Risk of Failure of a Clinical Drug Trial in Patients with Moderate to Severe Rheumatoid Arthritis

Objective. We conducted a systematic review to determine the risk of drug failure in clinical testing with patients with moderate to severe rheumatoid arthritis (RA). Methods. Therapies for RA were investigated by reviewing phase I to phase 111 studies conducted from December 1998 to March 2011. Clinical trial success rates were calculated and compared to industry standards. Trial failures were classified as either commercial or clinical failures. The exclusion criteria for drugs in this study: drugs that were started in phase 1 studies prior to January 1998 for this indication; or studies that enrolled patients who were methotrexate-naive and/or had failed biologic therapy. Results. A search in clinicaltrials.gov and approved drugs for the indication yielded a total of 69 drugs that met the study criteria. The cumulative success rate was determined to be 16%, which is equivalent to the industry standard of 16%. For each phase, the frequency of clinical failures exceeded commercial failures. Clinical studies equally comprised investigations of small molecules and biological agents, but biologics seemed to exhibit a higher success rate overall. Conclusion. Clinical trial risk in RA with the 84% failure rate reported here is at par with industry performance and phase II success rate seems to be highly predictive of phase III success. (First Release Sept 1 2012; J Rheumatol 2012;39:2066-70; doi:10.3899/jrheum.120005)