Sarcopenia is a nutrition-related skeletal muscle disease that occurs with advancing age and in many long-term conditions (2024 International Classification of Diseases ICD-10-CM Diagnosis Code M62.84: Sarcopenia) [1]. Originally first described as a “loss of muscle mass’’ [2], the knowledge about the disease has evolved in the last two decades, based on the progressive scientific findings and by consensus from the largest scientific societies and sarcopenia is focused on the loss of skeletal muscle function, particularly strength [3]. Several consecutive international definitions have been launched, being the most acknowledged one the revised version of the European Working Group on Sarcopenia in Older People, launched in 2019 [4], similarly adopted by the Asian Working Group for Sarcopenia in 2019 [5], and the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group in 2022 [6]. Global efforts are currently being undertaken to develop the globally acknowledged definition of the disease by the forthcoming Global Leadership Initiative on Sarcopenia, expected to be launched in 2024 [7].
One of the main reasons to understand the huge interest that sarcopenia arouses within the scientific and clinical community is because it is a reversible disease, as interventions on sarcopenia hold the potential to reverse or improve the disease, not solely one specific parameter of sarcopenia but sarcopenia itself. However, challenges linked to the nature of sarcopenia, such as the lack of a globally acknowledged definition until recent times and methodological issues, such as the challenge of conducting clinical trials in the target population, have interfered the development of interventions. Actions are needed to facilitate the development of more effective therapeutic interventions in sarcopenia.
An outcome is an endpoint or result used to assess the effect(s) of a disease, condition, intervention, treatment, or procedure and they serve to determine the efficacy and safety of the intervention being studied in clinical trials. A Core Outcome Set (COS) is “an agreed standardized set of outcomes that should be measured and reported, as a minimum, in all clinical trials in a disease or specific area of health”. Core outcome sets (COS) enhance efficiency of research, because harmonize endpoints and facilitate comparison among interventions [8]. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), provided recommendations for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults and the outcomes to be measured, but it is not a COS what has been developed [9]. Moreover, the registered COS in the COMET database entitled “Constructing a Core Outcome Set for the Clinical Evaluation of Nutritional and Functional Food for Patients with Sarcopenia” (https://www.comet-initiative.org/Studies/Details/1693), completed since 2021, explored this aspect, but the COS, aims, methodology, and targets are completely different and have a different scope, in the sense that it was focused mainly on functional food in the context of Chinese diets and the societal particularities of this population. We were aware of the steps given by previous initiatives and we take them into consideration. Despite the meaningful efforst given to date, there is still a genuine need for a COS for sarcopenia intervention studies, because the existing COS and initiatives do not cover the needs of the large population of patients with sarcopenia (plus clinicians, healthcare providers, policymakers, and stakeholders).
In fact, to date, no COS for interventional studies in sarcopenia, for Investigational medicinal products (IMP – “a medicine being studied in a clinical trial” - European Medicine Agency glossary 2022), nutritional supplements, and combined nutritional and physical interventions is available. A COS for sarcopenia intervention studies is urgently needed, because would allow to efficiently join efforts concerning the outcomes and pave the way towards an effective treatment for the disease. A COS for sarcopenia would improve efficiency in research and allow direct and indirect comparisons of clinical trials in sarcopenia. This protocol aims to outline the scope and methodology, stakeholders involvement, procedures, consensus processes of the COS for sarcopenia intervention studies. Our overall goal is improving people with sarcopenia’s life.
Subsection describing similar initiatives: There is no COS for Sarcopenia intervention studies registered in the COMET initiative database which covers the aims and scope of this project and there is no similar initiative registered in PROSPERO, or any other registry. Nevertheless, if conducting a search in the COMET initiative database by using the term “sarcopenia”, 4 studies appear (http://www.comet-initiative.org/studies/searchresults?guid=98a3dc73-cbfb-4f88-bafa-bb79c241df4b). From the 4 studies, 3 currently completed studies are identified as COS:
1. Abellan Van Kan., completed in 2011 and published as DOI:10.1016/j.cger.2011.03.010,
2. Reginster et al., completed in 2021 and published as DOI:10.1007/s40520-020-01663-4
3. Gong et al., whose findings have not been reported yet to scientific international societies and are not available in bibliographic databases since its completion in June 2021.
4. There is one extra fourth study which appears in the search by using the term “sarcopenia” in the COMET initiative database (https://www.fda.gov/media/108220/download).
Of the 4 studies, the first, second, and fourth studies were not actually COS, and they would not be considered as COS, because developing a COS was not among their objectives, which were totally different, as it is stated in these manuscripts. Consequently, these three studies did not follow the standardized methodology and procedures for COS development or COS reporting according to COS-STAD and the COMET Initiative.
Only the third study, by Gong et al., completed in June 2021, was aimed at developing a COS (“Constructing a Core Outcome Set for the Clinical Evaluation of the Nutritional and Functional Food for Patients with Sarcopenia in China”), and is actually a COS, because it is the only which intended to develop a COS, stablished that goal among its objectives, and followed the procedures and recommended methodology for COS development according to COS-STAD and the COMET Initiative. Nevertheless, the COS by Gong et al., completed in 2021, was focused on the development of “an indicator system for clinical trials of the nutritional and functional food in China”, therefore, its target, aims and scope and completely different and have a different scope, in the sense that it was focused mainly on functional food in the context of Chinese diets and the societal particularities of this population.
We were aware of the steps given by previous initiatives, and we take them into consideration. Despite the meaningful efforts given to date, there is still a genuine need for a COS for sarcopenia intervention studies, because the existing COS and previous initiatives do not cover the needs of the large population of patients with sarcopenia (plus clinicians, healthcare providers, policymakers, and stakeholders). The leaders of previous initiatives to provide recommendations or to develop COS which were related to the current one, would be kindly invited as experts, so the COS will benefit from more diverse perspectives.
Finally, there is an ongoing review registered in PROSPERO “Identifying generic core outcome domains from core outcome sets of musculoskeletal conditions: a systematic review” (PROSPERO 2021, CRD42021239141) [10] that is related to our COS, but is different in aims and scope. This review will be taken into consideration as a wider framework about the outcomes in the musculoskeletal system (the insight from the leading researchers will be requested for them to participate as experts, and also this COS has totally different aims and scope than the current COS for sarcopenia intervention studies (e.g., the key words of this review indicate a very different scope: “anaesthesia & pain control”, “orthopaedics & trauma”, “pain”, “rheumatology”, etc.).
References:
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2. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147:755–63.
3. Sayer AA, Cruz-Jentoft A. Sarcopenia definition, diagnosis and treatment: consensus is growing. Age Ageing. 2022;51:1–5.
4. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:601–601.
5. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020;21:300-307.e2.
6. Daly RM, Iuliano S, Fyfe JJ, Scott D, Kirk B, Thompson MQ, et al. Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group. J Nutr Health Aging. 2022;26:637–51.
7. Cawthon PM, Visser M, Arai H, Ávila-Funes JA, Barazzoni R, Bhasin S, et al. Defining terms commonly used in sarcopenia research: a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee. Eur Geriatr Med. 2022;13:1239–44.
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9. Reginster J-Y, Beaudart C, Al-Daghri N, Avouac B, Bauer J, Bere N, et al. Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults. Aging Clin Exp Res. 2021;33:3–17.
10. Sabet TS, Anderson DB, Stubbs PW, Buchbinder R, Terwee CB, Chiarotto A, et al. Identifying common core outcome domains from core outcome sets of musculoskeletal conditions: protocol for a systematic review. Syst Rev. 2022;11:248.
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Co-Principal Investigator: Charlotte Beaudart, PhD
Research Institute for Life Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur, Belgium
Co-PI: Dolores Sanchez-Rodriguez, MD PhD
Geriatrics Department, Brugmann University Hospital, Université Libre de Bruxelles, Place A. Van Gehuchten 4 (Bât. K - OK11), 1020 Brussels, Belgium. Tel: +32 493 43 27 50; Email: dolo.sanchezr@gmail.com and DoloresMaria.SANCHEZ-RODRIGUEZ@chu-brugmann.be;
World Health Organization Collaborating Center for Public Health aspects of Musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Campus Sart Tilman, Quartier Hôpital, Avenue Hippocrate 13 (Bât. B23), 4000 Liège, Belgium;
Geriatrics Department, Rehabilitation Research Group, Hospital del Mar Research Institute, Barcelona, Spain.
Contributors
• Ms Sophie Van Heden
Research Institute for Life Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur, Belgium
• Prof. Olivier Bruyère
• Prof. Jean-Yves Reginster
WHO Collaborating Centre for Public Health Aspects of Musculo-Skeletal Health and Ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
• Prof. Murielle Surquin
Medicine Department, Geriatrics Department, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, Belgium
Disease Category: Public health
Disease Name: Sarcopenia
Age Range: 60 - 120
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Consumers (patients)
- Epidemiologists
- Families
- Methodologists
- Researchers
- Service users
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Interview
- Literature review
- Survey
- Systematic review
The COS-STAndards for Development (COS-STAD) recommendations and COS-STAndardised Protocol Items (COS-STAP) Statement will be followed to conduct this research, and this study protocol will be registered in the Core Outcome Measures in Effectiveness Trials (COMET) Initiative database.
1. A working group will be gathered gathered under the auspices of the Department of Biomedical Sciences at the University of Namur, Namur (Belgium), two patients with sarcopenia, and experts from the WHO Collaborating Centre for Public Health Aspects of Musculo-Skeletal Health and Ageing, University of Liège (Belgium), the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), Brugmann university hospital – Universite Libre de Bruxelles, Brussels (Belgium), and the newly formed Global Leadership on Sarcopenia (GLIS) Consequences Working Group.
2. Literature review. The first step in COS development is reviewing existing evidence, to identify the outcomes and patient-reported outcome measures (PROMs) used in any randomized controlled trial (i.e., phase III clinical trials) in sarcopenia to date. The review entitled “Outcomes used in RCT in patients with sarcopenia (phase III; any intervention type, i.e., IMP, nutritional supplements, nutritional, and/or physical interventions): a scoping review” will be conducted, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses, extension for Scoping Reviews (PRISMA-ScR, registered in the International prospective register of systematic reviews (PROSPERO) database as PROSPERO CRD42024525506).
3. Interviews (in paralel with 1). As patients’ values and preferences are key for COS development and should be taken into consideration, the insight from older people with sarcopenia will be obtained by 90-minute duration semi-structured direct interviews of qualitative research. Interviews will be administered to between 5 and 10 patients =65-year-old with sarcopenia, with a definitive number depending on data saturation. Sarcopenia assessment [EWGSOP2 and updated definitions; muscle strength (Southampton protocol; JAMA®, Nottinghamshire, UK); muscle mass (BIA BWA2.0 InBody®, Cerritos, CA, US, and updated techniques) and the interviews will be conducted in Brugmann university hospital (Bât K – OK11), Brussels. The 38-category outcome taxonomy by the COMET Initiative and the Consolidated criteria for REporting Qualitative research (COREQ) will be used.
4. Two-round modified Delphi consensus process. The scoping review and the patients’ interviews will allow us to create a list of outcomes that will be reviewed during the Delphi. The outcomes will be discussed within a larger group of key stakeholders, including patient participants, and international experts from scientific societies during a Delphi process in two consecutive rounds, to achieve a consensus on the most relevant outcomes. Moreover, the leaders of previous initiatives to provide recommendations or to develop COS which were related to the current one, would be kindly invited as experts, so the COS will benefit from more diverse perspectives.
5. Consensus meetings. One or more consensus meeting among the working group members will be held to validate the results from the reviews, the patient interviews, and the Delphi process.
6. COS reporting and dissemination. Finally, the COS-STAndards for Reporting (COS-STAR) will be followed. Results from the COS will be communicated in scientific literature and shared in scientific congress. It is expected that the outcomes identified by the COS are taken into consideration in sarcopenia trials, and particularly, will be taken into consideration in the development of a clinical trial by our own team in the upcoming times. The COS for sarcopenia would facilitate comparisons among interventions, enhance transparency, and guide research and clinical care towards developing effective treatments of sarcopenia.