Some Cochrane risk-of-bias items are not important in osteoarthritis trials: a meta-epidemiological study based on Cochrane reviews

J Clin Epidemiol. 2018 Mar:95:128-136. doi: 10.1016/j.jclinepi.2017.11.026. Epub 2017 Dec 6.


Objective: To evaluate the impact of bias-related study characteristics on treatment effects in osteoarthritis (OA) trials.

Study design and setting: Based on OA trials included in Cochrane reviews, the impact of study characteristics on treatment effect estimates was evaluated. Characteristics included items of the risk of bias (RoB) tool, trial size, single vs. multisite, and source of funding. Effect sizes (ESs) were calculated as standardized mean differences (SMDs). Meta-regression was performed to identify "relevant study-level covariates" that decrease the between-study variance (τˆ2).

Results: Twenty reviews, including 126 OA trials with a high degree of heterogeneity, were included (τˆ2 = 0.1247). Among the RoB domains, only patient blinding had an impact on the results (reducing heterogeneity according to τˆ2 < 7%). Inadequate blinding of patients yielded larger effects (SMDDifference = 0.15; 95% confidence interval [CI]: 0.01-0.29, P = 0.035). The most important study characteristic was trial size (heterogeneity reduced by 25%), with small trials reporting larger effects (SMDDifference = 0.29; 95% CI: 0.16-0.42, P < 0.001).

Conclusion: In musculoskeletal reviews addressing pain, all the items included in the Cochrane RoB tool might not be equally important. OA trial results may be affected by bias constructs that are not yet fully elucidated.

Keywords: Bias; Meta-analysis; Meta-epidemiology; Meta-research; Osteoarthritis; Pain.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bias
  • Clinical Trials as Topic / standards*
  • Epidemiologic Methods
  • Humans
  • Osteoarthritis / therapy*
  • Regression Analysis