Let's Not Be Too Hasty

By Christine Gorman

Remember when AIDS activists staged die-ins on Wall Street, barricaded the doors at the Food and Drug Administration and threw smoke bombs at the National Institutes of Health? If there was a single, unifying battle cry among protesters, it was the charge that the Federal Government's delays in approving experimental treatments were responsible for killing thousands of desperately ill AIDS patients. Now, a mere two years after the FDA relaxed some of its standards and established a "fast track" to rush drugs from the test tube to the bedside, a growing number of activists are changing their minds. "We were naive," admits Spencer Cox, of the New York City-based Treatment Action Group. "There are standards for a reason."

Some activists have gone so far as to call for a return to a more thorough drug-testing process, even if it means postponing the approval of new treatments. Perhaps most stunning of all, the activists would agree -- under certain conditions -- to so-called placebo trials, in which some patients receive a sugar pill in place of an experimental drug. Just a few years ago, activists were unanimous in denouncing such traditional testing methods as unethical when it came to the treatment of AIDS. But then doctors and patients started to complain that the speeded-up approval process didn't provide them with enough information to make an intelligent decision about which drug to use.

The turnaround in thinking comes at a particularly crucial time, because pharmaceutical manufacturers are getting ready to launch a new group of anti- HIV drugs onto the fast track. Their success in doing so may hinge on the outcome of an FDA advisory-panel meeting that is taking place this week in Rockville, Maryland. Panel members are expected to consider the activists' criticisms and determine whether the agency's fast track has too many shortcuts in it and should be revamped yet again.

As originally conceived, the fast-track process makes a lot of sense. The goal is to streamline the necessary steps toward FDA approval so that they do not take years to complete. One way to accomplish that, the agency decided, was to accept preliminary evidence from small clinical trials rather than wait for final proof from a comprehensive study. Typically the trials consist of a few hundred people and last only a matter of months. In return, the pharmaceutical companies were supposed to conduct follow-up studies that confirmed their drugs' effectiveness after they were out on the market. The FDA held up its side of the bargain by approving two new antiviral drugs -- ddC and d4T -- but the follow-up studies have been delayed. Even so, it has since become clear that the treatments can trigger severe side effects. As a result, no one really knows if the drugs are worth the risk.

All the anti-HIV medications approved so far are chemical cousins of AZT, the first drug ever shown to put a damper on hiv infection, if only temporarily. AZT works by sabotaging an enzyme called reverse transcriptase that helps the virus copy itself. But the newest group of potential fast trackers, called protease inhibitors, interferes with a different part of the virus' reproductive cycle. Although protease inhibitors don't seem to slow down HIV for long, investigators hope a combination of an older AZT-like drug and one of the new pills could prove more effective than any single medication.

Under the accelerated approval plan, protease inhibitors could get the go- ahead from the FDA without much fuss within months. But members of the Treatment Action Group think they have a better idea. At this week's meeting of the FDA advisory panel, they plan to propose a large-scale, two-year to five-year study of the protease inhibitors. The study would include 18,000 participants, of whom all would receive standard aids care but only half would get a protease inhibitor; the other half would receive a placebo instead. Because so many people would be involved for a prolonged period, investigators would not have to depend on sketchy evidence but could accurately measure real clinical benefits, such as weight gain or longer life-span, to determine if protease inhibitors are an effective way to combat the AIDS virus.

It is tempting to point to the activists' change in philosophy as proof that their earlier zeal was misguided and dangerous to their cause. But the truth is that the entire AIDS research and medical community has been undergoing an intense period of reassessment. Activists were not the only people who assumed AIDS would quickly fall before some magic bullet molded by science. Perhaps, as that illusion fades, more realistic -- and successful -- strategies will slowly emerge.

With reporting by Dick Thompson/Washington