheer number themselves has a couple of potential harms. One is, it can provide a disincentive to do clinical research at all. And there are people who have written about the fact that they have decided not to pursue clinical research because it’s too burdensome. The regulatory burdens are too great.
  I agree wholeheartedly with what Susan Reverby said earlier, that clinical research is critical to making progress in advancing the understanding of health and treating diseases. And we need qualified people to want to do clinical research, and so, we don’t want to disincentivize them.
  At the same time, the sheer number of rules and guidances is an incentive for some to seek the least burdensome path. And in some cases, also to cut corners.
  There is clearly delay. And this can be a problem. People have begun to write and try to estimate, for example, how many people might have been treated by a particular drug or intervention that’s being studied in the two or three or four years that it takes sometimes to get the study approved to even begin.
  And so, a delay has not only cost to it and frustration to it, but it has potential negative impacts on individual patients. And, lastly, there’s a question about whether or not the rules, as they’re applied currently, actually hinder or maybe make impossible, certain kinds of research that’s otherwise ethically appropriate and could be done without so many rules.
  What about effectiveness though? I think maybe this is the most important thing I want to say, and I think that, you know, we have a lot of rules. We have a lot of guidance. The goal of them is to protect human subjects, but rules alone cannot protect research participants.
  There’s a lot of other things that need to be in place. Quality science is critical to protecting research participants. Responsible and engaged researchers and research teams thoughtfully applied principles, engagement of participants in the communities, and there are many other things that one could add.
  And even Sam said very carefully, I think, the mere formulation of the ethical guidelines for research involving human subjects will hardly resolve the doubts, the moral doubts that arise. And I think even one step further, even perfect compliance with the rules that are written doesn’t resolve all the moral ambiguities that pertain to doing research, so judgment is always part of the picture.
  In addition, there are a number of things that, especially in the context of international research, that the guidance either doesn’t address, or doesn’t address in a way that there can be agreement or consensus.
  Some of the very vexing issues that I think that people face are, what is the relevance on the background conditions and the background injustices to selecting a community to do research, to selecting a project to the methods and the design that the particular project uses, et cetera? And those things are not well addressed in the guidances that we have.
  Also, issues about what’s owed to participants in communities in the international or even in national research. And also, there are documented inconsistencies in the implementation of the guidances that we do have. So, more and more evidence showing that IRB’s following the same set of federal regulations often come out with different determinations at the end of their deliberations.
  Some of that might be justified, but it certainly can’t all be justified. Informed consent, everybody agrees is an important thing. The regulations require it. All of the guidances require it. And evidence continues to mount that people who are giving their informed consent are not always adequately informed or even voluntarily consenting.
  Last, I want to just say that I think especially again in international research, almost all international research that’s sponsored by the Federal Government is collaborative. And it’s collaborative with scientists, with communities, with all kinds of people. And in fact, many projects are collaborative with hundreds of people from different countries.
  And so, there’s a really important principle, I think, of collaborative partnership and respect that should govern the way that we do international research. And this is something that is hard to reconcile with rules, especially rules that these are our rules and other jurisdictions have their rules, and how do those two reconcile each other in a show of respect?
  We have an option in our regulations for recognizing what are called equivalent protections, but it’s an option that we haven’t exercised.
  There are also two other things that I think are critical to showing respect to collaborative partners around the world, and that is, capacity development in all of the right ways that it can be done and engaging the community. And these are things that still need a lot of attention and a lot of work in terms of how to do them right.
  And that’s, I think I’m finished. I just want to say balancing the need to do good research to benefit everybody and the need to protect the people that are involved.
  DR. WAGNER:  Oh, I’m on, good? Christine, thank you so much for that. I’ll entertain questions from the panel, from the Commission. But, I’m wondering, do you have concerns, particularly in this latter part and where we’re really going here, about our credibility when we look for cooperation abroad in such areas as harmonization and equivalency, equivalent protections?
  Do you have any concern about our credibility, if our American house is not in order?
  DR. GRADY:  I have two concerns, actually I would say. One is, I do think that there is a perception – although it evolves all the time, so I’ll say that too. There is a perception that there’s a little bit of imperialistic imposition of our rules on other jurisdictions when many jurisdictions have very developed rules and long standing research programs, et cetera. So there is that perception, I think, on the part of collaborators.
  I think the other thing though that’s happening simultaneously is that there are emerging economies and developing economies that are developing frameworks for human subjects protection. And they are looking to us as a model. And so, I think it’s a really critical time to be clear about what works with our model and what doesn’t work with our model so that as new systems get developed, it’s the best practices, not the unfortunate practices.
  DR. WAGNER:  [UNINTEL – OFF MIC].
  DR. GRADY:  Yeah.
  DR. WAGNER:  I think that John will ask a question? Here you go.
  DR. ARRAS:  Thank you, Chris. Chris, I discern a somewhat of something of a tension between the ideal of collaboration that you’re sketching here and what you describe as the current gold standard globally, which is the ICH GCP.
  As you’ve explained it, the ICH GCP developed out of a collaborative process that was very narrowly focused among Japan, Europe, United States, the FDA and so forth.
  So, do you perceive and do people out there in the research community perceive a tension there, that even though the harmonization standards have been adopted globally by many places, that they might lack legitimacy, vis a vi other standards like Helsinki, which were approved by, you know, the World Medical Association, which has hundreds and thousands really of members?
  DR. GRADY:  Right. So, it’s a great question. I think that there are two things that are worth pointing out. One is that actually in the ICH GCP, it says that they follow the principles enunciated in the Declaration of Helsinki.
  The interesting thing about that though is that they don’t elaborate on that in ICH GCP. And so, even though it has been adopted by people around the world, I think you’re exactly right, there are some people who think that its origin makes it not appropriate for as wide adoption as it has actually seen. But, I think maybe more importantly from my perspective, it’s not very thorough in terms of the ethical attention that some of the other codes and regulations have. Does that makes sense?
  DR. ARRAS:  Yeah, it does. Am I on here?
  DR. GRADY:  You are.
  DR. ARRAS:  You are.
  DR. GRADY:  Yeah, okay. I just find it ironic that the ICH, you know, GCP says that it follows the Helsinki guidelines, or incorporates them in a sense. But my understanding of it is that in large measure, the FDA has opted for the ICH GCP precisely because it deviates from Helsinki on the issue of placebos.
  DR. GRADY:  I think the reality is it doesn’t say much about placebo, ICH GCP.
  DR. ARRAS:  Yeah, right.
  DR. GRARDY:  So it leaves that open, yeah.
  DR. WAGNER:  I’ve got Anita, Raju and Dan and Barbara and then I think we’re going to be.
  DR. FARAHANY:  So thanks, Christine, that was fantastic and incredibly informative. I wanted to just ask you two questions. Toward the end of your presentation you wanted to highlight some of the challenges that we face. And so, given that you’ve really spent your lifetime focusing on this issue, first I wanted to get your sense of what unique issues you think the Commission can take on and address that other commissions or other institutions have not already addressed. So, what aspect of this problem – is it something you think is manageable that would make sense, would truly make a contribution?
  And one thing you mention was the equivalent protections. And so, do you think that the Commission not only should discuss equivalent protections, but to flesh out what that would mean?
  And then, to John’s point, if we were to do so without the weight of many different countries signing onto it, would you envision some way in which that should be rolled out internationally to try to get buy-in and cooperation to develop what that would look like meaningfully?
  DR. GRADY:  Those are hard questions. I have thought a lot about what the Commission might be able to do in this arena. And you’re right, I’ve spent a lot of years sort of immersed in it, so it’s harder in a certain way to sort of say, “What can we do in six months?”
  I do think a number of previous groups have – including NBAC, for example, have mentioned that equivalent protections, that that ought to be spelled out further.
  I do think that as we move forward, and there is an increasing number of studies that are done with collaborative partners around the world, that that takes on a different kind of urgency. And so, I think maybe fleshing out what is equivalent protections? What should it look like?
  I mean, there is this interesting tension of course between if we’re sponsoring research, we want to make sure it’s done well. And so, we want, you know, rules that can govern it that we are confident in.
  At the same time, we want to – I believe strongly – we want to trust our partners and we want to have respect for their rules. And sometimes their rules actually go above our rules.
  So, you know, figuring out how equivalent protections could be applied and could be used effectively, I think would be a wonderful contribution in this Commission.
  DR. WAGNER:  Anita?
  DR. ALLEN:  Hi, a very simple question, Christine. Thank you for those excellent comments. So, you focus primarily on researchers and their need to know and desire to know about the federal regulatory regime, but what about members of the general public, college students, patients, potential study subjects?
  Is there some convenient place to go to find a comprehensive and comprehensible list of the primary regulations that govern human subject research?
  DR. GRADY:  It’s a great question, Anita. I don’t think there is, actually. I think it’s actually interesting sometimes how hard it is to know the array of requirements, even for people who are in the business.
  So, I think for a simple compilation of this is what exists to protect research participants domestically or internationally doesn’t exist, and maybe that’s another thing the Commission could contribute.
  DR. ALLEN: It would really further President Obama’s Open Government agenda, I think to have that available.
  DR. GUTMANN: And it would compliment what we advised in the Symbio report about having a trustworthy agent that checked the factuality, the voracity of claims. So, thank you, Anita for that.
  DR. WAGNER:  Raj?
  DR. KUCHERLAPATI:  Just to pick up on one of the topics that you talked about. There are some people who argued that the way that the IRB’s are set up and the way that they operate today are number one, very heterogeneous and that sometimes they have a tendency to get into minutiae and not really promoting the goal of doing responsible clinical research.
  And you pointed that – can you enumerate on that and what kinds of things that one might be able to think of doing that would, you know, correct the issue, if that is the case?
  DR. GRADY:  Actually, this is something I’ve worked on a little bit myself. And, I think that the thing that’s needed the most is a way to describe very clearly what an IRB is supposed to do in a way that can be measured later to see if they’ve done it effectively. And we don’t have that. We don’t have any metrics at the moment for whether an IRB has successfully done their job.
  I’ve recently compiled a bunch of data to show that, you know, if you look at the data about how IRB’s have been evaluated, most of it has been structure, process and inconsistencies. And there’s very little about this, you know, what makes an IRB effective? And so, that’s something I think that we –
  DR. WAGNER:  Dan?
  DR. SULMASY:  Great. Well, like Nita, I was sort of hoping we might try to get a focus in some ways and think about international research as being the place we might do that. But, I think we always keep coming back to this problem of regulatory burden in the U.S. And I was trying to sort of think of ways in which those two things might be actually connected in ways that I hadn’t thought of until you sort of were talking.
  I think you’re right, and here’s the sort of 35,000 foot view of the connection. I think you’re right to say we begin with problems in virtue, right, of scientists just simply not behaving in a virtuous manner. And, we get a Presidential Commission, a previous one that develops ethical principles that sort of says how to do that, which then gets translated into rules by the government, which then has become – as many people have suggested really – a wide ranging bureaucracy, which makes things very difficult for people.
  And in fact, I think Raju was very right in many cases misses the big picture, in place of compliance with very particular rules, so that the big university scandals we’ve had, if you go through all the rules, they were sort of followed to the T. It’s just that people didn’t really evaluate what was really ethically wrong with those trials.

  And this leads, I think in many ways, to a sad concatenation, and this is the problem. An illogical concatenation between saying we’ve increased the costs of research, terribly because of the bureaucracy, but also this kind of dismissal of ethics is just compliance with all these rules.  Even the education procedures we have for Scientists, you know, these, the kinds of things that I have to do every year going through these online courses, are basically the things that I, as an Ethicist, resent taking because they’re just memorizing rules so you can pass the electronic test.  It becomes a bureaucratic chore.  If that’s my view of it, imagine the people who are not interested in ethics.  This leads people, as you were saying, to outsource compliance, but also then, now here’s where the other thing comes in, to now off-shoring the research, and that leads to avoiding the bureaucracy, but maybe also to therefore sub-rosa, avoiding the ethics as well as decreasing the costs, and all of that becomes the main view for getting the research off-shore. So I think that may be cynical, but I was wondering if you think that there’s a logic that sort of historical development with the state we’re in right now.
DR. GRADY:  There is some logic to that.  I think it’s very critical to think about this notion of what off-shoring clinical trials is about.  I mean, certainly, there are trials that are going to emerging economies because they’re more efficient, and less expensive, have large numbers of treatment, i.e. patients, and good science, good scientific facilities.  That is happening. But we also have to remember that we were asked to looked primarily at federally sponsored research, and federally sponsored research is very different in many ways.  First of all, I work at the NIH; so NIH has had as part of its mission from the day it was created, to do international research, so it’s been doing it.  And its been doing it for a number of reasons, one because it’s part of its mission, one because there are health problems and diseases on the ground and around the world that researchers within the United States can help with, can help, you know, do research.  There are diseases around the world that the whole world experiences, but that may be more prevalent in other parts of the world, so the research can be done, the quality of the research can be better, including the efficiency.  So, I mean, outsourcing has a lot of, there’s a lot of reasons for it, and I think it’s important to keep all those in mind.
DR. GUTMAN:  We should just make one factual claim, and I know Dan didn’t mean to suggest otherwise, but something you said suggested otherwise: if the research if federally funded, even if it’s off-shore, it’s still governed by all of these regulations, so you can’t avoid the regulations if you’re federally funded research by going off-shore.  Privately funded research is a whole other story.
DR. GRADY:  But even privately funded research, if it’s a company that wants to investigate a drug, or a biologic, or a device that they’re going to then want to get approved by the FDA, they still follow the federal regulations of the United States, or ICHDCP, or both.  And so, the regulations do, I mean, how they’re implemented is different in different places, but they do follow the researchers around.
DR. WAGNER: Final Question?
DR. ATKINSON:  That was the most clear and concise summary of the most complicated topic that I think we’ve ever heard.  It was very good.  Really quickly, I guess I’m interested in just the U.S., the harmonization and the burden issues: is there a will and a way by our 17 of our agencies to really do that, because it would be the single thing that would probably save the most time for all of our investigators and the people on IRB’s and whatever else.  Could it ever happen, is it possible?
DR. GRADY:  I’m a Philosopher, so anything’s possible.  Is there a will, I actually don’t know, I don’t have the, I’m not in the right corridors to know where the will is.  Yes, but you may remember that the, getting from the regulations that were first promulgated to the Common Rule itself, which was the idea to get everybody under the same sort of set of rules took 10 years.  And so, the fact that the different agencies have slight variations on the Common Rule, is, you know, I mean.  But agencies have different missions too, so it’s complicated in terms of where the variations lie.  I don’t know, I think harmonizing, having one set of, figuring out what the rational things are that people need to do, and making sure that one set of rules covers them all, that everybody can agree to.  And then maybe having a few branches, if you’re doing X, Y, Z, then you might have to add this and that, but for something like that would make a lot of sense.  Yeah.
DR. WAGNER: Final comment from our chair.
DR. GUTMAN:  Just to put this all of the Commission members’ questions and your responses, highlight for me our overarching goal here is to get human subjects protection right is like walking a tight rope.  If you err on the side of inadequate protections in rules and practices, then you harm, create really significant harm often.  And so you don’t want to do that, and that actually helps explain why we have all the regs we have.  On the other hand, if you err on the side of having too burdensome regs wrong, you also harm people by not developing the excellent possible medical treatments, drugs and so on that would otherwise be protected.  And that’s why we’re, in the best of intentions, put aside the people who don’t have good intentions, and what we’re going to try to do is figure out how we can walk that tight rope.  But it’s, you know, it’s good, we have fairy tales about Goldilocks, the porridge is too  hot, it’s too cold, no now, it’s just right.  Would it be that easy to just get porridge that’s just right?  So I would just say that our aim here is to figure out how we can give the best advice to get on that tight rope and not having even clarity about the regs makes it hopeless.  The kind of clarity you’ve given, I just want to emphasize, to be able to get more clarity that’s publicly accessible.  It’s certainly a first, it’s not a last step.
DR. WAGNER:  As we dismiss for a very brief break, I’ve been told by the front desk that if you plan to return after the break, as you leave, pick up a pass at the door.  Our limited seating is such, that’s the only way, I guess, that they can assure that you can get back in, so if you plan to get back in 5 minutes, it looks like is all we’ll have for a break, please grab a pass at the door.  Thank you, and thank you Christine.

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