Close-up of variety of pills [© Stockbyte\Getty Images](Close-up of variety of pills [© Stockbyte\Getty Images] )

When the AIDS activist group ACT UP staged a protest in 1988 in which it “seized control of the FDA,” it responded to widespread frustration with the agency. The FDA was seen as slow, bureaucratic and unresponsive to the plight of patients who needed better drugs—immediately.

Shortly afterwards, the drug approval process was streamlined and dying patients without alternatives were given early access to promising medications. For drugs given “priority review,” approval times dropped from just under three years in 1986 to as little as six months in 1995.

Now, however, many wonder if the FDA went too far in speeding up the approval process of drugs. Critics claim tragic failures like the approval of the painkiller Vioxx, which may have caused up to 100,000 heart attack and stroke deaths, are a direct result of prioritizing speed over safety reviews.

How AIDS changed drug approvals

The AIDS drugs story illustrates the complex challenges facing the FDA.

In 1988, there was only one AIDS drug—AZT. Activists pushed the FDA to rapidly approve the next drug, DDI; they didn’t want to wait for studies long enough to show that it saved lives, because long-term studies could last longer than the survival prognosis for many patients.

Instead, activists urged study of a “surrogate marker” of the drug’s effect on disease progression.  Researchers examined whether the medication could increase the number of disease-fighting CD4-cells.

DDI was approved under this testing regime—but the next drug, DDC, turned out to increase CD4-cells without improving survival.

“We lost faith in the marker,” says Mark Harrington, whose work in ACT UP on the FDA and other treatment-related issues led to his current position as Executive Director of the Treatment Action Group (TAG) and to serving on advisory panels to the FDA related to AIDS drugs.

When the FDA prepared to approve the first of a new class of drugs based on it, TAG urged caution. “Most of the people in the community didn’t agree and we were very unpopular for a while,” says Harrington.

Drugs in that new class—protease inhibitors—soon proved effective, and by the mid-90s the “AIDS cocktail,” which combines several drugs, had turned the condition from a death sentence to a severe chronic illness. Between 1995 and 1997, deaths from AIDS dropped by nearly two thirds.

Weaker standards

Loosening drug approval protocols may have dramatically increased the speed at which effective AIDS drugs became available, but now drug companies seeking approval for medications for much less serious conditions can utilize the weaker standards.

Vioxx was approved under these less stringent standards in 1999—and only after millions of people had taken it was research released showing that high doses quintupled the risk of heart attack compared to a similar painkiller, naproxen (Aleve).

“The arguments used for AIDS—which is a horrible killer—were extrapolated to other drugs. Some were appropriate, like cancer drugs—others [like Vioxx and similar drugs] were not. The abuse happened when drug companies made false analogies and were never forced by the FDA to do follow up research,” says Harrington.

The notion of surrogate markers and whether they really predict how well drugs work is an ongoing quandary.

“It’s fair to say that [at first] we didn’t have a complete understanding of the strengths of the FDA and the reasons why its practices were put in place,” says Harrington.

Consumer advocates and experts agree that the FDA needs to do a better job at evaluating drug risks and benefits before approval—and should require additional study afterwards.

Taking medications with minimal risk

So what can you do in the meantime to minimize risk from medications? The first thing is to be an informed consumer and be sure that the drugs you take are necessary and have not been flagged as potentially problematic. For example, the mild opioid drugs Darvon and Darvocet have been found to be no more effective than aspirin—and they can cause heart damage.

“Be careful with new drugs, particularly if other options are available,” says Curt Furberg, Professor of Public Health Science at Wake Forest University.

Some consumer groups advocate waiting seven years after approval of a new drug before taking it; by that time, any problems should have become apparent. But Allen Vaida, PharmD, Executive Vice President of the Institute for Safe Medication Practices, disagrees, noting that if everyone followed this advice, it would be worthless.