The Reverse Fragility Index for Mortality Endpoints in Randomized Trials Comparing Uncemented and Cemented Hemiarthroplasty for Intracapsular Hip Fractures.

BACKGROUND: Interpreting clinical relevance of randomized controlled trials (RCTs) is challenging when P-values are marginally above or below the P=0.05 threshold. This study utilized the reverse fragility index (RFI) to quantify the robustness of statistically insignificant events for mortality endpoints in RCTs comparing cemented versus uncemented hemiarthroplasty for displaced intracapsular hip fractures.

METHODS: RCTs were systematically identified using Pubmed, OVID/Medline, and Cochrane databases. Mortality endpoints were stratified into three categories: (1) within 30-days, (2) within 90-days, and (3) at latest follow-up. The RFI was derived by manipulating reported mortality events utilizing a 2x2 contingency table while maintaining a constant number of participants. The reverse fragility quotient (RFQ) was quantified by dividing the RFI by the study sample.

RESULTS: Eight RCTs (2,494 participants) were included. The median RFI and RFQ within 30-days was 3.0 (IQR:3.0-6.0) and 0.016 (IQR:0.015-0.021), suggesting that nonsignificant findings were contingent on only 1.6 mortality events/100 participants. The median RFI and RFQ within 90-days was 6.0 (IQR:4.0-7.0) and 0.028 (IQR:0.024-0.038), suggesting that nonsignificant findings were contingent on only 2.8 mortality events/100 participants. At latest follow-up, the median RFI and RFQ was 7.0 (IQR:6.0-12.0) and 0.038 (IQR:0.029-0.054), suggesting that nonsignificant findings were contingent on only 3.8 mortality events/100 participants. Median loss to follow-up was 16.0 (IQR:11.0-58.0), which was 228% greater than the RFI, and exceeded the RFI in 6/7 (85.7%) studies.

CONCLUSIONS: A relatively small number of events (median of 7) was required to convert a statistically nonsignificant finding to one that is significant for the endpoint of mortality. The median loss to follow-up exceeded the median RFI by greater than 200%, suggesting methodological limitations such as patient allocation could significantly alter conclusions. The high statistical fragility in these studies suggest that clinical decision-making regarding mortality should not depend on individual results of RCTs for hip hemiarthroplasty and warrants further investigation for additional endpoints.