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Individual participant data from digital sources informed and improved precision in the evaluation of predictive biomarkers in Bayesian network meta-analysis

Chinyereugo M. Umemneku-Chikere Orcid Logo, Lorna Wheaton Orcid Logo, Heather Poad Orcid Logo, Devleena Ray, Ilse Cuevas Andrade, Sam Khan, Paul Tappenden, Keith R. Abrams, Rhiannon Owen Orcid Logo, Sylwia Bujkiewicz Orcid Logo

Journal of Clinical Epidemiology, Volume: 164, Pages: 96 - 103

Swansea University Author: Rhiannon Owen Orcid Logo

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Abstract

Objectives: We aimed to develop a network meta-analytic model for the evaluation of treatment effectiveness within predictive biomarker subgroups, by combining evidence from individual participant data (IPD) from digital sources (in the absence of randomized controlled trials) and aggregate data (AD...

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Published in: Journal of Clinical Epidemiology
ISSN: 0895-4356
Published: Elsevier BV 2023
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa65015
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Abstract: Objectives: We aimed to develop a network meta-analytic model for the evaluation of treatment effectiveness within predictive biomarker subgroups, by combining evidence from individual participant data (IPD) from digital sources (in the absence of randomized controlled trials) and aggregate data (AD). Study Design and Setting: A Bayesian framework was developed for modeling time-to-event data to evaluate predictive biomarkers. IPD were sourced from electronic health records, using a target trial emulation approach, or digitized Kaplan-Meier curves. The model is illustrated using two examples: breast cancer with a hormone receptor biomarker, and metastatic colorectal cancer with the Kirsten Rat Sarcoma (KRAS) biomarker. Results: The model allowed for the estimation of treatment effects in two subgroups of patients defined by their biomarker status. Effectiveness of taxanes did not differ in hormone receptor positive and negative breast cancer patients. Epidermal growth factor receptor inhibitors were more effective than chemotherapy in KRAS wild type colorectal cancer patients but not in patients with KRAS mutant status. Use of IPD reduced uncertainty of the subgroup-specific treatment effect estimates by up to 49%. Conclusion: Utilization of IPD allowed for more detailed evaluation of predictive biomarkers and cancer therapies and improved precision of the estimates compared to use of AD alone.
Keywords: IPD network meta-analysis, Network meta-regression, Predictive biomarker, Colorectal cancer, Breast cancer, One-stage Bayesian hierarchical model
College: Faculty of Medicine, Health and Life Sciences
Funders: This research was funded by the Medical Research Council, Methodology Research Panel (grant no. MR/T025166/1) and partly supported by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health, and Social Care (England) and the devolved administrations, and leading medical research charities.
Start Page: 96
End Page: 103