Modeling Framework for Economic Evaluation of Disease-Modifying Therapies in Parkinson's Disease: Evidence Review and Expert Opinion.

backgroundParkinson's disease (PD) is associated with a substantial clinical, humanistic, and economic burden across its disease continuum. Economic models for PD have largely been developed to evaluate symptomatic therapies, and typically adopt narrow payer perspectives, focus on advanced disease stages, and rely on simplified state-transition structures that do not distinguish symptomatic relief from disease modification. As candidate disease-modifying therapies emerge, modeling approaches capable of evaluating long-term value under substantial uncertainty will become essential, particularly for health technology assessment decision makers.

objectiveWe aimed to (1) update and synthesize the evidence on published economic evaluations of PD treatments, and (2) develop an evidence-based, health technology assessment-aligned conceptual framework to inform future economic evaluations capable of assessing disease-modifying therapies across the full course of PD.

methodsWe conducted systematic searches from July 2022 to August 2025 to update the evidence base identified in an earlier systematic literature review, supplemented by pragmatic searches targeting PD conceptual models, natural history evidence, cost drivers, and outcome correlations. Based on evidence identified in the review, we developed a conceptual model and a modeling framework following international good-practice guidance. To assess face validity, we solicited structured feedback from an advisory panel comprising movement-disorder specialized clinicians with health-economic experience and representatives from PD patient advocacy organizations. After incorporating the panel's recommendations, we also evaluated potential modeling techniques for the framework implementation.

resultsWe identified persistent limitations in the evidence base, which comprised 30 economic evaluations. These included reliance on Hoehn and Yahr-based Markov cohort models, limited incorporation of the burden of non-motor symptoms, caregiver burden, societal costs, and inadequate representation of lifetime disease progression. Few models were structurally capable of separating disease-modifying from symptomatic treatment effects. Here, we developed a comprehensive conceptual model that spans the PD trajectory from diagnosis to death, distinguishes underlying neurodegeneration from symptomatic progression, and explicitly incorporates non-motor symptoms, long-term treatment complications, milestones such as institutionalization, and multi-perspective costs. We propose a hybrid modeling framework, combining early-stage continuous Movement Disorder Society-Unified Parkinson's Disease Rating Scale-based progression with advanced-stage discrete health states. Finally, we recommend an individual-level state-transition (microsimulation) approach to implement this hybrid framework.

conclusionsThe proposed clinician- and patient advocate-endorsed framework provides a structured foundation for future economic evaluations of disease-modifying therapies in PD. We recommend an individual-level state-transition (microsimulation) approach for the framework implementation, as a pragmatic balance between structural fidelity and health technology assessment feasibility, to support more credible lifetime value assessments of emerging disease-modifying therapies.