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Statistics in Medicine
Article . 2019
License: taverne
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Article . 2019
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Statistics in Medicine
Article . 2019 . Peer-reviewed
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Level of evidence for promising subgroup findings: The case of trends and multiple subgroups

The case of trends and multiple subgroups
Authors: Julien Tanniou; Sanne C. Smid; Ingeborg van der Tweel; Steven Teerenstra; Kit C.B. Roes;

Level of evidence for promising subgroup findings: The case of trends and multiple subgroups

Abstract

Subgroup analyses are an essential part of fully understanding the complete results from confirmatory clinical trials. However, they come with substantial methodological challenges. In case no statistically significant overall treatment effect is found in a clinical trial, this does not necessarily indicate that no patients will benefit from treatment. Subgroup analyses could be conducted to investigate whether a treatment might still be beneficial for particular subgroups of patients. Assessment of the level of evidence associated with such subgroup findings is primordial as it may form the basis for performing a new clinical trial or even drawing the conclusion that a specific patient group could benefit from a new therapy. Previous research addressed the overall type I error and the power associated with a single subgroup finding for continuous outcomes and suitable replication strategies. The current study aims at investigating two scenarios as part of a nonconfirmatory strategy in a trial with dichotomous outcomes: (a) when a covariate of interest is represented by ordered subgroups, eg, in case of biomarkers, and thus, a trend can be studied that may reflect an underlying mechanism, and (b) when multiple covariates, and thus multiple subgroups, are investigated at the same time. Based on simulation studies, this paper assesses the credibility of subgroup findings in overall nonsignificant trials and provides practical recommendations for evaluating the strength of evidence of subgroup findings in these settings.

Countries
France, Netherlands
Keywords

Statistics and Probability, Radboudumc 18: Healthcare improvement science RIHS: Radboud Institute for Health Sciences, clinical trials, Clinical Trials as Topic, failed study, overall nonsignificant trial, type I error, Epidemiology, [SDV]Life Sciences [q-bio], multiple testing, Radboud University Medical Center, [STAT]Statistics [stat], Bias, Data Interpretation, Statistical, Taverne, Outcome Assessment, Health Care, subgroup analysis, Health Evidence - Radboud University Medical Center

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
hybrid