Drug development risk in HIV‐1 clinical trials: the effect of drug class

Objectives  This study analysed the risk of clinical trial failure in drug development for Human Immunodeficiency Virus-1 (HIV) between 1998 and 2008 in order to develop recommendations to reduce clinical trial risk in future studies. Methods  All industry sponsored clinical trials (phases I–III) for HIV infection conducted within the USA between 1 January 1998 and 30 June 2008 were collected from the website http://www.clinicaltrials.gov and publicly available disclosures. Drugs were excluded if their phase I clinical programmes began before 1998, they were tested to treat secondary complications of HIV infection, they were sponsored by the public sector or did not belong to one of the three clinical trial testing phases. Key findings  Sixty-six drugs met our screening criteria with 11 of the 66 reaching drug approval. Cumulative success rate for drug development in HIV was 16.7% while industry rates as a whole were 16.5%. This translates into one drug achieving US Food and Drug Administration approval for every five to six fully funded clinical trial programmes covering phase I to approval. When factoring out commercial causes of failure cumulative success rates improved from 16.7% to 24.6%. The effect of drug class and their corresponding target varied with 7% for non-nucleoside reverse transcriptase inhibitors and 25% for protease inhibitors. Conclusions  There are clear differences in clinical trial risk for many drug classes, with some classes displaying very high risk in early clinical testing. This may be useful in reducing the anticipated risk of future drug development programmes in HIV.