Drug Shortages Research Articles

The operational impact of medicines shortages on pharmacy Procurement and Distribution (P&D) services at a large teaching hospital

Abstract Introduction There has been a nine-fold increase in medicines shortages in the UK over the last 5 years.1 The reasons are multifactorial including shortages in raw materials, as well as financial and geopolitical instability. The adverse impact on clinicians and patients is well documented however studies on the impact to P&D services is sparse. Aim This study aims to quantify the impact of increasing medicines shortages to P&D services who lead on sourcing and distributing alternative medicines to meet patient needs.1 Method The period between January 2021 and January 2024 of the Pharmacy “Drug Shortages Tracker” was reviewed by the P&D Specialist Pharmacist. Each Shortage was assigned at least one of eight potential managing solutions e.g. “Rationalising Usage” and “Sourcing Unlicensed Alternatives”. The time required to complete the tasks for each shortage was calculated using the following formula: [Sum of the Estimated Time to Complete Each Task* (minutes) x Duration of Shortage (weeks)] + Sum of the Estimated Time to Complete all ‘One Time Only’ Activities’* * Standardised times based on time in motion data [collected in June 2023] and feedback from specialist P&D staff. The data was recorded on a Microsoft Excel spreadsheet which had the following headings: Shortage, Method(s) of Resolution, Duration of Shortage and Total Time to Resolve. This study was deemed a service evaluation by the trust’s Research and Audit Group and therefore ethics approval was not required. Results All 332 shortages are included in the results totalling 1,841 hours of staff time. The year by year breakdown is as follows: From 2021 to 2022, 3 shortages accounting for 49 hours. From 2022 to 2023, an increase to 146 shortages accounting for 898 hours (18-fold increase from previous year). From 2023 to 2024, 183 shortages accounting for 894 hours. The number of shortages recorded per month was 0.24 from 2021 to 2022, 11.2 from 2022 to 2023 and 14 from 2023 to 2024. The mean time required to complete the P&D aspects of a single shortage was 332 minutes. With the most time consuming shortage requiring 1640 minutes in 2022. Discussion This increased volume of shortages nationally has put pressure on P&D services to allocate greater resources to support their management and maintain patient safety. P&D teams are assessed nationally on metrics relating to medicine expenditure.2 In practice, the core services that ensure medicines are available for patients’ takes precedent. The rising challenge of shortages poses a risk to the capacity of P&D teams to carry out both critical tasks and those relating to medicines expenditure. Notable limitations to this study include the numerous interpretations and definitions of shortages which produced inconsistent recordings within the trust3. This was exacerbated by changes to documentation procedures internally. As an example, the variable recording process in 2021 does not provide an accurate representation of the actual period. Other internal changes included the uptake of automated dispensing cabinets which added further complexity to shortage management. Conclusion The growing demands of shortages highlights the need for dedicated shortages teams.

Drug Shortages in Albania: Pharmacists’ Experiences and Perspectives

Drug Shortages in Albania: Pharmacists’ Experiences and Perspectives

List of Critical Drugs in Dermatology: Results of a Delphi Consensus in France.

Drug shortages are increasing nowadays, affecting every country worldwide. The French Ministry of Health asked various scientific societies to establish a list of “critical” drugs for each specialty. The aim of this list was to enable the public authorities to control the production chain and guarantee the availability of drugs. We present the list of critical dermatological drugs, which is the result of a strong consensus between all representative entities of the French Society of Dermatology.

Differences in Drug Shortages in the US and Canada

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. To compare how frequently reports of drug-related supply chain issues in the US vs Canada were associated with drug shortages. 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. 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). 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. 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]). 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.

The role of apheresis in the management of Philadelphia-negative chronic myeloproliferative syndromes following drug shortages

The role of apheresis in the management of Philadelphia-negative chronic myeloproliferative syndromes following drug shortages

Impact of the socioeconomic crisis in Lebanon on people with epilepsy.

The economic crisis in Lebanon, which began in 2019, has affected the healthcare system and patients' incomes. The aim of this study was to analyze the obstacles faced by people with epilepsy (PWE) during this crisis and to assess its impact on their quality of life. The method used was a cross-sectional study conducted among PWE aged 18-65 years, who were asked to complete a comprehensive questionnaire covering sociodemographic aspects, clinical aspects, the impact of the economic crisis, and the QOLIE-31 (version 1.0), validated in English and Arabic, which assesses the quality of life of PWE. 71 patients were included in the study with an average age of 35.2 years [23.5; 62.5] (53.5% were males). Their average QOLIE-31 score was 50.3 (+/- 17.9). A significant proportion (71%) of patients reported difficulties during the crisis, with 25% reporting having had seizure-related injuries in the years 2022-2023 and 36.6% reporting an increase in seizure frequency compared to that prior to 2020. Moreover, many patients had to change (33.8%) or discontinue (18.3%) antiseizure medications, due to drug shortages, rising costs, and high gas prices. To mitigate these challenges, patients sought solutions such as obtaining medications from abroad (34%) or through donations (8%) or purchasing from the black market (8%). Low quality of life was associated with unemployment, low education level, the presence of focal seizures with impaired awareness or generalized seizures, polytherapy, seizure-related injuries, and medication changes during the economic crisis. These results highlight the considerable challenges faced by PWE in Lebanon during the economic crisis, emphasizing the negative effect of the crisis on their quality of life and seizure control. This study analyzed the obstacles faced by 71 people with epilepsy during Lebanon's economic crisis and showed that many patients had to change (33.8%) or discontinue (18.3%) antiseizure medications, due to drug shortages, rising costs, and high gas prices. To mitigate these challenges, patients sought solutions such as obtaining medications from abroad (34%) or through donations (8%) or purchasing from the black market (8%). This affected their quality of life. In fact, low quality of life was associated with unemployment, low education level, focal seizures with impaired awareness or generalized seizures, polytherapy, seizure-related injuries, and medication changes.

Drug shortage stewardship: A novel solution for an old problem.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

An assessment of the factors contributing to the unavailability of drugs at outpatient pharmacy of tertiary care hospital: an observational study

Introduction Throughout history and up until the present, there has been a medicine shortage. In the early 1920s, there was a shortage of insulin, which is when drug scarcity first appeared in the records. Drug shortages are now more prevalent globally than they were back then. The goal of this essay is to pinpoint the key components that make up a definition for medication shortages and to pinpoint the circumstances that should be considered when reporting drug shortages in databases. Understanding the factors that led certain organizations to create their own definition of a medicine shortage was crucial for achieving these goals. The pharmaceutical regulatory environment can be connected to several reasons why there are medication shortages, including parallel trading, quality standards, and business choices to halt or reduce manufacturing. The many rules governing medicine shortages have not yet been the subject of a thorough investigation. This protocol’s objective is to analyze the pertinent legislative and regulatory frameworks in the European pharmaceutical system that affect medication shortages. The objectives of the study will be the non–availability of drugs at an outpatient pharmacy and to analyze the reason of non–availability of drugs. Methods An observational study will be adopted in this study. It includes a collection of data from the patient coming to the outpatient pharmacy of AVBRH Sawangi (Meghe) Wardha. Expected result It can lead to delayed treatment for patients seeking alternative medication. It can also lead to increased healthcare costs if patients seek alternative treatments that are more expensive or require additional medical care. The unavailability of drugs can also lead to frustration and anxiety for patients who need medication to manage their health condition. It can also negatively impact the reputation of the hospital.

Judicious Use of Benzathine Penicillin G in Response to a Medication Alert During a Critical Drug Shortage.

To evaluate judicious antibiotic prescribing of benzathine penicillin G (BPG) after implementation of an electronic health record-based medication shortage alert during a critical drug shortage. This was an institutional review board-approved retrospective cohort study of patients aged ≥3 months who received BPG between May 9, 2023, and February 28, 2024. The study included inpatient and outpatient visits after implementing a BPG medication shortage alert; patients with severe penicillin allergy, neurosyphilis, or congenital syphilis were excluded. Judicious BPG use was defined as use in patients diagnosed with primary, secondary, or latent syphilis or if they were prescribed a BPG alternative in response to the medication shortage alert; nonjudicious use included BPG for alternative diagnoses. Social determinants of health were assessed as exposure variables of interest. A separate cohort of syphilis patients receiving BPG or alternative therapy (i.e., doxycycline) was described. A total of 453 patients were included. Most patients were non-Hispanic Black (n = 273, 60%) men (n = 272, 60%) with a median (interquartile range) age of 32 (22-44) years. Of these, 318 (70%) received judicious BPG, whereas 135 (30%) received nonjudicious BPG. The most nonjudicious diagnosis was streptococcal pharyngitis (n = 128, 95%). Variables associated with judicious use included age >32 years (adjusted odds ratio [adjOR], 2.273; 95% CI, 1.488-3.472), male sex (adjOR, 1.835; 95% CI, 1.206-2.792), and black race (adjOR, 1.847; 95% CI, 1.212-2.815). Among a cohort of 128 syphilis patients who received BPG (n = 64, 50%) or doxycycline (n = 64, 50%), those who received doxycycline were more likely be uninsured (35 [54.7%] vs 43 [67.2%]; P = .15) and receive outpatient treatment (3 [4.7%] vs 12 [18.7%]; P = .13). Despite implementing an electronic health record drug shortage alert, 30% of BPG use was nonjudicious and mostly for pharyngitis.

Trends of drug shortages in China from 2018 to 2020: A retrospective observational study

Trends of drug shortages in China from 2018 to 2020: A retrospective observational study

Protamine Dosing for Heparin Reversal Following Cardiopulmonary Bypass: A Double-Blinded Prospective Randomized Control Trial Comparing Two Strategies.

Drug shortages are a frequent challenge in current clinical practice. Certain drugs, (e.g., protamine) lack alternatives and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal following CPB and may result in excess protamine utilization, and potential harm due to its intrinsic anticoagulation. We hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine to heparin ratio-based strategy for heparin reversal and that protamine would be conserved. In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without pre-existing coagulopathy or ongoing anticoagulation, and a calculated initial heparin dose of ≥ 27500 U were randomized to receive, following CPB, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time following initial protamine administration, assessed by Student's t-test. Secondary outcomes included total protamine, the need for additional protamine, and the cumulative 24-h chest tube output. There were 62 and 63 patients in the fixed- and ratio-based dose groups, respectively. The mean post-protamine ACT was not different between groups (-2.0 s, 95% CI -7.2 to 3.3 s, P = 0.47). Less total protamine per case was administered in the fixed-dose group (2.1 50-mg vials, 95% CI -2.4 to -1.8, P < 0.0001). There was no difference in the cumulative 24-h chest tube output (difference = -77 ml, 95% CI 220 to 65 ml, P = 0.28). A 1: 1 heparin ratio-based protamine dosing strategy compared to a fixed 250-mg dose resulted in the administration of a larger total dose of protamine no difference in either the initial ACT or the amount postoperative chest-tube bleeding.

Evaluating quality reward and other interventions to mitigate US drug shortages

AbstractDrug shortages have been persistent in the United States for over a decade, posing serious threats to public health and the healthcare system. While previous research has investigated the causes and effects of drug shortages, there is a dearth of research exploring potential solutions to mitigate this problem. Using a system dynamics model of the US generic drug market, we evaluate the long‐term effectiveness of two existing policy interventions (expediting drug approvals and nudging manufacturers to ramp up their production) and the “quality reward” initiative that is being actively explored by the FDA and industry. Our results indicate that while the existing interventions can be helpful in addressing shortages, their long‐term effect seems limited. In contrast, quality reward can mitigate drug shortages in a sustainable way. However, a caveat of quality reward is the potential emergence of a monopolistic supply market with negative consequences. We suggest that a carefully designed quality disclosure mechanism can address this issue. To the best of our knowledge, this is the first study to quantitatively and comparatively evaluate the long‐term effectiveness of quality reward and other interventions on drug shortages and provide structural explanations for their performance.

A call for further study and use of transformational leadership in pharmacy education and practice: Hope and reinvigoration

This paper calls for further study of transformational leadership and its further use in educating PharmD students as well as inclusion of continuing education programming and mentoring the behaviours of current pharmacists. It does not present an argument for reduction in use or diminishment of other leadership theories, many of which have at least some overlap with transformational leadership. Rather, emphasis on transformation leadership might be one of many solutions to challenges plaguing the profession currently, with some sense of negativity and challenging workplace conditions among many pharmacists; support personnel and drug shortages; and a need for more collegial citizenship behaviors and stronger organizational culture. Transformative leadership behaviors and communication, versus others particularly more transactional in nature, envisage a future for the entire profession as well as for the individuals who comprise them, articulate the value of the contributions made by the employee, and help imbue a sense of professional identity. These are things sorely needed in the modern workplace and are either explicitly stated or tacitly implied in educational standards and professional competencies. A recent study on transformational leadership as measured by the Multifactorial Leadership Questionnaire (MLQ) found more parsimonious structures toward the definition of transformational leadership and the outcomes resulting from its use, which actually makes it easier to discern and thus even more applicable to incorporate into models of pharmacy education and practice. The time to further study and employ transformational leadership is now.

Weight management medications for chronic use in 37 veterans affairs medical centers-A medication use evaluation.

Controlled trials have demonstrated successful weight loss associated with certain weight management medications (WMMs). However, there are limited real-world data on prescribing patterns and efficacy and safety profiles of WMMs in Veterans Affairs (VA) patients. To evaluate: utilization patterns of WMMs liraglutide, naltrexone/bupropion, orlistat, phentermine, phentermine/topiramate, and semaglutide; weight loss at three, six, twelve, and more than 12 months; safety; and treatment barriers. A retrospective, cross-sectional medication use evaluation (MUE) was conducted using electronic health records of outpatient Veterans newly initiated on WMMs at 37 VA Medical Centers between 1 March 2020 and 31 March 2022. Chart review was used to identify WMM utilization and capture rates of clinical response, defined as 5% and 10% or greater weight loss at the final weight, adverse drug events (ADEs), non-adherence, and discontinuations. Site-specific surveys evaluated local practices and barriers. Among 1959 eligible Veterans, semaglutide, phentermine/topiramate, and orlistat were most frequently prescribed. The clinical response was highest among phentermine/topiramate, liraglutide, and semaglutide. Naltrexone/bupropion and phentermine demonstrated the highest and lowest ADE rates, respectively. Potential barriers to WMM utilization and successful treatment by site reports were drug shortages, patient perceptions of therapeutic course, personal preferences, and VA WMM use criteria. Smaller weight loss and higher discontinuation rates were observed relative to clinical trials. The MUE data allow for better assessment of benefits and risks for Veterans prescribed WMMs.

Prescription predicament: Unveiling the financial fallout of drug shortages.

1 Background: Managing drug shortages has become a part of care delivery in oncology. Shortages have been reported to result in missed/delayed treatment, substitution of alternative therapy, increased costs, and significant administrative burden. A national shortage of cisplatin caused by manufacturing disruptions was reported by the Food and Drug Administration in the United States from February until August 2023 (shortage period). We assessed the effects of cisplatin shortage on the treatment of head and neck cancer (HNC) at practices in The US Oncology Network (The Network). Methods: Using drug administration data from medical records and claims for 26 practices in The Network prior to (July 2022 to January 2023), during, and after (September 2023 to March 2024) the shortage period, we assessed the utilization trends and financial impact (using Medicare average sale price (ASP)) of cisplatin and other anti-cancer drugs for HNC patients. Results: During the shortage period, cisplatin utilization for HNC decreased by 15% compared to pre-shortage levels. The lowest utilization occurred in June and July 2023, with a 60% decrease. Practices initially obtained supplies through an allocation model and fair-share utilization guidance from The Network Pharmacy &amp; Therapeutics Committee. During the shortage period, alternative chemotherapy drugs for HNC saw increased use: carboplatin by 40%, paclitaxel by 24%, 5-fluorouracil by 5.3%, and cetuximab by 15%. The increased use of alternative drugs corresponded to the decrease in cisplatin usage, with new starts shifting to carboplatin (with or without paclitaxel), cetuximab and 5-fluorouracil. Ten percent of existing cisplatin recipients were shifted to an alternative drug during the shortage period. Interestingly, 5-fluorouracil was also in short supply, albeit less acutely than cisplatin. After the shortage, cisplatin volumes rebounded by 8% of pre-shortage use, while carboplatin use dropped below pre-shortage levels. Cetuximab use remained consistently 12% higher. The average cost per administration was $18 for cisplatin, $14 for carboplatin, $16 for paclitaxel, $22 for 5-fluorouracil, and $2,607 for cetuximab, based on the ASP. The increased use of cetuximab instead of cisplatin resulted in a 16% total cost increase, leading to a 144-fold increase in costs at the administration level, impacting payer costs and patient cost-sharing amounts. Conclusions: Cisplatin shortage led to a shift in utilization to alternative therapies for HNC, resulting in significant cost increases for both payers and patients. These consequences may not be limited to specific cancer types or drugs and may have other undesirable effects. Even temporary shortages of drugs can lead to lasting utilization changes and have long-term financial implications. The impacts of drug shortages on treatment decisions, guideline concordance, costs, and patient outcomes are apt for further investigation.

Keep Your Guard Up: The Potential Impact of Drug Shortages on Pharmacoepidemiological Studies.

Keep Your Guard Up: The Potential Impact of Drug Shortages on Pharmacoepidemiological Studies.

The benefits (or detriments) of adapting to demand disruptions in a hospital pharmacy with supply chain disruptions.

Supply chain disruptions and demand disruptions make it challenging for hospital pharmacy managers to determine how much inventory to have on-hand. Having insufficient inventory leads to drug shortages, while having excess inventory leads to drug waste. To mitigate drug shortages and waste, hospital pharmacy managers can implement inventory policies that account for supply chain disruptions and adapt these inventory policies over time to respond to demand disruptions. Demand disruptions were prevalent during the Covid-19 pandemic. However, it remains unclear how a drug's shortage-waste weighting (i.e., concern for shortages versus concern for waste) as well as the duration of and time between supply chain disruptions influence the benefits (or detriments) of adapting to demand disruptions. We develop an adaptive inventory system (i.e., inventory policies change over time) and conduct an extensive numerical analysis using real-world demand data from the University of Michigan's Central Pharmacy to address this research question. For a fixed mean duration of and mean time between supply chain disruptions, we find a drug's shortage-waste weighting dictates the magnitude of the benefits (or detriments) of adaptive inventory policies. We create a ranking procedure that provides a way of discerning which drugs are of most concern and illustrates which policies to update given that a limited number of inventory policies can be updated. When applying our framework to over 300 drugs, we find a decision-maker needs to update a very small proportion of drugs (e.g., ) at any point in time to get the greatest benefits of adaptive inventory policies.

Considerations for developing a health-system 503B outsourcing strategy.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To provide guidance for health systems on how to develop a strategy for utilizing 503B outsourcing facilities for sterile product preparation. Health-system pharmacies face an increasingly complex set of challenges related to providing sterile products to patients. New United States Pharmacopeia <797> regulations, increasing drug shortages, and an ongoing pharmacy technician workforce shortage have made sterile compounding more difficult than ever for health-system pharmacies. Outsourcing of production to 503B outsourcing facilities is one strategy pharmacy leaders can use to help navigate these challenges. However, there are many factors to consider when deciding whether to outsource a product and which 503B vendors are safe and reliable. The Cleveland Clinic Health System (CCHS) has developed a robust internal structure to appropriately vet 503B outsourcing facilities for safety and reliability, as well as standardized criteria used to determine which products will be outsourced. This article describes the tools CCHS has used to evaluate 503B outsourcing vendors and to evaluate individual products to determine the pros and cons of outsourcing vs insourcing. Additionally, general considerations regarding outsourcing are described. Outsourcing to 503B facilities can be an effective strategy for navigating sterile compounding challenges but is not without some risk. Pharmacy leaders must develop a standardized approach to thoroughly evaluate 503B vendors and products to ensure their outsourcing strategy is both safe and cost-effective.

Physicians’ and patients’ perception of biosimilars and factors affecting biosimilar prescribing in selected Asian countries: a survey study

ABSTRACT Background This study evaluated physicians’ and patients’ beliefs about biosimilars in Hong Kong, India, Pakistan, Singapore, Taiwan, and Thailand. Research design and methods An online survey administered to physicians (dermatologists, n = 119; gastroenterologists, n = 148; rheumatologists, n = 161) between 22 October 2021 and 7 January 2022, and patients (n = 90) with rheumatic or inflammatory bowel disease between 25 October 2021 and 12 April 2022. Results Most (68%) physicians reported having a strong knowledge about biosimilars, yet 49% indicated that biosimilars are readily available to them. Physicians cited potential cost savings (81%) as the main benefit of biosimilars, and cost/coverage support (36%), patient support (25%), and increasing biosimilar awareness/education (24%) as main strategies for improving usage. Few (21%) patients reported having a strong knowledge about biosimilars. Patients cited offering alternatives in case of drug shortages (77%) as the main benefit of biosimilars, and cost/coverage support (53%), increasing awareness of product profile (22%), and providing biosimilars with a good efficacy profile/effective product (19%) as main strategies for improving usage. Conclusion Programs focused on cost/coverage support, patient support, and biosimilar awareness could improve acceptance of biosimilars for chronic immune-mediated inflammatory diseases in Asian countries, thereby increasing patient access to essential biologic therapies.

Drug Shortage in Italy: Retrospective Analysis from 2018 to 2024.

Drug Shortage in Italy: Retrospective Analysis from 2018 to 2024.