Identifying clinically relevant subgroups of knee osteoarthritis patients

Background Given the low to moderate effects of current symptomatic treatment options for knee osteoarthritis (OA) and the known heterogeneity of knee osteoarthritis patients, there is a general call for the evaluation of clinically relevant subgroups that could benefit more from certain interventions. Objectives To evaluate the presence of clinically relevant subgroups of OA patients for the core treatment options across the span of treatment options for knee OA; anti-inflammatory analgesics, corticosteroid injections and exercise therapy. Study design In data of two high-quality randomized controlled trials (RCTs), of which members of the project group were actively involved, we will evaluate several pre-defined subgroups of knee OA patients. Additionally, after a systematic search of the literature, we will reach out to all authors of all published RCTs on pre- and post-surgery exercise therapy for knee OA. Based on the Individual Patient Data (IPD) from these published trials, we will do an IPD meta-analyses for clinically relevant knee OA patients; the highest standard of subgroup analyses. Statistical analyses For the analyses in the two RCTs, we will use a random-effects linear regression model to look for interaction effects. The model includes the dependent variable, the treatment group, the subgroup indicator and the interaction term. For the IPD meta-analyses, a one-stage multilevel regression analysis will be performed. To assess possible subgroup effects, a random-effects linear regression model will be used to determine interaction effects. This model included the dependent variable (primary or secondary outcome measure), the independent variable, the subgroup indicator and an interaction term. Feasibility Our previous IPD-meta analyses, including trial identification, data request and analyses, were all finalized within three years. As data for the two other RCTs has already been collected and all required data sharing agreements are already in place, the current project should be deemed highly feasible. Time schedule Sept ’21 – Aug ’22 Identification of trials for IPD analyses and establishing data sharing agreements with the trial owners. Subgroup analyses of patients with knee OA for ibuprofen treatment, including reporting in an international publication. Sept ’22 – Aug ’23 Clinical training for the AIOTO Sept ’23 – Aug ’24 Finalizing data sharing with trial owners for IPD analyses, IPD meta-analyses, and reporting in two international publications. Sept ’24 – Aug ’25 Clinical training for the AIOTO Sept ’25 – June ’26 Subgroup analyses of patients with knee OA for corticosteroid injections, including reporting in an international publication. July ’26 – June ’27 Clinical training for the AIOTO