PANEL MEMBERS:

PANEL 1:

Claud Bailey
Harry Holloway
Gary Ellis
Susan Rose
Gary L. Chadwick
Sandra Reid
Jackie Kittrell
Caroline Szetela
Thomas Ensign
Sandra Marlow

PANEL MEMBERS:

Panel 2:

Eva Plaza
Paul Yanowitch
Rick Hornung
Jonathan Samet
Thomas Bell
Dan Brown
Phil Harrison
Banny deBrum
Dennis Roper
Timothy Benally
Ray Koonuk
Manual Pino
David Harding

SPEAKER

Gary Ellis
Gary Chadwick
Susan Rose
Caroline Szetela
Jackie Kittrell
Sandra Reid
Todd Ensign
Sandra Mallow
Paul Yanowitch
Rick Hornung
Jonathan Samet
Phil Harrison
Timothy Benally
Manual Pino
Thomas Bell
Banny deBrum
Dan Brown
Dennis Roper
David Harding

(8:00 A.M.)

MR. BAILEY: Good morning. It seems like I just left you a few minutes ago. I am glad to be back. We had a real productive day yesterday in my mind, real productive. We want to build on that today.

Before we get started though, I want to just address a few maintenance issues.

We need to stay focus, I ask that we refrain from personalizing and personal attacks on individual, both government and stakeholders. That is counter productive.

Today we are going to be addressing some current issues, human subject protection, where the Government and Stakeholders can make a difference ensuring that the things that occurred in the past don=t occur now or in the future. That is significant. So we want to be really focused. We have got a panel of very distinguished persons from both the Stakeholder side and the Government side to address those issues. Their concerns, their views and perhaps where we ought to go from here.

We will have another panel that will address uranium miners, Alaskan natives, and other issues that are of great concern to us but for now and in the future. And then we will later discussion the third panel, public openness issues. How can we, as both the Government and Stakeholders, make information more readily available to stakeholders, so that we can understand is happening, what has happened and how we can be much better in the future. An important day for us. But because of time constraints we are getting started a little bit late, we should keep our times to the absolute minimum. Let=s try to be crisp and on task.

Again, I had a great time yesterday, great learning experience for me. I have done moderation for, I mean some very, very contentious issues and this is a great experience. Get a chance for you all to say what you have to say. But, as a moderator, I am going to have call if, in fact, we violate the rules and my dear friend, Doris, will lay the rules out. And I will have to call as I see it within the rules.

But, I want to share with you all something that John Galvin, who as a supreme ally commander, shared with me when I worked for him. And we don=t want to get in what we call oozelfinch. When I worked for John Galvin, we would go to a lot of meetings and contentious meetings and people were screaming and yelling and screaming and yelling, and we would spend four hours and when we left he would say, AClaude, what the heck happened in that meeting?@ I said, ANothing.@ And John Galvin called that oozlefinch. Do you know what oozlefinch is? An oozlefinch, an oozlefinch rather, is an ugly little bird that flies ever decreasing concentric circles, until he flies up his own rear end. We don=t want to get into that today. We want to stay on task. We want to be respective. We make our points and from that, of course, we can look at the next step. But, again, we should have very great day today.

The first moderator is Dr. Holloway. Oh, that is right, I always forget. Excuse me, I am remiss. Doris Campos-Infantino, has done a remarkable job. We are pleased to have her. She wanted to make some comments, some maintenance comments and about the process.

MS. CAMPOS-INFANTINO: Thanks. In response to feedback from last night and some suggestions about trying to keep this a little more focused on the issues, what I am going to today is to summary major points made by each of the speakers to best of my ability. That is going to mean that as you are speaking, I am going to take notes, briefly, and if I can capture your ideas incorrectly, I would like you to correct me, please. And I may be asking, to paraphrasing to make sure that I have captured the idea correctly.

What that will hopefully be useful for is for future speakers and for participants during the question and answer period to focus on specific points made, just so that there is more of a dialogue and less a series of individual speeches. Now, that is what we experienced yesterday, is kind of what we experienced in the planning of this, in that there is a lot of tension between the need to be heard, for people to tell their stories, which are legitimate and important to do so in this kind of a forum, where people are present to validate things that have never been validated. That, there is tension between that and actually trying to make specific recommendations on advisory committee recommendations or what the Government=s response should be.

So, we will try to give people the opportunity to speak today, to say their peace and be heard. And also to summarize specific points made so that others can address them and there could be more of a dialogue.

Please remember that this meeting is being transcribed. And everything is being documented, so the ideas will not be lost.

In addition, I noticed that there were a lot of Agency people who are feverishly taking notes yesterday, because I did get some feedback that there were a lot of good ideas shared yesterday, that the agencies want to take into consideration. Now you may not have heard that or seen that, because you are spread around, but be assured that I don=t think your thoughts are getting lost.

Now, in order to be more concrete, and more specific and focused on the issues, and also constructive in how we dialogue, there are some norms that I have listed as ground rules and I have posted them centrally.

First, and foremost, is let=s use common courtesy. Let=s treat each other with dignity and respect as human beings. And let=s attack the issues openly. Let=s focus on the problem, what the problem is and not attack the people who are speaking. Because I know when I am attacked, I get defensive and I don=t want to listen to what you have to say. But, if you want your issues addressed, attack the problem and not the person. Let=s listen actively to see that we really understand the point of view that is being stated. Once that point of view is being stated, you can then make your points clearly by identifying what your main concern is, identify your issue, take responsibility for what that issue is, then identify any areas of agreement or disagreement, you know, what do I agree with, what do I see differently from you? And lastly, ways that you are concern can be addressed, taking into account the other concern as well. That will be more constructive in terms of getting to some problem solving today. And throughout the day, if necessary, you know, anyone can remind anybody that we need to do these things, because I know when you get to talking sometimes you lose track. But, if you want to make sure that you understand my point, it might be important for you to ask me to clarify it.

So, let=s try to stick to these things today. And I, personally, welcome your feedback with regards to this process or any process. And catch me in the hallway, whatever, I will welcome any suggestions that you have in ways that you think that we can improve this. And let=s get started.

MR. HOLLOWAY: Thank you very much, I am Harry Holloway, I am the Associate Administrator from Life Microgravity Sciences at NASA. And I will be moderating today, for this particular panel.

Our presentation is from Gary Ellis, who is with the Department of Health and Human Services, so with no further introduction, Gary.

MR. ELLIS: Thank you, Harry.

I am the Director of the Office for Protection from Research Risks. And it is my pleasure and privilege to be with you this morning. You know, yesterday, we heard Lincoln Grafhis tell us a moving story, his daughter is gravely ill, but he knew and she believed that the place for him was here at this meeting, because as he said, his greatest concern is about his grandchildren and great grandchildren, he noted. Jerry Mousso continued that same point, later on yesterday afternoon, when he said that his main goal is to keep this from happening again, he called for preventive measures. And that is where we start this morning. I want to describe to you the current system in place to protect human subjects when they volunteer for research.

You might that the current system is a three legged stool, all three legs are necessary to keep that stool righted and I am going to describe those three components.

First, whenever a human subject research is conducted, the Government wants to see in place at the research site, a committee to oversee that research. We call this an Institutional Review Board, because it is linked to an institution. The acronym is IRB. You might see that. By Federal Regulation the IRB is composed of at least five people, a scientist, a non-scientist. There must be one person who is not affiliated in any way with the institution other than service on the IRB. And this is a not a group of scientists governing scientists in any way. By Federal Regulation there must be at least one of the five members who is not affiliated.

The duties of the Institution Review Board in overseeing research are these: Before the research can be approved, so this is prospective review, before anything at all is done, the IRB must be satisfied that the risks to human subjects are minimized. That the risks are reasonable in relation to anticipated benefits. The selection of human subjects must be equitable. Informed consent will be sought from each human subject or from the subject=s legally authorized representative, with certain rare exceptions. Informed consent will be appropriately documented. When appropriate the Research Plan must make a provision for monitoring the data in real time as it is collected, to ensure the safety or human subjects.

When appropriate there must be adequate provisions to protect the privacy of the human subjects and the confidentiality of the data. And in addition, when some or all of the subjects are likely to vulnerable to coercion or undue influence, the IRB makes certain that there are additional safeguards in place to protect the rights and welfare of those human subjects.

I mentioned that the IRB is the guarantor of informed consent, and that is the second leg of the three legged stool, the informed consent process. I have provided each of you on your chair with a copy of the Federal Policy for the Protection of Human Subjects. And I am going to read from it, I am going to read you the elements of the informed consent, the requirements elements of informed consent because you may think that that is a casual term, you may equate it with simple permission to proceed. It is not. Informed consent is a highly specific, sophisticated process and there are eight required elements of informed consent.

First, there must be a statement that the study involves research and an explanation of the purposes of the research and the expected duration of the subject=s participation. There must be a description of procedures to be followed and identification of any procedures which may be, which are experimental.

The second element, a description of any reasonable foreseeable risks or discomforts to the subject.

Third, a description of any benefits to the subject or to others, which may reasonably be expected from the research.

Fourth, a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.

Fifth, a statement describing the extent, if any, to which confidentiality of records, identifying the subject, will be maintained.

Sixth, for research involving more than minimal risks, an explanation as to any compensation and an explanation as to whether any medical treatments are available if injury occurs. And if so, what they consist of and where further information may be obtained.

The seventh element an explanation of whom to contact for answers to pertinent questions about the research and research subject rights and whom to contact in the event of a research related injury to the subject.

Finally, a statement that participation is voluntary and refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled.

So, the first two legs of the stool, that local oversight by an Institutional Review Board, the second leg of the stool, the sophisticated informed consent process was very detailed requirements.

The third leg of the stool, historically we haven=t done a very good job in maintaining. And this is the presence of a national body to deliberate on difficult issues as they arise. For four years in the 1970's, we had a national commission for the Protection of Human Subjects of Biomedical and Behavior Research and it was active from 1974 to 1978. From 1978 to 1980 we had an Ethics Advisory Board at the national level. From 1980 to >83 we had a President=s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavior Research. For 13 years there has been a void. We haven=t had a national body to deliberate on these difficult issues since 1983. And last October the President in his wisdom, created the National Bio Ethics Advisory Commission. We are waiting now, looking forward to the President making appointments to that commission, so it can get started at an early time. I know that many of the issues of concern to you may find their way to the agenda of the National Bio Ethics Advisory Commission. It would be presumptions of you or me to decide to state what the commissioners in their wisdom will be interested in, but the President laid out the reasons why, specific concerns will find their way onto the agenda of the National Bio Ethics Advisory Commission in his Executive Order, which you had in your information packets from yesterday morning.

I had better stop because I got the time signal and I will be pleased to answer any questions.

MR. HOLLOWAY: We will proceed ahead here with a presentation by Gary Chadwick.

MR. CHADWICK: Hi, I am Gary Chadwick. I am public health officer, currently assigned to the Food and Drug Administration. And I thank you all for inviting me here to tell you a little bit about what the FDA is doing in the area of human subject protections.

The FDA is an agency of the Department of Health and Human Services. So, we are bound to the regulations that Gary has just outlined. And incidently you don=t need to be named Gary to be in this area, but it just worked out that way.

As you have just heard the common rule applies to research that is conducted and supported by the Federal Departments and Agencies. The FDA also has its own regulations and they are found in Part 21 CFR 50 and 56. And these regulations apply to research involving products that are regulated by the FDA. Neither federal support nor federal involvement is required in the research in order for it to be regulated by our regulations. And this is a very important distinction between these two sets of regulations.

Because the FDA=s regulations apply regardless of funding or support, most of the research activities regulated by the Agency=s rules, by the FDA=s rules, are conducted by private industry and not the Federal Government. But, taken together these two regulations compliment each other to cover much of the human subject research conducted in the United States.

Dating from the 1962 Harrison Kefauver Amendments to the Food, Drug and Cosmetic Act, the FDA has required that informed consent, as Gary outlined, has, be given by human subjects of regulated research. In 1971, the FDA regulations required that studies involving investigational drugs performed on subjects in institutions, receive review and approval by an Institutional Review Board, or an IRB. Medical devices were covered by the IRB regulations in 1976. And then in 1981, both the FDA and Health and Human Services, modified and revised their regulations and published separate, but similar regulations which require both informed consent and IRB review for all covered research.

FDA is a regulatory agency that protects the health and welfare of the American people by evaluating the safety and effectiveness of drugs, biologics and devices. In that effect the Agency is guided by two major principals, ensuring the quality and the integrity of the data that is submitted to the Agency in support of new drugs and devices. And also protecting the rights and the welfare of human subjects that are used in the studies that provide those data.

In order to ensure compliance FDA uses a combination of surveillance, enforcement and education.

In the surveillance area, FDA has developed a Bioresearch Monitoring Program or BIOMO and that is started in 1977. The Agency=s BIOMO program now involves site visits to clinical investigators, research sponsors, manufacturers, institutional review boards, contract research organizations, non clinical or animal laboratories, and all FDA product areas are involved, drugs, biologicals, medical devices, radiological products, foods, veterinary drugs.

The Headquarters staff in the Agency=s centers develop inspection assignments. And these assignments are either for routine surveillance or for reasons related to the mission of the FDA, such as product approval. The inspections are generally conducted by the staff of the 21 FDA district offices and 136 resident inspection posts that are located across the country. For IRB inspections at any one time, there are about 1,000 to 1500 IRBs that actively monitor FDA studies. And we assign about 300 inspections a year. So you can see that we go approximately once every five years to each of these IRBs.

In clinical investigator inspections the FDA inspects and compares the data that has been submitted to the Agency, compared to the base documents that the investigator has maintained in his office of institution.

Under Enforcement, each of these inspections, the reports from these inspections are sent back to the center that assigned the original inspection. And after reviewing these, the center may issue a letter and usually issue a letter to the institution describing any deficiencies. In addition to issuing these letters, the FDA may take other courses of action, regulatory or administrative sanctions.

FDA may disqualify clinical investigators from receiving investigational drugs. Currently the FDA has other compliance mechanisms for medical devices, but disqualification will be added in the near future. When an investigator is disqualified, the Agency will not accept the disqualified investigator=s work in support of claims of safety, and efficacy without validating or establishing that the study results were unaffected by removing the investigator=s work. This applies to both current applications, pending before the Agency and also prior actions that we have taken whenever the investigator was involved.

The Office of Health Affairs, which is my office, is the Agency=s lead office for educational efforts in the area of protection of human research subjects. Our main activities include presentations and conferences, telephone consultation and dissemination of various written materials. In addition to research communities specific information, and educational articles and professional journals, FDA also issues public information documents, such as the FDA Medical Bulletin and the FDA Consumer which are targeted specifically to both professional and consumer audiences.

So, in conclusion, FDA has been a leader within the Government in developing and requiring protection for human subjects of research and remains committed to promoting ethical biomedical research.

Thank you very much.

MR. HOLLOWAY: Thank you. And now we will be hearing from Susan Rose from the Office of the Energy Research of DOE.

MS. ROSE: You will get to hear my apology for just getting here. I would have been on time if this was where I was instead of where it is. So I apologize.

What I am going to do for what I a presume is like five minutes, seven, is to just sort of get everybody up to speed on what it is that we are doing in terms of contemporary protections for human subjects. I would like to at least make the pitch for us, that this effort was begun long in advance of the White House Radiation Advisory Committee. But, I think what that committee did for us was give us visibility and more support, certainly within in my office and also with the Department. One of the things that, I am going to go through a litany of events that we do, some of which you may be interested getting copies of or dialing into. But, I think one of the most important things was begun last week or two weeks ago and that was a commitment that was finally met to do on site audits of all Department of Energy facilities. There were things we found. We did four, the very first four. They were four California sites. There were things that the review group I brought with me didn=t like. So, I think I was a little disappointed but it did make me see that the system is, always needs some fine tuning and complacency can=t be allowed ever again. And it is our intention to see that doesn=t happen. The sites will have awhile to take corrective actions and there will be follow-up to our recommendations. So that is something the Department is committed. Eventually on a three year basis all sites will have those audits.

I would like to make a distinction for you for those of you who don=t understand how our department works. DOE essentially is the landlord or the owner for some sites. In other cases we support research in other academic institutions and places like that. In most cases those are medical schools and things where there is some shared interest by the Food and Drug Administration or the National Institutes of Health. So the protections and the reviews are a little different in those cases.

Some of the other things that I think may be important to this audience, are the things we do that the real work can have access to. One of this is our public data base and we can make information available as part of the record or part of what is transmitted to all of you. And I think Ellie Melamet is going to mention our data base later. We are ready with the >95 fiscal year research. It is just a system by which anybody can look up any project supported by DOE, conducted at a DOE facility or carried with DOE personnel in any way.

It is interesting, we did initially as a result of Secretary O=Leary=s openness initiative and we did some double checking on who was inquiring. We got some really strange, there has been a lot of foreign ones. I can=t imagine why Selvena, for example, is entrusted. But, we have had a lot of very unusual requesters. We can only tell sort of general location of where the inquires are, not who they are. But, there has been a serious interest in this data base. This year it is going to be a lot bigger because the definition of human subjects and I don=t think of our, I don=t know since I missed it, if our speakers mentioned it, but that has been an issue in the Department. We have drawn the line really broadly as to what constitutes a human subject=s project and that is something I think maybe is for a later discussion. But, if you are listening to something in a car or something like that, and there is a device or some pattern recognition to let somebody through an entrance gate, we have considered that human subject, but it has taken awhile to educate our sites.

Some of the other things I would like to mention, we have a system of educating the Department and that doesn=t mean the folks at Headquarters. It means people who are actually scientists, you know, many, many bosses and many pay lines removed from us, in the field, at DOE facilities. We have posters. We have brochures that we send out. Each site is expected this year to come up with an educational bioethics improvement plan. And some of them have come up with some good ones. And the main thing they are doing is upgrading and sensitizing their own personnel, so that none of these gray area projects slip through. Okay, so any of those materials are available.

We also have a human subject protection newsletter, that we have issue it twice a year. And the reason for that is, nobody wants to write letters, nobody wants to read faxes, so it is kind of a way of getting some detailed information throughout our system. That is also something that anybody who interested, we could you on our mailing list.

We hold educational workshops. We shared one with Gary Ellis and the Interagency Human Subject Committee last October, right after the White House Radiation Advisory Committee. And we felt the timing was not intentional to be a day before the release. It gave us all major headaches as it turned out because a lot of our speakers turned into maybes. But, it was a very effective way of communicating what these folks had contributed to and what the White House Radiation Advisory Committee found. So, we felt in a sense like that was the first step in following some of the recommendations.

Am I am in your way? Out, oh, all right.

I am a big ummering when we read the transcript of this, that is probably all I sound like.

We have also got a way of communicating with all the folks in the system to get a more immediate turnaround. And this is something that maybe isn=t a public interest, but it is a quick way of avoiding the problem of somebody saying, AGee, I didn=t know this was important.@ If an issue comes up or there is something we want everybody be alerted to, we have an E-mail update system, so that people can=t say this is something they didn=t know about.

And lastly, I might just finish with, I think I mentioned that we have revised our handbook, which we could make available, but I think the more important thing is the way we work with the folks, the program folks, the folks who are conducting the human subject research at our sites and that is besides these workshops that we shared with Gary and the rest, we have internal working groups in DOE. Fortunately or unfortunately, these are voluntary. So the real worker bees come and help us with local problems. For example, help us, raise the issue with us what local problems are and in turn have a broader base of people to help solve some of these issues. So, some of the interesting things are bigger than DOE. The issue of genetics in human subject research. But, the ones that are very personal to DOE, we do work as a family.

And I would like to reiterate what we just heard. I think the Department has been committed to protecting human subjects and thanks to the White House Radiation Advisory Committee, we will continue to be in a much more visible manner.

MR. HOLLOWAY: Thank you.