Drug trial in rheumatoid arthritis: a new design.

The comparative efficacy and safety of naproxen and ibuprofen were studied in 64 patients with rheumatoid arthritis. A new trial design with three aspirin periods interspersed during the study was used. By passing a smooth curve through the values obtained for the various measures of disease activity during the aspirin periods, one could calculate the difference between what would have been expected on aspirin therapy and what was found during therapy with the two trial drugs. These differences, or "incremental values," allowed each patient's variations to be analyzed individually, thus eliminating the necessity of assuming that a patient's disease was constant. Napoxen and ibuprofen were comparable in efficacy to each other and to aspirin, but both drugs caused significantly less severe side effects than aspirin. Although analysis of the incremental values showed essentially the same results as a standard analysis of the raw data with only a modest increase in sensitivity in this particular study, the novel trial design may prove useful in future drug studies in patients with rheumatoid arthritis and other chronic but fluctuating diseases.