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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]