The Success Rate of New Drug Development in Clinical Trials: Crohn's Disease

Purpose. To determine the risk of drug failure during clinical trial testing in Crohn's disease and determine what steps can be taken to improve outcomes. This is the first study to quantify such risk for a single disease. Methods. Moderate to severe Crohn's disease was investigated by reviewing Phase I to III clinical studies conducted during 1998 to June 2008. Clinical trial failure causes were classified as commercial or clinical and compared with industry expectations. Drugs were not eligible for inclusion in this study if: their Phase I study occurred before 1998; targeted mild Crohn's disease patients; did not test for remission or Crohn's disease activity index (CDAI) score reduction reflecting disease burden; did not involve industry support or were not conducted in the United States. Results. A search of clinicaltrial.gov yielded 37 drugs that met our search criteria. The cumulative success rate for drug development in Crohn's disease is 18%, from start to finish of clinical trial testing. New drug approvals are dominated by protein based therapeutics in this indication. Commercial and clinical failures both contributed substantially to the failure rates of new drugs. Phase I clinical testing appeared to offer little risk mitigation with pass rates at 92%. Conclusion. Funding intended to advance Crohn's disease must take into account the disease specific historical failure rate of drug development in forecasting any reasonable expectation of producing new therapies. As it currently stands, one in five drugs will be successfully approved that enter clinical trial testing in this indication. To manage this risk, continued development of biologics over small molecule drugs may be warranted in this disease.