Powerful Medicines; The Benefits, Risks and Costs of Prescription Drugs
By Jerry Avorn, M.D.
Responding to the travesties of a completely unfettered marketplace, the Progressive movement of the early 1900s called for the establishment of minimum standards to regulate the quality of foods and drugs that Americans consume. The Pure Food and Drug Act of 1906 marked the first official recognition that the wholesomeness of what people put into their bodies was too important to be left exclusively to the haphazard control of unregulated commerce. At this early stage, purity was the main concern: it would be several decades before the nation was ready to involve government in determining whether medications had any useful effects, or whether their inevitable risks were worth incurring to achieve that effectiveness.
A further requirement, that those ingredients be nonlethal, was not put into place until more than three decades later. In 1937, over a hundred patients died-many of them children-after taking a sulfanilamide product that had been manufactured with a toxic solvent. In the wake of this tragedy, named the Massengill Massacre after the company that produced the tainted drug. Congress strengthened the Pure Food and Drug Act to allow the federal government to require that drug products not be poisonous. But there was still no requirement that the drugs needed to work. That criterion was resisted for decades by manufacturers who successfully lobbied against the idea, depicting it as unbearably onerous government regulation of the free market. The notion was put forward again by Senator Estes Kefauver of Tennessee in the early 1960s. His bill was headed for certain legislative defeat in a Congress that was convinced government had no business intruding into commercial transactions among drug companies, physicians, and patients. Languishing on Capitol Hill, the Kefauver legislation was saved by another tragedy.
Thalidomide was being widely used overseas as a sedative and antinauseant, and was particularly popular among pregnant women. Its approval in the United States had been slowed by a diligent FDA medical officer named Dr. Frances Kelsey, who wasn't convinced that the manufacturer had adequately demonstrated its safety. The struggle was portrayed by many in the drug industry as another instance of a boneheaded, inept federal regulator unnecessarily delaying the availability of an important new product to the American public. Then reports began to appear in Europe of babies born with grotesque abnormalities of their arms and legs. Instead of normally formed limbs, the affected infants grew little malformed appendages that resembled flippers. Because this was such a rare aberration, it didn't take long to determine that the mothers had something in common: they had all taken thalidomide during the first trimester of their pregnancies, the period during which the basic architecture of the limbs is laid down in the developing fetus. Dr. Kelsey was transformed from an anonymous bumbling bureaucrat to a legendary public servant who saved untold numbers of American families from needless misery.
It suddenly seemed plausible that a government agency could protect the public health by evaluating drugs, and the Kefauver Act was passed by Congress in 1962 without a dissenting vote. This was a watershed in the nation's approach to medications, and an important development for the science of pharmacology as well. The new law completely changed the way doctors and patients thought about drugs. For the first time, the federal government, through the Food and Drug Administration, could require that a prescription medication had to be proven effective before it could be sold as a drug in the United States.
But what, exactly, does "effective" mean?
In 1962, armed with its new powers, the FDA faced a marketplace full of existing medicines that had never been shown to work, or were bizarre combinations of products whose use in tandem had little pharmacologic rationale. So great was the entrenchment of useless products in American medicine that it would take over twenty years to fully implement this new evidentiary requirement for drugs already in use. Like the oversized jet-fin appendages on the backs of late 1950s cars, many of those products had been seen as important modern developments in their day.