[House Hearing, 106 Congress] [From the U.S. Government Publishing Office] DO CURRENT FEDERAL REGULATIONS ADEQUATELY PROTECT PEOPLE WHO PARTICIPATE IN MEDICAL RESEARCH? ======================================================================= HEARING before the SUBCOMMITTEE ON CRIMINAL JUSTICE, DRUG POLICY, AND HUMAN RESOURCES of the COMMITTEE ON GOVERNMENT REFORM HOUSE OF REPRESENTATIVES ONE HUNDRED SIXTH CONGRESS FIRST SESSION __________ DECEMBER 9, 1999 __________ Serial No. 106-145 __________ Printed for the use of the Committee on Government Reform Available via the World Wide Web: http://www.gpo.gov/congress/house http://www.house.gov/reform __________ U.S. GOVERNMENT PRINTING OFFICE 66-523 WASHINGTON : 2000 ______ COMMITTEE ON GOVERNMENT REFORM DAN BURTON, Indiana, Chairman BENJAMIN A. GILMAN, New York HENRY A. WAXMAN, California CONSTANCE A. MORELLA, Maryland TOM LANTOS, California CHRISTOPHER SHAYS, Connecticut ROBERT E. WISE, Jr., West Virginia ILEANA ROS-LEHTINEN, Florida MAJOR R. OWENS, New York JOHN M. McHUGH, New York EDOLPHUS TOWNS, New York STEPHEN HORN, California PAUL E. KANJORSKI, Pennsylvania JOHN L. MICA, Florida PATSY T. MINK, Hawaii THOMAS M. DAVIS, Virginia CAROLYN B. MALONEY, New York DAVID M. McINTOSH, Indiana ELEANOR HOLMES NORTON, Washington, MARK E. SOUDER, Indiana DC JOE SCARBOROUGH, Florida CHAKA FATTAH, Pennsylvania STEVEN C. LaTOURETTE, Ohio ELIJAH E. CUMMINGS, Maryland MARSHALL ``MARK'' SANFORD, South DENNIS J. KUCINICH, Ohio Carolina ROD R. BLAGOJEVICH, Illinois BOB BARR, Georgia DANNY K. DAVIS, Illinois DAN MILLER, Florida JOHN F. TIERNEY, Massachusetts ASA HUTCHINSON, Arkansas JIM TURNER, Texas LEE TERRY, Nebraska THOMAS H. ALLEN, Maine JUDY BIGGERT, Illinois HAROLD E. FORD, Jr., Tennessee GREG WALDEN, Oregon JANICE D. SCHAKOWSKY, Illinois DOUG OSE, California ------ PAUL RYAN, Wisconsin BERNARD SANDERS, Vermont HELEN CHENOWETH-HAGE, Idaho (Independent) DAVID VITTER, Louisiana Kevin Binger, Staff Director Daniel R. Moll, Deputy Staff Director David A. Kass, Deputy Counsel and Parliamentarian Lisa Smith Arafune, Chief Clerk Phil Schiliro, Minority Staff Director ------ Subcommittee on Criminal Justice, Drug Policy, and Human Resources JOHN L. MICA, Florida, Chairman BOB BARR, Georgia PATSY T. MINK, Hawaii BENJAMIN A. GILMAN, New York EDOLPHUS TOWNS, New York CHRISTOPHER SHAYS, Connecticut ELIJAH E. CUMMINGS, Maryland ILEANA ROS-LEHTINEN, Florida DENNIS J. KUCINICH, Ohio MARK E. SOUDER, Indiana ROD R. BLAGOJEVICH, Illinois STEVEN C. LaTOURETTE, Ohio JOHN F. TIERNEY, Massachusetts ASA HUTCHINSON, Arkansas JIM TURNER, Texas DOUG OSE, California JANICE D. SCHAKOWSKY, Illinois DAVID VITTER, Louisiana Ex Officio DAN BURTON, Indiana HENRY A. WAXMAN, California Sharon Pinkerton, Staff Director and Chief Counsel Steve Dillingham, Special Counsel Lisa Wandler, Clerk Cherri Branson, Minority Counsel C O N T E N T S ---------- Page Hearing held on December 9, 1999................................. 1 Statement of: Lawrence, Arthur J., Ph.D., Deputy Assistant Secretary for Health, Office of Public Health and Science, U.S. Department of Health and Human Services, accompanied by Gary Ellis, Director, Office of Protection from Research Risks, National Institutes of Health; Mark Yessian, Regional Inspector General for Evaluations and Inspections, Office of Inspector General, U.S. Department of Health and Human Services, accompanied by Laura McBride, Policy Analyst; Eric Cassell, M.D., Commissioner, National Bioethics Advisory Commission, accompanied by Eric Maslin, executive director, National Biology Commission; and John Oldham, M.D., director, New York State Psychiatric Institute, accompanied by Timothy Walsh, M.D., former director of the IRB at the New York Institute.............. 8 Zucker, Cliff, executive director, Disability Advocates, Inc., Albany, NY; Adil Shamoo, Citizens for Responsible Care in Psychiatry and Research, New York, NY; Charisse Johnson, Brooklyn, NY; and Sherry Grenz, National Alliance of Mentally Ill............................................ 88 Letters, statements, et cetera, submitted for the record by: Cassell, Eric, M.D., Commissioner, National Bioethics Advisory Commission, prepared statement of................. 44 Grenz, Sherry, National Alliance of Mentally Ill, prepared statement of............................................... 120 Lawrence, Arthur J., Ph.D., Deputy Assistant Secretary for Health, Office of Public Health and Science, U.S. Department of Health and Human Services, prepared statement of......................................................... 12 Oldham, John, M.D., director, New York State Psychiatric Institute, prepared statement of........................... 52 Shamoo, Adil, Citizens for Responsible Care in Psychiatry and Research, New York, NY, prepared statement of.............. 106 Yessian, Mark, Regional Inspector General for Evaluations and Inspections, Office of Inspector General, U.S. Department of Health and Human Services, prepared statement of........ 24 Zucker, Cliff, executive director, Disability Advocates, Inc., Albany, NY, prepared statement of.................... 92 DO CURRENT FEDERAL REGULATIONS ADEQUATELY PROTECT PEOPLE WHO PARTICIPATE IN MEDICAL RESEARCH? ---------- THURSDAY, DECEMBER 9, 1999 House of Representatives, Subcommittee on Criminal Justice, Drug Policy, and Human Resources, Committee on Government Reform, New York, NY. The subcommittee met, pursuant to notice, at 10:38 a.m., in the Auditorium of the New York County Lawyers Association, 14 Vessey Street, New York, New York, Hon. John L. Mica (chairman of the subcommittee) presiding. Present: Representatives Mica and Towns. Staff present: Sharon Pinkerton, staff director and chief counsel; Steve Dillingham, special counsel; and Lisa Wandler, clerk. Mr. Mica. Good morning, I'd like to call to order the Subcommittee on Criminal Justice, Drug Policy, and Human Resources of the U.S. House of Representatives. We're pleased to be in New York City this morning for this field hearing, and I want to first extend my appreciation to our subcommittee member, Mr. Towns, who I've had the honor of working with in Congress since I came in 1993, and the previous chair of one of the subcommittees. We've worked together over the last four terms on issues of usual concern and I appreciate your persistence in the issues before us today and also the leadership that he has provided us both on this issue and on other matters we've worked together with in the Congress. I thank you for hosting us today, and we will proceed. I will proceed in this fashion. I will start with an opening statement. I'll recognize Mr. Towns. Then we will proceed to our panels, and there are two panels today, of witnesses. Today's hearing before the Subcommittee on Criminal Justice, Drug Policy, and Human Resources, will examine an issue of great importance and tremendous complexity. The issue before us today is whether Federal regulations offer adequate protection to participants in medical research, a topic that probably couldn't be more timely. In recent weeks, considerable national attention has been devoted to the tragic death of 18 year old Jessie Gelsinger of Tucson, AZ. He died in September as a result of a gene therapy experiment. Jessie died 4 days after being injected with a modified cold virus, and engineered genes into an artery leading to his liver. Researchers were shocked by his death and have not determined exactly why he died. The case has stirred a national debate on gene therapy experiments and the reporting of its adverse affects. It also prompted the National Institutes of Health to issue a solicitation to the medical community requesting related help. I noticed today in reading this morning's edition of the New York Times, Mr. Towns and others, FDA officials, I guess yesterday have come up with some disclosures on what took place with this case, and it said, let me just cite for the record, Officials of the Food and Drug Administration said today Jessie Gelsinger, an 18 year old Arizona man who lost his life in a gene therapy experiment in September was ineligible for the clinical trial and should not have been treated because his liver was not functioning well enough before doctors infused him with a dose of corrective genes. In announcing the preliminary results of their inquiry of Mr. Gelsinger's death, officials also said the University of Pennsylvania scientists running this has violated FDA requirements by failing to report immediately information about two patients long before the death who had experienced serious side effects and had said the informed consent form the investigators gave patients deviated from the one the agency had approved. I thought that was interesting and timely, given the subject before us today. NIH is now calling on researchers to report ill effects from experiments of this type. It appears, as this article points out, the previous deaths have occurred from experimental research that had not been reported to NIH. Accordingly, Federal regulatory changes have been proposed. The example of gene research illustrates a question before us today. What further Federal regulations are needed to reduce unnecessary health and safety risks to human subjects? I will keep an open mind throughout this hearing, but I do think there is a growing concern that current Federal regulations do not offer the full range of protections that many would like to see. This is true despite the fact that many Members of Congress, including myself, are often very skeptical of increasing government regulations, particularly Federal regulations imposed on business and private activities. I'd also add, one of the things that we do not want to do is to hamper legitimate research in any way, or deter legitimate research and basic fundamental human research, which is so important. Our focus today, however, is on research and institutions that receive Federal money. Our subcommittee has oversight responsibility to insure that such research is conducted both properly and safely. A key topic in this discussion is the critical roles played by institutional review boards, commonly referred to as IRBs. These IRBs oversee human subject research. IRBs are required to protect human subjects participating in federally funded research projects. IRBs are governed by common Federal regulations adopted by 17 agencies that are engaged in human subject research. IRBs typically review and approve research plans before research is carried out. This review includes research protocol, the informed consent document to be signed by the subjects, and advertisements to be used in recruiting subjects. In carrying out this review, the IRBs seem to insure that potential risks are warranted and reasonable in relation to potential benefits. IRBs insure that informed consent documents clearly identify known risks and the true nature of the research being conducted. This includes guarding against advertisements that might be misleading and selection procedures that might be biased or unfair. The responsibilities of IRBs do not stop once the research has begun. They're required to exercise continued oversight of research studies involving human subjects. Such oversight includes examining reports of adverse incidents involving research subjects and also requests for changes in the research methodology. The Federal department that has the greatest role in overseeing human subject research is the Department of Health and Human Services. Within HHS, the Food and Drug Administration [FDA], and the Office of Protection from Research Risk [OPRR], are the two agencies with primary responsibilities for overseeing activities and also for implementing human research subject regulations and protections. In studies involving biomedical research, the FDA monitors the safety of human subjects through its Center for Drug Evaluation and Research, also known by the CDER designation. The Office of Protection from Research Risk [OPRR], has the critical responsibility of implementing basic HHS policy for protecting human research subjects in HHS research and also overseeing the IRBs. HHS annually invests approximately $5 billion of its research dollars in approximately 16,000 research projects that involve human subjects. To provide oversight for these research projects, OPRR has agreements with more than 4,000 federally funded institutions to insure and protect the human subjects that are involved. Each institution that receives funding must establish an IRB. IRBs are typically made up of scientists, doctors and patient representatives to monitor and enforce ethical research standards. Federal regulations require that a non-scientist and an individual not affiliated with the institution be included in each of the IRB panels. Under OPRR guidelines, all potential research subjects must be fully briefed on the purpose, duration and procedures of a research project before agreeing to participate. OPRR has the authority to investigate and require corrective action or suspend funding to an institution until problems are resolved. For example, there was much publicity this year when OPRR temporarily suspended Duke University research funds because of Federal compliance concerns. Obviously, with so many departments and agencies involved, so many research protocols to enforce, so many projects to monitor, so many dollars invested, and so many human subjects at potential risk, the complicated task of insuring an adequate level of protection from avoidable risk, or even abuse, can become somewhat overwhelming. As we will hear today, there is significant concern that OPRR has been overwhelmed in the past and that reforms may be needed. This was the conclusion of the HHS Office of Inspector General in a report that they issued. Today we'll hear that some changes are underway in response to these concerns. For example, Secretary Shalala recently announced the relocation of OPRR from NIH. OPRR will now report to her office and leave the regulation of animal research within NIH. But are these minor changes enough? If not, what additional changes are needed? Furthermore, shouldn't we have a clear accounting of the 3,000 to 5,000 estimated IRBs that are bound and required to implement Federal standards? If we aren't sure of the number of IRBs, and how to contact them, how can an OPRR, FDA or anyone else adequately monitor their activities and their capabilities? In considering reforms, there are a number of specific concerns that I feel merit our closest attention. Foremost among these is the need to protect against conflicts of interest that might result in increased risk of research participants and others who may be impacted from the research. I read recent accounts, situations even here in New York, where IRB members may have received money and funds from pharmaceutical companies with a financial interest in research projects that they oversee. Pharmaceutical research, of course, can have enormous financial consequences. Doesn't this present a serious potential conflict that can influence research decisions and judgments? Is the mere disclosure of financial interest enough to assure scientific and medical objectivity? I'm concerned that while this subcommittee and HHS, Office of Inspector General have previously identified some of these problems, and have put forth some valuable solutions and recommendations, it appears that none of these solutions have been implemented to date. Why not? We'll also review today if legislative action or administrative additional action is necessary. Human subject research is an issue that is national in scope and deserves attention at all levels of government. Today's hearing hopefully will increase our understanding of what additional improvements and protections may be needed. We'll have with us today a number of distinguished government officials, medical researchers, and others who are knowledgeable and experienced with research involving human subjects. We appreciate their willingness to appear before the subcommittee to share both their knowledge and experience with us. We look forward to their insight, to their recommendations and also for their update on the progress that's being made with the recommendations that have been made in the past. I'm pleased at this time to yield to Mr. Towns, a member of our subcommittee, and as I said, Mr. Towns has pursued this matter for some time. I believe this is the third Federal congressional hearing on this matter, and his persistence has brought both attention and some reform that is needed, and we anticipate this hearing will result in some additional changes in procedures, but I thank him for his participation and for his leadership on this issue, I'm pleased at this time now to yield to the gentleman from New York, Mr. Towns. Mr. Towns. Thank you very much, Mr. Chairman. Let me also add that I really appreciate you taking the time from your busy schedule to come to New York to have this hearing. Also, it's been a pleasure to work with you on this issue and also other issues over the past 8 or 9 years, so I want to let you know I appreciate that as well. I want to take this opportunity to thank all of you for coming, especially those from Washington, DC, Albany, NY, and places near and far, to attend this hearing, and I want to thank the New York County Lawyers for providing space for us to have this hearing. Mr. Chairman, medical research on human subjects knowingly subjects some individuals to potential harm to seek benefits for a greater number of people. Federal regulations are intended to provide guidelines that protect the individual without reasonably hampering research goals. Under Federal regulations, research could only proceed if the research subject provides a valid, informed consent, has a capacity to understand the information, the ability to weigh the advantages and disadvantages of pursuing the research and access the benefit and risk of the drug or procedure. Yet numerous cases have been in the press lately, where this has not been the case, so it's so important for us to consider that and take a look at where we are today. In light of the risk and dangers posed by these types of experiments, we must seriously consider legislation that will make the IRBs fully independent of research institutions; that will assure that research methods meets customary standards of scientific excellence that will assure that children and parents are fully informed about the real purpose and intent of the research; that will permit them to decline or refuse to participate without fear of retaliation, and that will subject research programs that confer no benefits on the subject or that result in stigmatization of racial groups. Mr. Chairman, again, I want to thank you for taking the time out, and I say to you that we've had some success already, but we hope to be able to have some more, because I am also concerned about the fact that these independent review boards, IRBs, we don't even know how many are out there. We don't even know whether there are qualifications for them, we don't know that. The point is that it also has potential for all kinds of conflict, and if you don't know how many are out there, how can you regulate them? I think that's also a real concern, but also, I can't help but think about those experiments that took place in the time of the Tuskegee experiment, I can't help but think about that, and many, many others. Of course you referred to one in the Washington Post, so a lot of things are going on, and I think we can no longer close our eyes. We have to come to grips with this and begin to deal with it because we're talking about human beings. I think that's very, very important. And the last thing, Mr. Chairman, that, you know, I'm getting reports coming from various sources that people are being encouraged to participate in research groups and reported that many times they're given, like, toys, or being paid a few dollars to be in it, and they don't even know the danger or the risk that's involved, and that really bothers me as well, so I'm hoping that we can sort of come up with some guidelines and have some legislation, of course, that I think that will correct that, but my point is I think that through this hearing process maybe we can get a better handle on this. Because to have these review boards out there, and we don't even know how many that exist, there's no qualifications in terms of people on them, so you pick your friends, your buddies, that just to me should not be in the United States of America. So Mr. Chairman, here again, I thank you so much for coming to New York and having this hearing. Also, we've had some success, as I indicated early on. We have a letter from the Office of Surgeon General David Satcher and we have a note, I think I'll just read this paragraph, Mr. Chairman, before we go forward. It says, Moreover, we believe that no federally supported research should be compromised by any selection of human subjects that is not supportable by clear and advised scientific explanations. To this end, I will convene a group comprised of knowledgeable individuals who have not been associated with the investigation to examine the process and the context of the regulations, make recommendations, and to provide me with a summary report. I will contact you with the results upon completion. Then it goes on to say he will get back. The Department has not previously issued guidelines on these terms and the context of regulations and I agree that the terms need clarification. An essential element in the Secretary's decision to relocate human subject protection component of OPRR is the formation of an independent advisory body organized under the Federal Advisory Committee Act to provide guidance, assist in setting standards, review the operations of the new office and address human subjects' protection in general. This advisory committee will be known as National Advisory Council on Human Research and Protection, NACHRP. I believe the best approach to the development of a clarification of the term is for the question to be addressed by the council. In this way, multiple interests and views can be considered and methodology examined, thus providing a solution for acceptable regulatory clarification that protects both human subjects and does not necessarily impinge on the advancement of science. I will bring this issue to the council for their attention as one of the first matters of priority business. Mr. Chairman, I think that's a step in the right direction. I wish I could say it's a giant step. It's not a giant step, but it's a step in the right direction. So thank you so much for having this hearing today. Let me say this of note. It says--well, actually let me now yield. Mr. Mica. Mr. Towns, if you want that part of the record? Mr. Towns. Also, Mr. Chairman, may I add, that I'd like to put my entire statement in the record. Mr. Mica. Without objection, the entire statement, letter from the Surgeon General Satcher will be made part of the record. Mr. Towns, if it's appropriate, we will leave the record of this hearing open for 3 weeks for statements of Members who haven't been able to attend, and also the hearing may generate additional questions of these and other witnesses. Without objection, so ordered. We'll proceed now, and let me say at the outset that this is an investigations and oversight subcommittee of Congress. We have a broad range of authority and responsibility. We do swear in our witnesses, which I'll do in just a minute. I will introduce the first panel, and we have two panels today. The first panel consists of Dr. Arthur J. Lawrence, who is the Deputy Assistant Secretary for Health, Office of Public Health and Science in the U.S. Department of Health and Human Services. Some of you have accompanying witnesses. Dr. Lawrence, do you have anyone with you? Dr. Lawrence. Yes, sir, Dr. Ellis. Mr. Mica. Could you identify that individual for the record, please? Will he be testifying? Dr. Lawrence. I will be referring technical questions to him as needed, sir. Mr. Mica. Maybe he could pull up a chair. Could you again identify him for the record, and his title? Dr. Lawrence. Certainly. Accompanying me is Dr. Gary Ellis, who is the Director of the Office for Protection from Research Risks, National Institutes of Health. Mr. Mica. Thank you. We also have Dr. Mark Yessian, Regional Inspector General for Evaluations and Inspections, the Office of Inspector General, the U.S. Department of Health and Human Services. Dr. Yessian, do you have anyone accompanying you who will be testifying? Mr. Yessian. Yes, I do, Mr. Chairman. Mr. Mica. Could you identify that individual for the record and his title? Mr. Yessian. With me is Laura McBride, she's a policy analyst in our Boston office and was a major contributor to our work on IRBs. Mr. Mica. Thank you. We also have Dr. Eric Cassell, Commissioner of the National Bioethics Advisory Commission. Dr. Cassell, are you by yourself today? Dr. Cassell. No, I also have somebody with me. Mr. Mica. Could you identify that individual and also give us his title? Dr. Cassell. Yes, Dr. Eric Maslin, is who is the Executive Director of the National Biology Commission and who is right here. Mr. Mica. Welcome. Pull up a chair, please. Finally, is it Dr. John Oldham? Dr. Oldham. Right. Mr. Mica. Director of the New York State Psychiatric Institute. Do you have someone accompanying you, Doctor? Dr. Oldham. Yes, I do. Mr. Mica. Could you identify that individual and their title, for the record? Dr. Oldham. With me is Dr. Timothy Walsh who was former chair of the IRB at the New York State Psychiatric Institute. Mr. Mica. Thank you. I guess this will be our largest panel, Mr. Towns, in history. But we welcome each of you. We appreciate your participation in the hearing today, and helping us to find out how we can do a better job, and again, protecting people who participate in medical research and also making certain that we fulfill our legislative oversight responsibilities. With that, what we will do is begin, first I'll swear in all the witnesses that are here, and we will limit the principal witnesses to 5 minutes, approximately, of oral presentation. Then we'll proceed to questions after we've heard from all of the witnesses, and get their responses. However, I might say that upon request of the subcommittee, we will be glad to enter into the record, and it will be a full record of your statement, such as this house record. Any additional supporting information or documents, upon request, will be made part of the record. So again, I welcome you. If you will please all stand. Raise your right hands. [Witnesses sworn.] Mr. Mica. The witnesses answered in the affirmative. Thank you and welcome each of you. We will start with Dr. Arthur J. Lawrence, who is the Deputy Assistant Secretary for Health in the Office of Public Health and Science. Welcome, sir, and you are recognized. STATEMENTS OF ARTHUR J. LAWRENCE, Ph.D., DEPUTY ASSISTANT SECRETARY FOR HEALTH, OFFICE OF PUBLIC HEALTH AND SCIENCE, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPANIED BY GARY ELLIS, DIRECTOR, OFFICE OF PROTECTION FROM RESEARCH RISKS, NATIONAL INSTITUTES OF HEALTH; MARK YESSIAN, REGIONAL INSPECTOR GENERAL FOR EVALUATIONS AND INSPECTIONS, OFFICE OF INSPECTOR GENERAL, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPANIED BY LAURA McBRIDE, POLICY ANALYST; ERIC CASSELL, M.D., COMMISSIONER, NATIONAL BIOETHICS ADVISORY COMMISSION, ACCOMPANIED BY ERIC MASLIN, EXECUTIVE DIRECTOR, NATIONAL BIOLOGY COMMISSION; AND JOHN OLDHAM, M.D., DIRECTOR, NEW YORK STATE PSYCHIATRIC INSTITUTE, ACCOMPANIED BY TIMOTHY WALSH, M.D., FORMER DIRECTOR OF THE IRB AT THE NEW YORK INSTITUTE Dr. Lawrence. Thank you, Mr. Mica. Mr. Mica. You might have to pull that mic up closer. Dr. Lawrence. Thank you very much, Mr. Mica, Mr. Chairman and members of the subcommittee, good morning. As Mr. Mica as pointed out, my name is Art Lawrence, I am Assistant Surgeon General and Deputy Assistant Secretary for Health Operations in the Office of Public Health and Science within the Office of the Secretary of the Department of Health and Human Services. I am accompanied this morning by Dr. Gary Ellis, Director of the Office for Protection from Research Risks which is currently within the National Institutes of Health. Dr. Ellis also chairs the interagency agency committee on protecting research subjects, in which 17 Federal departments and agencies participate. We are pleased to appear before the subcommittee to describe our well developed, yet ever evolving system of protection for research subjects. I've submitted the Department's written testimony for the record. I ask that I be permitted to briefly summarize a few highlights from that testimony, and that my written testimony be entered into the record in full. Mr. Mica. Without objection, the entire statement will be made part of the record. Dr. Lawrence. Thank you sir. Together with Dr. Ellis I'll then be happy to entertain any questions the committee members might have concerning the importance of this subject meeting. First, Dr. Satcher has asked that I extend his best regards and his personal regrets for not being able to be here with you today. He has also asked me to extend his personal gratitude to you, Mr. Towns, for the leadership that you have taken in promoting high energy efforts to eliminate racial and ethnic disparities in health status in the United States. He looks forward to continuing to work with you on this and other matters of importance to the public's health. He also asked me to relate to you that he shares your concerns about research that is conducted on populations that lack diversity. And in particular, about research that is conducted entirely in minority populations, unless there is a clear and compelling need to do so. As the letter submitted today to Congressman Towns states, ``The Department has recognized the need to increase diversity of participants in clinical trials and has taken many steps to accomplish that in federally funded research.'' A good example of this is seen in the diversity of the Women's Health Initiative studies. The Department is committed to continue these efforts until our goals are met. In addition, we have made a commitment to involve communities in the design and conduct of research and are moving forward with plans to be sure that research addresses the needs of communities and is responsive, considerate of community concerns. This year has marked a quarter century of the formal promulgation of the Department's regulations for the protection of human subjects in research. This enduring and vigorous system of protections is designed to prevent physical injury, psychological injury, and harm to the dignity to the research subjects as biomedical and behavioral scientists pursue new knowledge for the common good. We are always interested in improving the system to make research as safe as possible. My written submission, gentlemen, outlines in some detail the multiple layers of protection for human subjects. These feature at least half dozen levels of protection. They include the system of institutional review boards or IRBs, the keystone of the system. These are boards of scientists and nonscientists who independently review research involving human subjects. By regulation, the Department and 16 other Federal agencies cannot provide funds for human subject research unless an IRB approves the protocols for such studies. Once such research is underway, the IRB must conduct continual review of the research at intervals that are appropriate to the degree of risk, at least once a year. Exerting oversight over the whole process are OPRR and when investigational drugs, devices or biologics are involved, the Food and Drug Administration as well. An additional layer of review which may be employed especially in large studies is an independent data and safety monitoring board or DSMB. These bodies are appointed to oversee and evaluate the research investigation. DSMB reviews accumulated study data and makes recommendations on continuation or modification of research or clinical studies involving human subjects. It is OPRR's role to make certain that the IRB process works at institutions within its jurisdiction. OPRR has taken a number of actions to bolster effective oversight of individual IRBs on a variety of fronts. We believe that with this system of IRBs that the risks are minimized by using research consistent with sound research design and which do not unnecessarily expose subjects to risks. It helps insure that the risks are reasonable to anticipated benefits, that the selection of subjects is equitable, that there are proper informed consents and that the rights and welfare of subjects are maintained in other ways as well. IRBs watch out especially for research involving children, prisoners, pregnant women, and individuals with mental disabilities. They also guard the rights and safety of other vulnerable populations, including the economically disadvantaged, and individuals who are also educationally disadvantaged. It is the IRB's responsibility to assure that additional safeguards are included in studies involving any of these responsibilities. OPRR oversees implementations of the regulations in all department facilities as well as domestic or foreign institutions or sites receiving Federal and Health and Human Services funds. OPRR requires all departmental agencies and extramural research institutions that conduct research involving human subjects to set forth the procedures it will use to protect human subjects in a policy statement formally called an assurance of compliance. This is a written commitment to ethical principles, and institutional procedures that are adequate to safeguard the rights and welfare of human subjects. The assurance statement becomes a specific instrument that OPRR uses to gauge an institution's compliance with human subject protections if there is a problem. This description, of course, gentlemen, is a brief outline of the human subjects research protection system. Additional details involving informed consent regulations and research education training methods are included in my written submission. I wanted to take a final moment here to convey a few facts about what the Department is doing to strengthen and expand the significant human research subjects protection apparatus. What I've outlined mandates a strong and effective OPRR operation. Responding to other concerns in May of this year, an expert panel transmitted a report to the Director of the National Institutes of Health where OPRR is now located. That report recommended that OPRR be relocated from NIH to the Office of the Secretary. It also suggested that the OPRR Director be at the Senior Executive Service or SES level following that transfer. Third, it was recommended to the Secretary that an independent advisory committee be created, this is the committee which Mr. Towns has just referred to, to provide guidance and to assist in standard setting and review the operation of the OPRR. Finally, the report suggested that resources currently available to the OPRR may be inadequate for fulfilling its mission. In turn, the Director of NIH transmitted its report to the Secretary indicating agreement with the panel in recommending that the Secretary accept and act on its findings. In August the Secretary took action on the central recommendations and findings and asked Dr. Satcher to undertake review processes to determine whether to relocate OPRR as a unit or rather to move only the human subjects protections component. A work group was formed to address organizational structure and management consultant has been engaged to examine the question of resources. In October the Secretary accepted the recommendation that the newly relocated office focus solely on human subjects protection with animal welfare functions remaining at NIH. The management study has not been completed yet and a target date has been set for completion of activities of March 2000. Finally, the Department has currently put out for comment a notice of proposed rulemaking or an NPRM on privacy. It shows a commitment to reviewing the human subjects protections regulations with an eye toward enhancing the privacy protections of research subjects. This is yet another example of the Department's commitment to another important area of strengthening protections for human research subjects. We believe we have a system in place which to the greatest degree possible minimizes the potential for harm, enables and protects individuals' autonomous choice and promotes the pursuit of new knowledge. Thank you, Mr. Chairman, and members for the opportunity to address you this morning on this critical topic. Dr. Ellis and I will be pleased to answer any questions you may have. Mr. Mica. Thank you. [The prepared statement of Dr. Lawrence follows:] [GRAPHIC] [TIFF OMITTED] T6523.001 [GRAPHIC] [TIFF OMITTED] T6523.002 [GRAPHIC] [TIFF OMITTED] T6523.003 [GRAPHIC] [TIFF OMITTED] T6523.004 [GRAPHIC] [TIFF OMITTED] T6523.005 [GRAPHIC] [TIFF OMITTED] T6523.006 [GRAPHIC] [TIFF OMITTED] T6523.007 [GRAPHIC] [TIFF OMITTED] T6523.008 [GRAPHIC] [TIFF OMITTED] T6523.009 Mr. Mica. We'll hear now from our second witness, Mark Yessian. Dr. Mark Yessian is Regional Inspector General for Evaluations and Inspections for the U.S. Department of Health and Human Services. Welcome. The chair will recognize him. Mr. Yessian. Mr. Chairman, Congressman Towns, the current system of protecting human subjects who participate in medical research is in need of major reform. This is a conclusion we emphasized in a June 1998 report; it's one that we reiterate here today. Our June 1998 report was based on a year-long inquiry into the work of the institutional review boards. That inquiry led us to sound a warning signal that the effectiveness of the boards is in jeopardy. Here's what we based that on: IRBs review too much, too quickly with too little expertise. They conduct minimal continuing review of approved research. They face conflicts that threaten their independence. They provide little training for investigators and board members. And, not least of all, they must cope with major changes that are fundamentally transforming the research environment from what it was a quarter of a century ago when the current Federal protections were put in place. In our report we made numerous recommendations to the National Institutes of Health and to the Food and Drug Administration. At the core of them was a search for ways to give IRBs more flexibility so they could do their job better, but to hold them much more clearly accountable for results. Let me provide an update, if I could, on what's happened in the year and a half or so since we issued our report. First, I'd say there are some encouraging developments. At the Federal level, the most notable action has been an increased enforcement effort by the Office of Protection from Research Risks [OPRR]. In the year prior to our report, OPRR had made only one site visit to investigate the adequacy of an IRB's efforts. Since that time, it has made numerous site visits, some very high profile and some resulting in the actual suspension of federally funded research at major medical centers. At the local level, a number of institutions have put more resources into their IRBs and a number of IRBs have undertaken training and other educational kinds of initiatives intended to sensitize principal investigators and IRB board members to issues involving human subject protection. Then also at the professional level it's important to note there's some stirring there, too. There's a movement toward certifying IRB administrators and one toward private accreditation of IRBs. Both of these movements have some significance. But as important as these developments are, the system of protections provided by IRBs remains in jeopardy. From the ground up, if you look at IRBs, you see the same danger signs. Expanded work loads, quick reviews, threats to their independence, inadequate information, insufficient training, minimal outside representation. Moreover, and this is the basic point, the underlying pressures on IRBs continue to build and to make it difficult for them to do their job adequately. Let me touch on three of those pressures. The most important one is the increased commercialization of the research environment. Industry sponsors, anxious to bring new products to market and to contain their development costs, seek to expedite the clinical trials process and to conduct their trials in the quickest, most efficient settings. For IRBs, this means doing more quicker and better. It also means that it can be quite difficult to slow down the research process by raising nettlesome questions for instance, about the adequacy of the informed consent process. A second pressure is the continuing and escalating pressure on the IRB members themselves. Most of the time these are volunteers that serve on these boards. They find it difficult to spend the time it takes to review proposals that are increasing both in numbers and complexity. Finally, I'll note there's an intensified quest for human subjects. If you look at this as a supply-demand situation, we have a substantial unmet demand for human subjects. This heightens recruitment pressures for research sponsors and investigators and leaves IRBs with many difficult questions to face. For instance, should they be concerned about recruitment bonuses that sponsors give to investigators for subjects? Should they be concerned about the mining of patient data bases to find potential human subjects? What about the payment of fees to physicians referring their patients as potential subjects? What are the standards or guidelines to answer such questions? Where are they? We end up as we did in 1998 calling for a much stronger Federal presence here, and I'll just touch four of the issues that we highlight. There are others, but certainly one would be more extensive onsite performance based reviews of IRBs. The OPRR has started this. It's a good start, but only a start. We recommend this kind of effort intensify and that it conduct both unannounced and announced site visits. We should also not forget the Food and Drug Administration here. They are actually onsite more often than the OPRR, and have a substantial responsibility here. As we said before, we think it's essential that they broaden their reviews to go beyond simple compliance matters and focus more on performance. My second point is that we need a strengthened commitment to educational outreach and mandates. Everybody says the answer is always more education, but I think it's really crucial to go beyond the talk and have some action. Action at the Federal level where we provide more in the way of web based tutorials and the like. But also mandates that investigators and board members participate in educational programs concerning human subject protections. The third direction we're emphasizing is much more extensive representation of non-scientific and non- institutional members on IRBs community members, if you will. It just simply doesn't seem adequate to have situations, as you often do, where there may be 14 or 15 IRB members and one, maybe two from outside the institution. This noninstitutional member can provide a vital counterbalance to the kind of pressures IRBs face. It's a way of sharpening the focus on subjects and what is in their best interest. And last, as Congressman Towns has already referred to, we simply need a mandate to register IRBs with the Federal Government. This need not be a major burden on anybody, but how can we provide effective oversight and guidance if we don't even know who the IRBs are and where they're at. So some kind of registration requirement with minimally descriptive information would seem to be important. In closing, I'd like to emphasize that notwithstanding what may sound like a rather harsh critique, we recognize the major contributions that investigators, sponsors, IRB members and staff are making in this area. There are a lot of committed, dedicated people here, but they work in a system that needs to be reformed. That's the basic point. Such reform is essential to provide necessary protections for human subjects. It's also essential to sustain the progress we are making in clinical research. Thanks for the opportunity to testify, we are certainly open to questions. Mr. Mica. Thank you. [The prepared statement of Mr. Yessian follows:] [GRAPHIC] [TIFF OMITTED] T6523.010 [GRAPHIC] [TIFF OMITTED] T6523.011 [GRAPHIC] [TIFF OMITTED] T6523.012 [GRAPHIC] [TIFF OMITTED] T6523.013 [GRAPHIC] [TIFF OMITTED] T6523.014 [GRAPHIC] [TIFF OMITTED] T6523.015 [GRAPHIC] [TIFF OMITTED] T6523.016 [GRAPHIC] [TIFF OMITTED] T6523.017 [GRAPHIC] [TIFF OMITTED] T6523.018 [GRAPHIC] [TIFF OMITTED] T6523.019 [GRAPHIC] [TIFF OMITTED] T6523.020 [GRAPHIC] [TIFF OMITTED] T6523.021 [GRAPHIC] [TIFF OMITTED] T6523.022 [GRAPHIC] [TIFF OMITTED] T6523.023 [GRAPHIC] [TIFF OMITTED] T6523.024 [GRAPHIC] [TIFF OMITTED] T6523.025 [GRAPHIC] [TIFF OMITTED] T6523.026 [GRAPHIC] [TIFF OMITTED] T6523.027 Mr. Mica. We'll now hear from Dr. Eric Cassell, who is the Commissioner of the National Bioethics Advisory Commission. Welcome, sir. You're recognized. Dr. Cassell. Thank you. I would like to thank the chair and members of the subcommittee for the opportunity to appear. I am Eric Cassell, Commissioner of the National Bioethics Advisory Commission. I would appreciate it if the entire statement could be included in the record. Mr. Mica. Without objection, so ordered. Dr. Cassell. I think it would be appropriate if the National Bioethics Commission report and its recommendations be included in the record. Mr. Mica. Without objection, so ordered. Dr. Cassell. Interest in this subject goes back to its very beginnings. It's a society's primary obligation to provide improved ways of protection of subjects in research. But in this instance, there are special problems. During its 18 months of study, NBAC held hearings, heard witnesses from community members to psychiatrists, from OPRR and other experts, and have confirmed the problem of lack of protection or inadequate protection for persons with mental disorders who are subjects of research. These persons have need for special protection, primarily arising from several things. First of all, persons with mental disorders have a really important need to find adequate treatment, which is often not available outside of the research setting, or at the very least, the most modern treatment is now in the research setting so that they are often forced to go into research protocol to get what they need. They are often stigmatized, and so they don't have the protection of the community that is normally present and often invisible, but is always there, people who know their rights and so forth. They have varying capacity to consent. Their illness may make it impossible for them to recognize what their needs are, what they should consent to, what they shouldn't consent to at some times, while at other times, they have the same capacity as persons without disorders. There also are problems that arise from the enthusiasm of investigators, and but most of all I'd like to echo what's just been said, from a lack of education of investigators about ethical issues in research. When you're hot on the trail of something exciting, and when that's your life's work, sometimes enthusiasm overcomes other objectives and people enter into research that otherwise might not, and the subject is a willing participant for the same reasons I noted before. Now, after reviewing all the problems that came before, in fact, we made a number of recommendations. The recommendations which are primarily what this, our large report is about, are 21 in nature. They are currently under review by Federal agencies that are subject to the common rule, and under review by the White House, and we are very hopeful that the role of this committee will in part be to move forward a review of those recommendations, and make them appear in regulations in the future. There are six categories of recommendations: The first has to do with the nature of IRB's and the importance of having membership in the IRB of persons from the community, of persons with mental disorders so that they are adequately represented. Also, there are questions that may come before IRBs which are beyond their competence and which should be reviewed by a special panel in the office of HHS that can bring before it problems of a more general nature that should be seen. Next, the research design for persons with mental disorders have to be more carefully gone over. For one thing, wherever possible, other subjects should be used who do not have mental disorders. There should be great concern about the use of placebo controls in people who have mental disorders because on occasion they may heal again by going back to a placebo state. Certain others, special projects like what happens when somebody has a washout period, that means their medication is removed, they're given time for their illness to appear, which is one thing with diabetes but a different thing with schizophrenia. Next thing, we were very concerned about the nature of informed consent. It is crucial whether it is clearly known whether a person has the capacity to consent, and in this we requested that there be assessment of individuals with mental disorders by a qualified, independent professional, something that is not used in other areas of research. Next, there are categories of research relating to levels of risk and the prospective benefit which must be clearly spelled out so people are not subjected to research where there's no benefit possible, but risk is present. We also recommended that it be possible for there to be certain decisionmakers who are members of the patient's family or are friends and who can represent them when they do not have the capacity to represent themselves. And finally, we, like everybody else, emphasize the importance of education. But I cannot state too strongly that we have to educate people in IRBs or we have to educate investigators; but then it just sort of trails off. It's not adequate. It requires resources to educate people and requires putting in place those resources and the people to do it, and I'm hoping very strongly that the subcommittee sees the importance of education and sees the importance of adding extra resources. We used to say that people who had a huge budget but didn't do research, that that was faulty. We should now say that where there's money for research, there should always be money for education of investigators and IRBs about ethical issues in research. I'd like to conclude by pointing out that NBAC's special mission is to look at the whole system of protection of human subject from research risk. That's our primary obligation, and we are now starting a long and detailed investigation of that issue and we expect to issue a report with detailed recommendations about changes in the IRB system and in the general system to protect human subjects of research. I appreciate very much the opportunity to testify. Mr. Mica. Thank you. [Note.--The report entitled, ``Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity,'' may be found in subcommittee files.] [The prepared statement of Dr. Cassell follows:] [GRAPHIC] [TIFF OMITTED] T6523.028 [GRAPHIC] [TIFF OMITTED] T6523.029 [GRAPHIC] [TIFF OMITTED] T6523.030 [GRAPHIC] [TIFF OMITTED] T6523.031 [GRAPHIC] [TIFF OMITTED] T6523.032 Mr. Mica. I can now recognize Dr. John Oldham, director of the New York State Psychiatric Institute. You're recognized, sir. Dr. Oldham. Thank you, Chairman Mica, Congressman Towns. I'd like to thank you for the opportunity to testify today on this important topic. Joining me today is Dr. Timothy Walsh, a research scientist at the New York State Psychiatric Institute and former chair of the Institute's IRB. Also I'd like to request that our entire testimony be entered into the record. Mr. Mica. Without objection so ordered. Dr. Oldham. It's been approximately 25 years that institutional review boards have been formally carrying out their function and it's appropriate to review the Federal regulations and the IRBs that are at their center. Currently institutions, such as New York Psychiatric Institute, which I'll refer to as NYPI, are required to enter into a multiple project assurance or MPA with OPRR, an agreement which governs research at that facility. Under an MPA, reporting mechanisms that are established for unanticipated problems that involve research risks and for suspension or termination of IRB approval for specific research protocols. OPRR provides oversight of research programs conducted under an MPA and it also conducts investigation of allegations of violations of human subject regulations. NYPI has chosen to apply the Federal regulations to all of its research, including that which is not federally funded. Elsewhere in the country, however, some non-federally funded research falls outside the scope of Federal regulations. One issue to consider in protection of research participants would be to mandate universal application of the Federal regulations. The IRB serves an important and useful role in the system of protecting human subject research. NYPI has a highly committed and responsible IRB. As this committee is aware, NYPI was the subject of allegations filed with OPRR regarding a portion of a particular study carried out in 1995. And Dr. Walsh and I testified before the Subcommittee on Human Resources in June 1998. OPRR conducted a lengthy and thorough investigation to determine whether NYPI complied with the detailed Federal regulations that applied to the research. They were provided with extensive documentation of the study and its IRB review and oversight. They made multiple requests for additional information and received lengthy responses to detailed questions. In March 1999 a team of six OPRR staff and three outside consultants questioned NYPI investigators, IRB chairs and members and institutional representatives at length and reviewed their decisions and actions in light of Federal regulations. After 16 months of investigation, OPRR concluded that not only were there no deficiencies in the IRB's review of the research and human subject protections provided, it also commended the psychiatric institute's IRB: for its ``detailed understanding of the specific requirements of the Federal human subject regulations,'' and for its members who are, ``enthusiastic and dedicated to the protection of human subjects and have the diversity, including consideration of race, gender and cultural backgrounds, and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects as required under Federal regulations.'' The study in question was one component of a larger study which sought to identify factors that contribute to the development of antisocial and violent behavior in young boys, a concern of pressing importance in our country today. It has been scientifically established in adults that violent behavior is correlated with low levels of a brain chemical called serotonin. Serotonin can be indirectly measured by blood tests after the administration of a drug called fenfluramine, a test for serotonin much like a glucose tolerance test, is a test for diabetes, and a cardiac stress test is a test for heart irregularities. For many years prior to the study at NYPI, fenfluramine studies were a well-established mechanism for measuring serotonin. Researchers outside of NYPI had described experiences with more than 2000 research subjects, including over 200 children and adolescents who had participated in fenfluramine studies. Even after concerns about the long term, large dose safety of the drug led to its withdrawal from approved use for obesity, which did not occur until almost 2 years after the NYPI study was concluded, the FDA still allowed it to be used in small, single dose research studies, since this had always been judged to be entirely safe and indeed, the FDA continues to permit this use today. The study at NYPI involved the administration of fenfluramine to younger brothers of already adjudicated delinquents. It has been scientifically well-established that these younger brothers are at high risk to develop behavioral problems. In fact, the majority of the boys in the study were described by their teachers and/or family as showing evidence of significant behavioral problems. The process for selecting participants in the overall study was approved by the IRB and did not exclude anyone on the basis of race. The investigators recognized that the study they proposed ultimately needed to be broad-based with a geographically and ethnically diverse sample, but as is generally the case in an initial phase of the investigation, funding and methodological issues dictated beginning with a smaller sample drawn from the surrounding community. For this reason, investigators obtained information on eligible families from records of the family courts of Manhattan and Bronx. The IRB specifically required that there be no ethnic or racial exclusions as a condition for approving the protocol. The consent process occurred over several visits and children participated only if both parents and children agreed to the procedures at all times. Families were specifically told that participation would not influence any court or correctional decisions. At the time of the selection, all of the older siblings had already been adjudicated. In the fenfluramine study, a small dose of fenfluramine was given in the form of a single, oral tablet, an amount that has always been judged safe. Although the IRB determined that the study provided no direct benefit to the individual participants, it was anticipated that the children would receive a number of indirect benefits, and they did. The children received expert neuropsychological, general medical and mental health evaluations. Findings from these evaluations led to referrals for visual, dental, pediatric and mental health care, and in the case of children with educational problems, were used to expedite appropriate educational assistance. The study helped provide a foundation for a new approach to help parents raise children who are at risk for behavioral problems. Studies to examine the utility of these interventions are now underway with Federal support, including a recent grant from the Department of Education. This is the goal of research, to lead to the development of effective services and treatments. Again, we appreciate the opportunity to testify at this hearing. We would be happy to respond to your inquiries. [The prepared statement of Dr. Oldham follows:] [GRAPHIC] [TIFF OMITTED] T6523.033 [GRAPHIC] [TIFF OMITTED] T6523.034 [GRAPHIC] [TIFF OMITTED] T6523.035 [GRAPHIC] [TIFF OMITTED] T6523.036 [GRAPHIC] [TIFF OMITTED] T6523.037 [GRAPHIC] [TIFF OMITTED] T6523.038 [GRAPHIC] [TIFF OMITTED] T6523.039 [GRAPHIC] [TIFF OMITTED] T6523.040 [GRAPHIC] [TIFF OMITTED] T6523.041 [GRAPHIC] [TIFF OMITTED] T6523.042 [GRAPHIC] [TIFF OMITTED] T6523.043 [GRAPHIC] [TIFF OMITTED] T6523.044 [GRAPHIC] [TIFF OMITTED] T6523.045 [GRAPHIC] [TIFF OMITTED] T6523.046 [GRAPHIC] [TIFF OMITTED] T6523.047 [GRAPHIC] [TIFF OMITTED] T6523.048 [GRAPHIC] [TIFF OMITTED] T6523.049 Mr. Mica. Thank you, and I thank each of our witnesses and our first panel, and what I'd like to do now is begin a series of questions and I'll yield to ranking member this morning, Mr. Towns. Obviously, there's an incredible explosion of research, probably beyond anything we could have imagined even a decade ago. And it's important that we move that research forward and human beings benefit by that process. As we heard from our witnesses, we have a system to deal with this in regulations to protect people that were developed some two and a half decades ago. There's a system somewhat convoluted in its structure, and antiquated, but progressing with the rapid advances we're making today and the sheer scope of research that's being conducted. The purpose of this hearing is to try to sort through the maze and there are many, many questions and aspects for all of us. I'd like to start today by asking the Inspector General, I read through all the testimony of the past hearing, and there was another hearing before this. You came today and said the system is badly in need of reform. There are many aspects of that reform. Let me deal first with structural aspects. The Secretary has moved OPRR from NIH to the Secretary's office. Is that sufficient structural change to deal, again, with the administration, the oversight, and the management of this whole order, or do we need other structural changes that have not been put in place? Let's deal with the structure first. Mr. Yessian. Mr. Chairman, we haven't focused on organizational structure. If the human subject protection function gains some independence and visibility that would seem to be desireable. But our position has been that that isn't an issue for us to address in any detail, and that there are basic issues that go much beyond structure. The basic reforms remain to be carried out. They have to do with the nature of oversight, the kind of educational mandates, if and how we change any of the regulations, what happens at the IRB level. There's still a full agenda there. Mr. Mica. The second question would be if you have identified any legislative changes that may be necessary to deal with the overall structure, and do you have any recommendations dealing with legislation that may be required either for structural changes or processes? Mr. Yessian. I think a number of our recommendations could be enhanced by legislative changes. It's possible in some cases they could be done administratively as well. But on call for a mandate that there be a registration of all IRBs would probably take legislation. Mr. Mica. That cannot be done by rule? Mr. Yessian. I defer to Dr. Ellis on that. Mr. Mica. Dr. Ellis, can that be done by rule? Mr. Ellis. The current regulations and statutes I think would permit registration of a large portion of the institutional review boards in the United States, but there are some that just simply fall outside of our current statutes. Mr. Mica. So you would need additional statutory authority to bring everyone into the fold, is that what you're saying? Mr. Ellis. For instance, currently OPRR has the name and address of every institutional review board within our authority. This registration not a problem for OPRR, I think it's an opening question for FDA, but even a combination of OPRR and FDA and their overlapping jurisdictions wouldn't reach a completely private institutional review board that doesn't engage in FDA regulated research, for example. Couldn't get every last one from where we stand right now. Mr. Mica. Back, if I may, to the Inspector General. The first hearing contained a substantial number of recommendations. Now, first of all, the Inspector General, your report had offered a number of recommendations. What percentage of your recommendations have been instituted; 10 percent; 8 percent; 5 percent performed? Mr. Yessian. Probably 5 to 10 percent. The most significant response is the enhanced enforcement effort from the Office of Protection from Research Risks. Mr. Mica. And you did cite whether there were some instances of changes in procedures? Mr. Yessian. But much remains to be done. A few highly visible enforcement efforts, by the way, have a lot of reverberations. Some have said, some of those efforts are like the nuclear bomb of enforcement. Many have sort of said there but for the grace of God go I, after they went into Duke University, so there has been some positive reverberations there. Mr. Mica. But you're saying 5 to 10 percent actually---- Mr. Yessian. I would say so. Mr. Mica. Dr. Lawrence, the Inspector General has made recommendations at this last hearing, the hearing that was conducted June 11, 1998, from some pretty substantial organizations; the Center For Biomedical Ethics offered recommendations. The American Association for Medical Ethics and the American Psychiatric Association offered recommendations. I read through some of these recommendations. Some of them are very similar to what the Inspector General has offered. These were recommended almost a year and a half ago. The National Bioethics Advisory Commission report was a year old. Why has there been such a delay in implementing the recommendations by the Department? Dr. Lawrence. Mr. Mica, I have no way of calculating percentages on this, I'll start by saying that. Mr. Mica. We can go over each of these one at a time. It appears that one or two minor changes or recommendations were instituted by the Department. Our responsibility in an oversight capacity is to find out, what's the holdup? Dr. Lawrence. Let me say this: The OPRR did move to increase its enforcement activities, and I think that the IG has underscored that. In response to the NBAC report that referred to human subjects with impaired capacities, while there is not a regulatory change, there are a set of NIH-issued guidelines that address many of the particular areas that the impact report pointed up. Third thing is that OPRR moved very, very aggressively in its educational forum to put more and more information on to the Internet so that those individuals who needed it most could be able to refer to, had it available, and also that patients had it available to take a look at to see what it is that they should be expecting. Now, let me add something about the structural change, for a moment, if I may. The structural change from NIH to OS, I think is very significant. Will the structural change itself make a difference? No. It's what the Secretary and what Dr. Satcher wishes to do with it. The structural change moves OPRR into a position where it will focus solely on human subjects protections. The office in OS will also have an increased capacity to have sway over the agencies within the Public Health Service that do fund services, making it much easier to communicate and it also makes it easier to communicate on a chief officer, as in Secretary to Secretary level with the other signatories to the common rule. So I think there are things that are currently moving. Now, let me give you a prognostication. OPRR is working assiduously on looking at the streamlining of assurances. We're almost there, I can't say that we are there. I would say that probably within the next 120 days OPRR will be in a position to directly respond by the simplification of the process without compromising patient safety. Mr. Mica. Let me ask you, Dr. Lawrence; I guess structurally and from an oversight standpoint, IRBs that receive Federal funds or projects that receive Federal funds that have IRBs, OK. It would be a given that we would want to make certain proper procedures and reforms are in place with that group, is that correct? Dr. Lawrence. Yes, sir. Mr. Mica. OK. Now, your colleague, Dr. Ellis, has said that there's a larger universe out there, and there are many research activities that don't receive Federal funds. Is it the Department's position that all of these should be covered? Dr. Lawrence. We believe very strongly that all participants in human subjects research should be afforded the maximal protections possible. We urge those groups that are not part of our funding, of course, to adopt our own approach to things. Where there is an MPA, a multiple project assurance, the institution signing that MPA actually pledges its entire research portfolio, as I recall---- Mr. Ellis. Essentially, 98 percent---- Mr. Mica. Dr. Ellis. Mr. Ellis. Thank you. Essentially 98 percent of the major biomedical research institutions that have a multiple project assurance, that's an umbrella agreement with our office, voluntarily pledged all their activities irrespective of funding to our rules. So that's one way we've been able by jawboning, I guess, to extend the coverage as far as we possibly can. Mr. Mica. Dr. Lawrence, so it is the intent of the Department to include all of those participating in human research projects, experimental projects, to come under an umbrella? Dr. Lawrence. We are currently operating a work group that takes a look at both FDA and OPRR human subjects protections activities to see where the overlaps are, where the gaps are. Mr. Mica. Now, Dr. Ellis testified that he did not believe that you had statutory authority to really include this other group that does not receive Federal funds and regulate them, and it would require, I don't want to take anything out of context, but it might require legislative change. Dr. Lawrence. Yes, sir. Mr. Mica. Is the Department preparing anything for Congress for legislative change or to expand that authority? Dr. Lawrence. The President has asked the National Bioethics Advisory Committee to take a very, very broad based look at this. Mr. Mica. Now, we've heard Dr. Cassell say that well, they've produced this document, but he said that in the research area, I believe he said it was going to be 6 more months before they complete their study and recommendations. Dr. Cassell, is that correct? Dr. Cassell. Yes. That's the goal. The goal is that comprehensive recommendations about the protection of human subjects, and it will be probably 6 or more months before those are finished. However, what is presently in the report that you have in your hands, if those recommendations were implemented, we would have already gone a large step forward. Mr. Mica. Now, how many of the recommendations contained in this December 1998 report have been instituted? Dr. Cassell. I think zero is probably an accurate number. Mr. Mica. So we're 5 to 10 percent with the IG and we're zero in this, and you're telling the subcommittee this morning that because there has not been action on your report, that has, in fact, delayed the next step in your process, is that correct? Dr. Cassell. Oh, yes, and I agree with the Inspector General, what they recommended would move the whole process forward. There's considerable inertia in making things happen. Mr. Mica. So let's go back to the Department. How does the Department respond to not taking action on 90 to 95 percent of IG's recommendations, and zero percent of these recommendations, and delaying the process to where we do not have any of these protocols, procedures, regulatory assurances in place? Dr. Lawrence. Dr. Lawrence. As I said, Mr. Mica, subject to that report, OPRR did take a very, very careful look, especially at the impaired participants section and they did take action. The second thing is that I think that we are in a position where structurally, and inside the Department, we want to be as careful as we can. We have to keep in mind when we take these steps, that there is also a potential for doing things wrong. We prefer to take very thoughtful, deliberative steps. I do take exception to the characterization that so little was done by the Department. I have outlined for the committee those things that were done as the result of the IG's report. Is it 100 percent? No, sir. I also think that the substantive steps that NIH took to produce guidance, specific guidance in response to NBAC to protect those individuals who are impaired were substantial. Have we done 100 percent? No, sir, and that's why the secretary has decided to move forward and to reorganize OPRR into OS, to give it a higher level of visibility, to give it a higher level of flexibility and also to start working on the actual activities to protect human subjects. Mr. Mica. My next area of concern would be individuals who are in a situation where they're not able to really make a decision, whether they be mentally ill, retarded, or children, and you're telling me that some changes in procedures have been made, then today's paper cites the case of this young man, who just turned 18, Jessie Gelsinger, and I guess your Department has said he should have been eligible for this, and then found out that the informed consent form that investigators gave patients deviated from the one the agency had approved. So I have concerns that while some of these procedures to protect children, to protect others who may not be able to make informed decisions, you're saying changes have been made and today's newspaper cites, maybe it's just one case but it appears that some of the protections, in any event, and changes have not been instituted. How would you respond? Dr. Lawrence. As to your reading the article, Mr. Mica, as it turns out, I was kind of ticking off some things here in taking notes. First off, let me say that the death of anyone or the injury of anyone is truly a regrettable event. And that's what we're all trying to protect. Now, in this case, I think if we reread the article again, what we would find is that had that investigator followed the existing requirements, that there would have been informed consent. So it seems to me that if this article was true, and I have no specific knowledge, that if there is an issue here, OPRR's regulations and guidance cover all of these areas. That's my answer, sir. Mr. Mica. Well, what concerned me when I read this report is one of the matters in which some of these IRBs proceed in and I can't find the passage, I thought I had it marked here. It said the way the IRB proceeded was if the patient, if some of the patients hadn't died, then they would proceed, and that, they tried it on a few, and if some didn't die, that would be the criteria for proceeding. I was a little bit concerned that some of the recommendations that had been made by almost every group relating to educational assistance of the IRB people who served has not been put into place. I was concerned a little bit about the representation on the Board, nothing in that area has been put into place that I know of, a requirement there. What also concerns me are the reports that some people who serve on these Boards, and they may be federally funded, may be receiving payments or some type of funds from pharmaceutical companies that have an interest in that particular research or the product that's being applicated by them. Where are we with those matters? Dr. Lawrence. I will answer part of that and ask Dr. Ellis to address part of the question about financial disclosures. Let me say a couple of things about education. Education is very important. NBAC has said it, everyone has said it. As we move forward in the restructuring of OPRR, we are going to be looking very carefully at how the current resources are being distributed. I think the strategy, Mr. Mica, that we're going to be using as we move forward with advancing OPRR and its ability to protect human subjects, to use the current phrase, is to pick the low hanging fruit. There are some things that we can do right now, there are things that we can do very, very quickly, not the least of which is to have an oversight and advisory board that is totally independent, where we can ask this kind of question, where we can go to this board and say what are the priorities. I think one of the important things in seeking to improve human subjects protections is we have to keep asking questions, because the target, quite frankly, sir, keeps moving. So I think that many of the recommendations that are in each of these reports, if not having been addressed in specifics, they're going to be addressed through the process of conversation with that advisory committee. Mr. Mica. Let me ask you this: Some of these things---- Dr. Lawrence. Would you like to have---- Mr. Mica. We'll get to Dr. Ellis on the disclosure and conflict of interest. Dr. Lawrence. Sure. Mr. Mica. But I come from a pretty conservative side of the spectrum. I don't like additional government regulations and red tape and bureaucracies. Has the Secretary or OPRR or any of these agencies sent out an advisory memo to--Dr. Ellis, didn't you tell me we could identify the IRBs that are getting Federal money? Mr. Ellis. That's correct. Mr. Mica. We can identify them. Have we sent out a simple advisory statement or recommended procedure asking them to address peer education, broader representation disclosure, or conflict of interest? Has any of the overseeing agencies involved sent out anything on this since the last hearing? Mr. Ellis. Well, the answer is emphatically yes. Mr. Mica. Can you produce copies of those for the record and the subcommittee, please? Mr. Ellis. Certainly. Mr. Mica. OK. In all of the areas or some of the areas? Mr. Ellis. Probably the single best integrated advice went to the 240,000 subscribers of the Journal of the American Medical Association November 24, 1999 where I wrote an editorial titled ``Keeping Research Subjects Out of Harm's Way.'' The main point of that was education, education, and education. I'll be glad to supply that and others. Mr. Mica. Has the Department sent an advisory notice or specific guidelines or recommendation to the IRBs outlining maybe what was in your probably excellent editorial comment? Mr. Ellis. You're too kind. We have addressed institutions and their IRBs directly by first class mail through the years with a 1993 edition of an IRB guidebook. Mr. Mica. My question dealt with since the last hearing, can you produce for the committee your advisory notices in any or all of these areas? Mr. Ellis. Sure. Let me submit for the record everything we've produced since June 11, 1998. I'll be glad to do it. Mr. Mica. Great, that would be excellent. Now, Dr. Ellis, if you could tell us about our addressing the problem of disclosure and conflict of interest, then I'll go to Mr. Towns. I have more questions, Mr. Towns, but I'll---- Mr. Towns. Go right ahead. Mr. Mica. Since we've gotten into this, I appreciate your patience. Go ahead, Dr. Ellis. Mr. Ellis. Mr. Chairman, this issue of the flow of money through human research is 1 of the 10 most frequently asked questions, 1 of the 10 most frequently discussed topics and there are two issues. One is payment to research subjects, but I think you're most interested now in payment to investigators, or a variant of that--conflicting financial interests of IRB members as they review research. The Department's human subject regulations get at this only peripherally. There's one very direct clause that says no voting IRB member may have a conflicting interest in the research put before that Board, and we see the widespread practice of recusal when a voting IRB member sees something that could be a conflict. A conflict many times is intellectual or academic, a collaborator's proposal, but it can be financial. Now, that's the strongest hold that the regulations have on this, and it is admittedly weak. The only other portion of the regulations that I can see that pertains to this is instruction that informed consent from a subject shall only be sought under circumstances that minimize the possibility of undue influence or coercion. My reading of that means that if the investigator is somehow reaping financial benefit, that the IRB has full entree to ask about all those circumstances, because the IRB has the absolute mandate to minimize the possibility of coercion or undue influence on the subject that the investigator is recruiting. Those are the two places I see it in the human subject regulations. This is something that's going to have to be addressed at the national level, and my guess is will eventuate in some additional detailed guidance, if not regulation, because it's a very important topic and a current topic. Mr. Mica. I see that the Inspector General wanted to respond. I would be interested--again, we want to insure that protections are there, particularly in this conflict area with IRB members. We don't want to dissuade people from serving and getting into all kinds of complicated disclosure mechanisms. That can be a deterrent to having people who are highly qualified participate. If you would. Mr. Yessian. Yes, Mr. Chairman. I wanted to comment on this, because since the last hearing, most of our work in this area has been on the issue of recruitment and industry sponsored trials and I have to say conflicts are just inherent in this process. They apply where there's a government grant as well as in industry trials, but it's important to emphasize how at the IRB level, at the ground up, how the environment is really turning into much more of a marketplace environment, and some major research institutions, one of the IRBs I just talked to, one of the best teaching centers in the United States has half of their proposals now come from industry sponsored research. This raises all kinds of questions and there's very little guidance that the IRBs have and they don't often know where to turn when it comes to OK, what's appropriate here, Dr. Ellis touched it. Are there circumstances in which informed consent is being provided, being tarnished in some way in is there coercion here, maybe unintentional. Is it really voluntary? Is confidentiality being broached if somebody is being called about participating in a project because of, without their, without their knowledge that their records are being accessed? These issues are really stirring up at the IRB and institutional level, and it's for this kind of reason in a way, notwithstanding the fact that some progress has been made, at the Federal level in addressing some of these issues, at the ground level in a way, the problems are extenuating even faster than our progress is, because it's not static there, it's a rapidly changing marketplace. Mr. Mica. Thank you, I'll probably go a second round. Mr. Towns, you're recognized. Mr. Towns. Thank you very much, Mr. Chairman. I want to point out this is a very important area to discuss, because we're talking about protecting people and I think based on that would be the New York Times article today, and of course the Washington Post yesterday, you know, we have some very serious problems. Let me begin by saying first, Dr. Lawrence, when will the move of the OPRR be complete? Dr. Lawrence. We are targeting March 2000. Mr. Towns. And how will this move improve the protection of human beings who are subject to biomedical research? Dr. Lawrence. Well, first off, Mr. Towns, I think it's important to have an office that focuses solely on human subjects. This is not to say that animal welfare protection is not important, they are, but to have a staff that focuses very, very specifically on the issue, I think is of great value. The second thing is having the cachet of having the office located in the Office of the Secretary, and the ability of the secretary to speak out on these issues, supported by her own staff, which is very, very important. The third thing is that I believe we will find communications inside the Department and intra departmentally improve significantly with the office on that level. How this translates exactly to human subjects protections, I cannot give you a number or a value. However, I do believe that it is a major step forward in what needs to be a sequence of events, including the appointment of the advisory committee that will then be able to identify the very, very specific solid steps that need to be taken to move forward. Mr. Towns. Have you consulted the Office of Personnel Management about the necessity to change Director of OPRR or to the position with the Senior Executive Service? Dr. Lawrence. Our administrative division, which is Assistant Secretary for Management and Budget now has all that paperwork and they are responsible for the interface with other agencies. I have no specific knowledge of exactly where it sits at the moment, sir. Mr. Towns. Right. So actually I can assume from that statement, no. That was a no, wasn't it? Dr. Lawrence. I have no knowledge of exactly where it is, so I can't say yes or no. Mr. Towns. So, then, I think we could say no. Maybe you don't have yes or no, I think we could be on the safe side and say no, OK? I don't want to--I think we can do that, no. Dr. Lawrence. Yes. Mr. Towns. I think when we move forward we don't forget about the fact that the Inspector General noted that last year OPRR has moved, improved and of course had been much more aggressive in conducting site visits and elevating the importance of protecting human subjects. I think that's important. So while I support the plan to move the office over to NIH, and some people, you know, feel that based on the fact that some folks have been very aggressive in doing things, they will not be rewarded, but they will be penalized, and I'm hoping that we don't see that in this particular instance. I'm talking about Dr. Ellis, who has done research in terms of, and written in terms of articles about harm's way, so I just want to pass that along, because there's rumors floating everywhere, which has nothing to do with anything, I'm sure, but I just sort of wanted to make that comment on the chance we had to have this exchange. Dr. Lawrence. Thank you, sir. Mr. Towns. Let me move forward. First of all, I want to ask the general question to any of you, how many IRBs do we have out there? Anybody know? How many IRBs are there? Mr. Shamoo. Around 5,000. Mr. Towns. I wish I could accept your answer, I wish it was true and all that, but anybody at the table here, if you could tell me how many we have. Yes, Dr. Ellis. Mr. Ellis. We have estimated there's some 3,500 to 5,000 IRBs in the United States. It's not really possible to give a more precise estimate. Mr. Towns. 3,500 to 5,000. Anyone else want to give me a number? Or you don't know? That's my problem. Even the person that knows is saying 3,500 to 5,000, there's 1,500 in there we're not certain about, and I think that's the real issue here today. I think that we need to some way or another come up with a way to know what's out there. I think that's the first thing, so--let me just move to one of the things that sort of keeps me involved in this in a very serious way. I want to let you know that I'm not going to go away on this one, I'm going to stick with it. I'm going to be here, you need to know this, I make it clear, it's not somebody who will come in, say something and then move on. Let me begin by asking you, Dr. Cassell, the fenfluramine study was that a central, valid piece of research based on your many years of professional work? Dr. Cassell. Well, I tell you, it's not for me to decide that. It's not within my competence, but I'll tell you what is important, that we heard testimony about that research in July 1997. It is research like that, whether valid or not, that raised issues of the protection of human subjects, and my own belief is, if we were talking 5 years from now, it would have more difficulty getting passed an IRB than it had now. I don't question for a moment the expertise of the people that did that research, it's their line of work, they're good people. I don't question the validity of the hypotheses that went into it, that's their work, and I believe they're correct, that isn't really the issue. There are a lot of good studies that people would like to do that will move science forward and so forth, but that's not the only value present. Progress isn't the only value. The protection of human subjects, the care of people who cannot take care or protect themselves, ranks as high or higher than scientific progress and that's really what we're talking about. Mr. Towns. Thank you very much. I couldn't agree with you more. Let me just go to you, Dr. Walsh. In your testimony, it was June 1998, before the committee, subcommittee, you said that all of the participants in the New York Psychiatric Institute fenfluramine research involving children were not members of minority groups. Dr. Walsh. If that's in the testimony, sir, that's an error. All of the members of the fenfluramine challenge study were members of minority groups. Mr. Towns. It's in the record. In fact, I want to be honest with you, I read it four times. Dr. Walsh. It is then my error, for which I apologize, if I failed to correct the record. Certainly there was no attempt to say that, in the fenfluramine study, the children were not African American. Mr. Towns. Let me give it to you, to correct the record, I think we should. What was the breakdown? Dr. Walsh. I'd have to look at the paper, sir. If you want accurate information, I'll have to look through my papers. Mr. Towns. Also in Dr. Oldham's testimony, he said that race was not an issue here. You mean to say by happenstance or coincidence, it just happened that everybody was minority? Dr. Walsh. Yes, sir. Mr. Towns. That's a strange coincidence. Dr. Walsh. Let me explain. Here's how the recruitment occurred. These investigators were interested in finding out ways to help families, help parents raise their kids in a difficult environment. They focused on the development of antisocial behavior and proposed in their research to identify families who were involved in the family court systems of Manhattan and the Bronx, because they were in close geographical proximity to where our institution is. They were proposing to do was to conduct home visits and follow these families for 4 years. It turns out that the overwhelming majority of families in these court systems are African American and Hispanic. In the study that was conducted, the overall study, I think the proportion of Caucasians are 2 or 3 percent, there are a few, but it's a very small number. But my understanding from the investigators is this is not different from the makeup of the Manhattan and Bronx family court systems. Mr. Towns. Dr. Walsh, you're a dancer. I want you to know I'm not your partner, either. You're a dancer. You mean to say you could not find one white kid? Dr. Walsh. No, sir, there were two or three Caucasians in the overall sample of 126 children. Mr. Towns. But they ended up being blacks and Hispanics. Dr. Walsh. Let's be careful to be clear. There was a broad study to look at factors that were related to the development of antisocial behavior among youth. It's well-established scientifically that one of the risk factors, one of the ways to identify kids at risk is to find kids with an older brother who has had some trouble, and that's the procedure that the researchers proposed. They chose to get them, as was described, from the Bronx and Manhattan court systems. People were recruited, families were recruited from that court system without regard for race or ethnicity. The investigators initially proposed to have an ethnic exclusion. The IRB did not permit it. We absolutely told them you cannot have ethnic exclusions in this research. Nonetheless, their final sample composition of 126 kids involved 3 Caucasians, and I am told, that that is a reasonable statistical reflection of the makeup of the families in the Bronx and Manhattan court systems. Mr. Towns. Dr. Walsh, really, we've been down this road before, and of course, and I don't want you to have to correct the record again when we talk. I want you to know that this is a little different from what was said the last time, which would be how you arrived at getting them. So I don't know how you change, I mean, you're going to have to correct the record again evidently. Yes, Dr. Oldham. Dr. Oldham. Congressman, let me clarify one thing I do not think is clear. Dr. Walsh described this as an initial overall sample of about 125 young boys. Of that 125, which did include a few nonminorities, there was a substudy of about 36. Those 36 boys were the 36 boys that participated in the fenfluramine study. Those 36 were entirely African American or Hispanic. That was a completely random result of the volunteers who participated in the substudy, in other words, those 36 who agreed to participate in the substudy by coincidence did not include the very few who were in the entire sample, but when a statement is made that the sample did not exclude any subjects on the basis of race or ethnicity, that is correct. Mr. Towns. Let me put it this way: Why don't we include Staten Island or Queens? Dr. Oldham. This is actually the first---- Mr. Towns. It's part of the city, I figured you would look at the city. Dr. Oldham. I think Dr. Walsh addressed part of that. We had a multi-phase design. This was step one of a multi- phase study and the second phase of the study was to move to other regions which would include other parts of the surrounding area, that would have included some other boroughs of New York as well as some other counties outside of New York City, which would have been a very different ethnic and racial distribution. This was actually submitted and approved by NIH as a followup study. So we began actually where we had contacts already with the court systems that were adjacent to our exact location, which were the court systems of Manhattan and the Bronx, as a pilot to start the study. We didn't know until we received the information from those courts what the specific racial profiles would be of these groups. Mr. Towns. I just want to ask you, before we move on, that's a strange coincidence that you had nobody, just black or Hispanic. That's a strange coincidence. Let me move on. I don't want to belabor that. In your testimony, you note that the children involved in the study had behavior problems, yet you do not state that these so-called behavior problems were the result of mental disorders. Was there ever a finding that all the children in this study had a specific mental disorder? Dr. Oldham. Let me ask Dr. Walsh to comment on that. There were a number of types of problems that were identified. Dr. Walsh. The majority of the children had symptoms of or met diagnostic criteria for mental disorders. At 1 year, in the overall sample, the number was I think about two-thirds. In the fenfluramine study to which you may be referring, it was about the same proportion, between two-thirds and three quarters of the subjects had behavioral problems, diagnosable behavioral problems. Mr. Towns. Let me ask you about the study itself, fenfluramine. Some of these children were under 12. Dr. Walsh. Yes, sir. Mr. Towns. I think all of them were all under 12. Now, even in the research, the pharmaceutical company didn't have anybody under 12 involved in the research of the trials initially. Now, they didn't have anybody, then you bring the youngsters in, and you use a drug on them that was not even tested in the trials with someone under 12. I mean, didn't that bother you? Dr. Walsh. It's actually a common problem in pediatrics. Many drugs that are widely used for children, have not been specifically tested and approved by the FDA for use in children. I think that's recently been addressed or there's a change in the FDA approval procedure, but---- Mr. Towns. Let me interrupt you here. That's a drug that's going to benefit the kid, but in this situation it does not benefit them in any way. Dr. Walsh. Yes, sir. Mr. Towns. That's a difference. Dr. Walsh. There was substantial data at the time in the literature about the use of fenfluramine in these very types of challenge tests in both children and adults prior to the initiation of the study at the Psychiatric Institute. There were thousands of adults and hundreds of children who prior to our approving this study, had participated in this kind of study without any significant risk or harm. And we determined that. We accessed that information, consulted with colleagues to try to determine that before the study was approved. Mr. Towns. Even though they were not involved in the research initially, you still felt that somebody else had done it, now you can do it. I mean, is that your rationale? Dr. Walsh. No---- Mr. Towns. I just want the record to reflect. Dr. Walsh. I think this reflects what the job of the IRB is. An investigator has a proposal, a proposal that certainly involves unknowns. Questions that have not been answered to which there are no firm answers available. It's the job of the IRB to use its best judgment to evaluate what the risks of those procedures are. I still believe we did a very conscientious job of doing so. We consulted with other people who did this kind of work, we looked at the literature, and we concluded, and it's a conclusion which I believe has not been seriously challenged: Fenfluramine used in the way it was used in this study, even in youngsters, poses no significant harm. Mr. Towns. Let me just say, I'm trying to move on. You stated in your testimony, Dr. Oldham, these children were at risk because they had a sibling who was in trouble with the law. Should everyone who has a sibling that's in trouble with the law be a candidate for biomedical research? If not, then what made these children candidates? Dr. Oldham. Well, certainly that would be too broad a generalization to make, but there is a very good body of scientific evidence that younger brothers, not any children, not any siblings, but younger brothers of males who have been already identified as delinquents with antisocial behavior that is clear enough so that there has actually been an adjudication and a guilty finding and a decision by the court system, that children of these families, if there are younger brothers, are at increased risk to develop this kind of behavior, we feel this is an important, enormously critical problem, that needs to be studied. We do not at all feel that this is something that should be done without careful, careful thought, and studies like this need to be very, very seriously considered, both because of their importance, but because one has to guard against inappropriate research with inappropriate individuals. However, if we feel that these younger brothers were in a category of high risk to develop similar problems and be on a course that would lead them to a very disturbed and difficult life course, if we could identify a way to intervene and to prevent some of this unfortunate outcome, we feel that this is very important. I mentioned in my testimony the fact that there had been federally funded studies based on the methodology and the initial preliminary findings of these studies that are underway, funded both by NIH and by the Department of Education to try to involve prevention and avoidance of this unfortunate path by the youngsters. Mr. Towns. Did you develop any treatment strategies? Dr. Oldham. There were intervention and prevention strategies, that's what it would be at this point for these individuals, and they were referred for treatment in every case where there was a willingness on the part of the family to accept treatment and treatment was indicated because of diagnosed conditions that needed treatment. Mr. Towns. Let me say that, you know, I'm trying to move on, but you know, I'm not sure that some of this is not society, poverty and all these kinds of things rather than being biological. I sort of raise that issue with you as well. Yes, Dr. Walsh? Dr. Walsh. I agree with you, sir, very much, and that in fact was the point of the research. I want to underline, I appreciate your concern, sir, and I am very interested in your opinions and concerns about how we can better help people in our community. And I think we're an institution well known to be located in a minority community and I think we have an obligation to try to help the people who come to our hospital and live around us. The problem is we have a lot of ignorance about what to do that would be helpful. A lot of the causes of some of the problems are social, environmental, economic, there's no doubt. But we're doctors and we try to find out ways that the medical and psychological professions can help these people, and the only way that we can help break through the ignorance is through research. So we have to do research with these people-- not on them, not to them, but with them, so we can get a better idea of what we might be able to do to help them, so that we can help them. And, sir, I strongly believe that that is what this study did. The broad study identified things that parents were doing with their children that helped children avoid problems. And yes, it explicitly led to treatment studies that are now ongoing in the same community, in northern Manhattan, with, what I understand to be, the strong support of the local community, to help families living under difficult circumstances, help raise their kids the way we all want our kids to grow up. So, sir, I understand your concerns. I deeply respect them, but I feel that we must continue to work with the community in which we live so we can help the people who come to us. I think it is our moral obligation. Mr. Towns. Let me just go back to the IRBs. How should we structure them? Because we're hearing all kinds of things about conflicts, we've heard even corruption, lack of training, lack of qualifications, and I think that these are the things that we have to be concerned about, and the other part, you know, I'm not hearing any kind of real sanctions, that if anybody is guilty of all of this or any of it, what happens? Are there any sanctions of any sort that would sort of discourage someone from being involved in a negative kind of way? I think, Dr. Ellis, let's start with you and then come around the room and let everybody comment on it. Mr. Ellis. Congressman Towns, the ultimate sanctions, I'm saying the extreme, under our Department human subject rules is denial to an institution of further research funds for human subject research. Mr. Towns. I'm sorry, repeat it? Mr. Ellis. The ultimate sanction under our Department human subject protection rules is denial of the opportunity for further research funds from this point forward, let's say, to do human subject research. Mr. Towns. Right, but if some of the things I'm hearing, you know, the point of that is if I'm hearing some of them might even have arrangements with the pharmaceutical companies, so all they need is one shot, and then after that, they can move on, so the point is that's my concern. For instance, all of a sudden you find out that there's conflict or corruption, whatever else, collusion, whatever you want to refer to it as, and then you say, well, from this point on, we're not going to deal with you, but the point is if a person has arrangements with a pharmaceutical company, then they're prepared to move on. So I think it has to be really thought out in a major kind of way where something happens that will further discourage people from being involved in that kind of way. Anybody have further comments on that? I think this is a real issue here. We have all these IRBs out there, and of course nobody seems to know the number, what they're doing and how they're doing. Dr. Cassell. Dr. Cassell. I think the points you raise are important, but the future for IRBs will not be improved simply by being able to slap, no matter how hard, the wrist of a misperforming one as it will be improved by adequate staff and adequate training and adequate connection to a larger structure of IRBs in the country. They labor under, really, inadequate resources. They were set up for something much easier than where they are now, but there wouldn't be adequate resources by just saying, there wouldn't be adequate resources, unless there is a legislative intent behind it, at least legislative intent behind it that provides enough people to run an IRB and enough money to do it properly and enough education so the people who are sitting on that IRB knows something, are not just good hearted or kind, and they know enough not to take money, we all know that there are bad people everywhere, that's hard to argue, but there are less bad people where a structure is set up that encourages goodness than where a structure isn't even in place. Mr. Towns. Any other comments on that? Yes. Mr. Yessian. Congressman Towns, I have one point, and Laura McBride has one. On your point of structure, we talked about OPRR's location in the Office of the Secretary, well there's a very concrete issue there you could apply with academic health centers where there are IRBs, and I would say there you should assure there's adequate independence of the IRB. You don't have that, it seems to me, where you have an IRB that's part of a grants office as is sometimes the case, with the very office that's responsible for bringing in grants and contracts, typically from the pharmaceutical industry is the office that would oversee the IRB, in some cases representatives of that office are on the IRB itself, so I would say that's a conflict that we ought to watch out for. Furthermore, investigators in these institutions are going to have industry money for their own projects. I don't think there's any getting around that or that there is anything wrong with that. But certainly, should recuse themselves for any project for any review that involves any project they're associated with, I think most probably do, but we should certainly make sure that happens. Did you want to add something? Ms. McBride. Along those same lines I'll reiterate a point we made before, the need for greater representation of independent members on the IRBs. As Dr. Lawrence said before, there could be 1 out of 20 or 50 IRB members, and independent voices can play a good role in balancing institutional voices, other members' conflicts, but also representing the interests and the perspectives of the community outside the institution. Mr. Yessian. We've seen places where independent members have played that role and have raised questions that have made a difference. Mr. Towns. Thank you very much. I yield, Mr. Chair. Mr. Mica. Thank you, Mr. Towns. Dr. Ellis, in the hearing June 11, 1998, I think you testified, we have to date eight separate complaints about a body of research in New York City under the auspices of four institutions, and at that time you said you had not concluded your investigation. Have all of those investigations been complete? Mr. Ellis. Yes, all four are complete. Mr. Mica. Could you provide us, for the record, with a summary of your resolution of those investigations? Mr. Ellis. Yes. Mr. Mica. Dr. Ellis, you testified also at that hearing the last time your office suspended an assurance for human subjects research, I believe it was in 1991. From the hearing last June, what's the status of suspended human research subjects? Mr. Ellis. Mr. Chairman, I'll just have to go back to the hearing record to see exactly which institution I would have been referring to. I can't tell from your reading. Mr. Mica. You said there was one suspension. Suspended an assurance for human subject research in 1991. Have there been any since the last? Mr. Ellis. Oh, I'm sorry, I misunderstood. Yes, OPRR suspended Rush Presbyterian St. Lukes Medical Center in October 1998. OPRR restricted the West Los Angeles VA Medical Center's assurance in March 1999, which caused the Department of Veterans Affairs to simultaneously suspend all research, human, animal and otherwise at its West Los Angeles VA facility. Then in May 1999 OPRR suspended the assurance at Duke University Medical Center. I think that captures all the actions of the type you inquired on. Mr. Mica. The IRBs that received Federal funds, is there in place a Federal registration requirement? Mr. Ellis. Yes, for any institution that receives research funds for human research from the Department of Health and Human Services, OPRR follows the money assiduously and receives a formal written agreement, we call it an assurance, from the institution. One component of that formal written assurance is the IRB roster or rosters, so I can say unequivocally for human subject research that falls within OPRR's purview, that we have the name and address of every IRB member. Mr. Mica. But they're not required to register, it would be through that document, is that right? Mr. Ellis. That's right. For us it's a de facto registration. Mr. Mica. And those who do not receive Federal funding are not required to register? Mr. Ellis. I shouldn't speak for FDA, but I understand that FDA has several data bases that include names and addresses of IRBs, but no comprehensive system of registration. Mr. Mica. And the Inspector General had recommended that there be a registration, I believe, for all of these groups, is that correct? Mr. Ellis. That is a principal recommendation of the June 1998 report. Mr. Mica. The other thing that concerns me is many of the recommendations that were presented by many of these groups could be instituted by at least for those who receive Federal funds to the IRBs, by an advisory memo from the Secretary or from the agency. Dr. Lawrence, do you think that might be possible? Dr. Lawrence. OPRR communicates with its IRBs and through the granting systems frequently, and we can go back---- Mr. Mica. We're going to get a copy of all of those communications. Dr. Lawrence. We can go back and take a look at the recommendations and see how we can educate our IRBs about what those recommendations are, and see if there are other actions that we need to take. I don't have a list of each and every, so---- Mr. Mica. Well, again, it seems like common sense. I come from the business sector, and it seems that some things can be done as advisory, and certainly these folks that are getting Federal money it can be made a condition of. I just can't understand why the Secretary or the agency cannot, at minimum, request some of these changes that have been recommended by the Inspector General, national medical college groups, American Psychiatric Association, by the President's Advisory Commission. Dr. Lawrence. I understand your question, and I appreciate it as well. I'll restate that some of these things already have happened, especially with the issuance of the guidance. However, we can go back, sir, and we can go through---- Mr. Mica. I just throw that out as a suggestion. Then when we do the next hearings, which I'm sure Mr. Towns will be requesting---- Mr. Towns. Right. Mr. Mica. You can't come in and say hey, we've done even this minute step in the right direction. A final question here. Dr. Cassell, some of the things that you recommended, they require the expenditure of some funds. Should it be a requirement in the case of Federal funds going for research that those who receive that money contribute out of those funds sufficient resources to make certain that the recommendations you have are in place? Dr. Cassell. Yes. Mr. Mica. Thank you. That's the best, most succinct answer we've had today. Well, there are many additional questions that I would like to ask, and we will, with the permission of our ranking memoranda submit them to you for submission to the panel. I'll yield at this time for any final questions to Mr. Towns. Mr. Towns. Thank you. I just have one final question. In this very vulnerable population that we're dealing with in some instances in research, the mentally ill and of course in some instances, I just sort of feel that maybe the structure should be different in research with that population. If the physician is involved in the research, it is my feeling that that physician is so involved that some of the other kinds of symptoms that they might not be watching them closely enough, so the structure should be in the case like that, that there should be a doctor that's not a part of the research really responsible for the medical well-being of his particular patient, because I think that they're very vulnerable, and you're so involved in research you just ignore everything else. So I think that the structure should be different when you have a vulnerable population. I just need some quick comments on that. Yes, sir, Dr. Cassell. Dr. Cassell. That is a specific recommendation that NBAC made as part of its report. A specific and wise recommendation that somebody besides the investigator have responsibility for the well-being of those patients. Mr. Towns. Yes? Dr. Walsh. I too think there's a lot of wisdom to that philosophy. IRB worried, when I was on it, and I hope still worries about it, because we still deal with a psychiatric population. So I think in many ways it's a solid recommendation that should be carried out. We in many instances have done it. We have, for example, a clinical team taking care of the patient and a research team who is not part of the clinical team. The issue that is a tough call is where to draw the line, where does this level of vulnerability start. And frankly from trying to work our way through assorted research protocols, it never became a crystal clear line, where you could say I'm not comfortable, for example, saying all psychiatric patients must participate in the way that's just been described. Because many psychiatric patients are not particularly vulnerable, but some are very vulnerable, and where, how that gets decided I think is a very important question, which at the moment is wrestled with by IRBs. Mr. Towns. Yes, Dr. Oldham. Dr. Oldham. Mr. Towns, if I may add one point, I think that's a very important suggestion and a very important concern. I would just want to add that I think there are many categories of vulnerable populations, and to focus on the mentally ill is one category and as Dr. Walsh said and I agree with this, some of these patients are particularly vulnerable, other of them may not be any different than the capable population. There are others who are also potentially vulnerable who may not have mental illness, for example people with stroke, people with other kinds of incapacity and other with life- threatening terminal diseases which put them in a very vulnerable state, so I think all of these need to be looked at very carefully with the same level of concern. Mr. Towns. I agree. Dr. Cassell. Dr. Cassell. There's no question what Dr. Oldham said is true, but that should not take away from the fact that the protection of persons with certain mental disorders require special attention if for no other reason than they have not received the attention up until this time whereas the other categories he mentioned are already, do already come under regulation and custom that is not present here. Mr. Towns. Any other comments before we close out? Yes? Mr. Yessian. I would just agree. Many have commented that the most vulnerable subjects are those that are already patients of the investigator. That's one of the reasons why I think it's especially important to look at informed consent, not just in the context of what's in that document, but how is it explained to a potential subject and who does it, and in certain kinds of trials, it may be especially important that that be a quite independent party that the potential subject can communicate with without getting in the way of the doctor patient relationship. Mr. Towns. All right. Thank you very, very much. Thank you, Mr. Chairman. I yield back. Mr. Mica. Just one question to Dr. Cassell. The Bioethic Commission that you're on, was formulated by Executive order, is that correct? It's still under Presidential Executive order? Dr. Cassell. That's correct. Mr. Mica. What's your feeling toward codifying that? Dr. Cassell. I think that's important. Mr. Mica. You would recommend it? Dr. Cassell. Yes. Mr. Mica. Thank you. We have additional questions which we will submit to the panel, and we are keeping the record open by unanimous consent for at least 3 weeks. At this time I'd like to thank each of our witnesses for being with us this morning into this afternoon, and for your cooperation. We have an important task before us. We need everyone's cooperation to make certain that we put in place proper safeguards and regulations and protections for people who participate in medical research and that's our intent, to see that that's done wisely, that we as Members of Congress see that the laws are changed and the administration of the laws and regulations is proper to protect the public and also public funds. I thank you and I'll excuse the panelists at this time and call our second panel. Our second panel today consists of Mr. Cliff Zucker, executive director of the Disability Advocates, Inc., of Albany, NY. Our second witness is Dr. Adil Shamoo, and Dr. Shamoo is with Citizens for Responsible Care in Psychiatry and Research in New York City. Our third panelist is Miss Charisse Johnson, and she is from Brooklyn, NY. Our fourth panelist is Ms. Sherry Grenz, and she is with the National Alliance of Mentally Ill. These four panelists make up our second panel. If they could all come forward, please. As I explained to our first panelists and witnesses, this is an investigations and oversight subcommittee of the U.S. House of Representatives. We do swear in our witnesses. We also allow approximately 5 minutes to present your oral testimony before the subcommittee. Any additional records or lengthy statements will be made part of the record upon request. We're going to try to hold the panelists to those constraints today, particularly since the first panel ran us a little bit behind schedule. I would like to welcome each and every one of you, and if you could please stand and be sworn. [Witnesses sworn.] Mr. Mica. The witnesses have answered in the affirmative. I would like to welcome you this afternoon to our subcommittee hearing, and I will first recognize the statement, and we will go through all of the statements, then go to questioning. I'll recognize Mr. Cliff Zucker, executive director of Disability Advocates of Albany, New York. Welcome, sir, and you're recognized. STATEMENTS OF CLIFF ZUCKER, EXECUTIVE DIRECTOR, DISABILITY ADVOCATES, INC., ALBANY, NY; ADIL SHAMOO, CITIZENS FOR RESPONSIBLE CARE IN PSYCHIATRY AND RESEARCH, NEW YORK, NY; CHARISSE JOHNSON, BROOKLYN, NY; AND SHERRY GRENZ, NATIONAL ALLIANCE OF MENTALLY ILL Mr. Zucker. Thank you, Chairman Mica. I appreciate very much the opportunity to testify before the committee today. I am executive director of Disability Advocates, which is a not for profit public interest law office in Albany, NY and for the last almost 10 years we have attempted to advocate for the rights of human subjects of medical experiments who have medical disabilities. The first thing I think that we have to remember is that if, to answer the question the committee poses, are Federal protections adequate, we need information, and that so long as IRB deliberations are cloaked in secrecy, that we can never really know what is going on there. A number of witnesses earlier made the point, but it really goes far beyond registration of IRBs and knowing how many IRBs there are. We also don't know what sort of experiments they approve, who the subjects are, what their characteristics are, whether they have mental disabilities, what the nature of the risks they are subjected to is, what the premises that are being studied are, and whether those are important premises. It's been said that sunlight is the best disinfectant. I think we will go a long way toward protecting subjects if you enact legislation that would require the, both the registration of IRBs and annual reports of all experiments that are approved by IRBs and additional characteristics of human subjects and of the experiments which are detailed in my written testimony, which I request be made part of the record. Mr. Mica. Without objection, so ordered. Mr. Zucker. What I'm proposing is somewhat similar to a bill that Congressman Towns drafted and introduced I believe a year or two ago, which has a similar purpose. The second thing that I'd like to call the committee's attention to is an experiment which was until very recently ongoing at Bellevue Hospital in New York City conducted there by New York University School of Medicine and funded by the Novartis Pharmaceutical Corp. The experiment was conducted using the experimental drug Iloperidone on homeless mentally ill individuals who were approached to be part of the research very shortly after admission to the hospital, within hours or days of being admitted to the hospital in a florid psychotic state. One thing I want to highlight before I get into the details of that experiment is that my office filed a complaint with the Office of Protection for Research Risks concerning problems which I am going to outline. The Office of Protection from Research Risks declined jurisdiction, said that they did not have any jurisdiction to review the experiment of what the IRB had done here. These are major research institutions in New York City and they get a lot of Federal money and they conduct a lot of Federal research. They have an insurance, which is this contract with the Office of Protection from Research Risks, which in most instances requires them to provide Federal protections to all of their research, even drug company funded research. However, NYU and Bellevue have exempted themselves from that and OPRR let them do it. So we're in the remarkable situation where very serious complaints are raised about research of homeless, psychotic individuals that is allegedly conducted on their consent and OPRR says we can't touch it. That's a problem, I think it needs to be addressed by legislation. Each of these subjects in this protocol arrived in the emergency room in a florid psychotic crisis. There were 14 subjects, we examined the records of all of them. Most of them are homeless. Within hours or days, they were approached to give informed consent to be patients in this experimental drug study and 14 of them did give that consent. In every instance, the very same day or the day before or the day after, there are concurrent notes from clinicians describing these patients as floridly psychotic, as disordered thinking, as having no insight or judgment into their mental illness, as responding to voices, and yet in every instance sandwiched in between those comments about their florid psychosis, we have a note that says ``we asked the patient to participate. We answered all his questions, we explained all the risks and benefits, and after that discussion he gave informed consent.'' It's an interesting thing. There are 14 patients. The notes describing the informed consent process are word-for-word identical, hand written, word-for-word identical notes for every patient and they're not all entered by the same person, either. So it's a boilerplate purported description of an informed consent process, which is very apparent when you read these records that these patients were floridly psychotic and at this particular time they certainly were not capable of giving informed consent. My written testimony contains, does not name the patient, uses a pseudonym, but it contains quotes from the record so you can judge for yourselves whether it's conceivable that these patients had a momentary, a moment of lucidity in which they could comprehend a multi page, complex informed consent document that I submit not too many college graduates could read and understand. It's also significant that none of these subjects were tried on nonexperimental drugs and had failed on it before they were put into the experimental drug protocol. These were people who very likely would have responded well to conventional medications, including some of the more newly developed antipsychotic medications, but those are expensive, and there's a financial conflict of interest here for Bellevue Hospital, if they offered respiradol, that's an expensive drug they had to pay for, if they instead offered the experimental drug iloperidone they're paid to do it by the drug companies, so there's a conflict of interest there. Every one of the patients did poorly on the study, they either withdrew themselves or were withdrawn by the experimenters, got much more psychotic. They were taken off the drugs, put on a placebo washout, then some of them were put on the drug, some put on placebo, they became so ill none of them could finish. When they were taken out of the program they were put on drugs, lo and behold they got better, and discharged into the community or other facilities. In my view it's unconscionable, when people are brought to the hospital in crisis, these are people dangerous to themselves or others, this is a life-threatening situation, some of them had dangerous histories of injuring themselves, threatening people, animals, that instead of given treatment, they're taken off treatment, given placebos and put on an experimental drug that wasn't proven to be effective and in every instance proven ineffective. The hospital has a desire to enroll patients, the institution has an impetus to enroll people and not pay for expensive drugs, who is looking out for the patient's interests? Supposedly it's the IRB. But it's interesting. The minutes of the IRB, the IRB considered this protocol on September 28th. On that day, the IRB considered 110 projects. The minutes, we were provided with the minutes of the September 28th IRB meeting. One page contains the minutes of five protocols. The minutes consist of at most three words per protocol, if you don't count the name of the protocol, the heading, if you count the substantive discussion of what happens, three words and the number voted for and against. What it demonstrates is, without knowing more, I think we all know, you can't consider 110 protocols on 1 day. The kind of consideration that should have happened, that's required by the Federal regulations isn't happening. Among other things, I think that you need to consider whether Federal law should limit the number of protocols that are considered by an IRB, should set actual limits for the workload, and should require that certain resources be devoted to this process, because right now these volunteer IRBs just can't possibly do the job. I might add again, echoing some of the things said earlier, that independent consent monitors would be very, very important, independent of the facility which has a lot to gain financially from enrolling subjects in these protocols. Furthermore, I think we need to consider legislation that would make it unlawful to place acutely psychotic individuals who come to the hospital seeking care in experiments without first determining that they won't benefit from nonexperimental treatment, I think we have an ethical duty to first offer people what we know might work and to then only experiment if those things are unsatisfactory to them. I want to also touch on the fenfluramine experiments. Mr. Mica. Could you begin to conclude? Mr. Zucker. OK, I'm going to refer you to my written testimony which contains very specific recommendations concerning changes in Federal law and statutory language that I think is worthy of your consideration. I think we need to make it clear that neither poverty, nor race, nor family relationship to a person who is accused of crime, nor being the parent, excuse me, being the child of parents who are allegedly poor parents is the kind of condition that permits children to be experimented on in a way that is impermissible with so- called normal, middle class children. What OPRR did in the fenfluramine case, if you look at what they did to Mt. Sinai, they condemned them for doing this challenge on middle class control children, but when they were poor children over here at Columbia University, it was OK. It's just inconceivable to me that you can, that because you're poor, because you have older brothers in trouble, that such experiments can be conducted if they're impermissible to other children. You don't get special rights because you're poor. Thank you very much. Mr. Mica. Thank you. [The prepared statement of Mr. Zucker follows:] [GRAPHIC] [TIFF OMITTED] T6523.050 [GRAPHIC] [TIFF OMITTED] T6523.051 [GRAPHIC] [TIFF OMITTED] T6523.052 [GRAPHIC] [TIFF OMITTED] T6523.053 [GRAPHIC] [TIFF OMITTED] T6523.054 [GRAPHIC] [TIFF OMITTED] T6523.055 [GRAPHIC] [TIFF OMITTED] T6523.056 [GRAPHIC] [TIFF OMITTED] T6523.057 [GRAPHIC] [TIFF OMITTED] T6523.058 [GRAPHIC] [TIFF OMITTED] T6523.059 [GRAPHIC] [TIFF OMITTED] T6523.060 Mr. Mica. I'll now recognize Dr. Shamoo who is with the Citizens for Responsible Care in Psychiatry and Research. Dr. Shamoo, you are welcome and recognized, sir. Mr. Shamoo. Thank you, sir. I'm Adil Shamoo from Columbia, MD. I am here to speak today on behalf of thousands of families who are not able or willing to speak for themselves. I'm here to speak on behalf of Citizens for Responsible Care in Research. Just for identification, I am a professor at the University of Maryland School of Medicine, former chairman, I have been addressing questions on issues of research, have written extensively for several years, I'm editor in chief of a journal called Accountability in Research where I study and the papers submitted to our journal study the issues of integrity in research and how it is conducted ethically. I also have chaired seven international conferences on issues of ethics on research. I would like to thank you, Mr. Chairman. I also would like to ask that my entire statement be entered into record. Mr. Mica. Without objection, so ordered. Mr. Shamoo. I will give simply highlights of my testimony, since the first panel covered a lot of ground. I would like to thank you, Mr. Chairman, and members of the subcommittee to give me this opportunity to inform you of my personal and organization's grave concerns regarding current ongoing and ethical research practices. Vulnerable human beings, such as children, veterans, and mentally disabled individuals are being used as human subjects in high risk experiments with no potential medical benefit which cause them harm. It was our organization that brought the public attention to the fact that fenfluramine was given experimentally to minority children. The voluntary, comprehending, informed consent is universally recognized as a fundamental human right. It must be applied to all human beings, be they privileged or disadvantaged. Our national public policy was formulated to provide safeguards aimed at preventing unethical human experimentation, such as the notorious New York Willowbrook hepatitis experiments conducted on mentally retarded children in the 1950's and 1960's and the Tuskegee syphilis study conducted on African American men in the 1940's to 1970's. But current Federal safeguards are inadequate, especially for mentally disabled persons and disadvantaged children. These groups are incapable of protecting themselves from unwanted, coercive even harmful experimentation. It is the government's obligation to strengthen protection because the current regulation have proved to be inadequate, leaving researchers to circumvent them. The rights of the powerless and disadvantaged individuals must not be compromised for the benefit of the powerful and the politically influential biomedical research establishment. To claim that individual rights must be sacrificed for the good of society is a self-serving motive which is not an ethical justification for overriding the rights of some incapacitated individuals. The universally adopted Declaration of Helsinki unequivocally affirms that, ``the interest of science and society must never take precedent over consideration related to the well-being of the subject.'' The violations and experimental procedures that greatly concern us are, and one is the abrupt washout experiment which you heard of and I will not give you more detail. Second is the chemical challenge, the studies conducted on various human beings and third, the wholesale violations of informed consent. The principle of informed consent is intrinsic to a democracy and can rarely if ever be violated. Perhaps in the event of national emergency, or for compelling public safety reasons. There are no compelling reasons to justifying experimenting on disabled human beings without gaining their informed consent. Involuntary research on disabled and the disenfranchised individuals does not serve the good of society. To the contrary, such research threatens its fundamental moral underpinnings. Drug washout and chemical challenge experiments designed to produce rather than prevent a psychotic relapse in order to study its effect and conduct-photo imaging brain scans. They have routinely been approved by IRBs, thereby demonstrating that IRBs do not protect the interests of a subject and let me digress. Those fenfluramine experiments were approved by four different IRBs, four different grant proposals to four different study sections within the NIH and they were funded and carried over by four different sites within our research institutions. I will give you some of our recommendations. These are concrete recommendations. One; a moratorium on abrupt drug washouts and chemical provocation experiments that are likely to exacerbate severe incapacitating illnesses and expose vulnerable persons to addictive drugs, which may with repeated exposure lead to addiction or cause toxic brain damage. The enactment of National Human Subject Welfare Act to cover all human subjects enrolled in research, whether supported by Federal or private sources of funding. This act, and I want everybody to pay attention to this, this act brings protections to human beings at least to a comparable level to the protections available since 1966 for animals through the National Animal Welfare Act. That means if we just take the National Animal Welfare Act and substitute ``human beings,'' human beings will have greater protection because in this country you cannot conduct an experiment on animals, regardless of the source of funding, regardless of the site of research conducted without going through, applying the requirement of the Federal regulations. That is not, ladies and gentlemen, the case with human beings. There is a lot of research, tens of thousands of patients in research experiments are not regulated, and he just gave you one of thousands of examples. Three; a prohibition of conducting above minimal risk experiments on those incapable of evaluating the risks or appreciating the consequence to themselves unless they can be demonstrated to be in their interests. Mental capacity should be assessed by an independent physician and informed consent procedures should be monitored by independent observers. I'm very pleased to see NBAC and Dr. Oldham himself say that's an appropriate way of evaluating that. When I stated that in 1993, that was considered a heresy. Four; establish an independent, community based, that's important, review board to provide oversight for research involving vulnerable human beings. Protected classes must be represented whenever such individuals are being considered as subjects, and investigators must be held accountable for the conduct of the research and the well-being of human subjects. Let me tell you something about IRBs. IRBs are employees of the research institution. They get their paycheck monthly from that research institution which is trying to get millions of dollars from the pharmaceutical company and Federal Government. There is an inherent conflict of interest in that design. Five, require no fault liability insurance for every human subject of research to cover, this should satisfy Congressman Mica this is not a Federal bureaucracy, require the human subject research to cover, that is no fault liability insurance to cover the duration of the research and 1 year following completion of the research. We believe such insurance, in the amount of about $250,000 per subject, would be an incentive to reduce unnecessary risks and would compensate individual families for undue harm. It would also reduce the taxpayers' burden for uninsured persons who may require costly aftercare as a result of experimental adverse consequences. In closing, Mr. Chairman, the current state of protection for the vulnerable among us is very poor and it requires Federal regulations to strengthen, close the loopholes and mandate accountability for the harm done to our citizens and I thank you, Mr. Chairman. Mr. Mica. Thank you. [The prepared statement of Dr. Shamoo follows:] [GRAPHIC] [TIFF OMITTED] T6523.061 [GRAPHIC] [TIFF OMITTED] T6523.062 [GRAPHIC] [TIFF OMITTED] T6523.063 [GRAPHIC] [TIFF OMITTED] T6523.064 [GRAPHIC] [TIFF OMITTED] T6523.065 [GRAPHIC] [TIFF OMITTED] T6523.066 [GRAPHIC] [TIFF OMITTED] T6523.067 [GRAPHIC] [TIFF OMITTED] T6523.068 [GRAPHIC] [TIFF OMITTED] T6523.069 [GRAPHIC] [TIFF OMITTED] T6523.070 [GRAPHIC] [TIFF OMITTED] T6523.071 Mr. Mica. I would now like to recognize Ms. Sherry Grenz. She's with National Alliance of Mentally Ill. You are recognized. Ms. Grenz. Thank you. I'd also like this to become part of the official record. Mr. Mica. Your entire statement will be made part of the official record without objection. Ms. Grenz. I apologize for leaving out the names of the dignitaries. I just heard about these hearings about 2 days ago on the Internet, so once again, I apologize if I left anybody's name out. My father recently died from a stroke and he developed depression during these last painful years of his life. My mother has Alzheimer's type disease. My uncle is mentally retarded, and my brother suffers from schizophrenia. I am a primary caregiver for all. So given my family background, you can certainly see why research is so very important to me. I am the first vice president of the National Alliance for the Mentally Ill of New York State, the largest family consumer organization in the country. We have tens of thousands of members nationally, more than 8,000 in New York State alone. I am president of the Albany chapter, and I was also the only citizen advocate to serve on the New York State Department of Health's work group charged with developing research recommendations for protected classes. The months I spent as a member of this prestigious DOH task force gave me the opportunity to learn in detail about ethical issues of research with persons too incapacitated to give consent themselves. It also sensitized me to the enormous variety of ways in which ethical issues present themselves in research studies. I was particularly interested to learn that many of our mentally ill loved ones feel quite strongly about participating in research studies, so future generations don't have to suffer as they have. You know just because someone is mentally ill doesn't mean they are incapacitated all the time and incapable of being altruistic like many others of us in the population. So I come here not only with a deep commitment to helping those who are mentally incapacitated, but with a solid background of knowledge in trying to deal with these complicated issues as well. I want to emphasize that I am not a professional and I am not speaking on behalf of any group or person other than myself. Now, let me just briefly share with you a story about my brother. I call him Steven in the testimony but that's not his real name. I assume that's acceptable, right? Yes, he did. Well, Steven was a handsome, outgoing young man who was so smart that he skipped 2 years in school. He was on the school football team and liked by his teachers and peers alike. His future looked bright and promising. However, while Steven was still attending college we noticed a startling change in his personality. He insisted that people were staring at him and making derogatory remarks behind his back. Well, things quickly started to unravel after that. Many months and many doctors later we were told that Steven suffered from one of the most serious mental illnesses known to man, paranoid schizophrenia. Our hearts were broken. His life was destroyed. For the next 25 years, Steven was in and out of hospitals, lived on the streets of New York City where he was often beaten and robbed, and lived a life that was controlled by the terror and the demons in his head. His future looked bleak. Then about 7 years ago I received a call from my parents who were living in Queens at that time telling me that Steven said he could not take it anymore and would be willing to go to a hospital if I could find a place that would treat him with dignity and give him a chance at a better life. He had heard that there was some promising medications out here, ones with less unpleasant side effects. He was desperate and so were we. Through my years in NAMI, I gained a wealth of people to network with, and as I called around and found out more information, it was suggested that I call this facility that had a wonderful reputation with NAMI folks, the New York State Psychiatric Institute, PI. Many NAMI people told me of their positive experiences with this institute, but I decided to find out for myself to be sure. Well, after days of filling out endless forms and participating in many interviews, Steven was hospitalized in the schizophrenia research unit at PI and enrolled in a research protocol. For the first time in years we dared to hope again. Steven received a thorough mental health workup as well as an outstanding physical workup. Sadly, families have found out that once our relatives are diagnosed with a mental illness and get into the system, their general health care is often neglected, leading to a significantly shorter life expectancy and this fact has been substantiated by those having done research on this matter. What this extensive health workup turned up was something we never dreamed of. Steven had a tumor on his kidney and it was cancerous. We were shocked. Specialists were called in and informed us that there was no choice but to operate, but Steven refused. In a psychotic state, he proclaimed he would only agree to surgery when he felt the pain of the advancing cancer. The oncologists and psychiatrists explained to him that by the time he felt this pain it would be too late, the cancer would have spread to his spine, but Steven still refused to cooperate. Out of desperation I came up with the idea that perhaps if we gave Steven something as innocuous as Epicac, the stuff that you gave to kids to make them throw up, he would be convinced that he was sick enough and agree to the surgery. Well, PI adamantly refused to allow such a plan to take place, of course, but they continued to spend endless hours with Steven patiently explaining to him the seriousness of his situation. They also spent many hours with me and with my parents, compassionately offering us the support and information we needed. Then 1 day miraculously Steven agreed to the surgery. The surgeon found that the cancer on his kidney was totally encapsulated and removed the kidney. Chemotherapy was not needed. The point I was making is that the thorough work of the physicians at PI literally saved Steven's life and that none of the many doctors that Steven had seen on a regular basis over the years even picked up on this problem. Sometime after that, Steven was readmitted to PI, tried on Clozapine, a new type of medication that was discovered through research only a few short years ago and joined the world of the living once again. All is thanks to the wonders of research and the dedication and medical excellence of those at PI. You know, I would like to quickly add something else to the testimony at this time that I think is very important. In light of the outstanding treatment my brother received at PI, I was really shocked to see the horrendous story that appeared in the New York Post. What the Post reported was really in total contrast to what my family and many other NAMI families experienced and believe me, I would never, ever support any person or research institute that conducted research in an unethical, dangerous, or cruel manner. What compassionate person would? I even tried calling the Post on several occasions to give them my perspective and share several NAMI families' experiences with them, but curiously my calls were never returned. As a member of the DOH task force on protected classes I received a report from OPRR which they addressed here saying that these New York Post allegations were unfounded and untrue. As I understand it, and it's been confirmed they even went on to say that the research being done at PI is to be of the highest caliber, so I'm still struggling to find out what this is really all about. Well, to wrap it up, the story of my brother's positive experience participating in a research program of PI is of course my own personal story, but I don't think it's unique. Of course we must always strive for the highest of standards, particularly when it comes to vulnerable populations and we advocates have to be ever vigilant to be sure that all research studies are done in the safest way possible with the least risk possible and the truth is that in any profession, be it judges, lawyers, doctors, even legislators, there is an occasional negative experience or bad apple that surfaces, but it's not reasonable to paint every one in every given profession with the same brush. Mistakes should not and must not be ignored, but let's not throw out the baby with the bathwater. Where would we be without the benefit of research; all research, cancer, diabetes, heart disease et cetera. After all, who of us has not had a beloved family member or friend who has been stricken with one of these devastating illnesses? Please remember, research is our hope for the future. Thank you. Mr. Mica. Thank you for your testimony. [The prepared statement of Ms. Grenz follows:] [GRAPHIC] [TIFF OMITTED] T6523.072 [GRAPHIC] [TIFF OMITTED] T6523.073 [GRAPHIC] [TIFF OMITTED] T6523.074 [GRAPHIC] [TIFF OMITTED] T6523.075 [GRAPHIC] [TIFF OMITTED] T6523.076 [GRAPHIC] [TIFF OMITTED] T6523.077 [GRAPHIC] [TIFF OMITTED] T6523.078 Mr. Mica. We'll now hear from Ms. Charisse Johnson of Brooklyn, NY. Welcome, and you're recognized. Ms. Johnson. Thank you, Mr. Chairman, and committee members who extended this invitation to me to testify at this public hearing---- Mr. Mica. If you could pull that mic up as close as possible. Ms. Johnson [continuing]. ``Do Current Federal Regulations Adequately Protect People who Participate in Medical Research?'' If my family's experience is taken into consideration, then there are really no protections for people like my family from the outrageous behavior for some researchers who are supposed to be regulated by State and Federal laws. How else can you explain the use of children as young as 6 years old by researchers? How did they decide that he and 33 other healthy African-American and Hispanic boys were perfect subjects for the experimentation for the dangerous drug fenfluramine? As you're aware, fenfluramine is the dangerous half of fen- phen, a diet drug taken off the market because it causes heart valve damage in adults. I later learned that these researchers specifically set out to experiment with African-American and Hispanic children while excluding white children. My involvement with this nightmare experience started in 1992 when my 16 year old son became a first time juvenile offender. I did not know how the juvenile justice system worked or exactly what to expect. A few months after my 16 year old son was sentenced to juvenile detention I was contacted by experimenters. They requested my involvement in a study being conducted at the New York Psychiatric Institute Columbia University by Danny Pines and Gail Wasserman and other experimenters. At first I did not understand how and from what source they obtained my name and knew I had a 6-year old son. I later came to the conclusion that this information came to them because of my 16 year old son's involvement with the juvenile justice system. Needless to say, I decided to cooperate with the experimenters. I felt at the time that if they could find me and knew I had a 6-year old son they had enough power to affect the well being of my 16 year old son who was being held in a detention facility. This started a series of visits by my 6 year old son and myself to the campus of Columbia University, where we were subject to a series of intimate, degrading questions, tests and interviews. The experimenters also took advantage of my fear for the well-being of my 16 year old son to intrude on my privacy of my home. Sometime in 1994 the experimenters Pine and Wasserman and the team decided it was time to take off the kid gloves and give the drug fenfluramine to my son, who was a normal healthy happy go lucky child until that day. Since being given fenfluramine by experimenters, my son and my family have suffered tremendously and continue to suffer. About 2 weeks after he was given the drug he started having sharp painful headaches. Then as the headaches became more unbearable, he started having anxiety attacks and hyperventilating. He would start gasping for breath as if he couldn't breathe, as with someone who was having an asthma attack. I then imagined that maybe he had asthma and took him to the doctor. The doctor after completing tests on him concluded that he did not have asthma. Nonetheless, the headaches, the anxiety attacks and the hyperventilating continued. Later his condition would only get worse. He started having horrible nightmares. He would wake up in the night screaming, thinking that someone was in his room. To this day my son continues to suffer the severe consequences of the reckless disregard for him as a human being by these experimenters. To them he was just another guinea pig. It may be asked by some why would you participate? I would answer the question by posing a question of my own. If you were in my position, had a son who was a first time offender in the juvenile system and out of nowhere people started writing you for information about your family, maybe you think that they had enough power to affect the well-being of your son who was locked up in the juvenile facility, what would you have done? If they did not give you a true explanation of the drug fenfluramine, if you had never heard of such a drug, if they also presented themselves as doctors who you have been thought to think only act in the best interests of you and your family, if they are operating out of the well known institution of Columbia University, I suspect that a lot of parents would be likely to cooperate with these seeming good doctors not knowing that they may be dealing with Dr. Jekyl and Mr. Hyde. At the end of these experiments, they did not have the human decency to admit that my son was used as a guinea pig for their selfish purposes. Requests by my attorneys for my sons records were met with refusals for 9 months. It was only after the involvement of the dedicated staff membership from the congressional committee office that the records of my son's experiments were finally realized. The records confirm that the nightmare experience was indeed a nightmare. Thank you. Mr. Mica. Thank you for your testimony. I'd like to thank all of our witnesses on this panel. A couple of quick questions. Mr. Zucker, you have reviewed the recommendations of the Bioethics Advisory Commission for protecting human subject research involving mentally ill patients. Do you have any additional recommendations other than what you provided us with? Mr. Zucker. We may be able to provide you with some additional recommendations. And I can, if I could take the liberty of submitting an additional statement. Mr. Mica. Would you recommend that these be instituted by statute or by regulation? Mr. Zucker. I think that it is important that the Congress act and enact statutes. First recommendations were imposed by the Belmont commission, they were proposed and they were defeated; there were special protections for other vulnerable groups. I am afraid in 20 years from now if the Legislature does not act, then we will be looking back at the impact of the Board in an unfavorable light. I think there are some key principles that the Congress could enact and I've made some proposals in my written testimony along those lines. Mr. Mica. Thank you. Dr. Shamoo, one of the members, I read the entire testimony but one of the Members' remarked sort of echoed yours in this June hearing over a year ago, that rodents, he said, had more protections than human beings, and you sort of echoed that in your testimony. You also said that some of the protections that are in law for an animal you could substitute human being. Would that in fact be adequate or would you certainly have to massage other language? Mr. Shamoo. Absolutely. I was sincere in that comparison. It was the first time I gave written testimony to 1995, I mentioned those facts. For example, in animal research, there is monitoring, there is audit at this time, there is inspection of the facilities. None of that exists for human beings, and the most important difference, that no matter what site of research is, who the source of funding, anywhere in the United States, you must comply with the Federal regulations. That is not the case, and I don't know what the percentage is, but I will guesstimate somewhere around 30 to 40 percent of all human subject experiments are not subject to any regulations in this country. Mr. Mica. Dr. Zucker, you said I think the Bellevue case, where you had sought to file a complaint with OPRR and that they said they had no jurisdiction. There's no other source for you to appeal to? Or can you file a complaint? Mr. Zucker. They referred the matter to the Food and Drug Administration. Mr. Mica. They did. Mr. Zucker. They did. It's unclear to me what has happened to the complaint in the Food and Drug Administration because it's my impression this is not the sort of investigation they normally conduct. We are also pursuing a complaint with the New York State Department of Health. Mr. Mica. So at the Federal level, you feel there's inadequate overall jurisdiction, and that should be specified by law? Mr. Zucker. I think so. OPRR does have, I think it is the agency within the Federal Government with the most expertise in overseeing the operation of institutional review boards, and it seems ridiculous to expect FDA to replicate that expertise within the FDA. Mr. Mica. It seems to be it would be better to have the most expert agency review complaints of this nature. And I would imagine both of you, dealing with either children or mentally ill individuals, would want to have some extra protections instituted or legal procedures that would be closer to follow, is that correct? Mr. Zucker. That is correct. In my written testimony I propose some statutory language and I'd be happy to work with your staff to fine tune that or to develop that. Mr. Mica. I thank you both. I yield now, if I may, to Mr. Towns. Mr. Towns. Thank you very much, Mr. Chairman. Let me thank all of the witnesses for their testimony. It was very enlightening. Let me ask you too, Mr. Zucker, in your testimony, you noted that the definition of the word ``condition'' was a pivotal concern in OPRR's failure to discipline New York State Psychiatric Institute. Could you elaborate on why the redefinition of the word ``condition'' as used in this decision would serve as a dangerous precedent in the future? Mr. Zucker. I think so. I mean, to really understand this, I think you have to contrast what OPRR said and did with the research that was occurring at Mt. Sinai and the results that were reached at PI, which are very hard to reconcile. Mt. Sinai was sharply criticized for putting so-called normal control children in a fenfluramine challenge, because it was said these children did not have a condition, and therefore, it was wrong to subject these children to the risks of a fenfluramine challenge. OPRR then turned around and said that it was OK to subject the children--the young minority boys at the Psychiatric Institute to the very same risks, because they were not normal controls, they were poor children who had an older brother who was a juvenile delinquent and some people thought maybe their parents weren't such great parents. That was the criteria. In a city like New York, I mean, they said it themselves. 90 percent, 98 percent I believe PI says of the children in the juvenile delinquent system in New York City are apparently minority children, so that if the law can be interpreted the way OPRR is now interpreting it, it means that minority children in New York don't have the same protections as middle class children who don't, presumably will not be labeled as coming from an adverse child rearing environment, and I don't think we want to create a two-tiered, class-based system that has a disparity impact on race in the major cities that after all where is this research primarily occurring, it's occurring in New York, Chicago, Los Angeles, in cities which large minority populations and where there's going to be a disproportionate number of minority kids found in the juvenile justice system. So I think Congress has to say that as a matter of public policy, this is not an acceptable interpretation of Federal law, that if you can't do this to middle class kids who may be largely white in a lot of communities, then you can't do it to poor children who are going to be predominantly minority children in the major cities where the research occurs. Mr. Towns. Thank you very much. Ms. Johnson, let me ask you, let me begin by first, wanting to express my sympathy for the ordeals that you and your son went through, and also to commend you on coming forward to testify, because I think as a result of your testimony, I think you're going to save a lot of folks some pain and agony as a result of your stepping forward and to share that which happened to you. As to the side effects that your son has experienced since his participation in the experiment, has your son been offered any treatment or assistance by the researchers? Talking about the New York State Psychiatric Institute or anyone affiliated with the organization. Ms. Johnson. No. Mr. Towns. I was concerned about the way in which you and your son were recruited as well. I thought that the juvenile court records were supposed to be confidential records. Ms. Johnson. Right. Mr. Towns. That was my impression. Ms. Johnson. Mine, too. Mr. Towns. Purely by releasing the names of you and your son to researchers, the confidential nature of those records, I think was breached. Were you ever told by the researchers, by the juvenile court or family court or any of the authorities that if you refused to participate, that refusal would in no way affect the case of your older son who was in the juvenile detention facility, were you ever told? Ms. Johnson. No. Mr. Towns. They never told you that? Ms. Johnson. No. Mr. Towns. So you probably just sort of felt it was important to cooperate, because you wouldn't do anything to further bring about harm to your older son. Ms. Johnson. Sure. Mr. Towns. Were you afraid that by coming forward you would place your older son in jeopardy, that you felt if by not coming forward, that would be a problem? Ms. Johnson. That's what I felt. Mr. Towns. So that's like a little form of intimidation. Representatives of the New York Psychiatric Institute have testified that the overwhelming majority of children in the study had behavioral problems. Did your son have any kind of behavior problems before he participated in the study? Ms. Johnson. None whatsoever, no. Mr. Towns. Were you told at any point in time that your son, who was 6 years old at the time, that the drug they were going to put him on had never been tested with anyone under the age of 12, never been tried on them at that time, were you told that? Ms. Johnson. No. Mr. Towns. Well, let me just say, Mr. Chairman, I think this further points out that we have to act in Congress in order to make certain that people are protected, and that I think the only way we could do that is by legislation, I think if we leave it out there loosely, I don't think the protection that's needed will come about. So I want to thank you very much for sharing and also to say also to Ms. Grenz that I really appreciate your coming forward and sharing as well, because here you have several situations wherein you feel yourself responsible for and I think that people might not be able to make the decision as to whether or not they should be involved in a research kind of setting, and you would be called upon, and I think being called upon to make those kinds of decisions without having all the information is not fair. So whether it's in your case, I think that you point out to us that you need to have information in order to be able to move forward, and I got that from your testimony, that it's important to have this data so you could make the decision as to what should happen from that point on. I guess the last one I sort of wanted to throw out there, Mr. Chairman, I guess that this is for Mr. Zucker. In your testimony you discuss washout. Do you believe that washout should be banned? Mr. Zucker. I think that would go too far, but I do think that washouts and placebos involve significant risks that are not therapeutic risks, and again, to bring it back to the situation at the Bellevue New York University School of Medicine study, there I think it was inappropriate there, because you had people who were coming into the hospital, histories of suicidal and other violent behavior, who either came to the hospital or were brought to the hospital because they were really in a psychiatric crisis and potentially dangerous, that to take those people and then put them on a placebo or just to wash them out of any medication and not to offer them care during that period, I think is unethical, because patients who come to the psychiatric hospital in crisis reasonably expect care. I think that they will have a very hard time understanding that it is a delusion, kind of a therapeutic delusion that when the doctor says would you like to participate in this experiment, that he's offering them something which is not in their best interests, which may allow them to suffer for weeks. There was a potential here. Everyone got a 1-week washout, and then some people were put on a placebo, and so continued to receive no medication and others did receive the experimental drug or another drug. Under those particular facts, I believe it is unethical to offer a washout and a placebo before you determine that you can't help this person using nonexperimental treatments that are readily available. Mr. Towns. Thank you. Thank you very much, Mr. Chairman. I really appreciate your coming to New York and having this hearing. I think it means a lot to a lot of people, because I think there's more going on, Mr. Chairman, than we really realize. I think that we feel the situation here, we read about an incident that occurred maybe in the newspaper, but I think that there's a lot more going on. I think that we have to sort of make certain that we put legislation into a new form, legislation that's going to help people, and I think there's a definite need to do that. When you think of a youngster 6 years old being put on a drug that not even the pharmaceutical company tested to find out whether or not it would do harm to anyone under 12, I mean, that to me is just something that should not happen in the United States of America, and Mr. Chairman, I think we have an obligation and responsibility to so provide. Mr. Mica. I thank the gentleman from New York for his persistence on this issue, and his leadership in Congress on this and many other issues, and I'm pleased to state that I've had the opportunity to work with him for many years, and we, when our side was in the minority, I've often cited Mr. Towns' respect for the minority and working with me as a Member at that time, in fact, I came in as a junior in Congress, and the respect with which he treated me, I thank him for that publicly and personally. And also for again his leadership on this issue. It is important that we fulfill our congressional responsibilities and oversight, as I said, and also legislatively to see that we have in place the adequate protections both under statute and regulation. We'll work with the administration to see the kinds of things that can be put into place and are put into place and don't have foot dragging on an area that's so important and where the public needs to be protected, not only the public at large, but particularly children, mentally ill and others who society must protect, so hopefully we can use this as a constructive basis to proceed and I know that knowing Mr. Towns very well, we will have additional followup to this inquiry that's taken place in New York today. There being no further business to come before this subcommittee, this meeting of this Subcommittee on Criminal Justice, Drug Policy, and Human Resources is adjourned. 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