Kim Pauwels

Insights into European drug shortages: a survey of hospital pharmacists.

Drug shortages are a complex and global phenomenon. When a drug cannot be delivered at the moment of patient demand, every stakeholder in the health care system is affected. The aim of this study was to investigate the characteristics, clinical impact, financial impact and management of drug shortages in European hospital pharmacies and identify opportunities for prevention and mitigation of drug shortages in Europe. An online survey was designed based on a review of the literature and interviews and was sent to subscribers of Hospital Pharmacy Europe between June and September 2013. Forty-five percent of respondents (n = 161) indicated that life sustaining or life preserving drugs such as oncology drugs were affected by drug shortages. More than 30% of respondents indicated that drug shortages in Europe were always or often associated with increased costs for hospitals, increased personnel costs and more expensive alternative drugs (n = 161). On the question when information about a drug shortage was obtained, 42% of respondents answered that information from the pharmaceutical company was obtained at the time of no delivery, 50% indicated that information from the wholesaler was obtained at the time of no delivery, while 40% of respondents indicated that information was never or rarely received from the government (n = 161). Fifty seven percent of respondents strongly agreed that an obligation to the producer to notify further shortages could help to solve the problem (n = 161). These results showed that pharmaceutical companies and wholesalers are already involved in the management of drug shortages, while a role is still reserved for the government. Mandatory notification in advance and centralized information can help to reduce workload for hospital pharmacists, will allow early anticipation of drug shortages and will facilitate mitigation of the clinical impact on patients.

Drug shortages in European countries: a trade-off between market attractiveness and cost containment?

BackgroundDrug shortages are a global problem. While extensively studied in the United States, numbers about drug shortages in European countries are scarce. This study aims to collect and present data about drug shortages in European countries.MethodsA reporting template for the collection of data about drug shortages was designed based on a literature search. Countries offering a reporting system for drug shortages such as Belgium, the Netherlands, England, Italy, France, Germany and Spain were included in this study. Data about the characteristics of the drugs in shortage and the causes of the shortage were collected from publicly available online reporting systems. Descriptive analyses were performed.ResultsDrug shortages included in the considered reporting systems can be characterized as branded, oral drugs that affect different disease domains. When considering essential medicines and oncology drugs, generic injectables are more involved. Causes for drug shortages are largely underreported. In case the cause is known, production problems take the lead.ConclusionsReporting of drug shortages in Europe needs to be standardized and more transparency about the reasons for drug shortage is required to investigate the problem. A link between production problems and market attractiveness and market capacity is recognized to be at the root of drug shortages in U.S. Such insights are highly lacking in Europe. Monitoring of the effect of national and European health policies on the sustainability of the drug market is required to present fundamental solutions and to tackle the problem of drug shortages in Europe.

Market access of cancer drugs in European countries: improving resource allocation

Public health systems need to make well-founded choices in order to distribute their scarce resources in the most efficient way. Given the number of cancer patients, public/private investments in oncology research, the growing number of new anti-cancer agents and consequent budget impact of cancer care, market access of cancer drugs has become delicate over the last decade. Furthermore, decision makers are challenged by ethical objections and endeavour to provide fair and equal access to treatments for cancer patients. The aim of this study is to generate an overview of market access procedures for cancer drugs in eight European countries and formulate advice for improvement of resource allocation. Results are obtained through a literature review and a qualitative questionnaire and validated by experts with proven knowledge about procedures for price setting and reimbursement of drugs. Diverse measures are applied in the studied countries to optimize reimbursement of cancer drugs such as adjusted cost-effectiveness threshold, regulations for off-label use and new market access agreements. Additionally, innovative cancer drugs are excluded from explicit cost control measures such as payback of budget excess by pharmaceutical companies and lump-sum payments per diagnostic related groups (DRG) in the hospital. The results suggest that cancer is prioritized above other disease areas. Further research is necessary to address the question if society attaches higher value to cancer drugs than to treatments for other diseases.

Managed Entry Agreements for Oncology Drugs: Lessons from the European Experience to Inform the Future

Objectives: The aim of this study is to conduct an analysis on the regulation and application of managed entry agreements (MEA) for oncology drugs across different European countries. Methods: Literature search and document analysis were performed between September 2015 and June 2016 to collect information on the regulatory framework and practice of MEA in Belgium, The Netherlands, Scotland, England and Wales, Sweden, Italy, Czech Republic and France. An overview of the content and typology of MEA applied for oncology drugs between 2008 and 2015 was generated based on publically available sources and contributions by national health authorities. Semi-structured interviews were conducted with representatives of national health authorities involved in the management or negotiation of MEA. Results: The application of MEA differs across countries and across different indications for the same drug. Financial based agreements are prevailing due to their simplicity compared to performance-based agreements. Performance-based agreements are less commonly applied in the European countries except for Italy. In the Netherlands, application of performance-based agreements was stopped due to their inability to deal with dynamics in the market, which is highly relevant for oncology drugs. Conclusions: MEA constitute a common policy tool that public payers in European countries use to ensure early access to highly priced oncology drugs. In light of strengths and weaknesses observed for MEA and the expected developments in the oncology area, the importance of MEA is likely to grow in the future.

Financial based agreements and performance based agreements: the Belgian experience.

Background In times of financial hardship, making innovative treatments affordable for society, accessible for patients and profitable for pharmaceutical companies is a challenge. Reimbursement is often threatened by uncertainties about the financial impact or evidence for a treatment. A contractual agreement between the payer and pharmaceutical company can link reimbursement to financial thresholds (financial-based agreements) or performance of a drug (performance-based agreements). The aim of this study was to investigate the experience with contractual agreements in Belgium.

Are products with an orphan designation for oncology indications different from products for other rare indications? A retrospective analysis of European orphan designations granted between 2002-2012

BackgroundOrphan designated medicinal products benefit from regulatory and economic incentives for orphan drug development. Approximately 40% of orphan designations target rare neoplastic disorders, referring to rare cancers. In order to provide more insights in drugs for rare neoplastic disorders that are under development and to better understand the role of orphan designation in the development of oncology drugs, this study investigates the characteristics of the product, the indication and the applicants as well as the stage of development of products with an orphan designation for rare neoplastic disorders and compares them with products with an orphan designation for other rare indications. Therefore, orphan designation application files and annual reports submitted by the applicant were reviewed at the premises of the European Medicines Agency.ResultsAt the time of application, 41.6% of products with orphan designation for rare neoplastic disorders were in pre-clinical phase; this was 65.1% for other rare conditions (p < 0.05). Thirty percent of orphan designations for rare neoplastic disorders had reached phase 1; compared to 19.3% of orphan designations targeting other rare conditions (p < 0.05). The same trend was observed for the stage of development at the time of the latest annual report. Significant benefit was more often considered for orphan designations for rare neoplastic disorders compared to orphan designations for other rare conditions.ConclusionOrphan designations for rare neoplastic disorders involve products that are in a more advanced stages of development compared to orphan designations for other (non-oncology) rare conditions.

Predictors for reimbursement of oncology drugs in Belgium between 2002 and 2013.

Background: Price setting and reimbursement decisions regarding drugs are competence of individual member states in Europe. These decisions involve important trade-offs between social, ethical, clinical and economic criteria. The aim of this study was to investigate the relative importance of criteria for reimbursement of oncology drugs in Belgium. Methods: Reimbursement dossiers on oncology drugs for which reimbursement was applied between 2002 and 2013 were consulted. Multivariate logistic regression was performed. Results: Results showed that clinical evidence and presence of alternative treatments have a significant impact on the reimbursement decisions. Conclusions: Evidence-based medicine still plays a role in Belgian reimbursement decision-making. In order to allow transition towards value-based medicine and avoid spending money on products with limited incremental benefit, therapeutic need at patient level need to be taken into account.

Industry Perspectives on Market Access of Innovative Drugs: The Relevance for Oncology Drugs

Key Points - Representatives of the pharmaceutical industry call for a broader recognition of value within the assessment and appraisal of innovative drugs - Focus on value within the assessment and appraisal of drugs is jeopardized by financial drives as the side of industry and at the side of the payers - A well–considered value-framework, with attention for patient reported outcomes, societal preferences and dynamic approach on the drug life cycle, needs to be incorporated in assessment and appraisal at national and European level in order to coordinate the views of different stakeholders and allow efficient resource allocation This study presents industry perspectives on the challenges related to market access of innovative drugs in general and oncology drugs in specific. Fifteen interviews were conducted with representatives of pharmaceutical companies and industry associations. Interviewees call for a broader recognition of value within the assessment and appraisal of drugs. According to interviewees, focus on value is jeopardized by the lack of a common value definition across Europe, poor availability and validity of value measures and cost-saving measures such as external reference price setting and cost-effectiveness analysis at the side of the payers. Centralized assessment of relative-effectiveness at European level would provide a common value estimate across member states, independent of financial drivers. Empirical evidence on PRO and societal preferences is however essential in the development of a value definition. Furthermore, value-based pricing would imply a dynamic approach where the price is differentiated across indications and across the lifecycle of the drug, especially in fields such as oncology. Financial drivers however also threat the application of value-based pricing at the side of the industry, making value-based profitability a more appropriate term.

DD-015 How should drug shortages be defined? a review

Background Drug shortages are currently on the rise. In-depth investigation of the problem of drug shortages is necessary; however, a variety of definitions for ‘drug shortages’ are adopted by different organisations, e.g. Food and Drug Administration (FDA) and the American Society of Hospital Pharmacies (ASHP). For international comparison, it is important to clearly denote which definition is used by the national authorities or by (inter)national organisations. Purpose To identify and compare different definitions and analyse the overlap and missing info in each definition. Material and methods A literature review was performed searching the scientific databases MEDLINE and Embase for definitions of drug shortages. Grey literature, such as websites and documents of (inter)national drug agencies, was also incorporated. Results More than 15 different definitions for drug shortages were identified. Articles in the scientific literature often refer to existing definitions. Only a few articles describe their own definition. After comparison of the definitions some overlap was observed. Sometimes drug shortages are defined as situations in which a drug is undeliverable for a certain period; this period ranges from one day to 20 days. However, delaying treatment of infectious diseases for 20 days will have a serious effect on patients. Other definitions only consider those drugs used for the treatment of serious diseases or drugs for which no alternative is available; this underestimates the size of the problem. Conclusion The ultimate goal is to formulate a general European definition for reporting drug shortages, which is essential for international comparison. Indicating a time limit in the definition is an essential element for the comparison of nationally reported drug shortages. This time limit might be even one day if the patient’s health warrants it. A definition of drug shortages covering all types of drugs is crucial to acknowledge the size of the problem. References and/or acknowledgements No conflict of interest.