The Rolls-Royce and the Túk-Túk
Over a year ago, sharing a cab on the way to the airport after a meeting at the NIH (National Institutes of Health), I had a conversation with two AIDS researchers about the Good Clinical Practice (GCP) guidelines for conducting clinical research. As soon as I got home I looked up the guidelines and was struck by the fact that, while these were supposed to be "universal" guidelines, they were obviously drawn up with the resource-rich world in mind. It seemed unlikely that the authors had asked anyone in Africa, Asia, Latin America or the Caribbean what they thought about these standards. I also recall hearing what these researchers thought were the "right" and "wrong" lessons to be learned from the HIVNET 012 trial (this was several years ago, shortly after questions about the study were first raised).
The "wrong lesson" to learn from HIVNET 012 is that it was a poorly executed trial with too many data irregularities, and that we need to "crack down" on trial sites in Africa and elsewhere until they can conform to the same standards found at a Hopkins or Harvard site.
The "right lesson" would be that HIVNET 012 was a pivotal trial that has saved thousands of babies from becoming HIV infected. While there were certainly irregularities in data reporting and recording, shouldn't the GCP guidelines pay more attention to the realities of doing clinical research in developing countries? And, if so, then shouldn't they be revised?
As a person with HIV, I want clinical trials to reflect the realities of how medications are used in the real world. While there is a role for high-tech clinical research, there is also a crying need for public health-based research that looks at interventions in settings where they will actually be used. This is exactly what HIVNET 012 did. I have no problem with the FDA setting GCP standards (or evaluating generics for use in other countries for that matter), but I do have a problem with taking a unilateralist approach to the development of such guidelines -- in other words, the FDA shouldn't simply hand down commandments from on high that determine what is good and what is useless research.
We need a collaborative process with significant input from researchers, regulators, and community in the developing world to help craft a revised set of GCP guidelines that can help produce desperately needed answers to some of the most crucial clinical questions. Simply satisfying a bureaucrat in Rockville who can't see beyond the checklist on his desk is not sufficient. While many of the components of the GCP guidelines are indeed essential for the conduct of quality clinical research everywhere and anywhere, there are still plenty of historical accretions that are included simply because, "that's the way we've always done it in the U.S., so that's how to do it everywhere else in the world."
The data discrepancies in the HIVNET 012 study never placed the basic conclusions of the trial into doubt and they never put any woman or child in jeopardy. What the current campaign to discredit the study may do is make it difficult to ever conduct similar public health-based research in the future, which would be a terrible disservice to people with AIDS or other diseases who need answers to questions about the real-world use of drugs and other medical interventions. Dr. Fishbein's crusade against the study makes him look less and less like a heroic whistleblower and more and more like an inflexible bureaucrat with little interest in exploring the complexities of clinical research outside of settings where he has his experience.
Women and their children living with HIV/AIDS need better and more interventions to treat HIV infection and prevent transmission. They also need to minimize the risk of developing drug resistance; to treat both mother and infant; and to protect the child while breast-feeding -- and these interventions must be evaluated in the settings where they will be eventually be used.
The NIH, FDA and other agencies concerned with the conduct of research need to convene a discussion about revising the GCP guidelines soon -- the world is much bigger than when these guidelines were first produced, and the sites in which studies are taking place are far different than what most regulators in the United States are used to. If we don't take this reality check, then obtaining key answers about how to treat and prevent HIV infection in the developing world will be put on hold until research sites in these countries finally attain the same infrastructure, resources and staffing found in Boston, New York or Los Angeles. We don't need to wait that long; we can't afford to.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.