title: Clinical Trial Risk in Chronic Obstructive Pulmonary Disease: The Effects of Drug Class and Inclusion Criteria.
abstract: 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.
  
  
  OBJECTIVE
  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 β-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.
authors.affiliation: Institute for Management and Innovation, Master of Biotechnology Program, University of Toronto Mississauga, Mississauga, Ont., Canada.
authors.forename: Jeffrey T Y
authors.initials: JT
authors.lastname: Tam
authors.forename: Jayson L
authors.initials: JL
authors.lastname: Parker
authors.forename: Demetri
authors.initials: D
authors.lastname: Anastasopulos
authors.forename: Meyer S
authors.initials: MS
authors.lastname: Balter
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004338:Drug Combinations; D055808:Drug Discovery; D006801:Humans; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D018579:Patient Selection; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists