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

Abstract

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 press releases from 1998 to June 2008. Clinical trial failure causes were classified as commercial or clinical and compared with industry expectations. The risk of failure was also reviewed based on whether the compound was a small molecule drug or a biologic. Lastly, the role of the sponsor was examined, in determining whether the size of the firm involved in a drug program was predictive of the outcome of the study.
 Results. More than a120 press releases were reviewed yielding 37 drugs that met our search criteria. The cumulative success rate for drug development in Crohn’s disease is 19%, 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 95%.
 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.

Clinical Trial Risk in Type-2 Diabetes: Importance of Patient History

“…In the past, many have viewed biologic molecules with more optimism in drug development when compared to small molecules (24), but in our research we have not seen a clear trend, as it appears to vary with the indication (11)(12)(13)(14)(15)(16). Based on cumulative success rates, small molecules are more successful in clinical trials for type-2 diabetes.…”

“…Based on these results, 1 out of 10 molecules initiating phase I clinical trials will eventually be available to patients. The cumulative success rate for type-2 diabetes molecules are therefore lower than molecules explored for the treatment of human immunodeficiency virus (11), Non-small cell lung cancer (12) and moderate to severe Crohn's disease (13). However, type-2 diabetes drug development shows more promise than clinical trials for castration resistant cancer (15).…”

“…Our study has many limitations, which have been discussed in examining other specific disease areas (11)(12)(13)(14)(15)(16). The trade-off in examining a specific indication is that we have a much smaller sample size in which to perform our analysis.…”

“…In order to do this, we have evaluated clinical studies in the USA pertaining to type-2 diabetes, and quantified the probability of a drug successfully advancing to the next phase of clinical trials and factors that may impact that risk estimate. The methodology used in this paper has been applied to other diseases areas (11)(12)(13)(14)(15)(16).…”

Actual Usage and Quality of Experimental Colitis Models in Preclinical Efficacy Testing

“…4 The likelihood of a drug passing all 3 test phases in the field of pharmaceutical development for the treatment of CD is 18%. 5 Why do so many compounds proven effective in animal models fail in clinical trials?…”