Thursday, March 08, 2007

Ethical Challenges: Microbicide Trials

From our blogger-scholar friend Sean Philpott. He is the Policy and Ethics Director of the Global Campaign for Microbicides, a broad-based, international effort to build support among policymakers, opinion leaders, and the general public for increased investment into microbicides and other user-controlled prevention methods. Dr. Philpott shares his thoughts on the recent microbicides trials:

Interventional studies designed to test new methods of preventing HIV transmission, such as microbicides, present a variety of ethical challenges. Researchers must ensure that locally acceptable means of preventing HIV and other STDs are available to all people who are screened or enrolled. Researchers also have a moral responsibility to ensure access to high quality care to all participants who seroconvert during the course of a trial.

When an prevention trial fails, as recently happened with Phase III trials of the candidate microbicide Cellulose Sulfate (Ushercell), researchers and trial sponsors are often accused of treating volunteers as guinea pigs. Worse yet, researchers may have to combat such rumors as the long-lived myth that participants are encouraged to have unprotected sex or deliberately exposed to HIV. At least two South African politicians have suggested precisely that. If anything, however, these two microbicide trials appear to be models of how transnational HIV prevention research should be conducted, through transparency and prioritization of participants’ rights.

In the CONRAD-sponsored Ushercell trial, 35 of 1,333 participants in both the experimental and the control groups seroconverted before the trial was discontinued. The rate of seroconversion was no greater than expected for at-risk women in these countries (48% of South African volunteers were found to already be HIV positive). There was, however, a slight increase in the rate of seroconversion in the experimental group. Although not statistically significant, researchers decided to stop the trial out of concern that Ushercell might increase risk of HIV infection. A second study, conducted at two sites in Nigeria by Family Health International, was also halted even though there was no evidence of increased risk. In all HIV prevention trials some volunteers will become infected despite the intensive counseling and support services they receive to help minimize their risk.

Contrary to what is being claimed by some politicians and journalists, however all study participants went through comprehensive informed consent procedures in their own languages, with key messages reinforced at every visit (including the fact that they should not count on the gel for protection and should always use condoms). All participants received monthly counseling, free condoms, and prompt diagnosis and treatment for any curable STIs. Trial sponsors also developed written agreements with local providers to assure that any women who seroconverted would get care, including antiretroviral drugs as needed; the CONRAD trial included a ”set-aside” in the research budget to support long-term care and treatment for participants.

Although disappointed by the results, leading microbicide and community activists like the Global Campaign for Microbicides and the African Microbicide Advocacy Group (AMAG) have been unanimous in their support of the Ushercell researchers, and continued microbicide research. These groups have been following the conduct of these studies, and have been directly engaged in the design, oversight and review of these and other microbicide trials.

The Campaign and AMAG have also been a resource for those seeking answers from site investigators, sponsors, microbicide experts and information publicly available about the trials at http://www.global-campaign.org/cellulose-sulfate.htm).

4 comments:

BuddhistValkyrie said...

Woo Sean! (Ahem.)

Putting down the pom-poms for a moment, this is actually really interesting information, and highlights how important it is to go to the source of media reports, or at least to find a reliable source. As Sean notes, the media is having a field-day with the idea of immoral scientists running amok in poor, third world countries. (One Michael Crichton novel, coming up...) It's good to see that these fears are just baseless and unresearched, rather than any sort of systematic failure on the part of multiple agencies and IRBs.

Sean Philpott said...

Well, I wouldn't say that these fears are always baseless, and there's a lot of ethics capacity building to be done in many resource-poor countries to ensure independent review of clinical research trials. It's important for advocates and policymakers to provide the technical and financial resources to improve ethical oversight and review of transnational research trials.

It is also important, however, as you point out to consider the source of media reports. In a world dominated by Fox News and the Drudge Report, we shouldn't assume a lack of bias on the part of reporters, or politicians, or even researchers. Especially when one of the politicans claiming misconduct in this case is South Africa's health minister, Manto Tshabalala-Msimang, a woman best known for her resistance to a government-sponsored plan for treating HIV-infected South Africans with antiretroviral medications while simultaneously promoting the benefits of garlic and lemons in the treatment of AIDS.

BuddhistValkyrie said...

Well, I wouldn't say that these fears are always baseless,
It's a good thing that's not what I said then, eh? ;)

I've to admit that when I first read the reports, I actually did exactly what my post and your followup suggest a reasonable and intelligent person should not do - I trusted the source, nodded my jaded little head at the thought of unethical researchers and non-existent ethical oversight, did that little sigh of "exploited human guinea pigs in a third world country" and then moved on to the next news post. And maybe that says something in and of itself; a sort of sad comment that I'd expect the norm to be these abuses, and be surprised to find out that's not the case at all. Even though I know, perfectly well, what an awful source of anything our news actually is.

Jenny Withers said...

Although there is real and proven potential for human subjects to be exploited in clinical trials, especially in developing nations or among other vulnerable populations, I'm glad Dr. Philpott has pointed out that not every trial is a bioethicist's nightmare. I just finished researching a similar topic for an article: clinical trials of HIV vaccine candidates. After doing my research, I feel more sympathetic toward the "typical" person who is conducting these studies. Trial sponsors and organizers have been beleaguered with accusations of abuse of power, some justified and some not. A disturbing number of people now think that HIV studies are conspiratorial or that one can become infected with HIV by participating in a vaccine trial.* Not surprisingly, it's become difficult to find people who are willing to participate in or cooperate with the trials. When drug companies finally get a promising vaccine candidate into the kind of large-scale trial that's needed to show efficacy (thousands of patients required), the sponsors are obliged to make every reasonable effort to prevent HIV among the participants. That is necessary, of course, but the catch is that if very few people in the placebo group become HIV infected during the course of the study, there's no way to get the results that will prove that the vaccine candidate works. Implementing these studies really does seem to be the monumental task the sponsors make it out to be.

* M. Allen et al., Journal of Acquired Immune Deficiency Syndromes. http://www.thebody.com/niaid/2005/hiv_vaccine_survey.html