Optimizing Economic Evaluation of First-Line Chemotherapies for Metastatic Pancreatic Cancer for the UK and the US

Abstract

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United Kingdom (UK) and the United States (US). Most of the cases are diagnosed in the metastatic stage (MPC) and the disease is associated with a significant economic and quality of life burden. Chemotherapy with gemcitabine (GEM) is the standard of care. Combination regimens such as cisplatin plus GEM (CIS+GEM), capecitabine plus GEM (CAP+GEM), nab-paclitaxel plus gemcitabine (NAB-P+GEM), FOLFIRINOX (FFX), and oxaliplatin plus GEM (OX+GEM) showed an improvement in the survival outcome when compared to GEM alone. The purpose of the pharmacoeconomic research program included in this dissertation-by-articles was to assess the benefits of these regimens as first-line treatment relative to their costs in the management of metastatic pancreatic cancer for the UK and the US-doing so by building upon a critical review of pharmaco-economic studies of treatments for MPC and using a newly developed algorithm for parametric model selection. The four objectives of this research program were: (1) to identify and critique previous economic evaluation studies that have been done in the pancreatic cancer setting; (2) to propose a transparent algorithm to justify parametric model selection in economic evaluation studies; (3) to conduct an economic evaluation of systemic chemotherapies as first-line treatment of MPC from the payer perspective for the UK; and (4) to conduct an economic evaluation of systemic chemotherapies as first-line treatment of MPC from the payer perspective for the US. This dissertation begins with an orientation to MPC, treatment options, innovation, and dissertation outline. From the critical review (Chapter 2) we concluded that no comprehensive economic evaluations for all treatment options for the UK and the US have been published; overall survival was the key driver for most of the economic evaluations; economic analyses were country-specific, not generalizable across countries, inconsistent in their use of model inputs and utility estimates; and their justification for selecting a specific parametric model. The latter led us to the development of a quantitative algorithm (Chapter 3) for objectively selecting parametric models to extrapolate the data beyond the time horizon reported in the clinical trials; showing also that the application of different parametric models impacted the economic evaluation estimates. Considering the likelihood of between-country differences, we then performed pharmacoeconomic evaluations of GEM alone, CAP+GEM, OX+GEM, CIS+GEM, NAB-P+GEM and FFX for the UK (Chapter 4), with its single-payer system, and for the US (Chapter 5), with its multiple-payer system. The UK analyses revealed that compared to CAP+GEM, OX+GEM and CIS+GEM were more costly but less effective. Treatment with either FFX or CAP+GEM was more costly but more effective than with GEM alone. In contrast, the US analyses showed that OX+GEM, CAP+GEM, NAB-P+GEM and FFX were found to be costlier and more effective than GEM alone. Compared to GEM alone, NAB-P+GEM was found to have the smallest incremental cost-effectiveness and utility ratio among all other regimens. We synthesize and examine the implications of these findings in Chapter 6.