Drug Trials Without the Drugs?
Luis Montaner, an AIDS researcher at the Wistar Institute in Philadelphia, Pennsylvania, received word last month from the National Institutes of Health (NIH) that a grant proposal he had submitted to stage a novel drug study in South Africa had come through peer review with flying colors. But rather than celebrating their success, Montaner and his collaborators find themselves all dressed up with nowhere to go: They can't afford the fare. They have been told that NIH will not pay for the anti-HIV drugs the researchers are planning to test.
Montaner's project, like several others in the pipeline, is caught in a kind of Catch-22. NIH's main AIDS branch, the National Institute of Allergy and Infectious Diseases (NIAID), wants to encourage research on the best ways to deliver AIDS therapies in developing countries, but it is concerned that the cost of buying drugs for such studies would swamp its research budget. This concern is spelled out in a draft document now circulating at NIAID, a copy of which has been obtained by Science. The document is sparking a spirited debate among AIDS researchers.
The draft policy states that the cost of purchasing drugs for clinical trials "would severely restrict the Institute's research capacity by limiting the number, scope, duration and focus of NIAID's international HIV-related research activities." It adds that only "under extraordinary circumstances" would NIAID foot the bill for test drugs. The document goes on to argue that it would be unethical to stop treatment when a trial ends. It says researchers should therefore be required to submit a plan "to provide appropriate care and [antiretroviral] treatment for study participants after completion of the trial." None of these requirements are new, the document notes: They simply formalize NIAID's existing policies.
Montaner's study crystallizes many of these issues. He is hoping to test whether there would be any downside to occasionally stopping anti-HIV drugs in a structured treatment program. If a stop-start regimen works as well as continuous treatment, patients could take one-third fewer drugs--which could amount to a huge cost savings in poor countries.
He says reviewers of his proposal and NIH staff members encouraged him to remove the cost of test drugs from earlier versions of his grant request. That means he would either have to find another source of funds to pay for the drugs or persuade companies to donate them, both of which he has just started to do. That wouldn't be a problem for clinical trials that are required for regulatory approval; companies are eager to donate drugs for such tests. But Montaner is planning to test regimens involving already approved drugs--and his study could result in cheaper treatments, which could cut into company profits.
Critical conundrum. NIH will fund an anti-HIV therapy trial at this South African clinic, but it won't pay for the drugs.
CREDIT: PER-ANDERS PETTERSSON/GETTY IMAGES
Montaner argues that "the drug costs should be addressed as any other research costs, as long as they're justified from ethical and research perspectives." Ed Tramont, head of NIAID's Division of AIDS, says NIAID will help investigators like Montaner find drugs, and he is exploring the possibility of a foundation acting as an intermediary with the drug companies. He agrees that "the incentive is not there" for companies themselves to donate drugs for such trials. And the requirement for post-trial treatment is an added disincentive, he says: "It's fear of an open-ended, longtime commitment."
Montaner isn't the only researcher facing such problems. An NIAID-funded drug testing network called the AIDS Clinical Trials Group (ACTG), in conjunction with the HIV Prevention Trials Network (HPTN), hopes to test the therapeutic effects of various combinations of drugs and assess whether patients become less infectious. Four companies have agreed to supply drugs for the study, which is scheduled to take place in 12 different countries. But the researchers still need two others, as well as backup drugs to help people who become resistant to the first-line treatments. "We're looking at donor agencies to cover the gap," explains the principal investigator of the HPTN study, Myron Cohen of the University of North Carolina, Chapel Hill. The cost could be substantial. Researchers are reluctant to use steeply discounted generic versions of the drugs because they want to avoid questions about potency and other manufacturing issues.
Both ACTG and HPTN are trying to figure out how to treat people after the studies end; neither has solved the puzzle yet. "Everybody wants to do the right thing," says Cohen. "We're trying to be good citizens, but it creates the situation where people may never get drugs."
AIDS immunologist Bruce Walker of Massachusetts General Hospital in Boston is facing similar difficulties. "Right now, there are plenty of groups like ours that are ready to treat people, and we can't get drugs," says Walker, whose study in South Africa has been on hold for a year. He is particularly worried that far-removed ethics concerns may affect "operational" research aimed at answering practical--and often unexciting--questions about how best to treat people in different settings. "The absurdity of the situation is that 95% of HIV infections exist in countries where you have minimal experience giving the drugs. There's a real problem here," he says.
Walker calls the NIAID draft policy "not very visionary," and he predicts that it will "stifle progress." And he takes strong exception to the suggestion that researchers must figure out how to provide treatment after a study ends. "We're letting a lot of people die because we're saying [you must treat] forever," Walker says. "We have plenty of people who were dying who are now alive because they're on therapy. People would rather be alive and faced with having to figure out what they're going to do in 3 years than be dead."
Tramont says NIH's Office of AIDS Research is now reviewing the policy. "It's very complicated," he concludes, "and has a lot of implications."
Issue of 23 May 2003,
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