The methods for handling missing data in clinical trials influence sample size requirements.

Abstract Objective Results of studies estimating osteoarthritis progression may be affected by missing values. In clinical trials assessing disease-modifying osteoarthritis drugs, sample sizes should be calculated using close estimates of outcome variables. Study design and setting Supposing a two-parallel group design in hip osteoarthritis clinical trials, we estimated sample sizes using the joint space width (JSW), number of patients with JSW progression >0.5 mm (JSN), time to total hip arthroplasty (THA), and time to JSN or THA using several approaches to deal with missing data. Results Three-year clinical trials testing a treatment effect of 50%, with a power of 80%, could require sample sizes of 121 patients for JSW, 57 for JS progression using multiple imputation for handling missing values; 200 for THA; and 47 for JSN or THA. These numbers vary greatly depending on the approach chosen for handling missing data. Conclusions These results can help investigators plan clinical trials to select the primary outcome and a priori specify the way missing data will be handled.