RESUMO
BACKGROUND: This study analyzed the risk of clinical trial failure in chronic obstructive pulmonary disease (COPD) drug development between 1998 and 2015. We investigated elements that influenced clinical trial risk and factors that could improve outcomes during development. OBJECTIVES: This study aims to quantify clinical trial risk for drug development in COPD and factors that affect clinical trial risk. METHODS: Drugs that commenced their phase I testing in this indication from 1998 onwards were retrieved from http://www.clinicaltrials.gov. Compounds investigated had to have an endpoint relevant to the treatment of COPD and be sponsored by the pharmaceutical industry. These compounds were then analyzed based on their mechanism of action and trial inclusion criteria. RESULTS: A total of 766 trials met our screening criteria representing 116 drugs. Of these, 9 gained approval by the US FDA during our study period. The cumulative success rate for clinical development in COPD was 13.4%. Combination therapies of long-acting ß-adrenoceptor agonists (LABA)/long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)/LABA had the highest success rates at 80 and 50%, respectively. The risk-adjusted cost for drug development in COPD was USD 532.4 million. CONCLUSIONS: A 13.4% success rate in COPD implies that less than 1 in 7 compounds enrolled into clinical testing would gain FDA approval. LABA/LAMA and ICS/LABA therapies had multiple fold increases in the success rate compared to other drug classes and sizably decreased the risk-adjusted cost of drug development. Moving forward, combination therapies may offer the lowest risk of clinical failure in COPD drug development.
