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

• Published in: Journal of clinical epidemiology 2023-12, Vol.164, p.96-103
• Main Authors: Umemneku-Chikere, Chinyereugo M, Wheaton, Lorna, Poad, Heather, Ray, Devleena, Andrade, Ilse Cuevas, Khan, Sam, Tappenden, Paul, Abrams, Keith R, Owen, Rhiannon K, Bujkiewicz, Sylwia
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Bayesian analysis; Biomarkers; Breast cancer; Cancer therapies; Chemotherapy; Clinical trials; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Digitization; Effectiveness; Electronic health records; Electronic medical records; Estimates; Estrogens; Growth factors; Humans; K-Ras protein; Mathematical models; Meta-analysis; Metastases; Network Meta-Analysis; Patients; Proto-Oncogene Proteins p21(ras) - therapeutic use; Receptors; Sarcoma; Subgroups; Systematic review; Vascular endothelial growth factor
• ISSN: 0895-4356; 1878-5921; 1878-5921
• DOI: 10.1016/j.jclinepi.2023.10.018

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). 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. 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%. 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.