Joint hypothesis testing and gatekeeping procedures for studies with multiple endpoints

Anesthesia and Analgesia
Edward J Mascha, Alparslan Turan

Abstract

A claim of superiority of one intervention over another often depends naturally on results from several outcomes of interest. For such studies the common practice of making conclusions about individual outcomes in isolation can be problematic. For example, an intervention might be shown to improve one outcome (e.g., pain score) but worsen another (e.g., opioid consumption), making interpretation difficult. We thus advocate joint hypothesis testing, in which the decision rule used to claim success of an intervention over its comparator with regard to the multiple outcomes are specified a priori, and the overall type I error is protected. Success might be claimed only if there is a significant improvement detected in all primary outcomes, or alternatively, in at least one of them. We focus more specifically on demonstrating superiority on at least one outcome and noninferiority (i.e., not worse) on the rest. We also advocate the more general "gatekeeping" procedures (both serial and parallel), in which primary and secondary hypotheses of interest are a priori organized into ordered sets, and testing does not proceed to the next set, i.e., through the "gate," unless the significance criteria for the previous sets are satisfied, th...Continue Reading

Associated Clinical Trials

Jun 7, 2018·Brian M. Ilfeld, MD, MSBrian M. Ilfeld, MD, MS

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Citations

Feb 26, 2013·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Ricardo RiverosJulie Niezgoda
Jun 8, 2013·The Journal of Pain : Official Journal of the American Pain Society·Feng DaiLi Qin
Dec 7, 2014·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Jiang WuDaniel I Sessler
May 30, 2016·The Journal of Thoracic and Cardiovascular Surgery·Negmeldeen F MamounAndra E Duncan
May 16, 2017·Journal of Clinical Epidemiology·Paco M WelsingUNKNOWN Work Package 3 of the GetReal Consortium
Jun 21, 2017·Anesthesia and Analgesia·Lars Peter Kloster AndersenMads Utke Werner
Jan 19, 2018·Anesthesia and Analgesia·Edward J Mascha, Thomas R Vetter
Dec 10, 2015·Regional Anesthesia and Pain Medicine·Abdullah S TerkawiMarcel E Durieux
Sep 18, 2015·Anesthesia and Analgesia·Daniel I Sessler, Peter B Imrey
Jun 8, 2017·Journal of Patient Safety·Jeffrey R DanielsSorin J Brull
Mar 19, 2015·Anesthesiology·Ehab FaragDaniel I Sessler
Dec 7, 2016·Statistical Methods in Medical Research·Roland A MatsouakaRebecca A Betensky
Nov 20, 2019·Anesthesia and Analgesia·Glenn S MurphyEdward J Mascha
Oct 18, 2020·Journal of Cardiothoracic and Vascular Anesthesia·Donn A MarciniakDaniel P Raymond

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