Medication Utilization, Clinical, and Prescriber Behavior Impacts of Drug Shortages on Patients with Hypertension: Analysis of the 2018-2019 Angiotensin-II-Receptor Blocker(ARB) Recalls and Drug Shortages

Drug recalls protect the public from potentially harmful products. However, recalls can result in drug shortages if insufficient infrastructure exists to compensate for recalled supply. Shortages impact how pharmacies dispense a drug and can influence patient care when prescribers must use alternatives. Global shortages occurred in 2018-2019 when FDA recalled three angiotensin-receptor-II-blockers (ARBs) – valsartan, irbesartan, losartan - due to ingredient impurities. ARBs are recommended treatments for hypertension, heart failure, and chronic kidney disease. This dissertation used national data to evaluate the impact of the ARB shortages on patient use and outcomes. Our difference-in-differences approach compared changes in outcomes for baseline users of the recalled ARBs versus changes among users of similar comparison drugs which did not experience shortages. Aim 1 used all-payer claims from IQVIA to evaluate changes in anti-hypertension medications and drug spending post-ARB-shortages. Many ARB users transitioned to alternatives within 90 days. There were no observable changes in insurer and out-of-pocket drug spending. Fewer switches among those enrolled in Medicaid fee-for-service highlighted potential disparities in therapeutic substitution for groups who may experience greater difficulty accessing care. Aim 2 used commercial claims and electronic-health-record data from Optum to evaluate changes in adherence, blood pressure and healthcare use post-ARB-shortages. Like Aim 1, switches to alternatives increased within 90 days. There were no changes in blood pressure, nor ambulatory care use. Delayed increases in medication gaps and cardiovascular-related hospitalizations may reveal clinical harm for some patients. Therapeutic switches require a new prescription. In Aim 3, we used IQVIA data and a mixed interrupted time series approach to evaluate changes in provider-level prescribing post-ARB-shortages. Most prescribers substituted away from valsartan and to other ARBs. We did not observe spillovers to other anti-hypertensive classes. Results were consistent across prescriber characteristics. Overall, our findings suggest that availability of alternatives during the ARB shortages may have mitigated gaps in access and subsequent harm. As policymakers consider solutions to shortages, increased availability for generic drugs of public health importance – as well as mitigation of barriers to therapeutic substitution - could increase resiliency and ensure consistent access for everyone.