Invited Commentary: Can You Do Trials of Behavioral Modification, Such as Diet or Exercise Intervention, With Hard Endpoints?

Blackburn (Am J Epidemiol. 2020;189(6):491-498) describes the evolution from the Makarska Conference in 1968 to the planning of the JUMBO trial and the decision by the National Institutes of Health (NIH) to do the Multiple Risk Factor Intervention Trial. He attributes the failure of the Multiple Risk Factor Intervention Trial to show a significant reduction in coronary heart disease or total mortality to the design of the trial, the multiple centers involved, and continued bureaucracy. The paper is important in raising 3 issues of continued relevance: 1) What is the relationship of the NIH staff in both development and monitoring of large cooperative studies, especially clinical trials, outside of the walls of the NIH? 2) Can clinical trials that utilize individual randomization to intervention and comparison be successful in evaluating a common-source epidemic, such as diet and coronary heart disease, especially in populations with readily available foods and competing advertising, etc.? 3) How much information obtained from, e.g., observational studies, animal models, and genetic studies, is necessary given limits of human population clinical trials of behavioral intervention to develop recommendations for strong public health programs to reduce morbidity and mortality, and what is the measure of successful intervention?