Debdipta Bose and Mahanjit Konwar*
Background: It is essential for Randomized controlled trials [RCTs] to report its results in a comprehensive manner. Hence, it is necessary to assess the robustness of the trials with statistically significant and as well as non-significant results. Robustness can be evaluated using fragility index (FI) and reverse fragility index [RFI] is for trials with statistically significant and as well as non-significant results. The primary aim of this study was to calculate FI and RFI for cardiovascular outcome trials [CVOT].
Materials & Methods: PubMed/MEDLINE was searched to identify all RCTs of antidiabetic drugs where the primary objective was to evaluate the cardiovascular outcomes. We recorded the trial characteristics of each CVOT trial. The FI, RFI, Fragility quotient [FQ] and reverse fragility quotient [FQ] was calculated to evaluate the robustness of the trials. Spearman rank correlation test was used for correlation.
Findings: A total of 889 studies were identified and 24 RCTs was included. Among the 24 trials, 12 [50%] trials achieved statistical significance. The median FI and RFI were 29 [4-12] and 22.5 [1-37] for trials with statistically significant and non-significant results. The median FQ and RFQ were 0.0075 [0.002-0.013] and 0.0003 [0.0001-0.004] for trials with statistically significant and non-significant results. The hazard ratio, p value and NNT-B had strong negative relation with FI.
Interpretation: Our study showed that half of the trials showing superiority of cardioprotective benefits have favourable FI. The trials failed to show superiority also have a reasonable RFI indicating the robustness of these trials. But the results pf the trials where patients lost to follow-up exceed the FI of that trial demands caution during interpretation.
Robustness, lost to follow-up, fragility quotient, p value
Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra, Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra