The broken drug supply chain: The impact of COVID-19 on drug shortages and Veteran health

Background: Few of the drugs Veterans take as a cornerstone to prevent and treat disease are produced domestically; the majority of medications consumed in the U.S. are produced in foreign facilities. Thus, the drug supply chain is global and susceptible to disruption due to unanticipated events, such as the 2019 Coronavirus pandemic (COVID-19). Significance: However, little is known on the frequency of drug shortages causing medication treatment gaps and subsequent impact on adverse clinical outcomes. This is especially true in the outpatient setting, where the majority of drug shortages occur. Innovation and Impact: The research is innovative by conducting formative work on: 1) the impact of the pan- demic on drug supply and outcomes, 2) differences in shortages in VA priority groups, 3) incorporating stake- holders to inform methods, 4) direct involvement of VA operations and an expert panel of federal partners, and [unique access to operations data.]. The majority of Rx use and drug shortages in VA occur in outpatients, but prior research on drug shortages has focused on inpatients. We will also evaluate the impact of drug shortages by race, ethnicity, age, location, and co-morbidities. The results obtained here will guide VA policy-makers in the identification of the most effective policies to address this growing problem. Specific aims: 1) Determine the impact of the COVID pandemic on the drug supply chain in VA; 2) Assess the impact of drug shortages on outpatient medication treatment disruption in the VA; and 3) Determine the asso- ciation between drug shortage-related treatment disruption in outpatient prescription refills and serious adverse clinical outcomes. Methodology: Drug supply chain issues will be identified through U.S. reporting systems (e.g., FDA). We will leverage VA data for the quantity of drugs ordered and supplied nationally using VA purchasing and outpatient prescription data. For each drug potentially used in the outpatient setting with a reported supply chain issue, purchase changes will be assessed monthly pre- (2017-2019) and during the pandemic. Aim 1 will use inter- rupted time series (ITS) analyses to test whether the incidence of supply chain issues triggering a decrease in supply increased after pandemic start. Aim 2 will identify outpatient drug shortages leading to treatment disrup- tion using ITS and structural break models. Aim 3 will define cohorts based on the indication for drugs with identified shortages using a time to event analysis with entropy balance weighting to evaluate if adverse out- comes (hospitalizations, death, emergency/urgent care) were greater for patients using drugs affected by short- ages (the exposed group) compared to unexposed controls. Next steps and Implementation: Dissemination will be guided by an expert panel comprised of VA operational partners, other federal partners and experts in drug supply and shortages. The quantitative results will be as- similated with the expert panel discussions to develop a support guide to mitigate drug shortages in VA. The next step will be to; 1) inform the US list of essential medicines and criteria for production (e.g., domestically) and 2) determine effectiveness of our support guide and future VA policy implemented based on our work. Our future research will work to ensure access and equitable distribution of drugs with limited supply and/or at risk for shortages. Even after the pandemic, the research proposed will provide results to mitigate drug shortages which remains a crucial public health issue even in the absence of a national emergency. Thus, this will be one step in our long-term goal to plan for future global emergencies, drug shortages at large, and inform national policy to decrease the impact of drug shortages on patient outcomes.