1. Epidemiology and Global Health

Region of attainable redaction, an extension of ellipse of insignificance analysis for gauging impacts of data redaction in dichotomous outcome trials

  1. David Robert Grimes  Is a corresponding author
  1. Trinity College Dublin, Ireland
https://doi.org/10.7554/eLife.93050
Share this article
Cite this article
  1. David Robert Grimes
(2024)
Region of attainable redaction, an extension of ellipse of insignificance analysis for gauging impacts of data redaction in dichotomous outcome trials
eLife 13:e93050.
https://doi.org/10.7554/eLife.93050
  2. Download BibTeX
  3. Download .RIS

Abstract

In biomedical science, it is a reality that many published results do not withstand deeper investigation, and there is growing concern over a replicability crisis in science. Recently, Ellipse of Insignificance (EOI) analysis was introduced as a tool to allow researchers to gauge the robustness of reported results in dichotomous outcome design trials, giving precise deterministic values for the degree of miscoding between events and non-events tolerable simultaneously in both control and experimental arms1 (Grimes 2022). While this is useful for situations where potential miscoding might transpire, it does not account for situations where apparently significant findings might result from accidental or deliberate data redaction in either the control or experimental arms of an experiment, or from missing data or systematic redaction. To address these scenarios, we introduce Region of Attainable Redaction (ROAR), a tool that extends EOI analysis to account for situations of potential data redaction. This produces a bounded cubic curve rather than an ellipse, and we outline how this can be used to identify potential redaction through an approach analogous to EOI. Applications are illustrated, and source code including a web-based implementation that performs EOI and ROAR analysis in tandem for dichotomous outcome trials is provided.

Data availability

All data is available in the paper and at github: https://github.com/drg85/EOIROAR_codeWeb implementation is available at: https://drg85.shinyapps.io/EOIROAR/

Article and author information

Author details

  1. David Robert Grimes

    School of Medicine, Trinity College Dublin, 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

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.

Reviewing Editor

  1. Philip Boonstra, University of Michigan, United States

Version history

  1. Preprint posted: September 25, 2023 (view preprint)
  2. Received: October 4, 2023
  3. Accepted: January 23, 2024
  4. Accepted Manuscript published: January 29, 2024 (version 1)
  5. Version of Record published: February 16, 2024 (version 2)

Copyright

© 2024, 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

  • 129
    views
  • 18
    downloads
  • 0
    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
(2024)
Region of attainable redaction, an extension of ellipse of insignificance analysis for gauging impacts of data redaction in dichotomous outcome trials
eLife 13:e93050.
https://doi.org/10.7554/eLife.93050

Share this article

https://doi.org/10.7554/eLife.93050

Categories and tags

Further reading

    1. Epidemiology and Global Health
    2. Medicine

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

    David Robert Grimes
    Tools and Resources Updated

    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.

    1. Epidemiology and Global Health

    A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients

    Zhanwei Du, Lin Wang ... Lauren A Meyers
    Short Report Updated

    Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0–16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.

    1. Cancer Biology
    2. Epidemiology and Global Health

    Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study

    Lijun Bian, Zhimin Ma ... Guangfu Jin
    Research Article

    Background:

    Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.

    Methods:

    Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).

    Results:

    Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p<0.001; Beta = –0.98 in women, p<0.001).

    Conclusions:

    Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.

    Funding:

    This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).