The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma
Authors Shafrin J, Sullivan J, Chou JW, Neely MN, Doan JF, Maclean JR
Received 3 August 2017
Accepted for publication 12 October 2017
Published 29 November 2017 Volume 2017:9 Pages 731—739
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Professor Alexandra Fernandes
Jason Shafrin,1 Jeffrey Sullivan,1 Jacquelyn W Chou,1 Michael N Neely,2 Justin F Doan,3 J Ross Maclean1
1Precision Health Economics, Los Angeles, CA, USA; 2Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA
Objective: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma.
Methods: We used an adherence–exposure–outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration–time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios.
Results: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus.
Conclusion: Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS.
Keywords: adherence, axitinib, everolimus, outcomes, pharmacokinetics/pharmacodynamics, progression-free survival, renal cell carcinoma, second-line
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