BACKGROUND: We recently developed a model of stratified exercise therapy, consisting of (i) a stratification algorithm allocating patients with knee osteoarthritis (OA) into one of the three subgroups ('high muscle strength subgroup' representing a post-traumatic phenotype, 'low muscle strength subgroup' representing an age-induced phenotype, and 'obesity subgroup' representing a metabolic phenotype) and (ii) subgroup-specific exercise therapy. In the present study, we aimed to test the construct validity of this algorithm.METHODS: Data from five studies (four exercise therapy trial cohorts and one cross-sectional cohort) were used to test the construct validity of our algorithm by 63 a priori formulated hypotheses regarding three research questions: (i) are the proportions of patients in each subgroup similar across cohorts? (15 hypotheses); (ii) are the characteristics of each of the subgroups in line with their proposed underlying phenotypes? (30 hypotheses); (iii) are the effects of usual exercise therapy in the 3 subgroups in line with the proposed effect sizes? (18 hypotheses).RESULTS: Baseline data from a total of 1211 patients with knee OA were analyzed for the first and second research question, and follow-up data from 584 patients who were part of an exercise therapy arm within a trial for the third research question. In total, the vast majority (73%) of the hypotheses were confirmed. Regarding our first research question, we found similar proportions in each of the three subgroups across cohorts, especially for three cohorts. Regarding our second research question, subgroup characteristics were almost completely in line with the proposed underlying phenotypes. Regarding our third research question, usual exercise therapy resulted in similar, medium to large effect sizes for knee pain and physical function for all three subgroups.CONCLUSION: We found mixed results regarding the construct validity of our stratification algorithm. On the one hand, it is a valid instrument to consistently allocate patients into subgroups that aligned our hypotheses. On the other hand, in contrast to our hypotheses, subgroups did not differ substantially in effects of usual exercise therapy. An ongoing trial will assess whether this algorithm accompanied by subgroup-specific exercise therapy improves clinical and economic outcomes.
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OBJECTIVES: Knee osteoarthritis (OA) is characterized by its heterogeneity, with large differences in clinical characteristics between patients. Therefore, a stratified approach to exercise therapy, whereby patients are allocated to homogeneous subgroups and receive a stratified, subgroup-specific intervention, can be expected to optimize current clinical effects. Recently, we developed and pilot tested a model of stratified exercise therapy based on clinically relevant subgroups of knee OA patients that we previously identified. Based on the promising results, it is timely to evaluate the (cost-)effectiveness of stratified exercise therapy compared with usual, "nonstratified" exercise therapy.METHODS: A pragmatic cluster randomized controlled trial including economic and process evaluation, comparing stratified exercise therapy with usual care by physical therapists (PTs) in primary care, in a total of 408 patients with clinically diagnosed knee OA. Eligible physical therapy practices are randomized in a 1:2 ratio to provide the experimental (in 204 patients) or control intervention (in 204 patients), respectively. The experimental intervention is a model of stratified exercise therapy consisting of (a) a stratification algorithm that allocates patients to a "high muscle strength subgroup," "low muscle strength subgroup," or "obesity subgroup" and (b) subgroup-specific, protocolized exercise therapy (with an additional dietary intervention from a dietician for the obesity subgroup only). The control intervention will be usual best practice by PTs (i.e., nonstratified exercise therapy). Our primary outcome measures are knee pain severity (Numeric Rating Scale) and physical functioning (Knee Injury and Osteoarthritis Outcome Score subscale daily living). Measurements will be performed at baseline, 3-month (primary endpoint), 6-month (questionnaires only), and 12-month follow-up, with an additional cost questionnaire at 9 months. Intention-to-treat, multilevel, regression analysis comparing stratified versus usual care will be performed.CONCLUSION: This study will demonstrate whether stratified care provided by primary care PTs is effective and cost-effective compared with usual best practice from PTs.
ObjectiveTo investigate whether duration of knee symptoms influenced the magnitude of the effect of exercise therapy compared to non-exercise control interventions on pain and physical function in people with knee osteoarthritis (OA).MethodWe undertook an individual participant data (IPD) meta-analysis utilising IPD stored within the OA Trial Bank from randomised controlled trials (RCTs) comparing exercise to non-exercise control interventions among people with knee OA. IPD from RCTs were analysed to determine the treatment effect by considering both study-level and individual-level covariates in the multilevel regression model. To estimate the interaction effect (i.e., treatment x duration of symptoms (dichotomised)), on self-reported pain or physical function (standardised to 0–100 scale), a one-stage multilevel regression model was applied.ResultsWe included IPD from 1767 participants with knee OA from 10 RCTs. Significant interaction effects between the study arm and symptom duration (≤1 year vs >1 year, and ≤2 years vs>2 years) were found for short- (∼3 months) (Mean Difference (MD) −3.57, 95%CI −6.76 to −0.38 and −4.12, 95% CI-6.58 to −1.66, respectively) and long-term (∼12 months) pain outcomes (MD −8.33, 95%CI −12.51 to −4.15 and −8.00, 95%CI −11.21 to −4.80, respectively), and long-term function outcomes (MD −5.46, 95%CI −9.22 to −1.70 and −4.56 95%CI −7.33 to-1.80, respectively).ConclusionsThis IPD meta-analysis demonstrated that people with a relatively short symptom duration benefit more from therapeutic exercise than those with a longer symptom duration. Therefore, there seems to be a window of opportunity to target therapeutic exercise in knee OA.
