Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)

doi:10.1007/s00198-023-06827-2

Review

. 2023 Aug;34(8):1283-1299.

doi: 10.1007/s00198-023-06827-2. Epub 2023 Jun 23.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)

Rebecca J Moon^{1

2}, Jean-Yves Reginster^{3

4}, Nasser M Al-Daghri⁵, Jotheeswaran A Thiyagarajan⁶, Charlotte Beaudart^{3

4}, Olivier Bruyère^{3

4}, Nansa Burlet⁴, Manju Chandran⁷, Mario Coelho da Silva⁸, Philip G Conaghan^{9

10}, Willard H Dere¹¹, Adolfo Diez-Perez¹², Peyman Hadji^{13

14}, Philippe Halbout¹⁵, Mickaël Hiligsmann¹⁶, John A Kanis^{17

18}, Eugene V McCloskey^{19

20}, Sif Ormarsdottir²¹, Daniel Prieto-Alhambra²², Régis P Radermecker²³, René Rizzoli²⁴, Yousef Al-Saleh^{25

26

27}, Stuart L Silverman²⁸, Lee S Simon²⁹, Friederike Thomasius¹³, Tjeerd van Staa³⁰, Andrea Laslop³¹, Cyrus Cooper^{1

32

33}, Nicholas C Harvey^{34

35}

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK.
² Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³ WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Ageing, Liège, Belgium.
⁴ Division of Epidemiology, Public Health and Health Economics, University of Liège, Liège, Belgium.
⁵ Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁶ Ageing and Health Unit, World Health Organisation, Geneva, Switzerland.
⁷ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
⁸ Laboratory of Clinical and Therapeutical Pharmacology, Lisbon, Portugal.
⁹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹⁰ NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
¹¹ Department of Internal Medicine, Utah Center for Clinical and Translational Science, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹² Department of Internal Medicine, Hospital del Mar-IMIM, Autonomous University of Barcelona and CIBERFES, Instituto Carlos III, Barcelona, Spain.
¹³ Frankfurt Centre for Bone Health, Frankfurt, Germany.
¹⁴ Philipps University of Marburg, Hesse, Germany.
¹⁵ International Osteoporosis Foundation, Nyon, Switzerland.
¹⁶ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
¹⁷ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
¹⁸ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
¹⁹ MRC Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK.
²⁰ Mellanby Centre for Musculoskeletal Research, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.
²¹ Icelandic Medicines Agency, Reykjavik, Iceland.
²² Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.
²³ Department of Clinical Pharmacology, Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium.
²⁴ Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
²⁵ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
²⁶ King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
²⁷ Department of Medicine, King Abdulaziz Medical City, Riyadh, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.
²⁸ Cedars Sinai Medical Center, Los Angeles, USA.
²⁹ SDG LLC, Cambridge, MA, USA.
³⁰ Centre for Health Informatics, University of Manchester, Manchester, UK.
³¹ Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria.
³² NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³³ National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Centre, University of Oxford, Oxford, UK.
³⁴ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK. nch@mrc.soton.ac.uk.
³⁵ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK. nch@mrc.soton.ac.uk.

PMID: 37351614
PMCID: PMC10382414
DOI: 10.1007/s00198-023-06827-2

Review

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)

Rebecca J Moon et al. Osteoporos Int. 2023 Aug.

. 2023 Aug;34(8):1283-1299.

doi: 10.1007/s00198-023-06827-2. Epub 2023 Jun 23.

Authors

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK.
² Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³ WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Ageing, Liège, Belgium.
⁴ Division of Epidemiology, Public Health and Health Economics, University of Liège, Liège, Belgium.
⁵ Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁶ Ageing and Health Unit, World Health Organisation, Geneva, Switzerland.
⁷ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
⁸ Laboratory of Clinical and Therapeutical Pharmacology, Lisbon, Portugal.
⁹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹⁰ NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
¹¹ Department of Internal Medicine, Utah Center for Clinical and Translational Science, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹² Department of Internal Medicine, Hospital del Mar-IMIM, Autonomous University of Barcelona and CIBERFES, Instituto Carlos III, Barcelona, Spain.
¹³ Frankfurt Centre for Bone Health, Frankfurt, Germany.
¹⁴ Philipps University of Marburg, Hesse, Germany.
¹⁵ International Osteoporosis Foundation, Nyon, Switzerland.
¹⁶ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
¹⁷ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
¹⁸ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
¹⁹ MRC Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK.
²⁰ Mellanby Centre for Musculoskeletal Research, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.
²¹ Icelandic Medicines Agency, Reykjavik, Iceland.
²² Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.
²³ Department of Clinical Pharmacology, Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium.
²⁴ Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
²⁵ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
²⁶ King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
²⁷ Department of Medicine, King Abdulaziz Medical City, Riyadh, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.
²⁸ Cedars Sinai Medical Center, Los Angeles, USA.
²⁹ SDG LLC, Cambridge, MA, USA.
³⁰ Centre for Health Informatics, University of Manchester, Manchester, UK.
³¹ Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria.
³² NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³³ National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Centre, University of Oxford, Oxford, UK.
³⁴ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK. nch@mrc.soton.ac.uk.
³⁵ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK. nch@mrc.soton.ac.uk.

PMID: 37351614
PMCID: PMC10382414
DOI: 10.1007/s00198-023-06827-2

Abstract

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research.

Purpose: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated.

Methods: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice.

Results: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research.

Conclusions: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Keywords: Drug effectiveness; Epidemiology; Fracture; Osteoporosis; Real-world evidence; Registry.

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Conflict of interest statement

RJM has received travel bursaries from Kyowa Kirin. OB has received consulting or lecture fees from Amgen, Aptissen, Biophytis, IBSA, Mylan, Novartis, Orifarm, Sanofi, UCB and Viatris. MC has received honoraria for speaking and chairing engagements from AMGEN, DKSH and Kyowa Kirin. PGC has received speakers bureaus or consultancies from AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Grunenthal, Merck, Novartis, Pfizer, Stryker and UCB, outside the submitted work. WHD is on the board of Directors for BioMarin, Seres, Mersana and Metagenomi, Chief Advisor to CEO at Angitia and is a former employee and shareholder at Eli Lilly and Amgen. MH has research grants paid to his institution from Amgen, Radius Health, and consulting fees from UCB. EVM reports research support and/or personal fees from Amgen, Eli Lilly, Fresenius Kabi, ObsEva and UCB, outside the submitted work. SO has received consultancy fees from Merck and Pfizer not related to the current work or therapeutic field. RR has speaker bureau or advisory board for Abiogen, Naturex, Nestlé and ObsEva. YAS reports lecture honoraria from Amgen, Eli Lilly and SAJA. SLS has acted as a consultant for Radius and Amgen, received funding from Radius for clinical trial and received travel support from Radius and grant support from Amgen. LSS discloses associations with Astrazeneca, Pfizer, Rigel, Eupraxia, Biosplice, EMDSerono, Horizon, Direct, Lilly, Kaniska, Protalix, Chemomab, TLC, SpineThera, Kyoto, PPD, Galvani, Urica, Transcode, Boehringer Ingelheim, Bristol Myers Squibb, Priovant, Roivant, Ampio, Aura, Aurinia, GSK, Xalud, Neumentum, Neema, Amzell, Applied Bio, Aptinyx, Bexson, Bone Med, Bone Therapeutics, Cancer Prevention, Cerebral Therapeutics, Chemocentryx, Diffusion Bio, Elorac, Enalare, Foundry Therapeutics, Galapagos, Histogen, Gilead, Idera, Intravital, Ingel, Kiel Labs, Mesoblast, Mpathix, Minerva, Regenosine, Samus, Sana, StageBio, Theraly, Unity and Viridian. FT reports personal fees from Amgen, Eli Lilly, Fresenius, Stada and UCB outside the submitted work. CC reports personal fees from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier and Takeda, outside the submitted work. NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma, outside the submitted work. JYR, NMA, JAT, CB, OB, NB, MCD, WHD, ADP, PH, PH, JAK, DPA, RPR, SLS, TVS and AL report no conflicts of interest related to this work.

Figures

**Fig. 1**
Uses of real-world data in intervention and non-intervention (observational) studies

**Fig. 2**
Confounding by indication. An example in which osteoporosis severity influences treatment choice and fracture risk. In observational work, knowledge of underlying disease severity or other risk factors might influence treatment choices made by the clinician and/or patient, with a potentially more powerful intervention used in those with more severe disease/higher risk. These same decision influencing factors might also influence the likelihood of the outcome being studied resulting in confounding by indication. For example, in the UK, teriparatide is only available for women with severe disease, who are by the same definitions used also at increased risk of fracture. Comparing fracture rate in women treated with teriparatide to those treated with other antiosteoporosis medications, would likely suggest that teriparatide had a higher fracture rate unless approaches to controlling confounding by indication, such as propensity matching, are used

**Fig. 3**
Considerations in the planning, conduct and reporting of RWE studies in osteoporosis

See this image and copyright information in PMC

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References

1. Kanis JA, Norton N, Harvey NC, Jacobson T, Johansson H, Lorentzon M, et al. SCOPE 2021: a new scorecard for osteoporosis in Europe. Arch Osteoporos. 2021;16(1):82. doi: 10.1007/s11657-020-00871-9. - DOI - PMC - PubMed
1. Odén A, McCloskey EV, Kanis JA, Harvey NC, Johansson H. Burden of high fracture probability worldwide: secular increases 2010–2040. Osteoporos Int. 2015;26(9):2243–2248. doi: 10.1007/s00198-015-3154-6. - DOI - PubMed
1. Söreskog E, Borgström F, Shepstone L, Clarke S, Cooper C, Harvey I, et al. Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study. Osteoporos Int. 2020;31(8):1499–1506. doi: 10.1007/s00198-020-05372-6. - DOI - PMC - PubMed
1. Chotiyarnwong P, McCloskey EV, Harvey NC, Lorentzon M, Prieto-Alhambra D, Abrahamsen B, et al. Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group. Arch Osteoporos. 2022;17(1):87. doi: 10.1007/s11657-022-01117-6. - DOI - PMC - PubMed
1. Lai F, Pei L, Chen X, Li J. Osteoporosis-related randomized clinical trials with middle-aged and older adults registered on the International Clinical Trials Registry Platform. Front Endocrinol. 2021;12:702261. doi: 10.3389/fendo.2021.702261. - DOI - PMC - PubMed

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[1] Kanis JA, Norton N, Harvey NC, Jacobson T, Johansson H, Lorentzon M, et al. SCOPE 2021: a new scorecard for osteoporosis in Europe. Arch Osteoporos. 2021;16(1):82. doi: 10.1007/s11657-020-00871-9. - DOI - PMC - PubMed

[2] Kanis JA, Norton N, Harvey NC, Jacobson T, Johansson H, Lorentzon M, et al. SCOPE 2021: a new scorecard for osteoporosis in Europe. Arch Osteoporos. 2021;16(1):82. doi: 10.1007/s11657-020-00871-9. - DOI - PMC - PubMed

[3] Odén A, McCloskey EV, Kanis JA, Harvey NC, Johansson H. Burden of high fracture probability worldwide: secular increases 2010–2040. Osteoporos Int. 2015;26(9):2243–2248. doi: 10.1007/s00198-015-3154-6. - DOI - PubMed

[4] Odén A, McCloskey EV, Kanis JA, Harvey NC, Johansson H. Burden of high fracture probability worldwide: secular increases 2010–2040. Osteoporos Int. 2015;26(9):2243–2248. doi: 10.1007/s00198-015-3154-6. - DOI - PubMed

[5] Söreskog E, Borgström F, Shepstone L, Clarke S, Cooper C, Harvey I, et al. Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study. Osteoporos Int. 2020;31(8):1499–1506. doi: 10.1007/s00198-020-05372-6. - DOI - PMC - PubMed

[6] Söreskog E, Borgström F, Shepstone L, Clarke S, Cooper C, Harvey I, et al. Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study. Osteoporos Int. 2020;31(8):1499–1506. doi: 10.1007/s00198-020-05372-6. - DOI - PMC - PubMed

[7] Chotiyarnwong P, McCloskey EV, Harvey NC, Lorentzon M, Prieto-Alhambra D, Abrahamsen B, et al. Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group. Arch Osteoporos. 2022;17(1):87. doi: 10.1007/s11657-022-01117-6. - DOI - PMC - PubMed

[8] Chotiyarnwong P, McCloskey EV, Harvey NC, Lorentzon M, Prieto-Alhambra D, Abrahamsen B, et al. Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group. Arch Osteoporos. 2022;17(1):87. doi: 10.1007/s11657-022-01117-6. - DOI - PMC - PubMed

[9] Lai F, Pei L, Chen X, Li J. Osteoporosis-related randomized clinical trials with middle-aged and older adults registered on the International Clinical Trials Registry Platform. Front Endocrinol. 2021;12:702261. doi: 10.3389/fendo.2021.702261. - DOI - PMC - PubMed

[10] Lai F, Pei L, Chen X, Li J. Osteoporosis-related randomized clinical trials with middle-aged and older adults registered on the International Clinical Trials Registry Platform. Front Endocrinol. 2021;12:702261. doi: 10.3389/fendo.2021.702261. - DOI - PMC - PubMed

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Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)

Affiliations

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)

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