The Politics of Risk and Regulation.
In a world that depends heavily on specialized expertise, decisions about risks increasingly are adjudicated by impersonal organizations and institutions. But particularly in cases of controversy and politicization, it becomes harder to "contain" such decisions within normal organizational routines. Thus the regulatory hearings that consider evidence from clinical trials in order to license pharmaceutical products for sale are often heated sites for the negotiation of credibility, risk, and trust. "Regulatory science," as Sheila Jasanoff calls it in her study of agencies such as the FDA and the Environmental Protection Agency, is indeed a legitimate variety of scientific enterprise, but it is a very particular variety—and at least in the United States, a particularly adversarial one at that. Regulatory science differs from research science in its goals, its
institutional locus, its formal products, its time frame, and its accountability.
A distinctive difficulty of regulatory science is that everyone involved in making assessments speaks a somewhat different language. The statistician wants to know if the "null hypothesis" of "no treatment effect" has been disconfirmed to a sufficient degree of statistical certainty. The clinician wants to know if her patients' symptoms show improvement. The pharmaceutical manufacturer is concerned with liability and profit margins. And the regulatory official assesses "safety and efficacy" by measuring compliance with statutory and administrative requirements. Patients and their activist representatives want to know if a drug "works": at times they may demand certainty from institutions ill-equipped to provide it; at other moments they may insist on their willingness—indeed, their right —to freely assume the risks of uncertainty and ingest substances about which researchers and regulators have doubts. Should the social priority be "access" or "answers"—rapid approval of experimental therapies or careful consideration of the accumulation of evidence? Are these goals in conflict or can they be advanced simultaneously? Regulators, researchers, doctors, patients, and activists have all held different opinions on these questions—opinions that in some cases have shifted markedly over the course of the past decade.
A small number of drugs, many of them chemical cousins of AZT, have been licensed in the United States as antiviral agents effective against HIV infection or AIDS. (Other drugs have been licensed to fight opportunistic infections and neoplasms that are characteristic of AIDS—the infections and cancers that afflict people with weakened immune systems.) It is universally agreed that none of these drugs is a cure for AIDS. Beyond that, the drugs are shrouded in controversy, and AZT, the drug most widely prescribed throughout the late 1980s and early to mid-1990s, has seen its star rise and then fall. What is "known" and "believed" about these drugs, by whom, and where?
The answers to these questions demonstrate how certainty and uncertainty about treatments—much like beliefs about causation—emerge out of multilateral struggles for credibility. I analyze these struggles by tracing the first decade of AIDS antiviral drug development, from 1984 to 1995, and emphasizing the following issues:
What were the approaches to treatment that emerged upon the "black-boxing" of the HIV hypothesis? How have treatment strategies
changed in relation to advances in virology and immunology?
How did AZT become credible as the treatment of choice for AIDS and for lesser HIV infection? How did a bandwagon form behind the promotion of this drug? Why was the drug recommended for many asymptomatic (outwardly healthy) HIV-infected people in 1989, and why did its value for those same patients come into doubt by 1993? Who has supported AZT, who has questioned it, who has labeled it a "poison," and why?
How did AZT's "cousins" ddI, ddC, d4T, and 3TC become the beneficiaries of novel accelerated mechanisms of drug testing and licensing? What is known about the long-term efficacy of these drugs and about newer, perhaps more promising drugs such as the "protease inhibitors"?
What impact has the "democratization of research" had on the assessment of credibility and the construction of belief about drugs? Specifically, what have been the consequences of lay participation on NIH committees and on community advisory boards for clinical trials? How has the development of a sophisticated activist press that evaluates treatments and regulatory policies affected the research and regulatory processes?
How have activists constructed their credibility as scientific actors in this domain? How have they pressed their critiques of the methods employed in the design and interpretation of clinical trials? How has the engagement with clinical and basic science affected the organization and identity of the movement?
In the debates surrounding treatments, just as in those concerning causation, we see participants engaged in disputes about the meaning of evidence that simultaneously are disputes about the standards of evidence—about what counts as proof and, crucially, who decides. In this respect, there is an underlying commonality between part one and part two of this book. (Indeed, many of the same players surface in both). At the same time, the causation and treatment controversies are in certain respects quite different, and they reveal distinct mechanisms for the establishment of credibility in science. In both cases, the AIDS movement, broadly construed, has played an important and visible role. But in the causation controversies, the most publicized challenges to mainstream views have come from highly credentialed researchers, and representatives of the AIDS movement have enjoyed more success
in assessing the claims of others than in asserting their own. By contrast, the crucial voices of heterodoxy in the treatment controversies have been those of lay activists.
Given the nature of scientific research, there is a certain logic to this difference. The investigation of the etiology and pathogenesis of illness is closer to the realm of "pure science"—the heavily-defended "core" of scientific practice to which few outsiders can successfully gain entry. By contrast, the investigation of treatments—and in particular the establishment of treatment efficacy through the mechanism of the clinical trial—is in part an "applied" science, located more on the "periphery" of scientific practice. It is more easily accessible to members of the patient community, whose participation in the process is indeed essential and who therefore have an immediate claim to a stake in the process and a basis for the development and assertion of their own expertise. A comparison of AIDS causation controversies and treatment controversies is therefore instructive, for it demonstrates how different kinds of scientific debates generate different possibilities for the manufacture of scientific expertise and credibility.