Jean-Yves Reginster1, Charlotte Beaudart2, Nasser Al-Daghri3, Bernard Avouac4, Jürgen Bauer5, Nathalie Bere6, Olivier Bruyère1, Francesca Cerreta6, Matteo Cesari7,8, Mario Miguel Rosa9, Cyrus Cooper10, Alfonso J Cruz Jentoft11, Elaine Dennison10, Anton Geerinck1, Evelien Gielen12,13, Francesco Landi14, Andrea Laslop15, Stefania Maggi16, María Concepción Prieto Yerro17, René Rizzoli18, Hildrun Sundseth19, Cornel Sieber20,21, Andrea Trombetti18, Bruno Vellas22, Nicola Veronese23, Marjolein Visser24, Mila Vlaskovska25, Roger A Fielding26. 1. WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Avenue Hippocrate 13, CHU B23, 4000, Liege, Belgium. 2. WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Avenue Hippocrate 13, CHU B23, 4000, Liege, Belgium. c.beaudart@uliege.be. 3. Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. 4. Department of Rheumatology, CHU Henri Mondor, Creteil, France. 5. Center for Geriatric Medicine and Network Aging Research, Heidelberg University, Heidelberg, Germany. 6. European Medicines Agency, Amsterdam, The Netherlands. 7. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 8. Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 9. Departamento de Neurociências/Laboratório de Farmacologia Clínica E Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. 10. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK. 11. Hospital Universitario Ramón Y Cajal (IRYCIS), Madrid, Spain. 12. Division of Geriatrics, UZ Leuven, Leuven, Belgium. 13. Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. 14. Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart Rome, Milan, Italy. 15. Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria. 16. CNR Aging Branch-IN, Padua, Italy. 17. Agencia Española de Medicamentos Y Productos Sanitarios, Madrid, Spain. 18. Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 19. European Institute of Women's Health, Dublin, Ireland. 20. Institute for Biomedicine of Aging Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. 21. Kantonsspital Winterthur, Winterthur, Switzerland. 22. Department of Internal and Geriatrics Medicine, Gerontopole, CHU de Toulouse, UMR 1027 INSERM, University Toulouse III, Toulouse, France. 23. Department of Internal Medicine, Geriatrics Section, University of Palermo, Palermo, Italy. 24. Department of Health Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 25. Medical Faculty, Department of Pharmacology and Toxicology, Medical University Sofia, Sofia, Bulgaria. 26. Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center On Aging, Tufts University, Boston, USA.
Abstract
BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.
BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.
Entities:
Keywords:
Clinical trial; Drug registration; Guidelines; Recommendations; Sarcopenia; Treatment
Authors: Mansour Ghasemikaram; Oliver Chaudry; Armin M Nagel; Michael Uder; Franz Jakob; Wolfgang Kemmler; Matthias Kohl; Klaus Engelke Journal: Geroscience Date: 2021-01-15 Impact factor: 7.713
Authors: A Geerinck; C Beaudart; J-Y Reginster; M Locquet; C Monseur; S Gillain; O Bruyère Journal: Qual Life Res Date: 2021-03-30 Impact factor: 4.147
Authors: Charlotte S Kramer; Inge Groenendijk; Sonja Beers; Hugo H Wijnen; Ondine van de Rest; Lisette C P G M de Groot Journal: Curr Dev Nutr Date: 2022-01-29