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Population characteristics as important contextual factors in rheumatological trials: an exploratory meta-epidemiological study from an OMERACT Working Group
  1. Sabrina Mai Nielsen1,2,
  2. Helene Storgaard1,3,
  3. Torkell Ellingsen2,
  4. Beverley J Shea4,
  5. George A Wells5,
  6. Vivian Andrea Welch5,6,
  7. Daniel E Furst7,8,9,
  8. Maarten de Wit10,
  9. Marieke Voshaar11,
  10. Carsten Bogh Juhl3,12,
  11. Maarten Boers13,
  12. Reuben Escorpizo14,15,
  13. Thasia G Woodworth7,
  14. Annelies Boonen16,17,
  15. Henning Bliddal1,
  16. Lyn M March18,
  17. Peter Tugwell19,20,
  18. Robin Christensen1,2
  1. 1 Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
  2. 2 Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark
  3. 3 Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
  4. 4 Ottawa Hospital Research Institute, and School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  5. 5 School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  6. 6 Bruyere Research Institute, Ottawa, Ontario, Canada
  7. 7 David Geffen School of Medicine, Division of Rheumatology, UCLA, Los Angeles, California, USA
  8. 8 University of Washington, Seattle, Washington, USA
  9. 9 University of Florence, Florence, Italy
  10. 10 OMERACT Patient Research Partner, Zaltbommel, The Netherlands
  11. 11 Department Psychology, Health and Technology, University of Twente, Twente, The Netherlands
  12. 12 Department of Physiotherapy and Occupational Therapy, Copenhagen University Hospital, Herlev & Gentofte, Denmark
  13. 13 Department of Epidemiology & Biostatistics, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  14. 14 Department of Rehabilitation and Movement Science, College of Nursing and Health Sciences, University of Vermont, Burlington, Vermont, USA
  15. 15 Swiss Paraplegic Research, Nottwil, Switzerland
  16. 16 Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
  17. 17 Care and Public Health Research Institute (CAPHRI), 6229 ER Maastricht University, Maastricht, The Netherlands
  18. 18 Florance and Cope Professorial Department of Rheumatology, Royal North Shore Hospital and Institute of Bone and Joint Research, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  19. 19 Division of Rheumatology, Department of Medicine, and School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  20. 20 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  1. Correspondence to Ms Sabrina Mai Nielsen, Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen DK-2000, Denmark; sabrina.mai.nielsen{at}


Objectives To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions.

Methods In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses.

Results We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion.

Conclusions This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials.

PROSPERO registration number CRD42019127642

  • arthritis
  • epidemiology
  • outcomes research

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  • SMN and HS are joint first authors.

  • Handling editor Gerd R Burmester

  • SMN and HS contributed equally.

  • Contributors RC, SMN and HS conceived the study and developed the protocol. HS collected the data. SMN and HS did the analysis and interpreted the analysis in collaboration with RC. SMN, HS and RC drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version of the manuscript. RC, TE and SMN obtained funding. SMN, HS and RC are the guarantors.

  • Funding The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). The Oak Foundation is a group of philanthropic organisations that, since its establishment in 1983, has given grants to not-for-profit organisations around the world. SMN has received PhD scholarships from the Faculty of Health Sciences, University of Southern Denmark and Odense University Hospital, and an introductory scholarship from the BFH Research Foundation. The funders had no role in the study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all data of the study and had final responsibility for the decision to submit for publication.

  • Competing interests MdW reports personal fees from Abbvie, through Stichting Tools; personal fees from BMS; personal fees from Celgene; personal fees from Lilly; personal fees from Novartis; personal fees from Pfizer; personal fees from Roche; from outside the submitted work. AB holds a research grant from Abbvie and received honoraria for participation in advisory boards from Lilly and Galapagos. All compensations were paid to the department.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Dataset available from the corresponding author after a postpublication period of 1 year allowing time for follow-up projects.