A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Autor:	Ciani O; Centre for Research on Health and Social Care Management, SDA Bocconi School of Management, Milan, Italy., Manyara AM; MRC/CSO Social and Public Health Sciences Unit, School of Health and Wellbeing, University of Glasgow, Glasgow, UK., Davies P; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Stewart D; Patient and Public Involvement Partner, UK., Weir CJ; Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK., Young AE; Bristol NIHR Biomedical Research Centre, Bristol, UK., Blazeby J; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol NIHR Biomedical Research Centre, Bristol, UK.; University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK., Butcher NJ; Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada.; Department of Psychiatry, University of Toronto, Toronto, Canada., Bujkiewicz S; Biostatistics Research Group, Department of Population Health Sciences, University of Leicester, Leicester, UK., Chan AW; Women's College Research Institute, Toronto, Canada.; Department of Medicine, University of Toronto, Toronto, Canada., Dawoud D; Science, Evidence and Analytics Directorate, Science Policy and Research Programme, National Institute for Health and Care Excellence, London, UK., Offringa M; Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada.; Department of Paediatrics, University of Toronto, Toronto, Canada., Ouwens M; AstraZeneca, Mölndal, Sweden., Hróbjartssson A; Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Open Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark., Amstutz A; CLEAR Methods Center, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland., Bertolaccini L; Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy., Bruno VD; Department of Minimally Invasive Cardiac Surgery, IRCCS Galeazzi - Sant'Ambrogio Hospital, Milan, Italy., Devane D; University of Galway, Galway, Ireland.; Health Research Board-Trials Methodology Research Network, University of Galway, Galway, Ireland., Faria CDCM; Department of Physical Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Gilbert PB; Fred Hutchinson Cancer Centre, Seattle, USA., Harris R; Patient and Public Involvement Partner, UK., Lassere M; St George Hospital and School of Population Health, The University of New South Wales, Sydney, Australia., Marinelli L; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genoa, Italy.; IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Markham S; Department of Biostatistics, King's College London, London, UK., Powers JH; George Washington University School of Medicine, Washington, USA., Rezaei Y; Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.; Ardabil University of Medical Sciences, Ardabil, Iran.; Behyan Clinic, Pardis New Town, Tehran, Iran., Richert L; University Bordeaux, INSERM, Institut Bergonié, CHU Bordeaux, BPH U1219, CIC-EC 1401, RECaP and Euclid/F-CRIN, Bordeaux, France., Schwendicke F; Charité Universitätsmedizin Berlin, Berlin, Germany., Tereshchenko LG; Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Thoma A; McMaster University, Hamilton, Ontario, Canada., Turan A; Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, OH, USA., Worrall A; Patient and Public Involvement Partner, UK., Christensen R; Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen & Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark., Collins GS; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK., Ross JS; Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA.; Section of General Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Taylor RS; MRC/CSO Social and Public Health Sciences Unit, School of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2023 Oct 17; Vol. 65, pp. 102283. Date of Electronic Publication: 2023 Oct 17 (Print Publication: 2023).
DOI:	10.1016/j.eclinm.2023.102283
Abstrakt:	Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded. Competing Interests: Sylwia Bujkiewicz is a member of the NICE Decision Support Unit (DSU) and NICE Guidelines Technical Support Unit (TSU), has served as a paid consultant, providing methodological advice, to NICE, Roche, IQVIA and RTI Health Solutions, received payments for educational events from NICE and Roche and has received research funding from European Federation of Pharmaceutical Industries & Associations (EEPIA) and Johnson & Johnson. Mario Ouwens works for and has shares in AstraZeneca. Joseph Ross is an Associate Editor at BMJ and co-founder (unpaid) of medRxiv; research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International; expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. Nancy Butcher has received consulting fees from Nobias Therapeutics, Inc. Alain Amstutz and Yousef Rezaei are Associate Editors at BMC Trials. Robin Christensen is a founding member of the OMERACT Technical Advisory Group which might be perceived as a possible conflict of interest. Ray Harris has shares in Johnson and Johnson. John Powers has been a consultant for Adaptive Phage, Arrevus, Atheln, Bavaria Nordic, Cellularity, Eicos, Evofem, Eyecheck, Gilead, GSK, Mustang, OPKO, Otsuka, Resolve, Romark, SpineBioPPharma, UTIlity, Vir. Achilles Thoma received royalties from Springer Publishing for his book “Evidence Based Surgery: A Guide to Understanding and Interpreting the Surgical Literature”, 2019. (© 2023 The Author(s).)
Databáze:	MEDLINE
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