Evaluating Partitioned Survival and Markov Decision-Analytic Modeling Approaches for Use in Cost-Effectiveness Analysis: Estimating and Comparing Survival Outcomes

Caitlin Smare (), Khalid Lakhdari, Justin Doan, John Posnett and Sukhvinder Johal
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Caitlin Smare: PAREXEL International
Khalid Lakhdari: Bristol-Myers Squibb Canada
Justin Doan: Bristol-Myers Squibb
John Posnett: PAREXEL International
Sukhvinder Johal: PAREXEL International

PharmacoEconomics, 2020, vol. 38, issue 1, No 8, 97-108

Abstract: Abstract Objective The objective of this study was to assess long-term survival outcomes for nivolumab and everolimus in renal cell carcinoma predicted by three model structures, a partitioned survival model (PSM) and two variations of a semi-Markov model (SMM), for use in cost-effectiveness analyses. Methods Three economic model structures were developed and populated using parametric curves fitted to patient-level data from the CheckMate 025 trial. Models consisted of three health states: progression-free, progressed disease, and death. The PSM estimated state occupancy using an area under-the-curve approach from overall survival (OS) and progression-free survival (PFS) curves. The SMMs derived transition probabilities to calculate patient flow between health states. One SMM assumed that post-progression survival (PPS) was independent of PFS duration (PPS Markov); the second SMM assumed differences in PPS based on PFS duration (PPS–PFS Markov). Results All models provide a reasonable fit to the observed OS data at 2 years. For estimating cost effectiveness, however, a more relevant comparison is between estimates of OS over the modeling horizon, because this will likely impact differences in costs and quality-adjusted life-years. Estimates of the incremental mean survival benefit of nivolumab versus everolimus over 20 years were 6.6 months (PSM), 7.6 months (PPS Markov), and 7.4 months (PPS–PFS Markov), reflecting non-trivial differences of + 14% and + 11%, respectively, compared with PSM. Conclusions The evidence from this study and previous work highlights the importance of the assumptions underlying any model structure, and the need to validate assumptions regarding survival and the application of treatment effects against what is known about the characteristics of the disease.

Date: 2020
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DOI: 10.1007/s40273-019-00845-x

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