Enhancing Health Policy Decisions in Diseases Affecting Disadvantaged Populations: Applied and Methodological Analyses

Abstract

In this dissertation, I employed three different analytic lenses to help improve health policy decisions. Each chapter focuses on either tuberculosis (TB) or sickle cell disease (SCD), conditions which predominantly affect systematically disadvantaged populations. I investigated the effectiveness and cost-effectiveness of shorter, all-oral regimens to treat rifampicin-resistant TB (RR-TB) in Moldova—a country with a high burden of RR-TB—and explored the impact of methodological decisions on the distributional (i.e., equity-weighted) cost-effectiveness of new gene therapies for Sickle Cell Disease (SCD) in the United States (US). In chapter 1, I evaluated the cost-effectiveness and budget impact of a 6-month regimen of bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) to treat pulmonary RR-TB in Moldova, as compared to established 9- to 18-month regimens. Using genomic data, I built a microsimulation model to estimate the quality-adjusted life expectancy and costs under each strategy, and tracked the evolution of resistance of M. tuberculosis to 12 anti-TB drugs. Compared to longer regimens, I found that 6 months of BPaLM was cost-effective across a broad range of scenarios, and would save Moldova’s national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million]) over the five year period from implementation. Six months of BPaLM also reduced the length of time spent with TB resistant to six drugs (including bedaquiline and moxifloxacin), while it increased the time spent with TB resistant to two drugs (delamanid and pretomanid), findings which could exert additional spillover effects. Overall, this study adds to the growing body of evidence in favor of shorter, more tolerable, all-oral regimens for RR-TB. In chapter 2, I compared the effectiveness of all-oral bedaquiline-containing regimens against injectable-containing regimens for pulmonary RR-TB in Moldova using data from routinely collected electronic medical records. In an intention-to-treat analysis of a cohort of adults initiating treatment for culture-positive RR-TB in 2019-2021, I found that all-oral bedaquiline-containing regimens were associated with improved probability and hazard rate of culture conversion in 6 months following treatment initiation, after adjusting for baseline covariates. These results contribute to both clinical and policy decisions alongside other empirical and modeling evidence on the tolerability, long-term health outcomes, and cost-effectiveness of these regimens. In chapter 3, I explored the impact of methodological decisions within distributional cost-effectiveness analysis (DCEA). DCEA is a modeling approach capable of balancing concerns for efficiency and equity, by affording extra priority to groups who are less well-off. Although interest is growing in applying these methods, guidance for conducting DCEA in the US setting is limited. Using an applied example in SCD, I modeled the US population in 2023, and showed that the choice of variables used to stratify the population into equity-relevant groups can affect whether a new SCD gene therapy would be recommended, even while holding the level of inequality aversion constant. Results may also be impacted by cost incidence assumptions, specifically as to how opportunity costs are experienced by those enrolled in Medicaid. This work highlights the need for awareness of the normative implications of modeling decisions in DCEA, and for reaching consensus on how these analyses are conducted in the US.