Comparison of Risk of Bias Ratings in Clinical Trials—Journal Publications Versus Clinical Study Reports
Many critical appraisers assess bias using tools such as the Cochrane risk of bias tool (Higgins 11) or tools freely available from us (http://www.delfini.org/delfiniTools.htm). Internal validity is assessed by evaluating important items such as generation of the randomization sequence, concealment of allocation, blinding, attrition and assessment of results.
Jefferson et al. recently compared the risk of bias in 14 oseltamivir trials using information from previous assessments based on the study publications and the newly acquired, more extensive clinical study reports (CSRs) obtained from the European Medicines Agency (EMA) and the manufacturer, Roche.
Key findings include the following:
- Evaluations using more complete information from the CSRs resulted in no difference in the number of previous assessment of “high” risk of bias.
- However, over half (55%, 34/62) of the previous “low” risk of bias ratings were reclassified as “high.”
- Most of the previous “unclear” risk of bias ratings (67%, 28/32) were changed to “high” risk of bias ratings when CSRs were available.
The authors discuss the idea that the risk of bias tools are important because they facilitate the process of critical appraisal of medical evidence. They also call for greater availability of the CSRs as the basic unit available for critical appraisal.
We believe that both sponsors and researchers need to provide more study detail so that critical appraisers can provide more precise ratings of risk of bias. Study publications frequently lack information needed by critical appraisers.
We agree that CSRs should be made available so they can be used to improve their assessments of clinical trials. However, our experience has been the opposite of that experienced by the authors. When companies have invited us to work with them to assess the reliability of their studies and made CSRs available to us, frequently we have found important information not otherwise available in the study publication. When this happens, studies otherwise given a rating at higher risk of bias have often been determined to be at low risk of bias and of high quality.
1. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18;343:d5928. doi: 10.1136/bmj.d5928. PubMed PMID: 22008217.
2. Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Onakpoya I, Heneghan CJ. Risk of bias in industry-funded oseltamivir trials: comparison of core reports versus full clinical study reports. BMJ Open. 2014 Sep 30;4(9):e005253. doi: 10.1136/bmjopen-2014-005253. PubMed PMID: 25270852.