AIDS Crisis Sparks a Quiet Revolution : Health: Clinical trials of new drugs, once mostly limited to white males, are now reaching out to other sorts of people.

Only a decade ago, critics of the therapeutic drug-approval process complained about a “drug lag.” Because of the strict regulations of the Food and Drug Adminis- tration, many drugs were marketed abroad long before they were approved for American patients.

Today, the pendulum has swung so far the other way that many people are worried about a “drug leap.” Driven by the urgency of finding treatments for people with AIDS and the human immunodeficiency virus, the FDA has lifted regulatory barriers. Promising but largely untested drugs will be made available to desperate patients who are ineligible for or unwilling to be enrolled in controlled clinical drug trials. The FDA recently made the antiviral drug AZT available to children suffering from AIDS.

But while the headlines focus on speeding up the drug-approval process, another, quieter revolution is under way. Many people who were previously considered too vulnerable to be research subjects stand to benefit most from a loosening of rules on who can participate in clinical trials. Pregnant women and women of childbearing age; infants and children; prisoners; current or former drug users; members of racial or ethnic minority groups; poor people--all traditionally excluded from research trials but hard hit by AIDS and HIV.

Restrictions on who could participate in clinical trials were a reaction to scandal and abuse. In the early 1960s in Europe and Australia, thousands of pregnant women were given thalidomide as a sedative; many of their babies were born horribly deformed. That disaster was largely avoided in the United States because of a cautious FDA official who refused to accept the drug companies’ safety data. In 1966, Henry Knowles Beecher, a highly respected Harvard University anesthesiologist, published an eye-opening article describing many examples of U.S. research studies that involved high levels of risk and low voluntary participation and consent.

The resulting wave of justifiable professional and public concern led to restrictive regulations. But AIDS is forcing a re-examination of these policies. For example, Gov. George Deukmejian on Sept. 29 signed into law a bill that lifted California’s ban on drug trials involving prisoners. The bill noted that “state law designed to protect prisoners from inappropriate medical experimentation has had the unintended effect of preventing prisoners from having access to drugs or treatments which might be required for good medical care.”

It was recently reported that only 20.4% of the subjects in the National Institute of Allergy and Infectious Diseases’ clinical trials were black and Latino, even though blacks and Latinos make up 42% of the adult AIDS patients in the United States. Only 11.3% of the participants in federal studies are intravenous drug users, yet they are 27.5% of adult AIDS patients, and the percentage is growing.

The information about dosage and side effects from drug trials on middle-class gay white men may not be applicable to poor minority drug users. It is scientifically as well as ethically important to include all affected groups in drug trials.

There are obvious hurdles. Many potential subjects lack access to primary care, the traditional route of referral to research, and to health insurance to pay for care (the drug itself is free to trial participants). Many subjects do not live near the academic centers where most research is conducted; they may need money for transportation and child care in order to participate.

These barriers are being overcome through extensive outreach efforts and greater sensitivity. In New York City, for example, three major medical centers have 40% or more minority participation in AIDS trials, and community-based research is becoming a much more accessible alternative to academic center trials.

Institutional Review Boards, committees that review research protocols for compliance with ethical standards, are also looking more closely at exclusion and inclusion criteria. Women of childbearing age with AIDS or HIV suffer from triple jeopardy. They are excluded from trials because they fit into three categories that researchers and drug companies want to avoid; potentially pregnant females, members of minority groups and intravenous drug users.

The Institutional Review Boards are now looking more closely at the justification for excluding women--whether it is simply automatic risk avoidance or whether there is a scientific rationale for believing that the particular trial poses unacceptable risks to the woman or a potential or actual fetus that outweigh the benefits.

Some trials involving children have already been conducted, and the federal Department of Health and Human Service’s Work Group on Pediatric HIV Infection and Disease has strongly endorsed expanded research on children.

Expanding subject selection to include the people who will be taking the drugs once they are approved makes good sense, and not just for AIDS. However, the current standards of consent, confidentiality and voluntary participation, as well as the special protections for vulnerable subjects like prisoners and children, must be maintained. If they are not, the quiet revolution will become a noisy counter-revolution.