Assessing the feasibility and impact of clinical trial trustworthiness checks via an application to Cochrane Reviews: Stage 2 of the INSPECT-SR project

Abstract

Background: The aim of the INSPECT-SR project is to develop a tool to identify problematic RCTs in systematic reviews. In Stage 1 of the project, a list of potential trustworthiness checks was created. The checks on this list must be evaluated to determine which should be included in the INSPECT-SR tool. Methods: We attempted to apply 72 trustworthiness checks to RCTs in 50 Cochrane Reviews. For each, we recorded whether the check was passed, failed or possibly failed, or whether it was not feasible to complete the check. Following application of the checks, we recorded whether we had concerns about the authenticity of each RCT. We repeated each meta-analysis after removing RCTs flagged by each check, and again after removing RCTs where we had concerns about authenticity, to estimate the impact of trustworthiness assessment. Trustworthiness assessments were compared to Risk of Bias and GRADE assessments in the reviews. Results: 95 RCTs were assessed. Following application of the checks, assessors had some or serious concerns about the authenticity of 25% and 6% of the RCTs, respectively. Removing RCTs with either some or serious concerns resulted in 22% of meta-analyses having no remaining RCTs. However, many checks proved difficult to understand or implement, which may have led to unwarranted scepticism in some instances. Furthermore, we restricted assessment to meta-analyses with no more than 5 RCTs (54% contained only 1 RCT), which will distort the impact on results. No relationship was identified between trustworthiness assessment and Risk of Bias or GRADE. Conclusions: This study supports the case for routine trustworthiness assessment in systematic reviews, as problematic studies do not appear to be flagged by Risk of Bias assessment. The study produced evidence on the feasibility and impact of trustworthiness checks. These results will be used, in conjunction with those from a subsequent Delphi process, to determine which checks should be included in the INSPECT-SR tool.