The effect of poor compliance and treatment side effects on sample size requirements in randomized clinical trials

Treatment side effects and associated noncompliance have methodological implications vital to the testing of new drugs. In this paper, we quantify the impact of these factors on sample size requirements in clinical trials. In the Lipid Research Clinics Trial, side effects caused treatment group compliance (50.8%) to be lower than placebo compliance (67.3%). Cholesterol reduction among treatment noncompliers was 35.2% of the reduction among com-pliers. Had treatment group compliance been as high as placebo compliance, 41% fewer patients would have been required to achieve.