Randomized clinical trials remain the most reliable means of identifying the drugs, devices, and treatment strategies that will improve human health. There is increasing interest in the possibility that “personalized” medicine can be evaluated in much smaller trials because the average treatment effect is expected to be larger in highly selected cohorts. Smaller, biomarker-driven trials can provide major insights into whom to treat and may be sufficient for selected disease states in which considerable treatment effects may be observed. However, a precise biological understanding of most chronic illnesses and biomarkers that might predict response has eluded investigators. Moreover, treatment effect sizes in chronic conditions are expected to be modest in most cases. As a result, determining the long-term balance of risk and benefit, particularly in comparative effectiveness trials, often requires large numbers of clinical events in representative populations.
Eapen ZJ, Lauer MS, Temple RJ. The Imperative of Overcoming Barriers to the Conduct of Large, Simple Trials. JAMA. 2014;311(14):1397-1398. doi:10.1001/jama.2014.1030