Date of Award
12-1-2025
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Dr. Sujith Ramachandran
Second Advisor
Dr. Kaustuv Bhattacharya
Third Advisor
Dr. John P. Bentley
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
The purpose of this dissertation was to: 1) determine out-of-pocket cost trend and the impact of Inflation Reduction Act (IRA) provisions on the out-of-pocket costs among Medicare-enrolled chronic lymphocytic leukemia (CLL) patients; 2) evaluate treatment patterns and comparative effectiveness of therapeutics classes for CLL treatment in adults; and 3) assess racial disparities and time to treatment initiation in survival outcomes among Medicare-enrolled beneficiaries with CLL.
In objective 1, a cohort study using SEER-Medicare linked data from 2006 to 2020 identified 13,356 eligible beneficiaries with incident CLL. Among them, 3,158 (23.7%) were projected to benefit from the IRA’s $2000 annual out-of-pocket Part D (OOPD) cap. Cap-eligible individuals were more likely to be younger, non-Hispanic White, and not enrolled in low-income subsidy (LIS) and without dual-eligibility status. The mean OOPD cost savings under the cap were $2,695 (SD: $2,667), with a median of $1,645 (IQR: $692 - $4,055). From 2007 to 2020, individuals without LIS experienced a 27.7% increase in mean annual OOPD costs, while those with full LIS had a 37.3% reduction. Similar trends were observed in total out-of-pocket costs.
In objective 2, the study cohort included 4,752 individuals who initiated first-line CLL therapy between 2007 and 2019. Monoclonal antibodies (59.1%) and chemotherapy (47.0%) were the most commonly used regimens, while targeted therapies accounted for 26.6% of first-line use. The use of targeted therapies increased substantially over time, particularly after 2014, reflecting the evolving treatment landscape. Adjusted Cox models showed that both chemotherapy and monoclonal antibody monotherapy as first-line therapy were associated with a higher risk of all-cause mortality, while chemoimmunotherapy was associated with lower risk, compared to targeted therapy-based regimen. Per-protocol analysis revealed even stronger associations, with chemotherapy and monoclonal antibody monotherapy, whereas chemoimmunotherapy was also found to be associated with significantly higher mortality.
In objective 3, among 14,426 Medicare beneficiaries newly diagnosed with CLL, 6,464 (3.3%) initiated treatment within the early treatment window (grace period of 365 days from diagnosis). Compared to non-early initiators, early initiators were older, more medically complex, and more socially vulnerable. Adjusted clone-censor-weighted models revealed that early treatment was associated with an increased hazard of mortality, with consistent results across sensitivity analyses using 6- and 24-month grace periods. Although the interaction between race and early treatment initiation was not statistically significant, stratified analyses showed a significant risk of mortality associated with early treatment among non-Hispanic White, Hispanic, and other racial groups except Black individuals.
Recommended Citation
Maharjan, Shishir, "Out-of-Pocket Costs, Treatment Pattern, and Disparities in Outcomes Among Adults with Chronic Lymphocytic Leukemia" (2025). Electronic Theses and Dissertations. 3523.
https://egrove.olemiss.edu/etd/3523