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

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults
Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults
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.
Clinical trial, Drug registration, Guidelines, Recommendations, Sarcopenia, Treatment
1594-0667
Reginster, Jean Yves
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Beaudart, Charlotte
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Al-Daghri, Nasser M.
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Avouac, Bernard
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Bauer, Jurgen
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Bere, Nathalie
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Bruyère, Olivier
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Cerreta, Francesca
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Cesari, Matteo
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Rosa, Mario Miguel
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Cooper, Cyrus
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Cruz-Jentoft, Alfonso Jose
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Dennison, Elaine
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Geerinck, Anton
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Gielen, Evelien
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Landi, Francesco
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Laslop, Andrea
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Maggi, Stefania
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Prieto Yerro, María Concepción
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Rizzoli, Rene
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Sundseth, Hildrun
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Sieber, Cornel
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Trombetti, Andrea
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Vellas, Bruno
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Veronese, Nicola
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Visser, Marjolein
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Vlaskovska, Mila
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Fielding, Roger A.
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Reginster, Jean Yves
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Beaudart, Charlotte
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Al-Daghri, Nasser M.
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Avouac, Bernard
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Bauer, Jurgen
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Bere, Nathalie
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Bruyère, Olivier
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Cerreta, Francesca
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Cesari, Matteo
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Rosa, Mario Miguel
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Cooper, Cyrus
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Cruz-Jentoft, Alfonso Jose
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Dennison, Elaine
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Geerinck, Anton
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Gielen, Evelien
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Landi, Francesco
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Laslop, Andrea
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Maggi, Stefania
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Prieto Yerro, María Concepción
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Rizzoli, Rene
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Sundseth, Hildrun
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Sieber, Cornel
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Trombetti, Andrea
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Vellas, Bruno
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Veronese, Nicola
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Visser, Marjolein
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Vlaskovska, Mila
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Fielding, Roger A.
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Reginster, Jean Yves, Beaudart, Charlotte, Al-Daghri, Nasser M., Avouac, Bernard, Bauer, Jurgen, Bere, Nathalie, Bruyère, Olivier, Cerreta, Francesca, Cesari, Matteo, Rosa, Mario Miguel, Cooper, Cyrus, Cruz-Jentoft, Alfonso Jose, Dennison, Elaine, Geerinck, Anton, Gielen, Evelien, Landi, Francesco, Laslop, Andrea, Maggi, Stefania, Prieto Yerro, María Concepción, Rizzoli, Rene, Sundseth, Hildrun, Sieber, Cornel, Trombetti, Andrea, Vellas, Bruno, Veronese, Nicola, Visser, Marjolein, Vlaskovska, Mila and Fielding, Roger 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 and Experimental Research. (doi:10.1007/s40520-020-01663-4).

Record type: Review

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.

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ESCEO WG RCT in sarc - FINAL14072020 - Accepted Manuscript
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Accepted/In Press date: 16 July 2020
Published date: 31 July 2020
Additional Information: Publisher Copyright: © 2020, The Author(s).
Keywords: Clinical trial, Drug registration, Guidelines, Recommendations, Sarcopenia, Treatment

Identifiers

Local EPrints ID: 443252
URI: http://eprints.soton.ac.uk/id/eprint/443252
ISSN: 1594-0667
PURE UUID: f05fd6e0-2109-4115-b433-8855a77fc9a3
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961

Catalogue record

Date deposited: 19 Aug 2020 16:31
Last modified: 18 Mar 2024 02:46

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Contributors

Author: Jean Yves Reginster
Author: Charlotte Beaudart
Author: Nasser M. Al-Daghri
Author: Bernard Avouac
Author: Jurgen Bauer
Author: Nathalie Bere
Author: Olivier Bruyère
Author: Francesca Cerreta
Author: Matteo Cesari
Author: Mario Miguel Rosa
Author: Cyrus Cooper ORCID iD
Author: Alfonso Jose Cruz-Jentoft
Author: Elaine Dennison ORCID iD
Author: Anton Geerinck
Author: Evelien Gielen
Author: Francesco Landi
Author: Andrea Laslop
Author: Stefania Maggi
Author: María Concepción Prieto Yerro
Author: Rene Rizzoli
Author: Hildrun Sundseth
Author: Cornel Sieber
Author: Andrea Trombetti
Author: Bruno Vellas
Author: Nicola Veronese
Author: Marjolein Visser
Author: Mila Vlaskovska
Author: Roger A. Fielding

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