National Association for Rights Protection and Advocacy

Office of the Secretary
Office of Public Health and Science

December 8, 1999

                            Assistant Secretary for Health
                            Surgeon General
                            Washington, DC 20201

The Honorable Edolphus Towns
U.S. House of Representatives
Washington, DC 20515

Dear Mr. Towns:

Thank you for your thoughtful letter concerning fenfluramine challenge research conducted at the New York State Psychiatric Institute (Neuroendocrine Response to Fenfluramine Challenge in Boys; Platelet Serotonin 2A (5-HT2A) Receptor Characteristics and Parenting Factors for Boys at Risk for Delinquency: A Preliminary Report).

As you know, the human subjects protections component of the Office for Protection from Research Risks (OPRR) will soon become a part of the Office of Public Health and Science (OPHS) in the Office of the Secretary and will be reporting to me.  The Secretary felt that with the impending transfer and the importance of your letter, I should assume responsibility for addressing your concerns.  Again, as I conveyed to you earlier, I regret not being able to attend today's hearing in person due to previous commitments.  I trust that the response outlined below will adequately address longstanding concerns you and your colleagues have had about the issues raised in your letter.

First, let me address the issue of the OPRR investigation.  The OPRR conducted an extensive investigation that included (i) review of all relevant Institutional Review Board (IRB) records and detailed written reports from the Psychiatric Institute; (ii) consultation with experts in child psychiatry and the bioethics of human subject research; and (iii) interviews with institutional officials, more than 20 IRB members, and the research investigators.  Without exception, a review of all informed consent documents by a panel of outside experts validated the judgement of the OPRR staff.  OPRR determined that the research was conducted in accordance with Department of Health and Human Services (HHS) regulations for the protection of human subjects (Title 45, Code of Federal Regulations, Part 46).  After further review, I am confident that the OPRR exercised full and appropriate authority under applicable regulations and support its finds.

However, it is clear that you continue to have concerns with the finding.  I share your belief that every person, and particularly every child, who is involved in HHS-supported research be afforded the utmost protection mandated by the human subjects protections regulations.  I share your concerns about research that is conducted in populations that lack diversity, and in particular, about research that is conducted entirely in minority populations unless there is a clear and compelling reason to do so.  As you know, the Department has recognized the need to increase diversity of participants in clinical trials, and has taken many steps to accomplish this 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 needs of communities and is responsive to community concerns.

Moreover, we believe that no federally-supported research should be compromised by any selection of human subjects that is not supportable by clear and unbiased scientific explanations.  To this end, I will convene a group comprised of knowledgeable individuals who have not been associated with this investigation to examine the process in the context of the regulations, make recommendations, and provide me with a summary report.  I will contact you with the results upon completion.  We will move this process expeditiously and trust that the outcome will provide you with a high level of confidence that the matter has been fully and properly addressed.

Your letter also refers to regulations that are relevant to the fenfluramine study.  As you indicate, Section 46.406 of the regulations permits the involvement of children in certain research of greater than minimal risk only when the research "is likely to yield generalizable knowledge about the subjects' disorder or condition."  It appears that many of your concerns emerge from how the study in question applied the interpretation of this regulation in the conduct of the research and how such an interpretation might be applied in the future.

Currently, there exists a spectrum of opinion within the research and ethics communities about whether the presence of social, behavioral, or biological risk factors constitute such a "condition."  Since the applicable regulations were crafted, research has advanced to the point where it is not unusual for studies to include individuals who are at higher risk for a given undesirable health outcome.  Primary prevention can be an extremely powerful tool to block the onset and serious effects associated with a disorder or condition.

For example, a "healthy" woman may be a subject in a study because she has close relatives with breast cancer, and therefore may be at a higher risk for the disease.  Similarly, identifying childhood precursors to diseases of adulthood, such as hypertension or adult onset diabetes, may lead us to prevent the emergence of these diseases or associated diseases, in this case such as stroke.  This may lead us to study children who present a family history of high blood pressure to understand how that risk might affect them. It is our hope that we can push the frontiers of knowledge so that we can gain insight to help people from ever experiencing a health deficit, not just treat them when they become ill.

The Department has not previously issued guidance on this term in the context of these regulations and I agree that the term needs clarification.  A central element in the Secretary's decision to relocate the human subjects protections 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 protections in general.  This advisory committee will be known at the National Advisory Council on Human Research Protections (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 methodically examined, thus providing the best opportunity for an acceptable regulatory clarification that both protects human subjects and does not unnecessarily 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.

I appreciate your taking my call this past week and I look forward to working with you and your colleagues to continue to improve subjects protections in HHS-funded research.  A similar letter of response will be sent to the co-signatories of your letter.


                            David Satcher, M.D., Ph.D.
                            Assistant Secretary for Health & Surgeon General

For more information contact:

Cliff Zucker
Executive Director
Disability Advocates, Inc.
5 Clinton Square, Third Floor
Albany, NY 12207
(518) 432-7861 voice and TDD
(518) 427-6561 fax

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