France's Minister of Health called the abortion pill recently approved in his country the "moral property" of women, not just the property of the drug company that makes it. That no U.S. public health official has taken a similar stand on behalf of AZT, this country's only approved antiviral AIDS drug, is a measure of how foreign the term "moral property" is to the U.S. drug development nexus. But the 45,000 AIDS deaths to date in the United States have finally forced a debate that cuts to the heart of this society's dollar-oriented medical philosophy by focusing increased attention on the Food and Drug Administration, the agency that must approve all drug treatments before they may be marketed.
The AIDS movement, a burgeoning coalition of health care practitioners and mostly gay activists has persistently challenged what it regards as the weak and ineffective role of the F.D.A., a role recently abetted by President-elect George Bush. Scarcely three weeks before his election, in his capacity as chair of President Reagan's Task Force on Regulatory Relief, Bush recommended streamlining the F.D.A.'s approval process for drugs that treat life-threatening conditions. The result, informally dubbed the "Bush initiative," has now been implemented by the agency as an interim rule and codifies the expedited procedure by which AZT was tested and released in 1987.
The F.D.A. touted the Bush initiative as proof of its commitment to help people with AIDS. "The procedures," says Commissioner Frank Young, "reflect a recognition that physicians and patients are generally willing to accept greater risks or side effects from products that treat life-threatening diseases." Young claims that the new plan shows "that F.D.A. is not 'part of the problem' but an integral, aggressive part of the solution to AIDS and other diseases."
Yet most doctors, legislators and AIDS activists are skeptical. Representative Ted Weiss, chair of the House Human Resources Subcommittee, called the initiative "a politically timed restatement of what the F.D.A. already can and does do"; and Dr. Mathilde Krim, co-founder and chair of the American Foundation for Aids Research (AmFAR), got to the cynical root of the initiative when she said that "without significant dollars, these proposals constitute a public relations ploy...by the Administration in the closing weeks of the presidential campaign."
Mark Harrington is a member of the AIDS Coalition to Unleash Power (ACT UP), the organization that has spearheaded the attack on the Bush initiative and the F.D.A. He is a gay man in his 20s who has made it his business to know all there is to know about the drug approval process in this country. "We want the drug companies to be more accountable to the public, not less," says Harrington, who argues that the F.D.A. is not nearly tough enough on the pharmaceutical firms.
At present, a drug must pass successfully through three phases of clinical (human) trials before it is approved. The first phase tests safety and dosage levels; the second, safety and efficacy; and the third, further efficacy by expanding the trial to a wider range of subjects over a longer period of time. The whole process takes eight to ten years, three times the average remaining life span of a person infected with HIV, the AIDS virus.
The Bush initiative, when fully effective, could lop three to five years off this process by eliminating the third phase of clinical testing. To compensate for this it proposes heightening F.D.A. consultation with the drug companies and Federal institutions performing the trials. Commissioner Young has stated, however, that only 20 percent of the drug companies consult with the F.D A., and the initiative offers little incentive for reluctant firms to increase such communication. And even if the F.D.A. is sincere in its proposal to oversee the trials more closely, where, Harrington asks, "are they going to get the resources to do this? There are neither funds nor staff positions to do what they must do now, let alone [carry out] the Bush initiative."
There are many other problems inherent in the agency's approval process that the new regulations do not address, and ACT UP argues that "the F.D.A. has the power under existing laws and regulations to change direction and provide many of our demands immediately." For this reason, the agency has become the focal point of AIDS activists: On October 11, 1,000 demonstrators converged on its headquarters in Rockvllle, Maryland, chanting, "WE'RE THE EXPERTS, LET US IN!" In a tightly orchestrated civil disobedience, they managed to shut the agency down for the day. "As people who have been struck by AIDS, we've had to seize control of our own treatment--the government isn't doing it for us," says Gregg Bordowitz of the Aids Coalition to Network, Organize and Win (ACT NOW), the national coalition of AIDS organizations that planned the action.
At present, people infected with HIV have one obvious treatment option: They may obtain a doctor's prescription and buy AZT. But many bodies cannot tolerate the drug's toxicity, and many pocketbooks cannot afford its cost, which can run as high as $800 a month. Moreover, the efficacy of AZT has been repeatedly questioned. So those infected with HIV often attempt to seize control by pursuing one of three other options: enrolling in the clinical trials of an experimental treatment; gaining access to unapproved experimental treatments that have been released through F.D.A.-monitored programs; or resorting to what has become known as the underground market.
The F.D.A. regulates all these options and is thus, according to ACT UP, "at the crux of virtually every issue concerning treatments for AIDS.'' Jim Eigo, a member of the ACT UP issues committee and one of the principal architects of the organization's demands, says the central problem is that "the F.D.A. refuses to see experimental medicine as health care." The agency's mandate is to protect consumers from treatments that might be unsafe or ineffective. This mandate requires the F.D.A. to protect sick people from getting sicker, to do everything within its power to help people with life-threatening conditions obtain treatments that might help them.
To its credit, the F.D.A. has finally turned a blind eye to the underground market: After AIDS activists complained repeatedly about crackdowns on drug buyers' groups, the Agency decided in July to allow those with the life-threatening conditions to bring unapproved drugs into the country for personal use. While this might help patients with the resources to find out about drugs used abroad and with the funds to import them, it doesn't address the needs of the thousands of HIV-infected i.v. drug users who, already on the margins of society, have difficulty obtaining even the most basic medical services.
The F.D.A. has also recently initiated a program designed to make available experimental drugs that have passed the first phase of the agency's testing process to people outside the clinical trials. This program, called Treatment I.N.D. (investigational new drug), has such narrowly defined entry criteria, however, that only ninety people gamed access to one drug recently being tested. And again, only those better connected and better off benefit, for the treatments require close supervision by a physician and are not covered by private insurance or Medicaid. The drug companies, which have the final say as to whether their products enter the F.D.A programs, resent the Treatment I.N.D. program because it draws potential subjects away from the clinical trials. The firms also complain that selling unapproved drugs leaves them more vulnerable to liability suits.
The last option available to a person with AIDS who can neither afford to import drugs nor gain access to I.N.D. programs is to enroll in a clinical trial. There are presently experimental trials for 80 potential AIDS treatments, 60 percent of which are run by private companies and 40 percent by the National Institutes of Health. All operational plans of these drug trials have to be reviewed and approved by the F.D.A. It 1s in the trials that the experimental medicine versus health care issue comes to a head.
The F.D.A. has traditionally recommended the use of placebos in drug trials-even in those that involve subjects with life-threatening conditions. In a typical placebo-control trial, half the subjects will be treated with medicine, the other half with an inert substance that has no curative powers. The scientific establishment regards this methodology as the cleanest, most effective means of research. AIDS activists argue, however, that placebos might be acceptable in the testing of a drug like aspirin, but their use on subjects who are at risk of death is unconscionable.
Jim Eigo of ACT UP says, "We've always argued against placebo control for ethical reasons, [but now] we have a practical argument--that these experiments actually impede research and testing." He tells of three major trials that have collapsed in the past few months because "people won't put their lives on the line, thus the trials cannot accrue patients and have to close." And if HIV-infected people do enter trials, he adds, "they try to protect themselves by taking every antiviral drug on the black market, so researchers are beginning to realize the data is unclean."
The F.D.A. will only forgo placebos if there is an effective substance available to substitute as a control. In its regulations, however, the agency lists four alternative methods to the use of placebos, and ACT UP'S researchers favor one of those, the use of experimental substances against each other. The F.D.A. is unwilling to recommend this, though, because it contends its primary aim is to facilitate the testing of drugs, not provide treatment, and "placebo-controlled trials are the fastest way to find out if an experimental drug is effective against a disease with no known cure."
The activists also are challenging the F.D.A. on the way the drug trial process treats women and i.v. drug users. The latter and their sexual partners are the group in which the HIV infection rate is currently the highest, yet they are systematically excluded from trials. There are often good reasons for this: The users may still be infusing vast quantities of methadone, heroin or other substances into their systems. But most trials will not accept even former users or sexual partners because, administrators say, these people are recalcitrant, unreliable and manipulative. ACT UP'S Margaret McCarthy, who works with New York City's AIDS discrimination unit, counters that "in trials done in Brooklyn, people who are and have been drug users have a very good record of cooperation." Women are also often excluded for fear that experimental treatments might cause fetal damage. To bar women of childbearing age from AIDS trials is absurd, says McCarthy, when official city figures show that AIDS is the number-one killer of women between the ages of 25 and 39 in the city.
As with the placebo issue, the activists are demanding equal access to trials not only for reasons of justice and humanity but also out of concern for scientific accuracy. AZT, for example, was not tested at all on i.v. drug users, who are now proving to be highly intolerant of the drug. AIDS activists say that populations should be excluded from drug trials only if there is a demonstrable scientific reason to set up a homogenous test group. And if this is the case, parallel trials for other groups must be mandated.
The F.D.A. 1s frustrated by the activists' relentless criticism: "At the same time they complain about the slow release of some drugs," said spokesman Don McLaren," they complain about lax standards surrounding AZT." The agency also repeatedly makes the point that there are simply no promising treatments at present, and that, in the face of this fact, all it can do is pursue the Bush initiative.
Such a response, ignoring the breadth of the AIDS activists' demands, is grossly inadequate. What is at stake in this confrontation is not only the release of promising drugs but the course public health is to take in this country, for the activists are posing profound questions about the relation-ship between private drug companies, Federal agencies and people in desperate need of treatment.
In an attempt to answer these questions, George Bush and Frank Young could have followed the lead of Admiral James Watkins and his unheeded President's Commission on AIDS. They could have listened to the AIDS activists and health care practitioners who are on the front line of this epidemic. They could have proposed sweeping structural reforms for the drug approval process and increased resources for the sorely tried institutions (like the F.D.A. itself) that are bearing the brunt of the work. Instead, they did no more than apply an election-eve layer of make-up. And the reason is devastatingly obvious: Drug development in this country has yet to find that balance--balance that determines humanity in a capitalist society--between profit and moral obligation.