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Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study

Addressing the heterogeneity of both the outcome of a disease and the treatment response to an intervention is a mandatory pathway for regulatory approval of medicines. In randomized clinical trials (RCTs), confirmatory subgroup analyses focus on the assessment of drugs in predefined subgroups, whil...

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Autores principales: Esnault, Cyril, Gadonna, May-Line, Queyrel, Maxence, Templier, Alexandre, Zucker, Jean-Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861304/
https://www.ncbi.nlm.nih.gov/pubmed/33733209
http://dx.doi.org/10.3389/frai.2020.559927
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author Esnault, Cyril
Gadonna, May-Line
Queyrel, Maxence
Templier, Alexandre
Zucker, Jean-Daniel
author_facet Esnault, Cyril
Gadonna, May-Line
Queyrel, Maxence
Templier, Alexandre
Zucker, Jean-Daniel
author_sort Esnault, Cyril
collection PubMed
description Addressing the heterogeneity of both the outcome of a disease and the treatment response to an intervention is a mandatory pathway for regulatory approval of medicines. In randomized clinical trials (RCTs), confirmatory subgroup analyses focus on the assessment of drugs in predefined subgroups, while exploratory ones allow a posteriori the identification of subsets of patients who respond differently. Within the latter area, subgroup discovery (SD) data mining approach is widely used—particularly in precision medicine—to evaluate treatment effect across different groups of patients from various data sources (be it from clinical trials or real-world data). However, both the limited consideration by standard SD algorithms of recommended criteria to define credible subgroups and the lack of statistical power of the findings after correcting for multiple testing hinder the generation of hypothesis and their acceptance by healthcare authorities and practitioners. In this paper, we present the Q-Finder algorithm that aims to generate statistically credible subgroups to answer clinical questions, such as finding drivers of natural disease progression or treatment response. It combines an exhaustive search with a cascade of filters based on metrics assessing key credibility criteria, including relative risk reduction assessment, adjustment on confounding factors, individual feature’s contribution to the subgroup’s effect, interaction tests for assessing between-subgroup treatment effect interactions and tests adjustment (multiple testing). This allows Q-Finder to directly target and assess subgroups on recommended credibility criteria. The top-k credible subgroups are then selected, while accounting for subgroups’ diversity and, possibly, clinical relevance. Those subgroups are tested on independent data to assess their consistency across databases, while preserving statistical power by limiting the number of tests. To illustrate this algorithm, we applied it on the database of the International Diabetes Management Practice Study (IDMPS) to better understand the drivers of improved glycemic control and rate of episodes of hypoglycemia in type 2 diabetics patients. We compared Q-Finder with state-of-the-art approaches from both Subgroup Identification and Knowledge Discovery in Databases literature. The results demonstrate its ability to identify and support a short list of highly credible and diverse data-driven subgroups for both prognostic and predictive tasks.
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spelling pubmed-78613042021-03-16 Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study Esnault, Cyril Gadonna, May-Line Queyrel, Maxence Templier, Alexandre Zucker, Jean-Daniel Front Artif Intell Artificial Intelligence Addressing the heterogeneity of both the outcome of a disease and the treatment response to an intervention is a mandatory pathway for regulatory approval of medicines. In randomized clinical trials (RCTs), confirmatory subgroup analyses focus on the assessment of drugs in predefined subgroups, while exploratory ones allow a posteriori the identification of subsets of patients who respond differently. Within the latter area, subgroup discovery (SD) data mining approach is widely used—particularly in precision medicine—to evaluate treatment effect across different groups of patients from various data sources (be it from clinical trials or real-world data). However, both the limited consideration by standard SD algorithms of recommended criteria to define credible subgroups and the lack of statistical power of the findings after correcting for multiple testing hinder the generation of hypothesis and their acceptance by healthcare authorities and practitioners. In this paper, we present the Q-Finder algorithm that aims to generate statistically credible subgroups to answer clinical questions, such as finding drivers of natural disease progression or treatment response. It combines an exhaustive search with a cascade of filters based on metrics assessing key credibility criteria, including relative risk reduction assessment, adjustment on confounding factors, individual feature’s contribution to the subgroup’s effect, interaction tests for assessing between-subgroup treatment effect interactions and tests adjustment (multiple testing). This allows Q-Finder to directly target and assess subgroups on recommended credibility criteria. The top-k credible subgroups are then selected, while accounting for subgroups’ diversity and, possibly, clinical relevance. Those subgroups are tested on independent data to assess their consistency across databases, while preserving statistical power by limiting the number of tests. To illustrate this algorithm, we applied it on the database of the International Diabetes Management Practice Study (IDMPS) to better understand the drivers of improved glycemic control and rate of episodes of hypoglycemia in type 2 diabetics patients. We compared Q-Finder with state-of-the-art approaches from both Subgroup Identification and Knowledge Discovery in Databases literature. The results demonstrate its ability to identify and support a short list of highly credible and diverse data-driven subgroups for both prognostic and predictive tasks. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7861304/ /pubmed/33733209 http://dx.doi.org/10.3389/frai.2020.559927 Text en Copyright © 2020 Esnault, Gadonna, Queyrel, Templier and Zucker. http://Creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://Creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Artificial Intelligence
Esnault, Cyril
Gadonna, May-Line
Queyrel, Maxence
Templier, Alexandre
Zucker, Jean-Daniel
Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title_full Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title_fullStr Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title_full_unstemmed Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title_short Q-Finder: An Algorithm for Credible Subgroup Discovery in Clinical Data Analysis — An Application to the International Diabetes Management Practice Study
title_sort q-finder: an algorithm for credible subgroup discovery in clinical data analysis — an application to the international diabetes management practice study
topic Artificial Intelligence
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861304/
https://www.ncbi.nlm.nih.gov/pubmed/33733209
http://dx.doi.org/10.3389/frai.2020.559927
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