Policy Memo for Masters in Public Healthreneo.kena87
To: Secretary General, Médecins San Frontières
From: Eric Goemaer, MD, Head, Mission for Médecins San Frontières, South Africa
Re: Moving forward after Maternal-to-Fetal Transmission Prevention Trials
Date: December 15, 1997
In February 1994, the Data Safety and Monitoring Board of the U.S. National Institute of Allergies and Infectious Diseases interrupted AIDS Clinical Trial Group (ACTG) Study 076. The preliminary data revealed a statistically significant and dramatic difference in vertical HIV transmission rates from mothers to their newborns, between women who received the active regimen and the placebo group.
The regimen quickly became the standard of care in industrialized nations, where no trial that would deny access to the ACTG 076 regimen or to a potentially equivalent intervention would satisfy the requirements of ethical review. In developing countries, however, the costs of the 076 regimen ($800 for the drug alone) put it out of reach. It was, therefore, a matter of some urgency that trials begin to determine whether radically cheaper alternatives could reduce maternal-fetal HIV transmission. The CDC and NIH launched nine placebo-controlled trials, all subject to careful ethical review, in developing countries.
Nevertheless, on 18 September 1997, Marcia Angell, executive editor of the New England Journal of Medicine, denounced the placebo-control trials in Africa, Asia, and the Caribbean. Citing the Declaration of Helsinki for authority, she noted that control groups had to be provided with the best current therapy, not simply that which was available locally. Angell argued, “The justifications are reminiscent of those for the Tuskegee study: Women in the Third World would not receive antiretroviral treatment anyway, so the investigators are simply observing what would happen to the subject's infants if there were no study.”
For Angell and other critics, the only acceptable solution is equivalency trials—that is, research in which an alternative drug is compared to a gold standard. Unfortunately, no one has yet challenged the underlying issue, which is not how to ethically find a cheaper therapeutic alternatives but the profound injustice that denies women and children proven therapeutic regimens in the first place.
But then any trial to find a cheaper and potentially less effective regimen—whether placebo controlled or not—would have been unethical as well. To the extent that the search for a less costly and potentially less effective intervention could be justified by the desperate need to find affordable interventions, the analogy to Tuskegee entailed a gross distortion.
Stationed as I am in South Africa, I have a frontline view of an unfolding humanitarian catastrophe. I find that this controversy gives me great pause and, more critically, requires our organization to speak out on a controversy that will have implications for the future of the epidemic. Given our commitment to ethics, the critiques raised by Angell and others are hardly academic. Yet I am concerned that attention methodological issues distracts from more fundamental questions. Regardless of what form a clinical trail takes, what is at stake is whether or not to develop a cheaper, more accessible therapy.
Issue: The question is whether our charter, which champions universal medical ethics and the right to humanitarian assistance, is best served by the development of cost-effective, pragmatic alternatives or advocacy for the highest standard of care available in developed countries.
Options: I see three quite different yet philosophically consistent alternatives for Médecins San Frontières:
1. Advocate for the investment of resources (and devote our own resources) to the distribution of the effective medication that is currently available in developed countries.
2. Recognize that the current infrastructure in most developing countries is not appropriate for adequate delivery of the current gold standard and focus both our finical and political resources on increasing access primary health care, with a focus on creating antenatal clinics where women can give birth; without investment in such settings the currently available therapy cannot be delivered to developing nations.
3. Address the current public health emergency by publicly supporting testing for affordable, feasible drugs in as short a timeframe as possible with an emphasis on placebo-control trials.
All three of the options easily fall within the mission of Médecins San Frontières. Prioritizing one does not exclude the others. Indeed, all three of these strategies will compete for resources in the coming years. For this very reason, I argue that it is imperative for the MSF to clearly prioritize these strategies.
In order to best serve populations in distress we must develop drugs suitable for the current context in which people are suffering and dying.
It would represent utopian thinking to argue, at this moment, that women in developing countries could be said to have a realizable claim on the care available in industrialized nations. While endorsing placebo-control trials now, we do not shut the door on the other two options. But in advocating for these trials we feel that we do help to effect a structural change in research standards designed for an entirely different set of circumstances—for groups within populations where the chief barriers to the standard of care for any disease and condition are a matter of political will, not infrastructure or resources.
Pursuing placebo control trials at this moment does, of course, take resources away from the distribution of currently available medication. But given the therapeutic regimen involved access to medication six months prior to delivery, intravenous medication during delivery, and treatment of the infant postpartum I have concluded that it is simply not realistic to make available a drug in contexts where the current distribution system is woefully inadequate. Indeed, the kind of access to the gold standard simply cannot be achieved in advance of option 2, which involves basic health care infrastructure development.
Our current priority on developing cost-effective, deliverable medications need not stand in the way of creating a health care infrastructure in poor countries, with an emphasis on antenatal care clinics. Indeed, it is entirely compatible with that goal. Nonetheless, we have to prioritize and feel that given the humanitarian crisis that is AIDS our first emphasis needs to be placed on drugs that can feasibly be made safely available even in current circumstances. We can’t wait.
No doubt this course will open us to the criticism that we continue to allow the exploitation of women. Yet it is very poverty of the nations within which these women live serve as a predicate for questions relating to both research and access. Further this decision does not, of course, relieve researchers from adhering to ethical guidelines appropriate for all contexts. However problematic the efforts to obtain informed consent in the Third World, investigators clearly made efforts to inform the enrolled women that they would be part of a study to reduce maternal transmission of HIV and that some would receive a placebo.