The Ellipse of Insignificance, a refined fragility indexfor ascertaining robustness of results indichotomous outcome trials

  1. David Robert Grimes  Is a corresponding author
  1. Dublin City University, Ireland

Abstract

There is increasing awareness throughout biomedical science that many results do not withstand the trials of repeat investigation. The growing abundance of medical literature has only increased the urgent need for tools to gauge the robustness and trustworthiness of published science. Dichotomous outcome designs are vital in randomized clinical trials, cohort studies, and observational data for ascertaining differences between experimental and control arms. It has however been shown with tools like the fragility index (FI) that many ostensibly impactful results fail to materialise when even small numbers of patients or subjects in either the control or experimental arms are recoded from event to non-event. Critics of this metric counter that there is no objective means to determine a meaningful FI. As currently used, FI is not multi-dimensional and is computationally expensive. In this work a conceptually similar geometrical approach is introduced, the ellipse of insignificance (EOI). This method yields precise deterministic values for the degree of manipulation or miscoding that can be tolerated simultaneously in both control and experimental arms, allowing for the derivation of objective measures of experimental robustness. More than this, the tool is intimately connected with sensitivity and specificity of the event / non-event tests, and is readily combined with knowledge of test parameters to reject unsound results. The method is outlined here, with illustrative clinical examples.

Data availability

The paper is a modelling study and methodology and contains no data, and code provided in the supplementary material allows reproduction of all methods.

Article and author information

Author details

  1. David Robert Grimes

    Dublin City University, Dublin, Ireland
    For correspondence
    davidrobert.grimes@dcu.ie
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3140-3278

Funding

Wellcome Trust (214461/A/18/Z)

  • David Robert Grimes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Grimes

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 655
    views
  • 114
    downloads
  • 4
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. David Robert Grimes
(2022)
The Ellipse of Insignificance, a refined fragility indexfor ascertaining robustness of results indichotomous outcome trials
eLife 11:e79573.
https://doi.org/10.7554/eLife.79573

Share this article

https://doi.org/10.7554/eLife.79573