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

Peter J. Godolphin; Philip M. Bath; Ale Algra; Eivind Berge; Martin M. Brown; John Chalmers; Lelia Duley; Misha Eliasziw; John Gregson; Jacoba P. Greving; Graeme J. Hankey; Naohisa Hosomi; S. Claiborne Johnston; Emily Patsko; Annamarei Ranta; Per Morten Sandset; Joaquin Serena; Christian Weimar; Alan A. Montgomery; S. C. Knipp; R. P. Giugliano; L. H. Bonati; Y. Nagai; M. Matsumoto; H. J. M. Barnett; A. J. Fox; M. Farrant; J. D. Easton; J. J. Elm; B. Neal; H. Arima; J. Serena; A. Davalos; P. Amarenco; S. Evans; N. Sprigg; R. Dineen; J. W. Eikelboom; C. Chen

doi:10.1161/STROKEAHA.119.025019

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

Peter J. Godolphin, Philip M. Bath, Ale Algra, Eivind Berge, Martin M. Brown, John Chalmers, Lelia Duley, Misha Eliasziw, John Gregson, Jacoba P. Greving, Graeme J. Hankey, Naohisa Hosomi, S. Claiborne Johnston, Emily Patsko, Annamarei Ranta, Per Morten Sandset, Joaquin Serena, Christian Weimar, Alan A. Montgomery, S. C. KnippR. P. Giugliano, L. H. Bonati, Y. Nagai, M. Matsumoto, H. J. M. Barnett, A. J. Fox, M. Farrant, J. D. Easton, J. J. Elm, B. Neal, H. Arima, J. Serena, A. Davalos, P. Amarenco, S. Evans, N. Sprigg, R. Dineen, J. W. Eikelboom, C. Chen

Research output: Contribution to journal › Review article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2187-2196
Number of pages	10
Journal	Stroke
Volume	50
Issue number	8
DOIs	https://doi.org/10.1161/STROKEAHA.119.025019
Publication status	Published - Aug 2019

Keywords

adjudication
clinical trial
meta-analysis
stroke
systematic review

Access to Document

10.1161/STROKEAHA.119.025019

Cite this

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., ... Chen, C. (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

@article{17400ec357b0467ba257f8caab5958cc,

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

abstract = "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.",

keywords = "adjudication, clinical trial, meta-analysis, stroke, systematic review",

author = "Godolphin, {Peter J.} and Bath, {Philip M.} and Ale Algra and Eivind Berge and Brown, {Martin M.} and John Chalmers and Lelia Duley and Misha Eliasziw and John Gregson and Greving, {Jacoba P.} and Hankey, {Graeme J.} and Naohisa Hosomi and Johnston, {S. Claiborne} and Emily Patsko and Annamarei Ranta and Sandset, {Per Morten} and Joaquin Serena and Christian Weimar and Montgomery, {Alan A.} and Knipp, {S. C.} and Giugliano, {R. P.} and Bonati, {L. H.} and Y. Nagai and M. Matsumoto and Barnett, {H. J. M.} and Fox, {A. J.} and M. Farrant and Easton, {J. D.} and Elm, {J. J.} and B. Neal and H. Arima and J. Serena and A. Davalos and P. Amarenco and S. Evans and N. Sprigg and R. Dineen and Eikelboom, {J. W.} and C. Chen",

note = "Publisher Copyright: {\textcopyright} 2019 American Heart Association, Inc.",

year = "2019",

month = aug,

doi = "10.1161/STROKEAHA.119.025019",

language = "English",

volume = "50",

pages = "2187--2196",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams & Wilkins",

number = "8",

}

Godolphin, PJ, Bath, PM, Algra, A, Berge, E, Brown, MM, Chalmers, J, Duley, L, Eliasziw, M, Gregson, J, Greving, JP, Hankey, GJ, Hosomi, N, Johnston, SC, Patsko, E, Ranta, A, Sandset, PM, Serena, J, Weimar, C, Montgomery, AA, Knipp, SC, Giugliano, RP, Bonati, LH, Nagai, Y, Matsumoto, M, Barnett, HJM, Fox, AJ, Farrant, M, Easton, JD, Elm, JJ, Neal, B, Arima, H, Serena, J, Davalos, A, Amarenco, P, Evans, S, Sprigg, N, Dineen, R, Eikelboom, JW & Chen, C 2019, 'Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis', Stroke, vol. 50, no. 8, pp. 2187-2196. https://doi.org/10.1161/STROKEAHA.119.025019

TY - JOUR

T1 - Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis

AU - Godolphin, Peter J.

AU - Bath, Philip M.

AU - Algra, Ale

AU - Berge, Eivind

AU - Brown, Martin M.

AU - Chalmers, John

AU - Duley, Lelia

AU - Eliasziw, Misha

AU - Gregson, John

AU - Greving, Jacoba P.

AU - Hankey, Graeme J.

AU - Hosomi, Naohisa

AU - Johnston, S. Claiborne

AU - Patsko, Emily

AU - Ranta, Annamarei

AU - Sandset, Per Morten

AU - Serena, Joaquin

AU - Weimar, Christian

AU - Montgomery, Alan A.

AU - Knipp, S. C.

AU - Giugliano, R. P.

AU - Bonati, L. H.

AU - Nagai, Y.

AU - Matsumoto, M.

AU - Barnett, H. J. M.

AU - Fox, A. J.

AU - Farrant, M.

AU - Easton, J. D.

AU - Elm, J. J.

AU - Neal, B.

AU - Arima, H.

AU - Serena, J.

AU - Davalos, A.

AU - Amarenco, P.

AU - Evans, S.

AU - Sprigg, N.

AU - Dineen, R.

AU - Eikelboom, J. W.

AU - Chen, C.

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

KW - adjudication

KW - clinical trial

KW - meta-analysis

KW - stroke

KW - systematic review

U2 - 10.1161/STROKEAHA.119.025019

DO - 10.1161/STROKEAHA.119.025019

M3 - Review article

SN - 0039-2499

VL - 50

SP - 2187

EP - 2196

JO - Stroke

JF - Stroke

IS - 8

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this