What Does Society Value About Cancer Medicines? A Discrete Choice Experiment in the Belgian Population.

BACKGROUND: Debate on pricing and reimbursement of cancer medicines highlights the need to establish the value of cancer medicines. OBJECTIVE: This study aims to elicit the trade-offs in cancer medicine characteristics that the Belgian population is willing to make. METHODS: A discrete choice experiment used six attributes with three levels each, based on literature and focus group discussions. The survey was sent to a random sample of 3500 Belgian citizens. Based on the choice of 961 respondents, individual parameters were estimated with a mixed logit model. RESULTS: Societal value of cancer medicines was positively affected by a higher number of patients eligible for treatment, a high initial life expectancy and quality of life of patients, a high gain in quality of life and life expectancy due to treatment, and a low treatment cost. The value of 1-year gain in life expectancy was independent from the initial life expectancy of the patient. However, the value of one-point gain in quality of life was higher for patients with a low initial quality of life than for patients with a high initial quality of life. CONCLUSIONS: This study has shown that gain in quality of life with cancer medicines is valued higher by Belgian society for patients who have lower initial quality of life before the start of treatment.

Patient Involvement in the Lifecycle of Medicines According to Belgian Stakeholders: The Gap Between Theory and Practice.

Background: Patient involvement is often acknowledged as an important aspect of the lifecycle of medicines. Although different typologies exist, patient involvement has been described as the involvement of patients in decision-making regarding medicines. In view of the diversity of stakeholders and types of decisions in which patients might be involved, an in-depth understanding of these stakeholders' views toward involving patients in the lifecycle of medicines is essential. Methods: Interviews and surveys were used to gain insights into the perspectives and experiences of Belgian healthcare stakeholders. Interviews (n = 22) were conducted with academics, hospital pharmacists and representatives from health insurance funds, the Belgian reimbursement agency, pharmaceutical industry and patient organizations. Interviews underwent a framework analysis. Surveys (n = 108) were completed by hospital visitors and analyzed descriptively. Results: Despite an increasing amount of efforts to involve patients, interviewees labeled the level of actively involving patients as rather low and scattered across the different phases of the lifecycle of medicines. The main opportunities for patient involvement highlighted by interviewees were for: (i) informing early development decisions on which treatments to develop, (ii) clinical trial endpoint selection and (iii) clinical trial protocol design. However, remaining questions surrounding patient knowledge, and particularly how and which patients to involve represent important barriers toward implementing patient involvement in the lifecycle of medicines. Of survey participants, 77% indicated to be willing to participate in patient preference studies. Reasons for participating mentioned most frequently were "to improve development of treatments," because "it is important to explore and listen to patient preferences" and "to have a voice as patients". Conclusions: The barriers identified in this study hamper transitioning patient involvement from theory to practice. Bridging this gap requires addressing the identified barriers and unresolved questions surrounding the right methodology for involving patients, the "right patients" to involve and means to increase patient knowledge. In order to do so, further research should focus on assessing the value of methods that allow to indirectly capture patients' perspective both in the context of development as well as in the context of evaluation.

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.

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.

BACKGROUND: Orphan 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. RESULTS: At 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. CONCLUSION: Orphan 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.

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.

[Drug shortages in the hospital: management, causes and budget impact]. / Indisponibilité des medicaments dans les hôpitaux: gestation, causes et impact sur le budget.

INTRODUCTION: Drug shortages have become an issue of growing interest for pharmacists. Both number and type of shortages have increased over the past decade and it is challenging to provide drug continuity. Aim To describe management and impact of drug shortages for the hospital pharmacy. To gain insight into the causes of shortages. METHODS: The management process for drug shortages was analysed for the hospital pharmacies of the Ghent University Hospital (GUH) and the Acute Care Hospital Sint-Lucas Ghent. Insights in possible causes were obtained by semi-structured interview with the Federation for Belgian Pharmacists (Association Pharmaceutique beIge (APB)), the Belgian association of the pharmaceutical industry (pharma.bel and the Federal Agency for Medicines and Health Products (FAMHPI. A database of 1329 drug shortages (Jan 2001-Feb 2014 of the GUH was used to define drug classes affected by shortages (mean shortage days per year, standard deviation (SDI), type of shortage [urgent/ important] %, total number (n)), formulation (parenteral:oral and duration of the shortages (median, interquartile range (IQR)). The total cost impact for the GUH pharmacy was estimated by calculating average, minimum and maximum time investment by the pharmacy team (Delphi-techniquel and by calculating the cost difference between original and alternative drug acquisition costs. Impact is presented as base case scenario (minimum as best and maximum as worst case scenario). RESULTS: The different management phases for the pharmacist are problem identification, preparation of solution and implementation. Communication and extensive administration are essential components. Causes are production related, next to distribution inequivalences, quota and European market flows. Shortages with anti-infectious, cardiovascular and hormonal system drugs have the highest and constant proportion of drug shortage days, with recently appearance of other important drug classes such as anticancer therapy [2011 and further). The average number of drug shortage days in 2011-2013 is 8020 (SD 2142 compared to period 2001-2010 with on average 4633 days (SD 1731]. Fifty-four percent of the shortages is important for the direct hospital care and 22.9% needs urgent action. The proportion parenteral versus oral in the database is 3.3:1. Median duration of a shortage is 29 [IQR 11-65]1 days. The average excess cost of an equipotent dose of the alternative drug was 4.9 (SD 31.3) Euro. Total cost impact (gross salary and drug acquisition cost] for GUH pharmacy in 2013 is 117 281.4 Euro (best case: 88 345.06 and worst case: 151,208.2 Euro. CONCLUSION: The importance of the shortages and the diversification of the drug classes involved have an impact on the hospital pharmacy management. For the GUH this represents an important workload and an increased drug acquisition cost. Causes of shortages are production related but also distributional inequivalences and quota play an important role.

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.

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?

BACKGROUND: Drug 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. METHODS: A 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. RESULTS: Drug 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. CONCLUSIONS: Reporting 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.