The Controlled Clinical Trial : An Analysis

PressureHarris L. Coulter, Ph.D.
Prior to 1962 the normal procedure, in use a century or longer, for bringing a new medicine to professional attention was to elicit testimonials from a handful of physicians. These were then employed in the manufacturer ’s marketing campaign.

While this horse-and-buggy technique readily lent itself to abuse, before 1945 it was little criticized. The pharmaceutical industry had a low rate of innovation, and new entities were introduced into commerce in a way which satisfied all parties.

But the drug industry was transformed by World War II. The rate of innovation accelerated, and medicines such as penicillin and the other antibiotics seemed amazingly effective. The postwarmarketplace rapidly became saturated with new entities and combinations, the period 1954-1959,especially, being marked by “fantastic growth.”

In 1939 Americans consumed a total of 182,000,000 drug prescriptions, four out of five being compounded on the premises by the druggist. By 1958 the volume had mounted to 655,000,000,and nine tenths were ready-made by the manufacturer.

Gross sales worldwide of U.S prescription drug products increased from $1.43 billion in 1950 to $2.86 billion in 1960 to $6.853 billion in 1970 to $2 1.9 billion in 1980 to $51.5 billion in 1989.

The number of new entities rose from less than 10 in 1940 to 45 in 1949, to 50 in 1953, and to a peek of 60 in 1959.

Furthermore, each new entity was accompanied by five or six drug combinations, the total number of new combinations introduced on the market reaching a high-water mark of 280 in 1955.

This increased volume of production demanded a technique for separating more effective medicines from less effective. The answer was the “controlled clinical trial” (CCT) or “randomized clinical trial” (RCT), first suggested in the 1930s by the British statistician, Austin Bradford Hill.

The results, of course, like physicians’ testimonials, could then be usefully employed in  manufacturers’ publicity campaigns.

While some controlled clinical research had been performed in Great Britain and the United  States before the war, the first major controlled clinical trial of a new drug was the 1946-1948 British study of streptomycin in tuberculosis, for which Hill provided statistical support.

The use of the controlled trial spread slowly in the 1950s as manufacturers realized its value in their unceasing maneuvering for market position and market share. Hedley Atkins, President of the Royal College of Surgeons, told Austin Hill at this time that his contribution to medicine “was as important and valuable as the discovery of penicillin.”

Emblematic of the later history of the clinical trial is the fact that the streptomycin study, extolled then and since as a breakthrough in medicine, in fact yielded disappointing results: the treated cases showed improvement only for three months and thereafter began to deteriorate. (Medical Research Council, 782)

Harris L. Coulter, Ph.D.
Center For Empirical Medicine
Project Cure
Washington, D.C.

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