Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis

Godolphin, Peter J.; Bath, Philip M.; Algra, Ale; Berge, Eivind; Brown, Martin M.; Chalmers, John; Duley, Lelia; Eliasziw, Misha; Gregson, John; Greving, Jacoba P.; Hankey, Graeme J.; Hosomi, Naohisa; Johnston, S. Claiborne; Patsko, Emily; Ranta, Annamarei; Sandset, Per Morten; Serena, Joaqu�n; Weimar, Christian; Montgomery, Alan A.; Knipp, S.C.; Giugliano, R.P.; Bonati, L.H.; Nagai, Y.; Matsumoto, M.; Barnett, H.J.M.; Fox, A.J.; Farrant, M.; Easton, J.D.; Elm, J.J.; Neal, B.; Arima, H.; D�valos, A.; Amarenco, P.; Evans, S.; Sprigg, N.; Dineen, R.; Eikelboom, J.W.; Chen, C.; on behalf of the Adjudicating Outcomes in Stroke Trials Collaboration*

Abstract

© 2019 American Heart Association, Inc. Background and Purpose-In randomized stroke trials, central adjudication of a trial's primary outcome is regularly implemented. However, recent evidence questions the importance of central adjudication in randomized trials. The aim of this review was to compare outcomes assessed by central adjudicators with outcomes assessed by site investigators. Methods-We included randomized stroke trials where the primary outcome had undergone an assessment by site investigators and central adjudicators. We searched MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, and Google Scholar for eligible studies. We extracted information about the adjudication process as well as the treatment effect for the primary outcome, assessed both by central adjudicators and by site investigators. We calculated the ratio of these treatment effects so that a ratio of these treatment effects >1 indicated that central adjudication resulted in a more beneficial treatment effect than assessment by the site investigator. A random-effects meta-analysis model was fitted to estimate a pooled effect. Results-Fifteen trials, comprising 69 560 participants, were included. The primary outcomes included were stroke (8/15, 53%), a composite event including stroke (6/15, 40%) and functional outcome after stroke measured on the modified Rankin Scale (1/15, 7%). The majority of site investigators were blind to treatment allocation (9/15, 60%). On average, there was no difference in treatment effect estimates based on data from central adjudicators and site investigators (pooled ratio of these treatment effects=1.02; 95% CI, [0.95-1.09]). Conclusions-We found no evidence that central adjudication of the primary outcome in stroke trials had any impact on trial conclusions. This suggests that potential advantages of central adjudication may not outweigh cost and time disadvantages in stroke studies if the primary purpose of adjudication is to ensure validity of trial findings.

Citation

Godolphin, P. J., Bath, P. M., Algra, A., Berge, E., Brown, M. M., Chalmers, J., Duley, L., Eliasziw, M., Gregson, J., Greving, J. P., Hankey, G. J., Hosomi, N., Johnston, S. C., Patsko, E., Ranta, A., Sandset, P. M., Serena, J., Weimar, C., Montgomery, A. A., Knipp, S., …on behalf of the Adjudicating Outcomes in Stroke Trials Collaboration*. (2019). Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis. Stroke, 50(8), 2187-2196. https://doi.org/10.1161/strokeaha.119.025019

• Journal Article Type: Article
• Acceptance Date: Apr 25, 2019
• Online Publication Date: Jun 10, 2019
• Publication Date: 2019-08
• Deposit Date: Jun 13, 2019
• Publicly Available Date: Jun 17, 2019
• Journal: Stroke
• Print ISSN: 0039-2499
• Electronic ISSN: 1524-4628
• Publisher: American Heart Association
• Peer Reviewed: Peer Reviewed
• Volume: 50
• Issue: 8
• Pages: 2187-2196
• DOI: https://doi.org/10.1161/strokeaha.119.025019
• Keywords: Advanced and Specialised Nursing; Clinical Neurology; Cardiology and Cardiovascular Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2183852
• Publisher URL: https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.025019
• Contract Date: Jun 14, 2019