Challenges of Bridging Studies in Biomarker Driven Clinical Trials: The Impact of Companion Diagnostic Device Performance on Clinical Efficacy

Szu Yu Tang, Bonnie LaFleur

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Personalized medicine involves the co-development of both the therapeutic agent (Rx) and a companion diagnostic device (CDx), which directs a group of patients to a particular treatment. There are instances, however, when there are competing, or multiple CDx products for a given Rx. Drivers for multiple CDx products can be driven by improved efficiency, cost, novel technologies, or updated techniques over time. In these instances, concordance between the old assay (e.g., the assay used in the clinical trial or comparator companion diagnostic device in this paper) and a new assay (follow-on companion diagnostic device) needs to be assessed. Discrepancies between the old and new assays, and specifically the impact of discordance on clinical efficacy, need to be evaluated. Studies that establish similarity between two or more CDx products are called bridging studies. We provide a statistical framework for method comparison studies where there is bias in measurement of one or both assessments. We then present a simulation study to evaluate the statistical impact of an imperfect CDx on the sensitivity and specificity of the follow-on companion diagnostic device. Further, we demonstrate the influence of the CDx accuracy on clinical efficacy in the context of an enrichment clinical trial.

Original languageEnglish (US)
Title of host publicationPharmaceutical Statistics - MBSW 39, 2016
EditorsRay Liu, Yi Tsong
PublisherSpringer New York LLC
Pages215-229
Number of pages15
ISBN (Print)9783319673851
DOIs
StatePublished - 2019
Externally publishedYes
Event39th Annual Midwest Biopharmaceutical Statistics Workshop, MBSW 2016 - Muncie, United States
Duration: May 16 2016May 18 2016

Publication series

NameSpringer Proceedings in Mathematics and Statistics
Volume218
ISSN (Print)2194-1009
ISSN (Electronic)2194-1017

Conference

Conference39th Annual Midwest Biopharmaceutical Statistics Workshop, MBSW 2016
Country/TerritoryUnited States
CityMuncie
Period5/16/165/18/16

Keywords

  • Bridging studies
  • Companion diagnostic device (CDx)
  • Comparator companion diagnostic device
  • Follow-on companion diagnostic device
  • Personalized medicine

ASJC Scopus subject areas

  • Mathematics(all)

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