Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia

Aging Clinical and Experimental Research, Dec 2015

Purpose Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. Methods A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication. Results A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. Conclusions The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk.

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Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia

Aging Clin Exp Res Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia Jean-Yves Reginster 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Cyrus Cooper 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Rene´ Rizzoli 0 1 2 3 4 5 6 7 8 9 10 11 12 13 John A. Kanis 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Geoff Appelboom 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Ivan Bautmans 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Heike A. Bischoff-Ferrari 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Maarten Boers 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Maria Luisa Brandi 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Olivier Bruye`re 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Antonio Cherubini 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Bruno Flamion 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Roger A. Fielding 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Andrea Ildiko Gasparik 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Luc Van Loon 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Eugene McCloskey 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Bruce H. Mitlak 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Alberto Pilotto 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Suzanne Reiter-Niesert 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Yves Rolland 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Yannis Tsouderos 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Marjolein Visser 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Alfonso J. Cruz-Jentoft 0 1 2 3 4 5 6 7 8 9 10 11 12 13 0 MRC Lifecourse Epidemiology Unit, University of Southampton , Southampton , UK 1 Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur , Namur , Belgium 2 Department of Public Health, Epidemiology and Health Economics, University of Liege , CHU Sart Tilman B23, 4000 Lie`ge , Belgium 3 Geriatrics and Geriatric Emergency Care, IRCCS-INRCA , Ancona , Italy 4 Department of Public Health and Health Management, University of Medicine and Pharmacy of Tirgu Mures , Tirgu Mures , Romania 5 & Olivier Bruye`re 6 Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston , USA 7 Department of Internal Medicine, University of Florence , Florence , Italy 8 Department of Epidemiology and Biostatistics; and Amsterdam Rheumatology and Immunology Center, VU University Medical Center , Amsterdam , Netherlands 9 Gerontology and Frailty in Ageing Research Department, Vrije Universiteit Brussel (VUB) , Brussels , Belgium 10 Columbia University Medical Center, The Neurological Institute , New York , USA 11 Centre for Metabolic Bone Diseases, and Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield , Sheffield , UK 12 Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine , Geneva , Switzerland 13 NIHR Musculoskeletal Biomedical Research Unit, University of Oxford , Oxford , UK Purpose Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disA multidisciplinary expert working group was ability and premature death. It has a high prevalence in hosted by the European Society for Clinical and Economic older populations and presents a considerable social and Aspects ment of pharmaceutical treatments for that indication. Results Osteoporosis - and Osteoarthritis, which economic burden. Potential treatments are under developreviewed and discussed the recent literature from a perment but, as yet, no guidelines support regulatory studies spective of clinical experience and guideline development. for new drugs to manage sarcopenia. The objective of this Relevant parallels were drawn from the development of position paper is therefore to suggest a set of potential definition of osteoporosis as a disease and clinical assessendpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. Methods A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or 8 9 Department of Geriatrics, University Hospital of Zurich, Zurich, Switzerland treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. Conclusions The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk. Sarcopenia Public health Frailty Introduction Sarcopenia is a syndrome characterised by progressive and generalized loss of skeletal muscle mass and strength; it is a major pathway leading to physical frailty [ 1 ]. Since, the loss of muscle mass and strength is inherent in normal ageing, the switch towards a pathological condition must be established empirically, by the combination of diagnostic thresholds and associated risk of mobility-related outcomes, poor quality of life and death [ 2–4 ]. (...truncated)


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Jean-Yves Reginster, Cyrus Cooper, René Rizzoli, John A. Kanis, Geoff Appelboom, Ivan Bautmans, Heike A. Bischoff-Ferrari, Maarten Boers, Maria Luisa Brandi, Olivier Bruyère, Antonio Cherubini, Bruno Flamion, Roger A. Fielding, Andrea Ildiko Gasparik, Luc Van Loon, Eugene McCloskey, Bruce H. Mitlak, Alberto Pilotto, Suzanne Reiter-Niesert, Yves Rolland, Yannis Tsouderos, Marjolein Visser, Alfonso J. Cruz-Jentoft. Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia, Aging Clinical and Experimental Research, 2016, pp. 47-58, Volume 28, Issue 1, DOI: 10.1007/s40520-015-0517-y