Drug Shortages Prior to and During the COVID-19 Pandemic

Abstract

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.

Figure 1.. Cohort Selection Diagram

MIDAS indicates Multinational Integrated Data Analysis. ^aDrugs were defined on the Anatomical Therapeutic Class, level-3 (ATC3)-molecule-formulation level. ^bExcludes drugs with less than 6 months of information prior to assigned index date. ^cA list of excluded topical and nonprescription medications can be found in eTable 2 in Supplement 1. The 1597 matched comparison drugs were allowed to be selected multiple times over the study period for a total sample size of 7296 matched comparison drugs over the study period. ^dCategories are not mutually exclusive since drugs could appear more than once in either group.

Figure 2.. Unadjusted Proportion of Drugs With Incident Supply Chain Issue Reports and Matched Comparison Drugs With Meaningful (≥33%) Drug Shortages Within 6 Months, by Quarter, 2017-2021

Figure 3.. Adjusted Marginal Odds Ratios (mORs) and Estimated Probabilities of Meaningful (≥33%) Drug Shortages Within 6 Months

Post hoc mORs and marginal estimated probabilities were obtained from the fitted logistic regression model. Full regression output is provided in eTable 5 in Supplement 1. Estimated probabilities represent absolute incidence outcomes. Estimated marginal outcomes were obtained by calculating the mean over drug formulation, years since US Food and Drug Administration approval, marketing category, World Health Organization essential medicine status, clinician vs self-administration, total sales, and number of manufacturers at baseline.

Figure 4.. Adjusted Marginal Odds Ratios and Predicted Probabilities of Meaningful (≥33%) Drug Shortages Within 6 Months, Supply Chain Issue Reports vs Matched Comparison Drugs, by Drug Characteristic

Post hoc mORs and marginal estimated probabilities were obtained from the fitted logistic regression model. Full regression output is provided in eTable 6 in Supplement 1. Estimated probabilities represent absolute incidence outcomes. Estimated marginal outcomes were obtained by calculating the mean over drug formulation, years since US FDA approval, marketing category, WHO essential medicine status, clinician vs self-administration, total sales, and number of manufacturers at baseline.