Just how long should the wait be before assuming that an answer to an important question will never be provided? It depends of course on the importance of the issue and the credibility of both the individual who is asking the question and the individual who is supposed to respond. In a letter written on September 10, 2010 to Dr. Amy Gutmann, Chair of the National Bioethics Advisory Committee, we expressed frustration that our concerns regarding the ethics of clinical research in vulnerable women and children in poor countries was ignored. (The September 10, 2010 letter is copied below). We felt that the issues were serious— withholding known effective HIV prevention and treatment from vulnerable women and children while conducting experiments that could not be conducted in the US. In spite of judiciously pointing out that the experiments had similarities to previous high visibility research that was deemed unethical, such as the Tuskegee and Guatemala studies (1,2), the response we received from the various individuals and the NIH was either absent, partial, or inadequate. No concrete measures were taken to thoroughly examine the issues or to prevent future abuses. In March, 2016 it was clear that our concerns were ignored. The NIH announced that an international research study (VRC01) would be conducted in over 4000 individuals with an experimental HIV monoclonal antibody that had no demonstrated efficacy in humans. Included in the study were infants at high-risk of perinatal HIV infection.(3)
From the very first letter in 2010 to the most recent letter sent to the IRBs who had approved the infant studies, with copies to the Presidential Commission, NIH, and OHRP, the clock kept ticking or as Randy Shilts , a San Francisco newspaper writer, author, and activist entitled his book on the AIDS epidemic, “And the Band Played On.”(4) As the clock “ticked” the precise number of individuals that would be adversely impacted by the monoclonal antibody study and by all of the studies that were conducted between our initial letter to the National Bioethics Advisory Committee until now is difficult to calculate. A reasonable estimate would be several thousand but it is likely to be even an order of magnitude greater. However, even if the number were only 10 it would be too many lives that were unnecessarily placed at risk of acquiring a fatal HIV infection or if already infected, would progress to AIDS and death without the benefit of highly active antiretroviral therapy (HAART).
Concluding that six years was much too long to wait for a response we took the opportunity of the announcement of the VRC01 study to point out that unethical studies were not only continuing but they were discriminatory against women and children in poor countries by ignoring US government rules for conducting research in vulnerable populations. Our position is articulated in our September 16, 2016 post (http://ethicsinhealth.org/?p=679). We are not certain what it will take to finally get the attention of the individuals and organizations who are responsible for insuring the ethical integrity of clinical research whether conducted in the US or in resource poor countries. Articles written by “insiders” who claim that all NIH research is ethical without agreeing to a thorough outside review of the clinical research approval process before reaching such conclusions must be questioned. Until then we will be certain that the clock remains wound up.(5,6,7)
1- Invoking “Tuskegee”: problems in health disparities, genetic assumptions, and history. Reverby SM. J Health Care Poor Underserved. 2010 Aug;21(3 Suppl):26-34.
2- Restorative Justice and Restorative History for the Sexually Transmitted Disease Inoculation Experiments in Guatemala. Reverby SM. Am J Public Health. 2016 Jul;106(7):1163-4.
3- NIH launches large clinical trials of antibody-based HIV prevention. 2016. https://www.eurekalert.org/pub_releases/2016-04/nioa-nll040716.php (accessed September 12,2016.
4-Shilts R. And the Band Played On. New York, N.Y.: St. Martins; 2007.
5- Toward a New Era of Trust and Transparency in Clinical Trials. Hudson KL, Lauer MS, Collins FS. 2016 Sep 16. doi: 10.1001/jama.2016.14668.
6- The ethics of expanding access to cheaper, less effective treatments. Persad GC, Emanuel EJ. Lancet. 2016 Aug 27;388(10047):932-4
7- The unintended ethics of Henry K Beecher. Stark L. Lancet. 2016 Jun 11;387(10036):2374-5
September 15, 2010
Amy Gutmann, Chair, National Bioethics Advisory Committee
Office of the President
The University of Pennsylvania
1 College Hall, Room 100
Philadelphia, PA 19104-6380
Dear Dr. Gutmann,
We are contacting you to express our deep concern regarding ethical issues in certain clinical research studies conducted by the National Institutes of Health in resource poor countries. Our purpose is to determine whether your organization will assist in investigating current NIH practices in designing research studies in resource poor countries among vulnerable populations. We have been unable to receive a satisfactory response [from NIH].
We believe that there are specific instances that result in harm to vulnerable women, men and children placing them at risk for HIV infection and disease progression. This is a matter of urgent concern as outlined in our most recent letter to NAIAD (attached). Our first inquires were initiated in 2009. The responses have been unacceptable slow and incomplete and do not adequately address the issues we raised. Below is a brief summary of our concerns.
In the past the NIH has distinguished itself by conducting highly ethical clinical research when enrolling individuals that are particularly vulnerable such has women and children in resource poor countries, maintaining high ethical standards and informed consents. These studies provided benefit to research subjects and significantly advanced public health throughout the developing world. Our concerns relate to what appears to be a deviation from previous high ethical standards:
NIH has deviated from previously high standards of conducting clinical research in resource poor countries by allowing comparison study arms of inferior treatment placing vulnerable study subjects at risk for HIV infection and disease progression.
NIH has ignored the results of its own studies and the recommendations of international organizations such WHO, the International AIDS Society and the US PHS to conduct clinical research sties which fail to offer standard of care to study participants.
NIH has not provided evidence that research study participants have been provided with updated information on treatment advances de facto withholding information for an informed decision.
NIH does not believe that there is a conflict of interest in the decision making process of approving research studies. We disagree. There is an inherent conflict of interest when decisions are made by a small group of research investigators who are themselves funded by NIH.
The justification that we have received from NIH for allowing research which provides inferior treatment to research study participants is as follows”
“We believe it is ethically appropriate in certain cases, for research to deviate from international standards in order to generate critical data to improve health in resource‐limited settings.”
“This is in keeping with the principle that clinical research studies that do not provide interventions recommended by international guidelines may be justified by public health value of the knowledge to be gained.”
We would like to point out that NIH acknowledges that it is providing inferior treatment in some of its research studies. Their rational is not an acceptable ethical standard for conducting research in resources poor countries for the following reasons:
This argument ignores an individual’s right to participate in clinical research trials that offer standard of care.
Study participants are not informed that they may be receiving inferior treatment as defined by international standards of care.
The rationale deviates from the mission of NIH to conduct research that elevates or exceeds standard of care for maximum public health benefit.
The rational places NIH in the position of supporting national policies that fail to protect individuals within a country. NIH should not be in the position of compromising its own high standards by proving data to support inferior health care delivery thereby inappropriately lending its authority to failing ministries of health, acting as an accomplice to the ongoing delivery of inferior treatment and compromising the health of individuals within its purview.
NIH, or individuals within NIH, have determined that they can ignore international recommendations of standard of care jeopardizing the lives of thousands of research study participants.
We respectfully request your consideration of this matter.
Arthur J Ammann MD President
Kerry Gough JD
Director and Legal Counsel on Gender and Justice
The following individuals and organizations have been sent the attached letter.
Harvey Fineberg, President, Institute of Medicine
Don Wright, Office of Research Integrity, U.S. Department of Health and Human Services
Amy Gutmann, Chair, National Bioethics Advisory Committee
Previously sent to:
Carl Dieffenbach Ph.D. Director, Division of AIDS
National Institutes of Allergy and Infectious Diseases