title: Predicting success in regulatory approval from Phase I results.
abstract: OBJECTIVE
  Drug development in oncology is resource intensive and has a high failure rate. In this exploratory analysis, we aimed to identify the characteristics and outcomes of published Phase I studies associated with future Food and Drug Administration (FDA) approval.
  
  
  METHODS
  Phase I studies of approved and non-approved anticancer agents between 2000 and 2013 were retrospectively examined. Fisher's exact and chi-squared tests were used to compare the potential predictive measures.
  
  
  RESULTS
  Phase I studies of 88 anticancer agents (54 approved and 34 non-approved by the FDA), treating a total of 4,423 subjects, were examined. The median number of patients in Phase I trials of approved and non-approved agents was 44.5 and 32, respectively. A total of 423 subjects (86 reporting studies) had a complete responses, and 342 subjects (80 reporting studies) had a partial responses (PR). A higher number of PR (P < 0.001), PR rate (P = 0.003) and longer PR duration (P = 0.001) were predictive of regulatory success.
  
  
  CONCLUSIONS
  These preliminary findings indicate that objective responses in Phase I trials may have predictive value for later regulatory approval.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, Malikl@uthscsa.edu.
authors.forename: Laeeq
authors.initials: L
authors.lastname: Malik
authors.forename: Alex
authors.initials: A
authors.lastname: Mejia
authors.forename: Helen
authors.initials: H
authors.lastname: Parsons
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ehler
authors.forename: Devalingam
authors.initials: D
authors.lastname: Mahalingam
authors.forename: Andrew
authors.initials: A
authors.lastname: Brenner
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.forename: Steven
authors.initials: S
authors.lastname: Weitman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D017277:Drug Approval / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D012189:Retrospective Studies; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents