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Towards consensus in defining and handling contextual factors within rheumatology trials: an initial qualitative study from an OMERACT working group
  1. Sabrina Mai Nielsen1,2,
  2. Marianne Uggen Rasmussen1,
  3. Maarten Boers3,
  4. Danielle A van der Windt4,
  5. Maarten de Wit5,
  6. Thasia G Woodworth6,
  7. Caroline A Flurey7,
  8. Dorcas Beaton8,
  9. Beverley Shea9,
  10. Reuben Escorpizo10,11,
  11. Daniel E Furst6,12,13,
  12. Josef S Smolen14,
  13. Karine Toupin-April15,
  14. Annelies Boonen16,17,
  15. Marieke Voshaar18,
  16. Torkell Ellingsen2,
  17. George A Wells19,
  18. Barnaby C Reeves20,
  19. Lyn March21,
  20. Peter Tugwell22,
  21. 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 Epidemiology & Data Science; and Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands
  4. 4 School of Medicine; Primary Care Centre Versus Arthritis; and Centre for Prognosis Research, Faculty of Medicine and Health Sciences, Keele University, Keele, Staffordshire, UK
  5. 5 OMERACT Patient Research Partner, Amsterdam, The Netherlands
  6. 6 Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA
  7. 7 Department of Health and Social Sciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK
  8. 8 Institute for Work and Health, and Department of Occupational Science and Occupational Therapy, Rehabilitation Sciences Institute and the Institute for Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  9. 9 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  10. 10 Department of Rehabilitation and Movement Science, College of Nursing and Health Sciences, University of Vermont, Burlington, Vermont, USA
  11. 11 Swiss Paraplegic Research, Nottwil, Switzerland
  12. 12 Division of Rheumatology, University of Washington, Seattle, Washington, USA
  13. 13 University of Florence, Florence, Italy
  14. 14 Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  15. 15 Children’s Hospital of Eastern Ontario Research Institute; Department of Pediatrics and School of Rehabilitation Sciences, University of Ottawa, Ottawa, Ontario, Canada
  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), Maastricht University, Maastricht, The Netherlands
  18. 18 University of Twente, Enschede, Faculty of Behavioural Management and Social sciences, Department Psychology, Health and Technology, University of Twente, Enschede, The Netherlands
  19. 19 School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  20. 20 Bristol Trials Centre, Bristol Medical School, University of Bristol, Bristol, UK
  21. 21 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
  22. 22 Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  1. Correspondence to Ms Sabrina Mai Nielsen, Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark; sabrina.mai.nielsen{at}


Objectives The Outcome Measures in Rheumatology Initiative established the Contextual Factors Working Group to guide the understanding, identification and handling of contextual factors for clinical trials. In clinical research, different uses of the term ‘contextual factors’ exist. This study explores the perspectives of researchers (including clinicians) and patients in defining 'contextual factor’ and its related terminology, identifying such factors and accounting for them in trials across rheumatology.

Methods We conducted individual semistructured interviews with researchers (including clinicians) who have experience within the field of contextual factors in clinical trials or other potentially relevant areas, and small focus group interviews with patients with rheumatic conditions. We transcribed the interviews and applied qualitative content analysis.

Results We interviewed 12 researchers and 7 patients. Researcher's and patient's descriptions of contextual factors were categorised into two broad themes, each comprising two contextual factors types. The ‘treatment effect’ theme focused on factors explaining variations in treatment effects (A) among patients and (B) among studies. The ‘outcome measurement’ theme focused on factors that explain (C) variations in the measurement result itself (apart from actual changes/differences in the outcome) and (D) variations in the outcome itself (beside treatment of interest). Methods for identifying and handling contextual factors differed among these themes and types.

Conclusions Two main themes for contextual factors with four types of contextual factors were identified based on input from researchers and patients. This will guide operationalisation of contextual factors. Further research should refine our findings and establish consensus among relevant stakeholders.

  • outcome assessment
  • health care
  • patient reported outcome measures
  • qualitative research
  • arthritis

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  • Handling editor David S Pisetsky

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  • Contributors RC and SMN conceived the study and developed the protocol. SMN collected the data, supported by TW and CF. SMN did the analysis and interpreted the results, supported by MR. SMN 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 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 corresponding author had full access to all data of the study and had final responsibility for the decision to submit for publication.

  • Disclaimer The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests AB received a research grant from Abbvie, and an honorarium for lecture or advisory boards from UCB, Galapagos and Lilly; all financial support was paid to her department. DB reports that she is on the executive of OMERACT (Outcome Measurement in Rheumatological Research) and chair its methodology group; this did not influence this current written work. DEF reports grant/research support from Corbus, Galapagos Golead, GSK, NIH, Pfizer, Talaris, CSL Behring, as well as consultant for Abbvie, Amgen, Corbus, Galapagos, Gilead, Novartis, Pfizer, Roche/Genentech, Talaris, CSL Behring, Boehringer Ingelheim. JSS reports grants from Abbvie, AstraZeneca, Janssen, Lilly, Merck Sharpe and Dohme, Pfizer, and Roche, from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp and Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB., outside the submitted work. RC reports non-financial support from Board membership, grants from Consultancy (AbbVie, Amgen, Axellus A/S, Biogen, Bristol-Myers Squibb, Cambridge Weight Plan, Celgene, Eli Lilly, Hospira, MSD, Norpharma, Novartis, Orkla Health, Pfizer, Roche, Sobi, Takeda), personal fees from Employment (Research Unit for Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark), non-financial support from Expert testimony, grants from Grants/grants pending (Axellus A/S, AbbVie, Cambridge Weight Plan, Janssen, MSD, Mundipharma, Novartis, and Roche), grants from Payment for lectures including service on speakers bureaus (Abbott, Amgen, Axellus, Bayer HealthCare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Cambridge Weight Plan, Ipsen, Janssen, Laboratoires Expanscience, MSD, Mundipharma, Norpharma, Novartis, Pfizer, Roche, Rottapharm-Madaus, Sobi, and Wyeth), grants from Payment for manuscript preparation (Axellus, Bristol-Myers Squibb, and Cambridge Weight Plan, Aleris-Hamlet (via Norpharma)), non-financial support from Patents (planned, pending or issued), non-financial support from Royalties, grants from Payment for development of educational presentations (Bristol-Myers Squibb, MSD, Pfizer), non-financial support from Stock/stock options, grants from Travel/accommodations/meeting expenses unrelated to activities listed (Abbott, AbbVie, Axellus, Biogen, Bristol-Myers Squibb, Cambridge Weight Plan, Celgene, Laboratoires Expanscience, Norpharma, Novartis, Pfizer, Roche, Rottapharm-Madaus, and Wyeth), non-financial support from Other (err on the side of full disclosure), outside the submitted work; and he is involved in many health-care initiatives and research that could benefit from wide uptake of this publication (including Cochrane, OMERACT, IDEOM, RADS, and the GRADE Working Group); Musculoskeletal Statistics Unit, The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. PT reports other from Amgen, Astra Zeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/ Roche, Genzyme / Sanofi, Horizon Pharma Inc., Merck, Novartis, Pfizer, PPD, Quintiles, Regeneron, Savient, Takeda Pharmaceutical, UCB Group, Vertex, Forest, Bioiberica, personal fees from UCB Biopharma and SPRL, Parexel International, Prahealth Sciences, personal fees from CHEOR Solutions (Canada), Innovative Science Solutions, Reformulary Group, other from Elsevier, Little Brown, Wolters Kluwer and John Wiley & Sons, other from Abbott, Roche, Schering Plough/Merck, UCB, BMS, outside the submitted work; and Peter Tugwell is the recipient of Canada Research Chair in Health Equity (Tier 1-2016–2024) from the Canadian Institutes of Health Research.

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

  • Patient consent for publication Not required.

  • Ethics approval The Danish Data Protection Agency approved the study (ID 06081, BFH-2017-127), and the study was carried out in accordance with the Declaration of Helsinki.

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

  • Data availability statement Data relevant to the study are included in the article or uploaded in a short version as online supplemental information.