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Statistics in Medicine
Article . 2018 . Peer-reviewed
License: Wiley Online Library User Agreement
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zbMATH Open
Article . 2018
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Auxiliary variable–enriched biomarker‐stratified design

Auxiliary variable-enriched biomarker-stratified design
Authors: Ting Wang; Xiaofei Wang; Haibo Zhou; Jianwen Cai; Stephen L. George;

Auxiliary variable–enriched biomarker‐stratified design

Abstract

Clinical trials in the era of precision medicine require assessment of biomarkers to identify appropriate subgroups of patients for targeted therapy. In a biomarker‐stratified design (BSD), biomarkers are measured on all patients and used as stratification variables. However, such a trial can be both inefficient and costly, especially when the prevalence of the subgroup of primary interest is low and the cost of assessing the biomarkers is high. Efficiency can be improved and costs reduced by using enriched biomarker‐stratified designs, in which patients of primary interest, typically the biomarker‐positive patients, are oversampled. We consider a special type of enrichment design, an auxiliary variable–enriched design (AEBSD), in which enrichment is based on some inexpensive auxiliary variable that is positively correlated with the true biomarker. The proposed AEBSD reduces the total cost of the trial compared with a standard BSD when the prevalence rate of true biomarker positivity is small and the positive predictive value (PPV) of the auxiliary biomarker is larger than the prevalence rate. In addition, for an AEBSD, we can immediately randomize the patients selected in the screening process without waiting for the result of the true biomarker test, reducing the treatment waiting time. We propose an adaptive Bayesian method to adjust the assumed PPV while the trial is ongoing. Numerical studies and an example illustrate the approach. An R package is available.

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Keywords

auxiliary variables, Models, Statistical, precision medicine, treatment selection, Bayes Theorem, Bayesian method, Applications of statistics to biology and medical sciences; meta analysis, biomarker-stratified design, Treatment Outcome, cost minimization, Cost Savings, adaptive design, Humans, enrichment strategy, Precision Medicine, survival time, Biomarkers, Randomized Controlled Trials as Topic

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    popularity
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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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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!
3
Average
Average
Average
bronze