Development of a core domain set for ankle osteoarthritis: An international consensus

Abstract

Ankle osteoarthritis (OA), a disabling condition characterised by severe pain, disability and poor quality of life, lacks high-quality clinical trials and evidence-informed clinical practice guidelines. A barrier to synthesising clinical trial research on ankle OA is the heterogeneity of outcome measures. As a first step towards synthesising the clinical trial research, this thesis aimed, through five studies, to develop an internationally agreed-upon core domain set – a minimum set of health-related domains that should be measured and reported – for clinical trials on ankle OA. This will standardise the reporting of outcome measures in ankle OA, facilitate data synthesis and lead to evidence-informed clinical practice guidelines. Study 1 systematically reviewed the literature on outcome measures in ankle OA research and proposed 19 aligned health-related domains. The review included 547 studies reporting 250 outcome measures. The large number of disparate outcome measures confirmed a lack of agreement on which outcome measures should be reported in clinical trials of ankle OA. The most commonly used outcome measures (reported ≥10 times) were grouped into a list of 19 preliminary domains according to the Outcome Measures in Rheumatology core areas (life impact, pathophysiological manifestations/abnormalities, death/adverse events and resource use). Study 2 explored the lived experiences of 23 individuals with symptomatic ankle OA through semi-structured interviews and canvassed potential domains from their perspectives. Thematic analysis of the interview data provided insights into the impact of the condition and identified five main themes: (1) pain, often severe, is a central feature of living with ankle OA; (2) stiffness and swelling are key symptoms; (3) mobility impairments induced by ankle OA compromise enjoyment of life; (4) instability and balance impairments caused by ankle OA lead to concerns about falling; and (5) living with ankle OA has financial implications. Seventeen additional domains to those identified in Study 1 were proposed. Study 3 complemented the findings of Studies 1 and 2 by investigating the perspectives of international multidisciplinary healthcare professionals (HCPs) on the main problems in patients with ankle OA. Four themes emerged from a thematic analysis: (1) people with ankle OA have difficulty with weight-bearing activities; (2) symptoms of pain and stiffness predominate, alongside swelling, instability, weakness and poor balance; (3) chronic pain in ankle OA has psychosocial consequences; and (4) the loss of independence/activities of daily living compromises quality of life. Fifteen potential domains were proposed from the interview data. In Study 4, an international multidisciplinary steering committee reviewed the candidate domains generated from the previous studies and endorsed them for use in an online Delphi study, which aimed to reach consensus on a core domain set for ankle OA with the involvement of 75 HCPs and 25 individuals with ankle OA from 18 countries across four continents. It involved three rounds of online questionnaires and a subsequent online consensus meeting. Consensus was a priori defined as ≥70% agreement that a domain should or should not be included in a core domain set for ankle OA. After the three online questionnaires and the consensus meeting, a set of five core domains was agreed upon: (1) pain severity, (2) health-related quality of life, (3) function, (4) disability and (5) range of motion. Participants were undecided on three of the proposed domains (ankle instability, physical capacity and mental health) and agreed that the remaining 21 domains should not be included in the core domain set. Study 5 was a systematic review of six studies of the measurement properties (clinimetrics/psychometrics) of 10 pain assessment tools, undertaken as a subsequent step in determining which outcome measurement tools are appropriate for the pain domains of the ankle OA core domain set developed in Study 4. The COnsensus-based Standards for the Selection of health Measurement INstruments (COSMIN) methodology was followed to assess/review the clinimetric/psychometric properties of pain severity in individuals with ankle OA. As the review revealed very low-quality evidence of content validity and undetermined internal consistency, no pain measurement tool was recommended for use. The paucity of research on the clinimetric properties of pain measurement tools for individuals with ankle OA indicates a need for high-quality research to develop tools with acceptable validity. This thesis has established an evidence-based, internationally agreed-upon core domain set for ankle OA, which will guide the selection of domains that should be measured and reported in clinical trials on ankle OA. Future research is needed to ascertain the outcome measurement instruments/tools that should be used to represent each core domain.