The ellipse of insignificance, a refined fragility index for ascertaining robustness of results in dichotomous outcome trials

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 materialize 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 multidimensional and is computationally expensive. In this work, a conceptually similar geometrical approach is introduced, the ellipse of insignificance. 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.