title: Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.
abstract: BACKGROUND
  Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials.
  
  
  METHODS
  Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature.
  
  
  RESULTS
  Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95).
  
  
  CONCLUSIONS
  RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.
authors.affiliation: Clinical Research Centre Nijmegen, Department of Pharmacology - Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands. Marlies.vanLent@radboudumc.nl.
authors.forename: Marlies
authors.initials: M
authors.lastname: van Lent
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Out
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics*; D032962:Consent Forms; D004345:Drug Industry / Q000941:ethics*; D026724:Ethical Review; D028744:Ethics Committees, Research / Q000941:ethics; D006801:Humans; D007258:Informed Consent / Q000941:ethics; D009426:Netherlands; D012107:Research Design / Q000592:standards*; D012109:Research Support as Topic / Q000941:ethics*; D012189:Retrospective Studies