Background Randomized clinical trials (RCTs) generally assess efficacy and safety separately, with the conclusion of whether a treatment is beneficial based solely on the efficacy endpoint. However, assessing and combining efficacy and safety domains, using a single composite outcome measure, can provide a more comprehensive assessment of the overall effect of a treatment. Furthermore, composite outcomes can incorporate information regarding the relationship between the individual outcomes. In fact, such outcomes have been suggested in the clinical trials literature for at least 15 years.
Objectives To (1) identify whether recent primary publications of chronic pain RCTs from major pain journals included a composite outcome measure of benefits and harms and (2) discuss the potential benefits of such outcomes in various stages of treatment development, including as outcome measures in RCTs, and to support decisions of Data and Safety Monitoring Boards and ordering of treatments in the context of treatment guidelines.
Evidence review RCTs published in 6 major pain journals published between 2016 and 2021 that investigated interventions for chronic pain were reviewed.
Findings Of 73 RCTs identified, only 2 included a composite outcome measure of benefits and harms. Both of these articles compared 2 active treatments.
Conclusions Composite outcomes of benefits and harms are underutilized in chronic pain RCTs. The advantages and challenges of using such outcomes are discussed.
- pain management
- chronic pain
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MN and RM are joint first authors.
Funding This study was supported by funding from the National Institutes of Health (K24NS126861- PI Gewandter) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The views expressed in this article are those of the authors, and no official endorsement by the Food and Drug Administration (FDA) or the companies that provided support for the ACTTION public-private partnership should be inferred. Financial support for this project was provided by the ACTTION public-private partnership, which has received research contracts, grants, or other revenue from the FDA, multiple pharmaceutical and device companies, philanthropy, royalties, and other sources (a list of industry sponsors can be found at https://www.acttion.org/partners).
Competing interests RHD has received in the past 5 years research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health, and compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CoimbiGene, 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, Teva, Theranexus, Vertex, Vizuri, and WCG. JG, in the past 36 months, has received (unrelated to this work) grant support from the NIH and Neurometrix, consulting income from AlgoTX, GW pharmaceuticals, Eikonozo, and Saluda, and shares for consulting from Eisana Corp. DL, in the past 36 months, has received (unrelated to this work) support from the NIH and the US Food & Drug Administration. DT, in the last 36 months, have received (unrelated to this work) grant support from NIH and NIOSH, consulting fees from Eli Lilly, Pfizer, GSK/Novartis, and Omnicom Health Group, and is Editor-in-Chief of the Clinical Journal of Pain.
Provenance and peer review Not commissioned; externally peer reviewed.
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