Prevention of Heart Disease: Clinical Trials at What Cost?

In this 1975 review, Gina Kolata comments on the cost and necessity of two major clinical trial investments by the National Heart and Lung Institute (NHLI, now the NHLBI): the Lipid Research Clinics Primary Prevention Trial (LRC-PPT) and Multiple Risk Factor Intervention Trial (MRFIT). The former randomized 3,600 men with high cholesterol (in the top 5% of the population) to a control group or a cholesterol-lowering diet and cholestyramine for 7 years. The latter randomized 12,000 men to a control or complex intervention (drug- and diet-based, along with smoking cessation) designed to reduce cholesterol, blood pressure, and weight.

NHLI allocated $80 million for these trials in 1972, in light of a larger NHLI budget and an ambition to tackle the leading cause of death in the U.S., heart disease. By 1975, the cost of these trials had ballooned to $200 million while the NHLI budget had shrunk. Investigators particularly struggled with standardizing measurements between sites and screening the hundreds of thousands of men required to meet subject number requirements. And yet these trials were likely cheaper than a study of a truly representative population; since only 1 in 100 middle-aged men suffered a heart attack over 7 years, a primary prevention trial drawn from a population sample would require between 50,000 and 100,000 subjects and cost $1 billion. (Note: All dollar values are in 1975 dollars; multiply by ~4.5 to convert to 2019 dollars.)

Kolata notes that researchers agree “there is a need for more information on whether the variables affecting incidences of coronary heart disease can be controlled.” She continues:

A national obsession with dietary fats and cholesterol seems to have developed despite the fact that there is as yet no conclusive evidence that people can voluntarily decrease their risks of heart attacks by changing their diets. Nor is there conclusive evidence that modifying other risk factors, such as smoking and high blood pressure, can affect incidences of heart disease. Until more is known about the biochemical etiology of heart disease, the only way to decide whether incidences of heart disease can be reduced is to conduct large-scale clinical trials.

Despite the challenges, NHLI leaders and funders continued to justify these programs in their search for evidence in support of the diet-heart hypothesis—even, as Gary Taubes writes, going so far as to launch a massive public health campaign against dietary fat, with which “the media obligingly went along.”