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.

Abstract

BACKGROUND Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. METHODS The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. RESULTS Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. CONCLUSION Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. LEVEL OF EVIDENCE Level II, therapeutic study.