Bidirectional fragility is a step forward but not far enough: the case for a global fragility index

Authors

  • Thomas F Heston Internet Medical Journal

DOI:

https://doi.org/10.5281/zenodo.19464166

Keywords:

fragility index, bidirectional fragility index, global fragility index, statistical fragility, risk quotient, statistical robustness, neutrality boundary framework, p-value, clinical trials, 2x2 contingency table

Abstract

Commentary responding to Kahana, Perets, and Emile (Journal of Clinical Epidemiology, 2026; doi:10.1016/j.jclinepi.2026.112255), who propose a bidirectional fragility index (bFI) for 2×2 contingency tables. This paper demonstrates that the bFI, while a genuine improvement over the unidirectional fragility index, inherits structural limitations: (1) it restricts perturbations to within-arm toggles (fixed row margins), which is a subset of the full perturbation space; (2) it is mathematically incomplete (not attainable for some valid tables); and (3) it conflates classification stability with robustness. The Global Fragility Index (GFI) resolves the first two limitations by searching all cell-to-cell reallocations without fixing any marginal totals. Exhaustive enumeration of all valid 2×2 tables (N = 7–30, 45,230 tables) confirms that GFI ≤ bFI always, GFI < bFI in 21.5% of cases, and GFI is attainable for every table in the domain. The Risk Quotient (RQ) addresses the third limitation by providing a normalized robustness metric orthogonal to fragility. Includes the R enumeration code and complete output dataset.

References

1. Kahana N, Perets M, Emile SH. Beyond One Direction: Revisiting the Fragility Index. J Clin Epidemiol. 2026; 112255-. doi:10.1016/j.jclinepi.2026.112255

2. Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, et al. The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. J Clin Epidemiol. 2014;67: 622–628. doi:10.1016/j.jclinepi.2013.10.019

3. Lin L, Chu H. Assessing and visualizing fragility of clinical results with binary outcomes in R using the fragility package. Gagniuc PA, editor. PLOS ONE. 2022;17: e0268754. doi:10.1371/journal.pone.0268754

4. Heston TF. The Global Fragility Index: A Path-Independent Measure of Statistical Fragility. Zenodo. 2025 [cited 4 Apr 2026]. doi:10.5281/zenodo.18078509

5. Feinstein AR. The unit fragility index: an additional appraisal of “statistical significance” for a contrast of two proportions. J Clin Epidemiol. 1990;43: 201–209. doi:10.1016/0895-4356(90)90186-s

6. Walter SD. Statistical significance and fragility criteria for assessing a difference of two proportions. J Clin Epidemiol. 1991;44: 1373–1378. doi:10.1016/0895-4356(91)90098-T

7. Heston TF. Adjusting fragility metrics for unequal trial randomizations. Autoimmun Rev. 2025;24: 103935. doi:10.1016/j.autrev.2025.103935

8. Heston TF. The Neutrality Boundary Framework: Quantifying Statistical Robustness Geometrically. arXiv. 2025; 2511.00982. doi:10.48550/arXiv.2511.00982

9. Heston TF. Redefining the Risk Quotient: A Generalized Framework for Fragility Analysis Across Study Designs. 2025 [cited 5 Oct 2025]. doi:10.5281/zenodo.17204904

10. Heston TF. Significance, Fragility, and Robustness in Clinical Trials: Stratifying Statistical Evidence. Cureus. 2025;17. doi:10.7759/cureus.100494

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Published

2026-04-08

How to Cite

Heston, T. F. (2026). Bidirectional fragility is a step forward but not far enough: the case for a global fragility index. Internet Medical Journal, 1(1), e19464166. https://doi.org/10.5281/zenodo.19464166