Added Value of a Blinded Outcome Adjudication Committee in an Open-Label Randomized Stroke Trial
Authors: van der Ende Nadinda A.M. , Roozenbeek Bob , Berkhemer Olvert A. , Koudstaal Peter J. , Boiten Jelis , van Dijk Ewoud J. , Roos Yvo B.W.E.M. , van Oostenbrugge Robert J. , Majoie Charles B.L.M. , van Zwam Wim , Lingsma Hester F. , van der Lugt Aad , Dippel Diederik W.J. , Fransen Puck S.S. , Beumer Debbie , van den Berg Lucie A. , Yoo Albert J. , Schonewille Wouter J. , Vos Jan Albert , Nederkoorn Paul J. , Wermer Marieke J.H. , van Walderveen Marianne A.A. , Staals Julie , Hofmeijer Jeannette , van Oostayen Jacques A. , Lycklama a Nijeholt Geert J. , Brouwer Patrick A. , Emmer Bart J. , de Bruijn Sebastiaan F. , van Dijk Lukas C. , Kappelle L. Jaap , Lo Rob H. , de Vries Joost , de Kort Paul L.M. , van Rooij Willem Jan J. , van den Berg Jan S.P. , van Hasselt Boudewijn A.A.M. , Aerden Leo A.M. , Dallinga Rene J. , Visser Marieke C. , Bot Joseph C.J. , Vroomen Patrick C. , Eshghi Omid , Schreuder Tobien H.C.M.L. , Heijboer Roel J.J. , Keizer Koos , Tielbeek Alexander V. , den Hertog Heleen M. , Gerrits Dick G. , van den Berg-Vos Renske M. , Karas Giorgos B. , Steyerberg Ewout W. , Flach H. Zwenneke , Marquering Henk A. , Sprengers Marieke E.S. , Jenniskens Sjoerd F.M. , Beenen Ludo F.M. , van den Berg Rene 
Published: October 2021

Background and Purpose:

Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design.

Methods:

We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression.

Results:

In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (
P
=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]).

Conclusions:

Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation.

Registration:

URL:
https://www.isrctn.com
; Unique identifier: ISRCTN10888758.