Minimizing levothyroxine overuse

Background: Levothyroxine (LT4) is the second most prescribed drug in the United States (U.S.), with around 20 million Americans receiving LT4. Among those starting LT4, 61% have subclinical hypothyroidism (SCH) and 31% have normal thyroid function (euthyroid). One in 3 people are diagnosed with SCH and start LT4 because of only one abnormal thyrotropin test result. These practices contrast with guidelines that recommend 1) confirming initially abnormal thyroid tests before initiating LT4 treatment and 2) against LT4 use in euthyroid patients. Such non-evidence-based use of LT4 not only does not benefit patients, but also exposes them to treatment burden (e.g., lifestyle changes) and harm (e.g., death), and increases costs to the healthcare system (e.g., $3.2 billion U.S. healthcare expenditures for LT4 in 2016). Significance: There is widespread, wasteful, and harmful overprescribing of LT4. There is an urgent need for rigorous evidence about drivers of inappropriate LT4 use, including those that may lead to disparities in hypothyroidism care, which can inform the development of targeted implementation strategies for evidence-based and equitable use of LT4. Our study, consistent with the VA HSR priority area: Quality, Safety, and Value, will address this knowledge gap and has the potential to improve the care delivered to millions of Veterans. Innovation & Impact: This innovative study marks the inaugural exhaustive exploration of factors associated with evidence-based use of LT4 within the VHA health system. We will use an innovative conceptual framework, the Health Equity Implementation Framework (HEIF), to guide our assessments and an innovative machine learning approach, Bayesian network and cluster analysis, to examine how multi-level factors contribute to evidence-based use of LT4. Successful completion of this novel work will lead to the definitive assessment of factors hindering or promoting evidence-based use of LT4 in the VHA and subsequent development of an acceptable and feasible implementation strategy package to support evidence-based use of LT4. Specific Aims: Our hypothesis is that multi-level implementation strategies are needed to enhance evidence-based use of LT4 in the VHA and reduce the substantial and unnecessary economic and treatment burden, and even harm to Veterans from LT4 overuse. In this proposal we aim to: 1) Identify factors associated with evidence-based use of LT4. 2) Investigate barriers and facilitators to evidence- based use of LT4. 3) Develop a multi-level implementation strategy package to enhance evidence-based use of LT4. Methodology: We will conduct a retrospective cohort study using the Corporate Data Warehouse- Centers for Medicare & Medicaid Services linkage to identify adult VHA patients, who were newly initiated on LT4 therapy between January 1, 2013, and December 31, 2023. For the primary outcome, we will calculate the proportion of VHA patients with non-evidence-based LT4 prescriptions (e.g., normal thyroid levels, incomplete thyroid function testing) and identify the patient (e.g., age, sex, race/ethnicity), clinician (e.g., specialty), and practice (e.g., rurality) characteristics associated with evidence-based use of LT4. We will then use a mixed-methods sequential explanatory design to conduct surveys followed by interviews employing the HEIF with patients, clinicians (e.g., primary care, endocrinology), and key VA organizational stakeholders (e.g., service chiefs, core group leaders, administrators) at the Central Arkansas Veterans Healthcare System (CAVHS), to understand individual perspectives, attitudes, organizational, and societal factors that serve as barriers or facilitators to the evidence-based and equitable use of LT4. Finally, we will use a modified Delphi-based implementation mapping approach to engage a panel of CAVHS patients, caregivers, clinicians, and other stakeholders and develop a feasible and acceptable multi-level implementation strategy package that t Project Number: 1I01HX003952-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Spyridoula Maraka | Institution: CENTRAL ARKANSAS VETERANS HLTHCARE SYS, NORTH LITTLE ROCK, AR | Activity Code: I01 | Study Section: HSR-1 Health Care and Clinical Management[HSR1] View on NIH RePORTER: https://reporter.nih.gov/project-details/11111033