Carly Rodriguez, MPH
Comparative Effectiveness and the Safety of Multidrug-Resistant Tuberculosis Treatment
Approximately 10 million people globally developed tuberculosis disease in 2019. Of these, nearly 500,000 were sick with isolates resistant to at least isoniazid and/or rifampin, referred to as multidrug-resistant TB (MDR-TB). Conventional treatment for MDR-TB is long in duration, often results in debilitating side effects and cures only half of patients. However, after nearly four decades of stagnancy in the TB drug pipeline, several promising drugs and regimens have recently gained regulatory approval by stringent authorities such as the United States Food and Drug Administration. These developments have outpaced the ability for clinical trials in MDR-TB — which can take five to ten years from inception to reporting of results — to produce timely evidence. Global guidance for the treatment of MDR-TB, issued by the World Health Organization, increasingly relies on observational data from patients treated under real-life conditions. Thus, comparative effectiveness and safety research from observational cohorts using appropriate statistical methods is required in order to inform global policy. This research will use observational data from the endTB Project. The observational study of the endTB Project is the largest study cohort of MDR-TB patients receiving treatment with bedaquiline and delamanid to date. Robust causal inference methods will be applied in the data to identify whether adding delamanid to MDR-TB regimens containing a background regimen comprised of three drugs likely to be effective improves culture conversion. Additionally, the optimal adverse event management strategy that maximizes safety and effectiveness for patients receiving linezolid will be evaluated. Lastly, the potential for bias when failing to account for MDR-TB treatment regimen changes will be assessed.
The PhRMA Foundation Predoctoral Fellowship in Health Outcomes has provided me with the opportunity to immerse myself in my dissertation research. Without the award, I would not have had protected time to pursue additional research training in statistical theory and techniques related to my dissertation. These skills will undoubtedly contribute to my future success as an independent investigator in the field of comparative effectiveness research.