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Outcome assessment by central adjudicators in randomised stroke trials: Simulation of differential and non-differential misclassification

Godolphin, PJ; Bath, PM; Partlett, C; Berge, E; Brown, MM; Eliasziw, M; Sandset, PM; ... Montgomery, AA; + view all (2020) Outcome assessment by central adjudicators in randomised stroke trials: Simulation of differential and non-differential misclassification. European Stroke Journal 10.1177/2396987320910047. (In press). Green open access

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Abstract

INTRODUCTION: Adjudication of the primary outcome in randomised trials is thought to control misclassification. We investigated the amount of misclassification needed before adjudication changed the primary trial results. Patients (or materials) and methods: We included data from five randomised stroke trials. Differential misclassification was introduced for each primary outcome until the estimated treatment effect was altered. This was simulated 1000 times. We calculated the between-simulation mean proportion of participants that needed to be differentially misclassified to alter the treatment effect. In addition, we simulated hypothetical trials with a binary outcome and varying sample size (1000–10,000), overall event rate (10%–50%) and treatment effect (0.67–0.90). We introduced non-differential misclassification until the treatment effect was non-significant at 5% level. RESULTS: For the five trials, the range of unweighted kappa values were reduced from 0.89–0.97 to 0.65–0.85 before the treatment effect was altered. This corresponded to 2.1%–6% of participants misclassified differentially for trials with a binary outcome. For the hypothetical trials, those with a larger sample size, stronger treatment effect and overall event rate closer to 50% needed a higher proportion of events non-differentially misclassified before the treatment effect became non-significant. DISCUSSION: We found that only a small amount of differential misclassification was required before adjudication altered the primary trial results, whereas a considerable proportion of participants needed to be misclassified non-differentially before adjudication changed trial conclusions. Given that differential misclassification should not occur in trials with sufficient blinding, these results suggest that central adjudication is of most use in studies with unblinded outcome assessment. CONCLUSION: For trials without adequate blinding, central adjudication is vital to control for differential misclassification. However, for large blinded trials, adjudication is of less importance and may not be necessary.

Type: Article
Title: Outcome assessment by central adjudicators in randomised stroke trials: Simulation of differential and non-differential misclassification
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/2396987320910047
Publisher version: https://doi.org/10.1177%2F2396987320910047
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Adjudication, stroke, clinical trial, simulation, detection bias, misclassification
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10092472
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