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; Lorna Wheaton; Heather Poad; Devleena Ray; Ilse Cuevas Andrade; Sam Khan; Paul Tappenden; Keith R Abrams; Rhiannon K Owen; Sylwia Bujkiewicz

arXiv · 2308.03597

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·Lorna Wheaton·Heather Poad·Devleena Ray·Ilse Cuevas Andrade·Sam Khan·Paul Tappenden·Keith R Abrams·Rhiannon K Owen·Sylwia Bujkiewicz

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Abstract

Objective: We aimed to develop a meta-analytic model for evaluation of predictive biomarkers and targeted therapies, utilising data from digital sources when individual participant data (IPD) from randomised controlled trials (RCTs) are unavailable. Methods: A Bayesian network meta-regression model, combining aggregate data (AD) from RCTs and IPD, was developed for modelling time-to-event data to evaluate predictive biomarkers. IPD were sourced from electronic health records, using target trial emulation approach, or digitised 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 developed allowed for estimation of treatment effects in two subgroups of patients defined by their biomarker status. Effectiveness of taxane did not differ in hormone receptor positive and negative breast cancer patients. Epidermal growth factor receptor (EGFR) 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 sub-group specific treatment effect estimates by up to 49%. Conclusion: Utilisation 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.

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Chinyereugo M Umemneku-Chikere, Lorna Wheaton, Heather Poad, Devleena Ray, Ilse Cuevas Andrade, Sam Khan, Paul Tappenden, Keith R Abrams, Rhiannon K Owen, Sylwia Bujkiewicz. 2023-08-07. Individual participant data from digital sources informed and improved precision in the evaluation of predictive biomarkers in Bayesian network meta-analysis. https://arxiv.org/abs/2308.03597

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