CLINICAL-TRIAL DESIGN FOR EVALUATING COMBINATION THERAPIES

Because the differences in efficacy between a disease-modifying antirh eumatic drug (DMARD) combination and its constituent drugs are likely to be smaller than those between placebo and the single DMARDs, it has been difficult to prove that any combination of DMARDs has either add itive or synergistic benefit. The discriminatory power of the study de sign can be enhanced by careful attention to the details of patient se lection, study design and duration, and choices of primary outcome mea sures and analytical methods. Use of the American College of Rheumatol ogy (ACR) 'core set' of outcome measures and the proposed ACR 'definit ion of improvement' for rheumatoid arthritis (RA) clinical trials, wit h intent-to-treat analysis, in a balanced, prospective, double-blind r andomized clinical trial of 1-2 yr duration will optimize the chances of discriminating between the clinical benefit of the combination and its components if a real difference is present.