INTEGRATION OF QUANTITATIVE SYSTEMS PHARMACOLOGY AND HEALTH ECONOMICS MODELS FOR DRUG DEVELOPMENT DECISION MAKING: APPLICATION TO TREATMENT OF SKELETAL RELATED EVENTS IN PATIENTS WITH BONE METASTASES
Author(s)
Gastonguay M, Riggs M, Johnson M
Metrum Research Group, Tariffville, CT, USA
OBJECTIVES To provide a proof of concept for the integration of quantitative systems pharmacology (QSP) and health economics (HE) models for the purpose of informing early drug development decision making. METHODS The QSP of denosumab (DMB) and a hypothetical novel bone therapeutic (Drug X) were described based on a previously developed multi-scale physiologic model for bone. The QSP model quantified drug effects on bone turnover markers, bone mineral density, and fracture rate (FR) as a system of ordinary differential and algebraic equations. For these simulations, Drug X properties were assumed to be similar to DMB, but with a two-fold longer elimination half-life. Cost effectiveness (CE) of treating skeletal related events in patients with bone metastases was described using a published lifetime Markov HE model, which incorporated states of “on treatment”, “off treatment”, and “dead”. Simulations of CE metrics were conducted for Drug X under a range of dosing intervals (4, 8, 16 weeks), and for DMB according to the labeled dosing. The CE of zolendronic acid (ZA) in this same indication served as a reference. RESULTS Simulations of Drug X administered every 8-weeks resulted in comparative efficacy similar to previously published results for DMB, with an incremental benefit of approximately 0.125 quality-adjusted life-years (QALYs). Lifetime cost per QALY was less than $70,000, and net monetary benefit relative to ZA favored DMB and Drug X (at the 8-week interval). Simulations of Drug X at the 4 week interval did not result in an improvement in QALY, while the 16 week interval resulted in insufficient effects on BMD and fracture rate and reduced QALY relative to DMB. CONCLUSIONS This proof of concept simulation study demonstrated the potential utility of linking a quantitative understanding of pharmacology with mathematical models of cost-effectiveness for the purpose of informing early clinical development.
Conference/Value in Health Info
2020-05, ISPOR 2020, Orlando, FL, USA
Value in Health, Volume 23, Issue 5, S1 (May 2020)
Code
PCN47
Topic
Economic Evaluation, Health Technology Assessment, Methodological & Statistical Research, Organizational Practices
Topic Subcategory
Cost-comparison, Effectiveness, Utility, Benefit Analysis, Decision & Deliberative Processes, Industry
Disease
Multiple Diseases, Musculoskeletal Disorders, Oncology