The Statistical Fragility of Platelet-Rich Plasma as Treatment for Plantar Fasciitis: A Systematic Review and Simulated Fragility Analysis

Abstract

Background: Plantar fasciitis (PF) is the most common cause of heel pain and can be a source of extensive physical disability and financial burden. Platelet-rich plasma (PRP) offers a potentially definitive, regenerative treatment modality that, if effective, could change the current paradigm of PF care. However, randomized controlled trials (RCTs) on the clinical benefits of PRP for refractory PF offer inconsistent conclusions, potentially because of the broader limitations of using P value thresholds to declare statistical and clinical significance. In this study, we use the Continuous Fragility Index (CFI) and Quotient (CFQ) to appraise the statistical robustness of data from RCTs evaluating PRP for treatment of PF. Methods: RCTs comparing outcomes after PRP injection vs alternative treatment in patients with chronic PF were evaluated. Representative simulated data sets were generated for each reported outcome event using summary statistics. The CFI was determined by manipulating each data set until reversal of significance (α=0.05) was achieved. The corresponding CFQ was calculated by dividing the CFI by the sample size. Results: Of 259 studies screened, 20 studies (59 outcome events) were included in this analysis. From these simulations, the median CFI for all events was 9, suggesting that varying the treatment of 9 patients would be required to reverse trial significance. The corresponding CFQ was 0.177. Studies with reported P value <.05 were more statistically fragile (CFI=10, CFQ=0.122) than studies with reported P value >.05 (CFI=5, CFQ=0.179). Of 36 outcome events reporting lost to follow-up data, 10 events (27.8%) lost ≥9 patients. Conclusion: Our findings suggest that, on average, the statistical fragility of RCTs evaluating PRP for nonoperative PF therapy is at least comparable to that of the sports medicine literature. However, several included studies had concerningly low simulated fragility scores. Orthopaedic surgeons may benefit from preferentially relying on studies with higher CFI and CFQ values when evaluating the utility of PRP for chronic PF in their own clinical practice. Given the importance of RCT data in clinical decision making, fragility indices could help give context to the stability of statistical findings. Level of Evidence: Level I, systematic review.