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

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 turn (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. (C) 2004 Elsevier Inc. All rights reserved.