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Tadrous M, Callaway Kim K, Hernandez I, Rothenberger SD, Devine JW, Hershey TB, Maillart LM, Gellad WF, Suda KJ. Differences in Drug Shortages in the US and Canada. JAMA 2024; 332:1912-1922. [PMID: 39480469 PMCID: PMC11528343 DOI: 10.1001/jama.2024.17688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/13/2024] [Indexed: 11/03/2024]
Abstract
Importance Drug shortages are a persistent public health issue that increased during the COVID-19 pandemic. Both the US and Canada follow similar regulatory standards and require reporting of drug-related supply chain issues that may result in shortages. However, it is unknown what proportion are associated with meaningful shortages (defined by a significant decrease in drug supply) and whether differences exist between Canada and the US. Objective To compare how frequently reports of drug-related supply chain issues in the US vs Canada were associated with drug shortages. Design, Setting, and Participants Longitudinal cross-sectional study conducted from January 2023 to March 2024 using drug-related reports of supply chain issues from 2017 to 2021 that were less than 180 days apart in Canada and the US. Shortages were assessed using data from the IQVIA Multinational Integrated Data Analysis database, comprising 89% of US and 100% of Canadian drug purchases. Exposure Country (Canada vs US), timing of report issuance (before vs after the COVID-19 pandemic), and characteristics of the supply chain prior to the reports of drug-related supply chain issues (including World Health Organization essential medicine status, Health Canada tier 3 medicine [moderate risk classification], whether there was sole-source manufacturing of the drug, the formulation, the price per unit, ≥20 years since drug approval, and the number of therapeutic alternatives). Main Outcomes and Measures A drug shortage (a decrease of ≥33% in monthly purchased standardized drug units) within 12 months, relative to the average units purchased during the 6 months prior to the report of supply chain issues to a US or Canadian reporting system. Results Among the 104 drug-related reports of supply chain issues in both countries, 49.0% (95% CI, 39.3%-59.7%) were associated with drug shortages in the US vs 34.0% (95% CI, 25.0%-45.0%) in Canada (adjusted hazard ratio [HR], 0.53 [95% CI, 0.36-0.79]). The lower risk of drug shortages in Canada vs the US was consistent before the COVID-19 pandemic (adjusted HR, 0.47 [95% CI, 0.30-0.75]) and after the pandemic (adjusted HR, 0.31 [95% CI, 0.15-0.66]). After combining reports of supply chain issues in both countries, the shortage risk was double for sole-sourced drugs (adjusted HR, 2.58 [95% CI, 1.57-4.24]) and nearly half for Canadian tier 3 medicines (moderate risk) (adjusted HR, 0.56 [95% CI, 0.32-0.98]). Conclusions and Relevance Drug-related reports of supply chain issues were 40% less likely to result in meaningful drug shortages in Canada compared with the US. These findings highlight the need for international cooperation between countries to curb the effects of drug shortages and improve resiliency of the supply chain for drugs.
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Affiliation(s)
- Mina Tadrous
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Katherine Callaway Kim
- Division of General Internal Medicine, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Health Policy and Management, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Inmaculada Hernandez
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego, La Jolla
| | - Scott D. Rothenberger
- Division of General Internal Medicine, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Joshua W. Devine
- Department of Public Health, Des Moines University, Des Moines, Iowa
| | - Tina B. Hershey
- Department of Health Policy and Management, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Lisa M. Maillart
- Department of Industrial Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Walid F. Gellad
- Division of General Internal Medicine, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Katie J. Suda
- Division of General Internal Medicine, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
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Ravela R, Lyles A, Airaksinen M. National and transnational drug shortages: a quantitative descriptive study of public registers in Europe and the USA. BMC Health Serv Res 2022; 22:940. [PMID: 35869486 PMCID: PMC9306441 DOI: 10.1186/s12913-022-08309-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
Background Drug shortages are a growing global problem, posing clinical and economic challenges. To understand them better, we conducted an inventory of national public drug shortage registers and their comparability in Europe and the USA. Methods The study was based on openly accessible drug shortage notifications published by national drug authorities. These data were obtained from all national data sources mentioned on the European Medicines Agency’s (EMA’s) web page and FDA in the USA. After selection of the countries with comparable data, descriptive statistics were used to present characteristics of the shortages both across countries and within countries for 9 months (January–September) in 2020. We studied whether the shortages that occurred in these countries were the same, and how shortages were distributed by therapeutic uses and formulations. We also investigated price variation between the United States and Finland among drugs in shortage in one formulation category (creams and gels). Results Finland, Sweden, Norway, Spain, and the United States had suitable registers and were included. Altogether 5132 shortage reports from Finland (n = 1522), Sweden (n = 890), Norway (n = 800), Spain (n = 814), and the United States (n = 1106) were published during the study period. Of active ingredient level shortages 54% occurred in only one country, and 1% occurred in all five. However, at the country level, where there was one or more shortage notifications in an ATC active ingredient category, 19–41% were in a single country. The distributions by ATC therapeutic class and drug formulation differed substantially between countries, particularly between the USA and European countries. Injectables had a high shortage risk in the USA (57% of all shortages versus 17–31% of all shortages in the European countries). By contrast, shortages in gels and creams occurred only in European data (4–6% of all shortages). In the price comparison, creams and gels in shortage in Finland were 160% more expensive in the USA where these shortages were not detected. Conclusions Public drug shortage registers are vital data sources for proactively maintaining and managing a reliable drug supply. However, our study demonstrates that much work remains to standardize the contents and quality of public register data. Shortages may not be solely a consequence of manufacturing disruptions but may reflect other contributing factors in the international drug distribution and supply mechanisms, including price differences and profit margins between national pharmaceutical markets. Data to perform practical and useful international comparisons to understand these shortages are required. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-022-08309-3.
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Davey S, Grover S, Bilker WB, Setlhako DI, Ralefala TB, Manshimba P, Gross R, DeMichele A, Shulman LN, Martei YM. Retrospective cohort analysis of prescription patterns of cancer medications during periods of drug stockouts in Botswana. BMJ Open 2021; 11:e049574. [PMID: 34253674 PMCID: PMC8276292 DOI: 10.1136/bmjopen-2021-049574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply. DESIGN A retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016. SETTING Princess Marina Hospital in Gaborone, Botswana. PARTICIPANTS Patients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy. PRIMARY AND SECONDARY OUTCOME MEASURES Frequency of delays and patterns of prescription changes for specific regimens and cancer types. RESULTS 167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout. CONCLUSIONS The aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery.
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Affiliation(s)
- Sonya Davey
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Surbhi Grover
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Warren B Bilker
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Dipho I Setlhako
- Oncology Department, Princess Marina Hospital, Gaborone, Botswana
| | | | | | - Robert Gross
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine (Infectious Diseases), University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Angela DeMichele
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine (Hematology-Oncology), University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Lawrence N Shulman
- Department of Medicine (Hematology-Oncology), University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yehoda M Martei
- Department of Medicine (Hematology-Oncology), University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Shukar S, Zahoor F, Hayat K, Saeed A, Gillani AH, Omer S, Hu S, Babar ZUD, Fang Y, Yang C. Drug Shortage: Causes, Impact, and Mitigation Strategies. Front Pharmacol 2021; 12:693426. [PMID: 34305603 PMCID: PMC8299364 DOI: 10.3389/fphar.2021.693426] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/29/2021] [Indexed: 11/13/2022] Open
Abstract
Drug shortage is a global issue affecting low, middle, and high-income countries. Many countries have developed various strategies to overcome the problem, while the problem is accelerating, affecting the whole world. All types of drugs, such as essential life-saving drugs, oncology medicines, antimicrobial drugs, analgesics, opioids, cardiovascular drugs, radiopharmaceutical, and parenteral products, are liable to the shortage. Among all pharmaceutical dosage forms, sterile injectable products have a higher risk of shortage than other forms. The causes of shortage are multifactorial, including supply issues, demand issues, and regulatory issues. Supply issues consist of manufacturing problems, unavailability of raw materials, logistic problems, and business problems. In contrast, demand issues include just-in-time inventory, higher demand for a product, seasonal demand, and unpredictable demand. For regulatory issues, one important factor is the lack of a unified definition of drug shortage. Drug shortage affects all stakeholders from economic, clinical, and humanistic aspects. WHO established global mitigation strategies from four levels to overcome drug shortages globally. It includes a workaround to tackle the current shortage, operational improvements to reduce the shortage risk and achieve early warning, changes in governmental policies, and education and training of all health professionals about managing shortages.
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Affiliation(s)
- Sundus Shukar
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Fatima Zahoor
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
- Yusra Institute of Pharmaceutical Sciences, Islamabad, Pakistan
| | - Khezar Hayat
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Amna Saeed
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Ali Hassan Gillani
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Sumaira Omer
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Shuchen Hu
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Zaheer-Ud-Din Babar
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom
| | - Yu Fang
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
| | - Caijun Yang
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
- Center for Drug Safety and Policy Research, Xian Jiaotong University, Xi’an, China
- Shaanxi Centre for Health Reform and Development Research, Xi’an, China
- Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technological Innovation Harbor, Xi’an, China
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van Langenberg DR, Cheng RKY, Garg M. Outcomes of a drug shortage requiring switching in patients with ulcerative colitis. World J Gastrointest Pathophysiol 2020; 11:32-42. [PMID: 32318313 PMCID: PMC7156848 DOI: 10.4291/wjgp.v11.i2.32] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/04/2020] [Accepted: 03/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Drug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched. In Australia a shortage of balsalazide (2012-2013) necessitated substitution with alternative 5-aminosalicylate (5-ASA) formulations for ulcerative colitis (UC).
AIM To assess and compare the clinical and commercial sequelae of non-medical switching from balsalazide to another 5-ASA and/or return to balsalazide once supply resumed.
METHODS A prospective cohort study of patients on balsalazide for mild-moderate UC was conducted where, strictly due to the national shortage (November 2012- January 2013), were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed. Clinical (Partial Mayo), endoscopic (Mayo score) activity, adverse effects (to alternative 5-ASA) and percentage market share (of continuous 5-ASA users) from baseline (i.e., time of switching due to shortage) through to five years were assessed.
RESULTS Of 31 patients switched due to the shortage, 12 (38.7%) resumed balsalazide immediately once supply resumed, 8 (25.8%) prompted by adverse effects to the alternative 5-ASA used. Three patients (9.7%) had documented symptomatic improvement, 15 (48.4%) were unchanged and 13 (41.9%) had symptomatic worsening vs baseline (P < 0.01), after switching to an alternative 5-ASA. At 3 and 5y post switch, overall 26/31 (83.9%) and 23/31 (74.2%) had remained continuously on any 5-ASA therapy respectively. Twelve (38.7%) and 11 (35.5%) patients remained on balsalazide continuously at three and five years respectively after drug supply returned, equating to a loss of market share (within 5-ASA class) of 45.2% and 38.7% respectively.
CONCLUSION This study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient, disease and commercial outcomes.
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Affiliation(s)
- Daniel R van Langenberg
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria 3128, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria 3128, Australia
| | - Richard Kai-Yuan Cheng
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria 3128, Australia
- Department of Gastroenterology, Redcliffe Hospital, Redcliffe, Queensland 4020, Australia
| | - Mayur Garg
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria 3128, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria 3128, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Victoria 3052, Australia
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