Date of Award

January 2023

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Shi-Yi Wang

Abstract

IMPORTANCE Most NSCLC patients are diagnosed at an advanced stage. Given recent advancements in immunotherapy and targeted therapies, identifying the biomarker status—such as targetable gene alterations and immune checkpoints—of patients becomes critical in selecting the appropriate treatment. Despite the substantial economic burden of lung cancer, little is known about the medication costs associated with advanced NSCLC treatment by different biomarkers.OBJECTIVE To investigate the association between biomarker status and first-year direct medication costs associated with advanced NSCLC treatment. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted using the Flatiron Health electronic health record (EHR)-derived de-identified database. The study population consisted of patients who received at least one biomarker testing and were diagnosed between January 1, 2011 and December 31, 2020. A coarsened exact matching method was applied to reduce potential confoundedness from covariates as it could better construct statistically comparable groups for our dataset than the propensity score matching method while achieving greater data retention than the exact matching method EXPOSURE AND CONTROL ALK+, BRAF+, EGFR+, MET+, NTRK+, RET+, ROS1+, PD-L1>1%, and PD-L1<1% were considered as exposures. Patients with unknown status of PD-L1 and unknown status or negative expression on other biomarkers served as the control group. MAIN OUTCOMES Mean first-year direct medication costs associated with advanced NSCLC treatment among all patients and patients stratified by biomarker status; Mean cost differences between the exposed and control groups estimated by coarsened exact matching. RESULTS A total of 36,022 patients with advanced NSCLC were included in the study. From 2013 to 2020, the mean first-year direct medication costs associated with advanced NSCLC treatment increased from $13,730 to $27,460. The unadjusted mean medication costs were $13,228 for ALK+, $30,157 for BRAF+, $15,792 for EGFR+, $27,774 for MET+, $27,919 for NTRK+, $31,704 for RET+, $20,954 for ROS1+, $25,662 for PDL1>1%, $23,487 for PDL1<1%, and $16,657 for the controls. After coarsened exact matching, the medication costs for patients with RET+, BRAF+, NTRK+, MET+, PD-L1>1%, or PD-L1<1% advanced NSCLC were found to be significantly higher than that for the controls. The cost differences were $13,547 (95% CI: $8,644, $18,449), $12,192 (95% CI: $8,455, $15,929), $11,337 (95% CI: $7,749, $14,924), $10,877 (95% CI: $7,895, $13,859), $7,861 (95% CI: $6,636, $9,086), $7,135 (95%CI: $5,645, $8,625), respectively. In contrast, patients with ALK+ (-$14,634; 95% CI: -$16,423, -$12,845) or EGFR+ (-$9,752; 95% CI: -$11,523, -$7,981) advanced NSCLC had significantly lower medication costs than the controls. No significant cost difference was found between patients with ROS1+ advanced NSCLC and the controls. CONCLUSIONS Overall, the mean first-year direct medication costs for patients with advanced NSCLC increased over the study period. Patients with RET+, BRAF+, NTRK+, MET+, PD-L1>1%, or PD-L1<1% advanced NSCLC had higher medication costs, while patients with ALK+ or EGFR+ advanced NSCLC had lower medication costs, compared to the control group. The study findings provide the most recent medication cost estimates for advanced NSCLC treatment by biomarkers and suggest that the medication cost for advanced NSCLC treatment was associated with biomarker status, which can guide future NSCLC cost-effectiveness analyses.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 05/22/2026

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