Platelet-Rich Plasma Versus Alternative Injections for Osteoarthritis of the Knee: A Systematic Review and Statistical Fragility Index–Based Meta-analysis of Randomized Controlled Trials

Background: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. Purpose: To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. Study Design: Systematic review and meta-analysis; Level of evidence, 2. Methods: All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. Results: In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (P =.002; odds ratio [OR], 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief (P =.019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment (P =.002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement (P =.007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. Conclusion: Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context.