A consensus-based framework for conducting and reporting osteoarthritis phenotype research

Spil et al. Arthritis Research & Therapy (2020) 22:54 https://doi.org/10.1186/s13075-020-2143-0 RESEARCH ARTICLE Open Access A consensus-based framework for conducting and reporting osteoarthritis phenotype research W. E. van Spil1* , S. M. A. Bierma-Zeinstra2,3, L. A. Deveza4, N. K. Arden5,6, A.-C. Bay-Jensen7, V. Byers Kraus8, L. Carlesso9, R. Christensen10,11, M. Van Der Esch12, P. Kent13,14, J. Knoop15, C. Ladel16, C. B. Little17, R. F. Loeser18, E. Losina19, K. Mills20, A. Mobasheri21, A. E. Nelson18, T. Neogi22, G. M. Peat23,24, A.-C. Rat25, M. Steultjens26, M. J. Thomas23,24, A. M. Valdes27 and D. J. Hunter4 Abstract Background: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. Methods: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. Results: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. Conclusions: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients. Keywords: Osteoarthritis, Phenotypes, Framework, Consensus (maximum 10) * Correspondence: 1 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Spil et al. Arthritis Research & Therapy (2020) 22:54 Background There has been longstanding acceptance of the heterogeneity of osteoarthritis (OA), but this topic is attracting increasing interest given an expanding armamentarium for classification (biological, psychosocial, and statistical); new insights into the pathophysiology, prognosis, and patterns of response to new and existing interventions; and a general move towards personalized care to improve efficiency and effectiveness [1]. A specific development more recently has been to invoke the concept of OA phenotypes. According to this concept, OA is composed of a number of phenotypes that may be present to a varying extent among patients spanning the spectrum of disease [2]. These phenotypes may differ in their compatibility with study designs in research and diagnostic and therapeutic strategies in clinical care. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept, and similarly, a variety of approaches have been used to explore heterogeneity in empirical studies. Studies focused on OA phenotypes published up to day differ in approach, criteria to distinguish phenotypes, and their outcomes. Furthermore, different papers used different and sometimes confusing terminologies. A more consistent use of terminology would increase the synergy between studies and facilitate the progress of the field as a whole. Furthermore, to allow effective comparison between studies and meta-analyses, complete reporting of relevant data is important. In the field of back pain, the pathway from basic research to successful phenotyping has been argued as composing of a number of steps [3]. First, there are studies of assessment methods that could potentially provide important data on one or more phenotypes. For example, one may develop a new imaging technique to assess the glycosaminoglycan content of articular cartilage. Second, hypothesis-generating studies aim to determine which characteristics identify people in clinically important subgroups. For example, a biochemical marker level could be higher in a particular subgroup of knee OA patients. Third, hypothesis-testing studies test a priori hypotheses about subgrouping effects in samples of people independent from, but similar to, those people involved in the hypothesis-setting phase. Studies in this phase typically follow a more stringent approach than those at the hypothesis-generating stage. For example, the biochemical marker is now evaluated in a larger, well-characterized patient sample and might include healthy controls. Fourth, relatively narrow validation studies attempt to replicate findings of hypothesis-testing studies in independent samples of people who are similar to those originally studied. Fifth, broader validation studies try to replicate the findings of hypothesis-generating studies in independent samples from broader populations than those originally tested. For example, the biochemical markers for phenotyping Page 2 of 7 OA patients in specialist outpatient clinics would be tested in a primary care setting. Sixth and last, impact-analysis studies examine the capacity of a specific (...truncated)