TY - JOUR
T1 - Added Value of a Blinded Outcome Adjudication Committee in an Open-Label Randomized Stroke Trial
AU - van der Ende, Nadinda A. M.
AU - Roozenbeek, Bob
AU - Berkhemer, Olvert A.
AU - Koudstaal, Peter J.
AU - Boiten, Jelis
AU - van Dijk, Ewoud J.
AU - Roos, Yvo B. W. E. M.
AU - van Oostenbrugge, Robert J.
AU - Majoie, Charles B. L. M.
AU - van Zwam, Wim
AU - Lingsma, Hester F.
AU - van der Lugt, Aad
AU - Dippel, Diederik W. J.
N1 - Funding Information: The MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) was partly funded by the Dutch Heart Foundation and by unrestricted grants from Angiocare BV, Medtronic/Covidien/EV3, MEDAC gmbh/LAMEPRO, Penumbra Inc, Stryker, and Top Medical/Concentric. All funding sources had no role in the study design and conduct; collection, management, analysis, and interpretation of data; preparation, review, or approval of the article; and decision to submit the article for publication. Funding Information: Drs Dippel and van der Lugt report funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC, and Cerenovus for research, all paid to institution. Dr van Zwam reports speaker fees from Stryker and Cerenovus, paid to institution. Dr Majoie is a recipient of research grants from CVON/Dutch Heart Foundation, European Commission, Dutch Healt Evaluation Program, TWIN Foundation and Stryker, paid to the institution; and is a minority shareholder of Nico-lab. Dr Roos reports being a minority shareholder of Nico-lab. The other authors report no conflicts. Publisher Copyright: © 2021 The Authors. Stroke is published on behalf of the American Heart Association, Inc
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - Algorithm
KW - Clinical trial
KW - Ischemic stroke
KW - Odds ratio
KW - Telephone
UR - http://www.scopus.com/inward/record.url?scp=85122376209&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/STROKEAHA.121.035301
DO - https://doi.org/10.1161/STROKEAHA.121.035301
M3 - Article
C2 - 34607469
SN - 0039-2499
VL - 53
SP - 61
EP - 69
JO - Stroke
JF - Stroke
IS - 1
ER -