Lack of standardization among clinical trials of injection therapies for knee osteoarthritis: a systematic review

Purpose: Osteoarthritis (OA) of the knee is a debilitating, expensive, and prevalent disease, and interest in the non-surgical management of knee OA has grown recently. Our objective was to systematically assess the level of heterogeneity among all clinical trials and published studies regarding injections for knee osteoarthritis, in terms of treatment of interest, outcomes evaluated, and time points of outcome assessment. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to review all published studies and publically available clinical trials from 1 January 2013 to 3 May 2019evaluating intra-articular injections to treat knee OA. Their treatment group and specifics of methodology were scrutinized and compared. Results: 84 published studies and 114 clinical trials were included. Within the 84 published studies, the most common injection treatment studied was hyaluronic acid [N = 22; 26.2%]. In total, 29 different injection treatment groups were utilized. The most common time point for patient evaluation post-injection was 6 months (N = 33 studies; 50.0%), and ranged from 1 week (N = 9 studies; 13.6%) to 7 years (N = 1 study; 1.5%). The most common patient-reported outcome (PRO) measure assessed in the included studies was Western Ontario and McMaster's University Osteoarthritis Index (WOMAC) [N = 44 studies; 66.7%]. For the 114 clinical trials identified, the most common injection treatment studied is platelet-rich plasma in isolation (N = 19; 16.7%). Forty-two different injection treatment types/groups are utilized. The most common PRO measure assessed was WOMAC (N = 77 trials; 67.5%). Overall there were 34 different patient-reported outcome measures used. Conclusions: Research efforts to find the most effective injection therapy for knee OA continue with a tremendous number of injection therapies still being evaluated. Substantial heterogeneity exists in these completed and ongoing trials in terms of patient demographics, OA grades, outcome scores and relatively short-term timing of assessments, with no clear standardization of testing protocol despite proposing to answer the same clinical question. We recommend that studies of this genre going forward be standardized in terms of outcome measures and longer-term follow-up time points, and should incorporate functional assessment evaluations and imaging studies.