Drug Shortages Prior to and During the COVID-19 Pandemic.

Importance: Drug shortages are a chronic and worsening issue that compromises patient safety. Despite the destabilizing impact of the COVID-19 pandemic on pharmaceutical production, it remains unclear whether issues affecting the drug supply chain were more likely to result in meaningful shortages during the pandemic. Objective: To estimate the proportion of supply chain issue reports associated with drug shortages overall and with the COVID-19 pandemic. Design, Setting, and Participants: This longitudinal cross-sectional study used data from the IQVIA Multinational Integrated Data Analysis database, comprising more than 85% of drug purchases by US pharmacies from wholesalers and manufacturers, from 2017 to 2021. Data were analyzed from January to May 2023. Exposure: Presence of a supply chain issue report to the US Food and Drug Administration or the American Society of Health-Systems Pharmacists (ASHP). Main Outcomes and Measures: The main outcome was drug shortage, defined as at least 33% decrease in units purchased within 6 months of a supply chain issue report. Random-effects logistic regression models compared the marginal odds of shortages for drugs with vs without reports. Interaction terms assessed heterogeneity prior to vs during the COVID-19 pandemic and by drug characteristics (formulation, age, essential medicine status, clinician- vs self-administered, sales volume, and number of manufacturers). Results: A total of 571 drugs exposed to 731 supply chain issue reports were matched to 7296 comparison medications with no reports. After adjusting for drug characteristics, 13.7% (95% CI, 10.4%-17.8%) of supply chain issue reports were associated with subsequent drug shortages vs 4.1% (95% CI, 3.6%-4.8%) of comparators (marginal odds ratio [mOR], 3.7 [95% CI, 2.6-5.1]). Shortages increased among both drugs with and without reports in February to April 2020 (34.2% of drugs with supply chain issue reports and 9.5% of comparison drugs; mOR, 4.9 [95% CI, 2.1-11.6]), and then decreased after May 2020 (9.8% of drugs with reports and 3.6% of comparison drugs; mOR, 2.9 [95% CI, 1.6-5.3]). Significant associations were identified by formulation (parenteral mOR, 1.9 [95% CI, 1.1-3.2] vs oral mOR, 5.4 [95% CI, 3.3-8.8]; P for interaction = .008), WHO essential medicine status (essential mOR, 2.2 [95% CI, 1.3-5.2] vs nonessential mOR, 4.6 [95% CI, 3.2-6.7]; P = .02), and for brand-name vs generic status (brand-name mOR, 8.1 [95% CI, 4.0-16.0] vs generic mOR, 2.4 [95% CI, 1.7-3.6]; P = .002). Conclusions and Relevance: In this national cross-sectional study, supply chain issues associated with drug shortages increased at the beginning of the COVID-19 pandemic. Ongoing policy work is needed to protect US drug supplies from future shocks and to prioritize clinically valuable drugs at greatest shortage risk.

Effects of the valsartan recall on heart failure patients: A nationwide analysis.

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12). CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

A Retrospective Cohort Study of the 2018 Angiotensin Receptor Blocker Recalls and Subsequent Drug Shortages in Patients With Hypertension.

BACKGROUND: Valsartan was recalled by the US Food and Drug Administration in July 2018 for carcinogenic impurities, resulting in a drug shortage and management challenges for valsartan users. The influence of the valsartan recall on clinical outcomes is unknown. We compared the risk of adverse events between hypertensive patients using valsartan and a propensity score-matched group using nonrecalled angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. METHODS AND RESULTS: We used Optum's deidentified Clinformatics Datamart (July 2017-January 2019). Hypertensive patients who received valsartan or nonrecalled angiotensin receptor blockers/angiotensin-converting enzyme inhibitors for 1 year before and on the recall date were compared. Primary outcomes were measured in the 6 months following the recall and included: (1) a composite measure of all-cause hospitalization, all-cause emergency department visit, and all-cause urgent care visit, and (2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/emergency department visits/urgent care visits for stroke/transient ischemic attack, heart failure, or hypertension. We compared the risk of outcomes between treatment groups using Cox proportional hazard models. Of the hypertensive patients, 76 934 received valsartan, and 509 472 received a nonrecalled angiotensin receptor blocker/angiotensin-converting enzyme inhibitor. Valsartan use at the time of recall was associated with a higher risk of all-cause hospitalization, emergency department use, or urgent care use (hazard ratio [HR], 1.02 [95% CI, 1.00-1.04]) and the composite of cardiac events (HR, 1.22 [95% CI, 1.15-1.29]) within 6 months after the recall. CONCLUSIONS: The valsartan recall and shortage affected hypertensive patients. Local- and national-level systems need to be enhanced to protect patients from drug shortages by providing safe and reliable medication alternatives.

Evaluation of Out-of-Pocket Costs and Treatment Intensification With an SGLT2 Inhibitor or GLP-1 RA in Patients With Type 2 Diabetes and Cardiovascular Disease.

Importance: The latest guidelines continue to recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). Despite this, overall use of these 2 drug classes has been suboptimal. Objective: To assess the association of high out-of-pocket (OOP) costs and the initiation of an SGLT2 inhibitor or GLP-1 RA among adults with T2D and established CVD who are treated with metformin-treated. Design, Setting, and Participants: This retrospective cohort study used 2017 to 2021 data from the Optum deidentified Clinformatics Data Mart Database. Each individual in the cohort was categorized into quartiles of OOP costs for a 1-month supply of SGLT2 inhibitor and GLP-1 RA based on their health plan assignment. Data were analyzed from April 2021 to October 2022. Exposures: OOP cost for SGLT2 inhibitors and GLP-1 RA. Main Outcomes and Measures: The primary outcome was treatment intensification, defined as a new dispensing (ie, initiation) of either an SGLT2 inhibitor or GLP-1 RA, among patients with T2D previously treated with metformin monotherapy. For each drug class separately, Cox proportional hazards models were used to adjust for demographic, clinical, plan, clinician, and laboratory characteristics to estimate the hazard ratios of treatment intensification comparing the highest vs the lowest quartile of OOP costs. Results: Our cohort included 80 807 adult patients (mean [SD] age, 72 [9.5] years, 45 129 [55.8%] male; 71 128 [88%] were insured with Medicare Advantage) with T2D and established CVD on metformin monotherapy. Patients were followed for a median (IQR) of 1080 days (528 to 1337). The mean (SD) of OOP costs in the highest vs lowest quartile was $118 [32] vs $25 [12] for GLP-1 RA, and $91 [25] vs $23 [9] for SGLT2 inhibitors. Compared with patients in plans with the lowest quartile (Q1) of OOP costs, patients in plans with the highest quartile (Q4) of costs were less likely to initiate a GLP-1 RA (adjusted HR, 0.87 [95% CI, 0.78 to 0.97]) or an SGLT2 inhibitor (adjusted HR, 0.80 [95% CI, 0.73 to 0.88]). The median (IQR) number of days to initiating a GLP-1 RA was 481 (207-820) days in Q1 and 556 (237-917) days in Q4 of OOP costs and 520 (193-876) days in Q1 vs 685 (309-1017) days in Q4 for SGLT2 inhibitors. Conclusions and Relevance: In this cohort study of more than 80 000 older adults with T2D and established CVD covered by Medicare Advantage and commercial plans, those in the highest quartile of OOP cost were 13% and 20% less likely to initiate a GLP-1 RA or SGLT2 inhibitor, respectively, when compared with those in the lowest quartile of OOP costs.

Impact of COVID-19-related regulatory changes on nationwide access to buprenorphine: An interrupted time series design.

Background: The impact of COVID-19-related healthcare changes on access to buprenorphine (BUP) nationwide in the US is unknown. Methods: We conducted an interrupted time series with the IQVIA LRx database. The study timeline included BUP prescriptions from 52 weeks before (2/23/19-2/21/20) to 52 weeks after (4/4/20-4/2/21) the initial pandemic period (2/22/20-4/3/20). Segmented regression estimated relative changes in total milligrams (MG) of BUP available per week nationwide at 1, 26, and 52 weeks post-initial-pandemic. We evaluated treatment disruptions in previously stable patients, defined as ≥6 months of BUP prescriptions. Results: A total of 31 617 849 prescriptions were included. Total MG BUP dispensed increased at 1 and 26 weeks and then returned to baseline trends at 52 weeks post-initial pandemic period (4.1% [95% CI: 3.7,4.5], 2.1% [1.5,2.6], 0.1% [-0.6,0.9]). Stably-treated patients saw a decrease in 7-, 14-, and 28-day treatment disruptions at 52 weeks post-initial-pandemic period (-21.6% [-25.6,-17.7]; -10.8% [-16.3,-5.3]; -27.3% [-33.0,-21.6]). Men retained an increase in MG BUP compared to women at 52 weeks (0.7% [0.01,1.4] versus -0.6% [-1.5,0.2]). Younger age groups (18-29 years and 30-39 years) had a decrease in MG BUP at 52 weeks compared to expected baseline trend (-16.6 [-24.2, -9.0]; -1.6 [-3.0, -0.1). Patients with Medicaid demonstrated an increase in MG BUP at 52 weeks (8.3% [6.3,10.3]). MG BUP prescribed by APP prescribing increased by over 140 000 mg per week prior to the pandemic and continued to increase. Conclusions: Regulatory changes around buprenorphine prescribing facilitated patient access to buprenorphine during the pandemic.

Acute Care Utilization and Costs Up to 4 Years After Index Sleeve Gastrectomy or Roux-en-Y Gastric Bypass: A National Claims-based Study.

OBJECTIVE: To compare acute care utilization and costs following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). SUMMARY BACKGROUND DATA: Comparing postbariatric emergency department (ED) and inpatient care use patterns could assist with procedure choice and provide insights about complication risk. METHODS: We used a national insurance claims database to identify adults undergoing SG and RYGB between 2008 and 2016. Patients were matched on age, sex, calendar-time, diabetes, and baseline acute care use. We used adjusted Cox proportional hazards to compare acute care utilization and 2-part logistic regression models to compare annual associated costs (odds of any cost, and odds of high costs, defined as ≥80th percentile), between SG and RYGB, overall and within several clinical categories. RESULTS: The matched cohort included 4263 SG and 4520 RYGB patients. Up to 4 years after surgery, SG patients had slightly lower risk of ED visits [adjusted hazard ratio (aHR): 0.90; 95% confidence interval (CI): 0.85,0.96] and inpatient stays (aHR: 0.80; 95% CI: 0.73,0.88), especially for events associated with digestive-system diagnoses (ED aHR: 0.68; 95% CI: 0.62,0.75; inpatient aHR: 0.61; 95% CI: 0.53,0.72). SG patients also had lower odds of high ED and high total acute costs (eg, year-1 acute costs adjusted odds ratio (aOR) 0.77; 95% CI: 0.66,0.90) in early follow-up. However, observed cost differences decreased by years 3 and 4 (eg, year-4 acute care costs aOR 1.10; 95% CI: 0.92,1.31). CONCLUSIONS: SG may have fewer complications requiring emergency care and hospitalization, especially as related to digestive system disease. However, any acute care cost advantages of SG may wane over time.

Trends in dispensed prescriptions for opioids, sedatives, benzodiazepines, gabapentin, and stimulants to children by general dentists, 2012-2019.

PURPOSE: Opioids, benzodiazepines and sedatives can manage dental pain, fear and anxiety but have a narrow margin of safety in children. General dentists may inappropriately prescribe gabapentin and stimulants. National evidence on dispensing rates of these high-alert medicines by dentists to children is limited. METHODS: We utilize join-point regression to identify changes in fills for opioids, sedatives, benzodiazepines, gabapentin, and stimulants to children <18 years from 2012 to 2019 in a national dataset comprising 92% of dispensed outpatient prescriptions by dentists. RESULTS: From 2012 to 2019, 3.8 million children filled prescriptions for high-alert drugs from general dentists. National quarterly dispensing of high-alert drugs decreased 63.1%, from 10456.0 to 3858.8 days per million. Opioids accounted for 69.4% of high-alert prescriptions. From 2012 to 2019, fills for opioids, sedatives, benzodiazepines, and stimulants decreased by 65.2% (7651.8 to 2662.7), 43.4% (810.9 to 458.7), 43.6% (785.7 to 442.7) and 89.3% (825.6 to 88.6 days per million), respectively. Gabapentin increased 8.1% (121.8 to 131.7 days per million). A significant decrease in high-alert fills occurred in 2016, (-6.0% per quarter vs. -1.6% pre-2016, P-value<0.001), especially for opioids (-7.0% vs. -1.2%, P-value<0.001). Older teenagers (15-17 years) received 42.5% of high-alert prescriptions. Low-income counties in the South were overrepresented among top-prescribing areas in 2019. CONCLUSIONS: We found promising national decreases in fills for high-alert medicines to children by general dentists from 2012 to 2019. However, older teenagers and children in some counties continued to receive dental opioids at high rates. Future efforts should address non-evidence-based pain management in these groups.

Changes in Purchases for Intensive Care Medicines During the COVID-19 Pandemic: A Global Time Series Study.

BACKGROUND: Drug supply disruptions have increased during the COVID-19 pandemic, especially for medicines used in the ICU. Despite reported shortages in wealthy countries, global analyses of ICU drug purchasing during COVID-19 are limited. RESEARCH QUESTION: Has COVID-19 impacted global drug purchases of first-, second-, and third-choice agents used in intensive care? STUDY DESIGN AND METHODS: We conducted a cross-sectional time series study in a global pharmacy sales dataset comprising approximately 60% of the world's population. We analyzed pandemic-related changes in units purchased per 1,000 population for 69 ICU agents. Interventional autoregressive integrated moving average models tested for significant changes when the pandemic was declared (March 2020) and during its first stage from April through August 2020, globally and by development status. RESULTS: Relative to 2019, ICU drug purchases increased by 23.6% (95% CI, 7.9%-37.9%) in March 2020 (P < .001) and then decreased by 10.3% (95% CI, -16.9% to -3.5%) from April through August (P = .006). Purchases for second-choice medicines changed the most, especially in developing countries (eg, 29.3% increase in March 2020). Despite similar relative changes (P = .88), absolute purchasing rates in developing nations remained low. The observed decrease from April through August 2020 was significant only in developed countries (-13.1%; 95% CI, -17.4% to -4.4%; P < .001). Country-level variation seemed unrelated to expected demand and health care infrastructure. INTERPRETATION: Purchases for intensive care medicines increased globally in the month of the COVID-19 pandemic declaration, but before peak infection rates. These changes were most pronounced for second-choice agents, suggesting that inexpensive, generic medicines may be purchased more easily in anticipation of pandemic-related ICU surges. Nevertheless, disparities in access persisted. Trends seemed unrelated to expected demand, and decreased purchasing from April through August 2020 may suggest overbuying. National and international policies are needed to ensure equitable drug purchasing during future pandemics.