Preprint Assessing the feasibility and impact of clinical trial trustworthiness checks via an application to Cochrane Reviews:... 2024 Wilkinson et al

Full title: 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, 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.


Plain language summary

Systematic reviews collate evidence from randomised controlled trials (RCTs) to find out whether health interventions are safe and effective. However, it is now recognised that the findings of some RCTs are not genuine, and some of these studies appear to have been fabricated. Various checks for these “problematic” RCTs have been proposed, but it is necessary to evaluate these checks to find out which are useful and which are feasible.

We applied a comprehensive list of “trustworthiness checks” to 95 RCTs in 50 systematic reviews to learn more about them, and to see how often performing the checks would lead us to classify RCTs as being potentially inauthentic. We found that applying the checks led to concerns about the authenticity of around 1 in 3 RCTs. However, we found that many of the checks were difficult to perform and could have been misinterpreted. This might have led us to be overly sceptical in some cases. The findings from this study will be used, alongside other evidence, to decide which of these checks should be performed routinely to try to identify problematic RCTs, to stop them from being mistaken for genuine studies and potentially being used to inform healthcare decisions.

What is new

• An extensive list of potential checks for assessing study trustworthiness was assessed via an application to 95 randomised controlled trials (RCTs) in 50 Cochrane Reviews.
  
  
• Following application of the checks, assessors had concerns about the authenticity of 32% of the RCTs.
  
  
• If these RCTs were excluded, 22% of meta-analyses would have no remaining RCTs.
  
  
• However, the study showed that some checks were frequently infeasible, and others could be easily misunderstood or misinterpreted.
  
  
• The study restricted assessment to meta-analyses including five or fewer RCTs, which might distort the impact of applying the checks.
  

https://www.medrxiv.org/content/10.1101/2024.11.25.24316905v1.full-text

 

Giant study finds untrustworthy trials pollute gold-standard medical reviews

A huge collaboration has confirmed growing concerns that fake or flawed research is polluting medical systematic reviews, which summarize evidence from multiple clinical trials and shape treatment guidelines worldwide. The study is part of an effort to address the problem by creating a short checklist that will help researchers to spot untrustworthy trials. Combined with automated integrity tools, this could help those conducting systematic reviews to filter out flawed work — in medicine and beyond.

In the study, which has taken two years and was posted on 26 November to the medRxiv preprint server1, a team of more than 60 researchers trawled through 50 systematic reviews published under the aegis of Cochrane, an organization renowned for its gold-standard reviews of medical evidence.

After applying a barrage of checks, the authors — many of whom are themselves editors or authors of Cochrane reviews — reported that they had “some concerns” about 25% of the clinical trials in the reviews, and “serious concerns” about 6% of them.

https://www.nature.com/articles/d41586-024-04206-3