Objectives: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia., Design: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions., Setting: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus., Subjects: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience., Interventions: None., Measurements and Main Results: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium., Conclusions: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients., Competing Interests: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article, and no official endorsement by the U.S. Food and Drug Administration or those entities that provided grants to support the activities of the Analgesic, Anesthetic, Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership. Drs. Lee, Jackson, Biagas, Houck, Smith, Ward, Zimmerman, and Huang received funding from Analgesic, Anesthetic, Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION). Dr. Beers disclosed that she is part-time ad hoc faculty at the University of Pittsburgh. Dr. Berkenbosch received funding from Innovation Consulting; he disclosed that he is a consulting bureau member for Medtronic; and he received support for article research from ACTTION-Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER)-public-private consortium with the U.S. Food and Drug Administration (FDA). Dr. Dworkin’s institution received funding from the FDA; he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CombiGene, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, GlaxoSmithKline, Glenmark, Gloriana, Hope, Kriya, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OliPass, Orion, Oxford Cannabinoid Technologies, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Rho, Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPM Therapeutics, SPRIM Health, Teva, Theranexus, Vertex, Vizuri, and WCG. Dr. Smith received funding for an ongoing sedation trial in mechanically ventilated pediatric patients from the National Heart, Lung, and Blood Institute. Dr. Ward received funding from the Maine State Board of Education. Dr. Zimmerman’s institution received funding from the National Institutes of Health (NIH), the FDA, and the Biogen Foundation. Dr. Horvat’s institution received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke. Drs. Horvat and Sun received support for article research from the NIH. Drs. Salorio and Slomine received funding from the Innovations Consulting Group. Dr. Slater’s institution received funding from Wellcome and the Annabels Foundation; she received funding from Reckitt; she received support for article research from Wellcome Trust/Charity Open Access Fund. Dr. Slomine received funding from Cambridge University Press and Goodell, Devries, Leech & Dann, LLP. Dr. West disclosed that she is employed at Georgia Tech and that she is the President of International Children’s Advisory Network. Dr. Wypij received funding from SCEPTER IV. Dr. Yeates’ institution received funding from the Canadian Institutes of Health Research; he received funding from Guilford Publications and the American Psychological Association. Dr. Sun received funding from McGraw Hill; she disclosed that she is Co-Editor-in-Chief of Anesthesiology UpToDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)