Flexible Approaches Based on Multistate Models and Microsimulation to Perform Real-World Cost-Effectiveness Analyses: An Application to Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors

Caterina Gregorio; Federico Rea; Francesca Ieva; Arjuna Scagnetto; Carla Indennidate; Chiara Cappelletto; Andrea Di Lenarda; Giulia Barbati

doi:10.1016/j.jval.2024.03.008

Flexible Approaches Based on Multistate Models and Microsimulation to Perform Real-World Cost-Effectiveness Analyses: An Application to Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors

Value Health. 2024 Mar 26:S1098-3015(24)00123-2. doi: 10.1016/j.jval.2024.03.008. Online ahead of print.

Authors

Caterina Gregorio¹, Federico Rea², Francesca Ieva³, Arjuna Scagnetto⁴, Carla Indennidate⁴, Chiara Cappelletto⁴, Andrea Di Lenarda⁴, Giulia Barbati⁵

Affiliations

¹ MOX-Modelling and Scientific Computing Laboratory, Department of Mathematics, Politecnico di Milano, Milano, Italy; Biostatistics Unit, Department of Medical Sciences, University of Trieste, Trieste, Italy; Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden. Electronic address: caterina.gregorio@units.it.
² Department of Statistics and Quantitative Methods, Unit of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy; National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.
³ MOX-Modelling and Scientific Computing Laboratory, Department of Mathematics, Politecnico di Milano, Milano, Italy; HDS, Health Data Science center, Human Technopole, Milan, Italy.
⁴ Cardiovascular Center, Territorial Specialistic Department, University Hospital and Health Services of Trieste, Italy.
⁵ Biostatistics Unit, Department of Medical Sciences, University of Trieste, Trieste, Italy.

PMID: 38548178
DOI: 10.1016/j.jval.2024.03.008

Abstract

Objectives: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia.

Methods: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models.

Results: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained.

Conclusions: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights.

Keywords: cost-effectiveness; electronic health records; microsimulation; real-world data; target trial emulation.