Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults

Authors: REGINSTER, JEAN YVES - University Of Liege; BEAUDART, CHARLOTTE - University Of Liege; AL-DAGHRI, NASSER - King Saud University; AVOUAC, BERNARD - Henri Mondor University Hospital; BAUER, JURGEN - Heidelberg University; BERE, NATHALIE - European Medicines Agency; BRUYERE, OLIVIER - University Of Liege; CERRETA, FRANCESCA - European Medicines Agency; CESARI, MATTEO - University Of Milan; ROSA, MARIO MIGUEL - University Of Lisbon; COOPER, CYRUS - University Of Southampton; CRUZ JENTOFT, ALFONSO - Hospital Ramon Y Cajal; DENNISON, ELAINE - University Of Southampton; GEERINCK, ANTON - University Of Liege; GIELEN, EVELIEN - University Of Leuven; LANDI, FRANCESCO - Catholic University Of The Sacred Heart Italy; LASLOP, ANDREA - Austrian Federal Office For Safety In Health Care; MAGGI, STEFANIA - Consiglio Nazionale Delle Ricerche; CONCEPCION PRIETO, YERRMARIA - Spanish Agency Of Medicines And Medical Products; RIZZOLI, RENE - University Hospitals Of Geneva; SUNDSETH, HILDRUN - European Institute Of Women’s Health; SIEBER, CORNEL - Friedrich-Alexander University; TROMBETTI, ANDREA - Geneva University Hospital; VELLAS, BRUNO - Gerontopole De Toulouse Center Hospital University; VERONESE, NICOLA - University Of Palermo Italy; VISSER, MARJOLEIN - Vrije University; VLASKOVSKA, MILA - Reina Sofia University; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Aging Clinical and Experimental Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/16/2020
Publication Date: 7/31/2020
Citation: Reginster, J., Beaudart, C., Al-Daghri, N., Avouac, B., Bauer, J., Bere, N., Bruyere, O., Cerreta, F., Cesari, M., Rosa, M., Cooper, C., Cruz Jentoft, A.J., Dennison, E., Geerinck, A., Gielen, E., Landi, F., Laslop, A., Maggi, S., Concepcion Prieto, Y., Rizzoli, R., Sundseth, H., Sieber, C., Trombetti, A., Vellas, B., Veronese, N., Visser, M., Vlaskovska, M., Fielding, R.A. 2020. Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults. Aging Clinical Experimental Research. https://doi.org/10.1007/s40520-020-01663-4.
DOI: https://doi.org/10.1007/s40520-020-01663-4

Interpretive Summary: In 2016, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for medicines to prevent or treat sarcopenia. In this recent paper we updated the previous recommendations in accordance with the evidence that has become available since our original recommendations. We conducted literature reviews and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. We recommended that the randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both early and later phase trial. The length of treatment and follow-up should optimally be 6 to 12 months for all trials. Participants in these trials should be at least 70-years-old and have a combination of low muscle strength and low physical performance to be enrolled. Multiple study measures are recommended for early phase trials, including, as example, physical performance, muscle strength and mass, and muscle-bone interaction. For larger later phase trials, we recommended that study measures should include both measures of physical function and self-reported measures of how a patient feels or functions (Patient Reported Outcomes) These recommendation should help advance the field by allowing better comparison across studies and develop promising therapies for sarcopenia.

Technical Abstract: 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.