Extent of a valsartan drug shortage and its effect on antihypertensive drug use in the Canadian population: a national cross-sectional study.

BACKGROUND: Drug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada. METHODS: We conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period. RESULTS: After the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes. INTERPRETATION: Our findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.

Patterns of prescription dispensation and over-the-counter medication sales in Sweden during the COVID-19 pandemic.

INTRODUCTION: On February 26th 2020, a high alert was issued in Sweden in response to the diagnosis of the first few coronavirus disease 2019 (COVID-19) cases in the country. Subsequently, a decreased supply of essential goods, including medical products, was anticipated. We aimed to explore the weekly patterns of prescription dispensing and over-the-counter (OTC) medication sales in Sweden in 2020 compared with previous years, to assess the influence of the government restrictions on medication sales, and to assess whether there is evidence of medication stockpiling in the population. METHODS: Aggregated data on the weekly volume of defined daily doses (DDDs) of prescription medication dispensed and OTC sales from 2015 to 2020 were examined. From 2015-2019 data, the predicted weekly volume of DDDs for 2020 was estimated and compared to the observed volume for each ATC anatomical main group and therapeutic subgroup. RESULTS: From mid-February to mid-March 2020, there were increases in the weekly volumes of dispensed medication, peaking in the second week of March with a 46% increase in the observed versus predicted number of DDDs dispensed (16,440 vs 11,260 DDDs per 1000 inhabitants). A similar pattern was found in all age groups, in both sexes, and across metropolitan and non-metropolitan regions. In the same week in March, there was a 96% increase in the volume of OTC sold (2,504 vs 1,277 DDDs per 1000 inhabitants), specifically in ATC therapeutic subgroups including vitamins, antipyretics, painkillers, and nasal, throat, cough and cold preparations. CONCLUSION: Beginning in mid-February 2020, there were significant changes in the volume of prescription medication dispensed and OTC drugs sold. The weekly volume of DDDs quickly decreased following recommendations from public authorities. Overall, our findings suggest stockpiling behavior over a surge in new users of medication.

A Non-Profit Approach to Address Foreign Dependence of Generic Drugs.

The COVID-19 pandemic has revealed the vulnerability of the US generic drug supply chain to foreign production. Many policies have been proposed to mitigate this vulnerability. In this article, we argue that nonprofit drug manufacturers have the potential to make important contributions.

How patients in Denmark acquire their medicines: overview, data sources and implications for pharmacoepidemiology.

The means by which patients acquire their medications differ between countries, and a knowledge of this is essential when conducting and interpreting pharmacoepidemiological studies. The aim of this paper is to provide an overview of how patients obtain medicines in Denmark, to relate these to nationwide registries available for research and to discuss the implications for research. Health services are predominantly tax-funded in Denmark, with dentistry and some medicine bought at community pharmacies being exceptions, involving partial reimbursement of charges. The paper gives an overview of prescription medicines acquired from community pharmacies (including magistral preparations), over-the-counter medicines, vaccinations and in-hospital medicine including so-called "free medicine" (in Danish: "vederlagsfri medicin"). "Free medicine" is medicines for a defined list of diseases and indications that is provided free of charge to patients in outpatient clinics. The paper also describes the content of the various Danish data sources about medicine use, summarizes their strengths and limitations, and exemplifies the ways of evaluating their completeness. An example is provided of the regional variation in the means by which medicines are acquired.

Factors associated with drug shortages in Canada: a retrospective cohort study.

BACKGROUND: To monitor the magnitude of the drug shortage problem in Canada, since 2017, Health Canada has required manufacturers to report drug shortages. This study aimed to identify the factors associated with drug shortages in Canada. METHODS: We conducted a retrospective cohort study of all prescription drugs available on the market between Mar. 14, 2017, and Sept. 12, 2018, in Canada. All drugs of the same active ingredient, dosage form, route of administration and strength were grouped into a "market." Our main outcome was shortages at the market level, determined using the Drug Shortages Canada database. We used logistic regression to identify associated factors such as market structure, route or dosage form, and Anatomic Therapeutic Chemical (ATC) classification. RESULTS: Among the 3470 markets included in our analysis, 13.3% were reported to be in shortage. Markets with a single generic manufacturer were more likely to be in shortage than other markets. Markets with oral nonsolid route or dosage form were more likely to be in shortage than those that were oral solid with regular release (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.11 to 2.49). Markets for sensory organs were more likely to be in shortage than most other ATC classes. Markets with a higher proportion of drugs covered by public insurance programs were more likely to be in shortage (OR 1.03, 95% CI 1.00 to 1.05 per 10% increase). INTERPRETATION: Markets with a single generic manufacturer were most likely to be in shortage. To ensure the security of drug supply, governments should be vigilant in monitoring markets with a single generic manufacturer, with complex manufacturing processes, with higher demand from public programs or those that are in certain ATC classes.

Toward health system strengthening in low- and middle-income countries: insights from mathematical modeling of drug supply chains.

BACKGROUND: Global health priority setting increasingly focuses on understanding the functioning of health systems and on how they can be strengthened. Beyond vertical programs, health systems research should examine system-wide delivery platforms (e.g. health facilities) and operational elements (e.g. supply chains) as primary units of study and evaluation. METHODS: We use dynamical system methods to develop a simple analytical model for the supply chain of a low-income country's health system. In doing so, we emphasize the dynamic links that integrate the supply chain within other elements of the health system; and we examine how the evolution over time of such connections would affect drug delivery, following the implementation of selected interventions (e.g. enhancing road networks, expanding workforce). We also test feedback loops and forecasts to study the potential impact of setting up a digital system for tracking drug delivery to prevent drug stockout and expiration. RESULTS: Numerical simulations that capture a range of supply chain scenarios demonstrate the impact of different health system strengthening interventions on drug stock levels within health facilities. Our mathematical modeling also points to how implementing a digital drug tracking system could help anticipate and prevent drug stockout and expiration. CONCLUSION: Our mathematical model of drug supply chain delivery represents an important component toward the development of comprehensive quantitative frameworks that aim at describing health systems as complex dynamical systems. Such models can help predict how investments in system-wide interventions, like strengthening drug supply chains in low-income settings, may improve population health outcomes.

Association of Medicare Part D Benzodiazepine Coverage Expansion With Changes in Fall-Related Injuries and Overdoses Among Medicare Advantage Beneficiaries.

Importance: Benzodiazepines, which are associated with safety-related harms for older adults, were not covered when the US Medicare Part D prescription drug benefit began. Coverage was extended to benzodiazepines in 2013. Objective: To examine whether the expansion of benzodiazepine coverage among Medicare Advantage (MA) beneficiaries was associated with increases in fall-related injuries or overdoses among older adults. Design, Setting, and Participants: This ecological study used interrupted time-series with comparison-series analyses of MA claims data from 4 635 312 age-eligible MA beneficiaries and 940 629 commercially insured individuals (comparison group) stratified by age (65-69, 70-74, 75-79, and ≥80 years) to separately compare trends in fall-related injury and overdose before (January 1, 2010, to December 31, 2012) and after (January 1, 2013, to December 31, 2015) coverage expansion for benzodiazepines. Data analysis was performed from September 1, 2018, to August 31, 2019. Exposures: Expansion of benzodiazepine coverage in Medicare Part D in 2013. Main Outcomes and Measures: Monthly rate of fall-related injury and overdose. Results: In 2012 (the year before the policy change), women constituted 57.5% of the MA group and 47.4% of the comparison group. A total of 25.8% of individuals in the MA group were aged 65 to 69 years, and 29.3% were 80 years or older (mean [SD], 75.1 [6.4] years); 56.7% of individuals in the comparison group were aged 65 to 69 years, and 15.1% were 80 years or older (mean [SD] age, 70.9 [6.5] years). In the MA group, 4 635 312 individuals contributed 156 754 749 person-months from 2010 through 2015; in the comparison group, 940 629 individuals contributed 25 104 534 person-months. After coverage of benzodiazepines began, the rate (ie, slope) of fall-related injury among MA beneficiaries increased from before to after coverage among all age groups. Compared with the comparison group, the increase in rate was statistically significant for those 80 years or older (rate changes for the MA vs comparison groups: 0.12 [95% CI, 0.07 to 0.17] vs -0.01 [95% CI, -0.11 to 0.10]; P = .04 for interaction). The overdose trend changed from decreasing to increasing among MA beneficiaries after coverage for all age groups, with a statistically significant increase compared with the comparison group among those aged 65 to 69 years (rate changes for the MA vs comparison groups: 0.23 [95% CI, 0.17 to 0.30] vs 0.02 [95% CI, -0.06 to 0.11]; P < .001 for interaction) and among those 80 years or older (rate changes for the MA vs comparison groups: 0.07 [95% CI, 0.00 to 0.14] vs -0.20 [95% CI, -0.35 to -0.05]; P = .002 for interaction). Results among MA beneficiaries were consistent when stratified by sex and when limited to those prescribed opioids. Conclusions and Relevance: Medicare's expansion of benzodiazepine coverage may have been associated with increases in the rates of overdose among adults ages 65 to 69 years and in the rates of overdose and fall-related injury among those 80 years or older.

Combating drug shortages in China: surveillance warning and practice standardization.

Like other countries, China has been experiencing drug shortages during the past years, including drugs on the National Essential Medicine List and emergency drugs. Drug shortages have raised public concerns in China and have severe impacts on all stakeholders in the supply chain, especially patients and hospitals. Recently, Chinese governments have ramped up several measures to ensure a steady supply of essential and first-aid drugs. In this commentary, we share our experiences of addressing drug shortages at Hunan Province, central China. We focus on the establishment of a provincial drug shortage monitoring center, and the Center's efforts to standardize practices on the management of drug shortages and identify therapeutic alternatives for drugs in short supply based on international best practices.

The Effect Of Veterans Health Administration Coverage On Cost-Related Medication Nonadherence.

High out-of-pocket drug spending worsens adherence and outcomes, especially for patients who are poor, chronically ill, or members of minority groups. The Veterans Health Administration (VHA) system provides drugs at minimal cost, which could reduce cost-related medication nonadherence. Using data for 2013-17 from the National Health Interview Survey, we evaluated the association of VHA coverage with such nonadherence. Although people with VHA coverage were older and in worse health and had lower incomes than those with other coverage, VHA patients had lower rates of cost-related medication nonadherence: 6.1 percent versus 10.9 percent for non-VHA patients, an adjusted 5.9-percentage-point difference. VHA coverage was associated with especially large reductions in nonadherence among people with chronic illnesses and with reduced racial/ethnic and socioeconomic disparities in nonadherence. The VHA pharmacy benefit is a model for reform to address the crisis in prescription drug affordability.

Barriers to Ensuring Access to Affordable Prescription Drugs.

High and rising prescription drug costs have become a preoccupying policy problem in the United States. Notwithstanding broad, bipartisan interest in finding effective policy solutions, several aspects of the drug affordability problem make it an uncommonly difficult one to solve. This article reviews the moral, market, and political factors contributing to the difficulty. Among the moral problems is lack of agreement about how to weigh the fundamental tradeoff involved in regulating drug prices-affordability versus incentives for innovation-and about what constitutes a fair price. Market-related factors include the lack of price transparency and a myriad of perverse incentives in the system through which prescription drugs are supplied to patients. Finally, current policy choices are constrained by past political compromises, and an atmosphere of scandal focusing on egregious instances of price gouging has made rational deliberation about fixes to deeper problems in the system difficult.

Managing supply chain uncertainty and risk in the pharmaceutical industry.

The purpose of the conceptual paper is to present a framework for managing pharmaceutical supply chain uncertainty and risk. The supply chain risk management strategy is critical and significant to strategically support the firms to success in the long run. However, very little research has been conducted in the pharmaceutical firms so far. Based on literature review, the supply chain integration capability is considered as effective risk management tools for mitigating the supply chain uncertainty and risk. The authors identified main types of pharmaceutical supply chain uncertainty and risk. The conceptual framework focuses on the relationships among the supply chain integration capability and pharmaceutical supply chain uncertainty and risk. This provides insights into the pharmaceutical supply chain risk management. The study focuses on the pharmaceutical industry. However, the proposed framework can be validated with an empirical work in different sectors. Moreover, this contributes to the pharmaceutical supply chain management literature.

Understanding profit margins of medical providers from prescription drugs: evidence from Taiwan.

BACKGROUND: This study empirically estimates the magnitude and associated determinants of profit margins that medical providers earn from prescription drugs based on Taiwan's pharmaceutical market. METHODS: Our main data set is from the population-based claims data compiled by the National Health Insurance Research Database covering three waves of price adjustment: July-December 2004, October 2007-September 2008 and October 2009-September 2010. Only drugs whose reimbursement prices were adjusted using the R-zone formula were used as samples for this study. By calculating the difference between retail and wholesale prices for 796 pharmaceutical products, we can estimate the profit margin determinants using the regression model. RESULTS: We found evidence that suppliers of generic drugs tend to offer larger discounts to medical providers than suppliers of brand-name drugs. In addition, the countervailing power of wholesale pharmaceuticals, as measured by the discount rate offered by pharmaceutical manufacturers, is positively associated with the degree of competition within the pharmaceutical market and the size of the market itself. CONCLUSIONS: Our findings imply that the profit-seeking behaviour exhibited by medical providers is the engine of competitive forces in Taiwan's prescription drug market. This creates financial incentives for them, which in turn influences their choices of prescription drugs.

Understanding the Implications of a Shifting Opioid Landscape in Ontario.

North America is currently in the midst of an opioid overdose crisis, leading to changes in drug policy and clinical practice guideline recommendations. Data from Ontario's prescription monitoring program and the Office of the Chief Coroner for Ontario can be used to characterize changing prescription opioid trends and their role in fatal opioid overdoses. A better understanding of historical patterns of opioid use and overdose can help inform a more nuanced drug policy in the future.