Contemporary Perspective on Supply Chain Management Regarding Drug Sourcing Shortages

Safeguarding the supply of drugs and satisfying the needs of patients is a strategic priority of any healthcare system especially in these pandemic times. The pharmaceutical supply chain is subject to many pressures including non-availability and shortage of requisite drugs. A drug shortage is a deficiency in the supply of medicines or products that affects the ability of a patient to get the required treatment in due time. The roots of drug shortages are multifaceted, varied, and the issue can be due to supply or demand. However, the situation affects almost every stakeholder in the healthcare system, which is why collaboration is a must to deal with drug shortages. Hence, adopting an exploratory and single-case approach of the largest public hospital in the context of Namibia, the objective of this chapter is to provide a contemporary perspective of supply chain management re drug sourcing shortages, analyze the causes of drug shortages, recommend measures to minimize the crisis, and suggest strategies for enhanced efficiency in drug supply.

A Latin-American Cancer Center Experience in the Treatment of Hodgkin's Lymphoma during a Drug Shortage

The treatment of Hodgkin's lymphoma has been characterized by a story of success with the use tried-and-true protocols. During the second half of 2019 to the first-half of the 2021 the Mexican health system experienced a shortage of drugs, which compromised the possibility of using in most of the common protocols for this cancer: ABVD, BEACOPP, IGEV, ESHAP, DHAP, GEMOX. Clinician had option of using a common protocol with incomplete doses or applying an alternative complete CHOEP protocol, which has been used with some success in exploratory studies [1,2]. For 12 months, we treated a total of 58 patients of which we compared the base characteristics and response rates to 10-year compiled data from pre-shortage patients (PS) (total 475). The baseline characteristics of the PS vs shortage (S) group showed a statistical similar gender distribution (males 55.2% vs 63.8%, P 0.21), histologic subtype (P 0.24), international prognostic score (IPS ≥3 57.7% vs 58.6%, P 0.89) and clinical stage (advanced 78.1% vs 84.5%, P 0.26). The S patients did show higher frequency of B symptoms (P 0.002), extranodal disease (P 0.0001), while the PS group had a higher frequency of bulky disease (P 0.001), ABVD protocol (96% vs 63.8%, P 0.0001) and radiotherapy use. In the S group a total of 37 ABVD (29 incomplete), 7 BEACOPP (5 incomplete) and 14 CHOEP protocols (1 incomplete) were infused, it means only 10 (17.7%) were able to receive a standard complete treatment, while the rest received an incomplete or alternative treatment. Complete response for the PS and S group were 71.4% vs 56.9% with the corresponding therapeutic failure 28.6% vs 43.1% (p 0.023) respectively. Analyzing the response rate of each chemotherapy protocol in the S group, the complete ABVD vs incomplete ABVD demonstrated an 87.5% vs 69% (p 0.28) respectively. The complete BEACOPP vs incomplete showed 50% vs 40% (p 0.7) and CHOEP exhibited an unexceptional complete response rate of 21.4%. The median follow up was 48 months (1-148) for all cohort. One year OS were 98% vs 82% on PS vs S group respectively (log rank 0.0001). One year-PFS for the PS and S group were 96% and 61% respectively (log rank 0.003). The risk factors associated with lower PFS were B symptoms (OR 1.7, 1.1-2.6), advanced disease (OR 1.66, 1-0-2.7) and IPS≥3 (OR 2.1, 1.4-3.3); as favorable factors we observed radiotherapy (OR 0.07, 0.6-0.8) and the PS group (OR 0.5, 0.3-1.0); however, in the Cox regression, only the IPS≥3 remained as an independent unfavorable factor (HR 1.8, 1.2-2.6), as did radiotherapy (HR 0.4, 0.3-0.6) as favorable. For the OS the drug shortage were an independent risk factor (HR 2.2, 1.1-4.3) like IPS ≥3 (HR 2.8, 1.5-5.1). Analyzing the 1-year PFS in the S group according to which chemotherapy protocol they received, those with ABVD or BEACOPP (regardless of the complete dose status) was of 72%, compared to 20% (P 0.001) in the CHOEP regimen. CHOEP regimen in LH patients is ineffective treatment. In times of shortages, continuing with incomplete standard schemes offers better response rates than alternative schemes. Despite Hodgkin's lymphoma is considered a neoplasm with high cure rates when an economic recession followed by an international event (for example a global pandemic) limited our availability for the use of standard treatments, an area of opportunity for considering alternative protocols has risen for resource-limited countries and institutions. [1] Walewski J,et al. CHOP-21 for unfavorable Hodgkin's lymphoma. An exploratory study. Med Oncol. 2010;27(2):262-7 [2] Kolstad A, et al. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's lymphoma. Leuk Lymphoma. 2007;48(3):570-6 Disclosures No relevant conflicts of interest to declare.

150. Improved Susceptibility of Pseudomonas aeruginosa to Cefepime (CEF) at a Veterans Tertiary Care Hospital, over a 7-Year Period (2011-2017): The Impact of Antibiotic Rotation/Cycling and Reversal of Drug Resistance in P. aeruginosa

Background Background: Pseudomonas aeruginosa continues to be an important cause of nosocomial infections associated with a high morbidity and mortality. Despite the availability of ceftazidime-avibactam (CAZ-AVI) and ceftolozone-tazobactam (CFT-TAZO), CEF continues to be an empiric agent of choice in several institutions. Aim: To evaluate the prevalence and trend in susceptibilities of P. aeruginosa to CEF over a 7-year period, identify possible correlation with the use of CAZ, AZT, PTZ, CIP, and CAR, (DOT/1000 patient days), as a quality improvement (QI) measure for optimizing CEF use, introduce antibiotic cycling as a tool to avoid emergence of drug-resistance in P. aeuriginosa. Methods A retrospective review of antimicrobial susceptibility data of all isolates of P. aeruginosa, (inpatient and outpatient) at the Detroit VAMC pre and post implementation of antibiotic cycling, over a 7-year period (2011-2017) was performed. Susceptibility testing was performed by reference broth micro-dilution methods in a central laboratory. Data analysis was performed using Pearson correlation coefficient score. Being a QI project, clinical data were not reviewed. Results A total of 977 isolates were identified during the study period. (drug usage are in DOT/1000 PD); CAZ and AZT use surged during 2013-14 from 5 to 8 dropping in 2015-17 to < 3; PTZ usage increased to 100 during 2011-14 but dropped to 38 in 2015-17 (drug shortage); CAR use averaged at 10 until 2016 and dropped to 8 in 2017; CIP use dropped by 50% from 30 in 2012 to 15 in 2017; P. aeruginosa susceptible to CEF decreased from 88% in 2012 to 81% in 2014 mirroring the increased use of CEF, AZT, CAZ, and CIP; AG use was very low at < 5. With restrictions on the use of AZT, CAZ, and CIP, from 2014-15, CEF susceptibility increased significantly to 95.5% in 2015. Drug shortage of PTZ in 2015 and increased use of CEF from 2015-17 led to a drop in susceptibility to (82%); P. aeruginosa susceptible to CAR and AG averaged at 88% and 97% respectively (2011-17). However, reintroduction PTZ, resulted in improved susceptibility of P. aeuruginosa to CEF by 40% within a year. Conclusion Judicious antimicrobial use and antibiotic rotation play a significant role in reversing drug resistance in P. aeuruginosa. Disclosures All Authors: No reported disclosures

Creation of a State Drug Shortage Dashboard in the COVID-19 Pandemic

Purpose: Drug shortages are anticipated to worsen with time as the Coronavirus Disease 2019 (COVID-19) pandemic continues. The aim of this study is to track drug shortages within Illinois and identify causes and trends to this time-sensitive problem. Methods: In order to communicate between health systems within the state, the Illinois Council of Health-System Pharmacists (ICHP) developed a medication shortage dashboard, which collects information from health systems in the state on current drug shortages. Classes of medications inquired about included: anti-infectives, neuromuscular blocking agents (NMBAs), sedatives/analgesics, vasopressors, and “others.” Data was gathered from 6 different medication shortage dashboards, ranging from May 20, 2020 to June 22, 2020 and was used to track drug shortages within Illinois. Additionally, this data was analyzed in conjunction with the number of hospital beds utilized by COVID-19 patients at the time. Results: Illinois’s medication shortage dashboard tracked the supply level of 42 medications used in the treatment of patient’s hospitalized with COVID-19. Data from an average of 75 health systems was analyzed each week (average response rate: 52%). For each medication, health systems identified if they had ample supply, mild shortage, moderate shortage, or critical shortage. Overall the trends of these medications positively correlated with the number of hospital beds utilized by COVID-19 patients in Illinois ( r2 = 0.7). Conclusion: The data from this study supports the conclusion that increased hospital bed utilization by COVID-19 patients is correlated with increased drug shortages of medications used in the treatment of COVID-19. It is imperative that health systems take appropriate action to prevent and manage drug shortages.

Evaluation of Prolonged Versus Continuous Infusions of Piperacillin/Tazobactam During Shortages of Small Volume Parenteral Solutions

Background: In 2017, a national drug shortage of small volume solutions significantly affected the preparation of intravenous antibiotics. In response, a continuous infusion administration protocol for piperacillin/tazobactam (PIP/TAZ) was implemented. Objective: To compare the outcomes of continuous to prolonged infusions of PIP/TAZ in the setting of drug shortages. Methods: This study is a single-center, retrospective cohort study in a community hospital of patients 18 years and older who received intravenous PIP/TAZ through 2 different dosing strategies of intravenous antibiotics from December 2016 to January 2018. Data were collected for 2 months on patients receiving prolonged infusions of PIP/TAZ prior to November 2017 and for 2 months on patients receiving continuous infusions of PIP/TAZ after November 2017. Results: A total of 90 patients who received PIP/TAZ via either prolonged (n = 47) or continuous infusion (n = 43) were evaluated. There were no differences between the groups in mortality (3 vs 2 deaths, P = 1.00), length of therapy (6 ± 4 vs 6 ± 3 days, P = .86), or length of stay (9 ± 7 vs 8 ± 6 days, P = .47). Additionally, no differences were noted between incidences of thrombocytopenia ( P = .41), Clostridioides difficile infection ( P = .48), acute renal failure ( P = 1.00), seizures ( P = 1.0), or 30-day readmission rates ( P = .27). Conclusions: Administration of continuous infusion PIP/TAZ appears to be a viable mitigation strategy during small volume fluid shortages. Future cost-effectiveness studies may provide information on the financial impact of continuous infusions during costly drug shortages.

Patients perspectives on drug shortages in six European hospital settings – a cross sectional study

Background It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients′ awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. Methods A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher’s exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher’s test. Post-hoc hospital-wise analyses were performed using Fisher’s exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). Results 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p < 0.001) while the fewest patients were in H-SE (1 %, N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. Conclusions Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.

Drug Shortage: Causes, Impact, and Mitigation Strategies

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.