Kefauver-Harris Drug Amendments

By the late 1950s, Senator Estes Kefauver of Tennessee was already pressing for drug industry reform on antitrust and pricing grounds when the thalidomide crisis supplied a different and more urgent argument. Thalidomide, marketed in Europe as a sedative and treatment for morning sickness, caused severe limb malformations in thousands of children born to mothers who took it during the first trimester. It had not been approved in the United States, largely because Frances Kelsey, an FDA reviewer, had repeatedly demanded safety data the manufacturer could not produce. The legislation that followed drew its political force from that near-miss.

Passed in October 1962, the Kefauver-Harris amendments overhauled the Federal Food, Drug, and Cosmetic Act in two fundamental ways. First, manufacturers now had to provide substantial evidence of efficacy from adequate and well-controlled studies before approval, not merely evidence of safety. That requirement had never appeared in federal law before, and drug research came to be organized overwhelmingly around the placebo-controlled randomized trial. Second, the law directed the government to set rules for testing new drugs in people, including a requirement for the informed consent of study subjects, a principle the Nuremberg Code had set out in 1947 after the Nazi experiments.

Kelsey received the President's Award for Distinguished Federal Civilian Service from John F. Kennedy in 1962, the same year the amendments passed. She had insisted on scientifically reliable evidence despite constant pressure from the manufacturer, and that standard now had the force of law. Because the new rules covered investigational drugs, the FDA began overseeing trials in progress and not only reviewing completed applications.

The requirement for controlled evidence had immediate consequences for drugs already on the market. Through the Drug Efficacy Study Implementation program, the FDA reviewed every drug approved between 1938 and 1962, when approval had required evidence of safety alone. By the early 1970s the program had classed about 600 medicines as ineffective and forced them off the market.

The efficacy requirement tied drug approval to the sequence of phase 1, phase 2 and phase 3 trials that is now standard. Much of Kefauver's original bill did not survive: his provisions on patents and compulsory licensing were dropped in June 1962, and the industry defeated proposals to require proof that a new drug worked better than existing ones, arguing that comparative efficacy would be impracticable to prove.