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

背景：退伍军人作为预防和治疗疾病基石的药物很少生产 在美国消费的大多数药物都是在国外生产的。因此，药物 供应链是全球性的，容易因2019年冠状病毒等意外事件而中断 新冠肺炎疫情。 意义：然而，对药物短缺导致药物治疗缺口的频率知之甚少 以及对不良临床结局的后续影响。这在门诊设置中尤其如此， 大多数药品短缺。 创新和影响：该研究是创新的，通过进行以下方面的形成性工作：1）泛 流行病的药物供应和结果，2）在VA优先组短缺的差异，3）纳入利益- 4）退伍军人事务部行动和联邦伙伴专家小组的直接参与， [操作数据的唯一访问权限。]。VA中的大多数Rx使用和药物短缺发生在门诊患者中， 以前对药品短缺的研究集中在住院病人身上。我们还将评估药品短缺的影响 按种族、民族、年龄、地点和合并症分类。这里获得的结果将指导退伍军人事务部决策者 确定解决这一日益严重问题的最有效政策。 具体目标：1）确定COVID大流行对VA药品供应链的影响; 2）评估 药物短缺对VA门诊药物治疗中断的影响; 3）确定 门诊处方补充中药物短缺相关治疗中断与严重不良反应之间的联系 临床结果。 方法：将通过美国报告系统（例如，FDA）。我们将 利用VA数据，通过VA采购和门诊服务， 处方数据。对于可能在门诊环境中使用并报告供应链问题的每种药物， 在疫情爆发前（2017-2019年）和疫情期间，将每月评估采购变化。Aim 1将使用inter- 中断的时间序列（ITS）分析，以测试是否发生供应链问题触发减少， 疫情开始后供应增加。目标2将确定导致治疗中断的门诊药物短缺- 使用ITS和结构突变模型。目标3将根据药物适应症定义队列， 使用具有熵平衡加权的事件时间分析来识别短缺，以评估是否存在不利的外部影响， comes（住院，死亡，急诊/紧急护理）对于使用受短期影响药物的患者更大， 年龄（暴露组）与未暴露对照组相比。 今后的步骤和实施：传播工作将由一个专家小组指导， 合作伙伴、其他联邦合作伙伴和药物供应和短缺方面的专家。定量结果如下- 类似于专家小组讨论，以制定一个支持指南，以缓解VA的药物短缺。的 下一步将是：1）告知美国基本药物清单和生产标准（例如，国内） 以及2）确定我们的支持指南的有效性以及基于我们的工作实施的未来VA政策。我们 今后的研究将致力于确保供应有限和/或有风险的药物的获得和公平分配 因为短缺。即使在大流行之后，拟议的研究也将提供缓解药物短缺的结果 即使在没有国家紧急情况的情况下，这仍然是一个关键的公共卫生问题。这将是一个 这是我们长期目标的一步，即为未来的全球紧急情况、普遍的药物短缺问题作出规划， 减少药物短缺对患者结果的影响。

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.