phase III trials compare the prospective drug with standard therapy, usually on a randomized, double-blind basis. This process can take considerable time, and a variety of approaches to streamlining the procedures have been proposed. In the view of the pharmaceutical industry, which typically bears the costs of clinical trials, the Kefauver-Harris amendments raised the cost of researching, developing, and marketing new products.
In the face of the AIDS epidemic, FDA's policies of cautious protection came under fire. Given attempts to modify regulatory practices, it will be critical in the future to monitor the potential effects of changes on new drug development, both for HIV and other diseases. How, in the context of the AIDS epidemic, has the FDA balanced its duties to ensure safe and effective drugs against its duty to make potentially beneficial agents available on a timely basis? (Edgar and Rothman, 1991). And how are changes in the regulatory environment likely to affect research and development in the pharmaceutical industry?
Just as changes in the regulation of new drugs were spurred by a series of scandals, so, too, were attempts to protect human subjects driven by reports of serious abuses. Efforts to improve the regulatory capacities of the FDA were followed by a heightened public concern about the ethics of human subject research. Widespread reports of experiments in which research subjects were unaware of their involvement led to calls for more vigorous protections (Gray, 1975; Barber, 1976; Katz, 1984). Henry Beecher's (1966) review of unethical experimental protocols in the New England Journal of Medicine (see also Rothman, 1987b) was soon followed by exposes of the Public Health Service's Tuskegee syphilis experiment, in which some 400 African American sharecroppers were denied treatment in a study of the natural history of the disease (Brandt, 1978b; Jones, 1981; Thomas and Quinn, 1991).
As a result of these reports, Congress in 1974 established the National Commission for the Protection of Human Subjects (Rothman, 1991; Jonsen, 1984). The commission devised general ethical principles for the conduct of human experimentation, which it issued in its 1978 "Belmont report" (National Commission for the Protection of Human Subjects, 1978). Three principles were to form the basis for the evaluation of experimental protocols and provide a guide for obtaining informed consent, establishing favorable risk-benefit ratios, and equitably selecting test subjects: respect for persons, beneficence, and justice. A central tenet of the Belmont report was the need to be rigorous in differentiating experimentation from therapy. The commission argued that therapeutic research had the potential of subjecting patients to risky and dangerous experimentation offered in the hope