Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations from Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III

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  • Denham S. Ward
  • Anthony R. Absalom
  • Leanne M. Aitken
  • Michele C. Balas
  • David L. Brown
  • Lisa Burry
  • Elizabeth Colantuoni
  • Douglas Coursin
  • John W. Devlin
  • Franklin Dexter
  • Robert H. Dworkin
  • Talmage D. Egan
  • Doug Elliott
  • Pamela Flood
  • Gilles L. Fraser
  • Timothy D. Girard
  • David Gozal
  • Ramona O. Hopkins
  • John Kress
  • Mervyn Maze
  • Dale M. Needham
  • Pratik Pandharipande
  • Richard Riker
  • Daniel I. Sessler
  • Steven L. Shafer
  • Yahya Shehabi
  • Claudia Spies
  • Lena S. Sun
  • Avery Tung
  • Richard D. Urman

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

OriginalsprogEngelsk
TidsskriftCritical Care Medicine
Vol/bind49
Udgave nummer10
Sider (fra-til)1684-1693
Antal sider10
ISSN0090-3493
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Drs. Ward, Aitken, Colantuoni, Maze, and Needham received funding from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, and Networks (ACTTION). Dr. Ward received support for article research from the University of Rochester Maine Medical Center Spectrum Medical Partners. Dr. Absalom’s institution received funding from The Medicines Company, Carefusion (BD), and Rigel; he received support for article research from Philips, Janssen Pharma, Johnson & Johnson, Ever Pharma, Orion, and Paion. Drs. Aitken, Brown, and Coursin received funding from Innovations Consulting Group LLC. Dr. Aitken also received funding from Elsevier Australia. Dr. Balas’ institution received funding from the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, AACN research grant; she received funding from H3C and received support for article research from the NIH. Dr. Colantuoni received support for article research from ACTTION. Dr. Dexter received funding from the Division of Management Consulting of the University of Iowa’s Department of Anesthesia. Dr. Dworkin’s institution received funding from the U.S. Food and Drug Administration (FDA); he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Collegium, Concert, Coronado, Daiichi Sankyo, Decibel, Dong-A, Editas, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Lotus Clinical Research, Mainstay, Medavante, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, NSGene, Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sanifit, Scilex, Semnur, SK Life Sciences, Sollis, Spinifex, Syntrix, Teva, Thar, Theranexus, Trevena, Vertex, and Vizuri. Dr. Girard received funding from Haisco Pharmaceutical. Dr. Hopkins’ institution received funding from Intermountain Medical and Research Foundation. Dr. Maze received funding from the University of California Office of the President and Cambridge University Press; he received support for article research from the NIH. Dr. Needham received funding from the FDA, Haisco-USA Pharmaceuticals, GlaxoSmithKline, and Novartis Pharma; he disclosed he is a principal investigator on a NIH-funded, multicentered randomized trial (R01HL132887) funded by Baxter Healthcare Corporation and Reck Medical Devices. Dr. Pandharipande’s institution received funding from Pfizer. Dr. Shehabi’s institution received funding from Orion Pharma and Pfizer; he received funding from Pfizer, Orion Pharma, Abbott Laboratories, and Ever Pharma. Dr. Sun received funding from UpToDate; she disclosed she is the Editor in Chief for UpToDate/Anesthesiology. Dr. Tung received funding from Anesthesia and Analgesia. Dr. Urman’s institution received funding from Medtronic/Covidien and AcelRx; he received funding from Merck, Sandoz, Heron, Takeda, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Funding Information:
Supported, in part, by Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, which has received research contracts, grants, or other revenue from the Food and Drug Administration, multiple pharmaceutical and device companies, philanthropy, and other sources.

Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.

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