Completeness of clinical evidence citation in trial protocols: A cross-sectional analysis

Med (N Y). 2022 May 13;3(5):335-343.e6. doi: 10.1016/j.medj.2022.03.002. Epub 2022 Apr 8.

Abstract

Background: Human protection policies require assessment of how proposed clinical trials relate to prior and ongoing studies testing similar hypotheses. We assessed the extent to which clinical trial protocols cited relevant published and ongoing clinical trials that would have been easily accessible with reference searches.

Methods: We created a random sample of trial protocols using ClinicalTrials.gov, stratifying by industry and non-industry-sponsored studies. We then conducted reference searches to determine the extent to which protocols cited clinical trials with identical intervention-indication pairings that were accessible in PubMed and ClinicalTrials.gov at the time of trial initiation.

Findings: Of the 101 trial protocols evaluated, 73 had at least one identified citable trial. None contained statements suggesting a systematic search for relevant clinical evidence. Of industry-sponsored trial protocols with at least one identified citable trial, 7 of 23 (30.4%) did not cite any published clinical trials and 10 of 33 (30.3%) did not cite any ongoing relevant trials. Of the non-industry-sponsored trial protocols with at least one identified citable trial, 5 of 28 (17.9%) did not cite any published clinical trials and 14 of 19 (73.7%) did not cite any ongoing trials.

Conclusions: Clinical trial protocols undercite accessible, relevant trials and do not document systematic searches for relevant clinical trials. Consequently, ethics review committees often receive an incomplete picture of the research landscape if they review protocols similar to those deposited on ClinicalTrials.gov.

Funding: This study was funded by the Canadian Institutes of Health Research and the Greenwall Foundation.

Keywords: Foundational research; IRB; citation bias; clinical trials; ethical review; research ethics; research integrity; risk/benefit analysis; trial protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada
  • Clinical Trial Protocols as Topic*
  • Cross-Sectional Studies
  • Humans
  • PubMed
  • Research Design*

Grant support