Intensity of End-of-Life Care in a Cohort of Commercially Insured Women With Metastatic Breast Cancer in the United States.

PURPOSE: There is limited evidence on the intensity of end-of-life (EOL) care for women < 65 years old, who account for about 40% of breast cancer deaths in the United States. Using established indicators, we estimated the intensity of EOL care among these women. METHODS: We used 2000-2014 claims data from a large US insurer to identify women with metastatic breast cancer who, in the last month of their lives, had more than one hospital admission, emergency department visit, or an intensive care unit (ICU) admission and/or used antineoplastic therapy in the last 14 days of life. Using multivariate logistic regression, we assessed whether intensity of EOL care differed by demographic characteristics, socioeconomic factors, or regions. RESULTS: Adjusted estimates show an increase in EOL ICU admissions between 2000-2003 and 2010-2014 from 14% (95% CI, 10% to 17%) to 23% (95% CI, 20% to 26%) and a small increase in emergency department visits from 10% (95% CI, 7% to 13%) to 12% (95% CI, 9% to 15%), both statistically significant. There was no statistically significant change in the proportions of women experiencing more than one EOL hospitalization (14% in 2010-2014; 95% CI, 11% to 17%) and of those receiving EOL antineoplastic treatment (24% in 2010-2014; 95% CI, 21% to 27%). Living in predominantly mixed, Hispanic, Black, or Asian neighborhoods correlated with more intense care (odds ratio, 1.39; 95% CI, 1.10 to 1.77 for ICU). CONCLUSION: Consistent with findings in the Medicare population, our results suggest an overall increase in the number of ICU admissions at the EOL over time. They also suggest that patients from non-White neighborhoods receive more intense acute care.

What are the volume and budget needs to provide chemotherapy to all children with acute lymphoblastic leukaemia in Thailand? Development and application of an estimation tool.

OBJECTIVE: Insufficient access to anticancer medicines may contribute to the wide survival differences of children with cancers across the globe. We developed a tool to estimate the volume of medicines and budget requirements to provide chemotherapy to children with acute lymphoblastic leukaemia (ALL). DESIGN: Development and application of an estimation tool. SETTING: Paediatric oncology hospital departments in Thailand. PARTICIPANTS: 318 children aged 0-14 years diagnosed with ALL and 215 children with undiagnosed ALL. INTERVENTIONS: Estimates of volume and budget requirements for administering a full course of chemotherapy for ALL and a further course for children who relapse, according to National Treatment Guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were the volume (mg) and cost (US$) of medicines needed to treat children with ALL. For medicines whose main indication is paediatric ALL (asparaginase and 6-mercaptopurine), we estimated the difference between volume needed and actual sales in 2017 (secondary outcome). RESULTS: Ten anticancer medicines and four chemoprotective agents are needed for the treatment of paediatric ALL according to the Thai treatment guidelines. Of these 14 medicines, 13 are included in the WHO essential medicines list for children. All are available as generics. We estimated that essential chemotherapy and chemoprotective agents to treat all children diagnosed with ALL in Thailand in 2017 would cost US$ 814 952 (US$ 1 365 422 for diagnosed and undiagnosed children), which corresponds to 0.005% (0.008%) of the country's total health expenditure. The volumes of asparaginase and 6-mercaptopurine available on the Thai market in 2017 were more than sufficient (2.3 and 1.5 times the amounts needed, respectively) to treat all children diagnosed with ALL. CONCLUSIONS: Procuring sufficient quantities of essential medicines to treat children with ALL requires relatively modest resources. Medicine cost should not be a major barrier to ALL treatment in similar settings.

Sales of anti-cancer medicines; China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand.

OBJECTIVE: To assess sales of anti-cancer medicines in the 2017 World Health Organization's WHO Model list of essential medicines in China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand from 2007 (2008 for Kazakhstan and Malaysia) to 2017. METHODS: We extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year. FINDINGS: We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017. CONCLUSION: The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

INTRODUCTION: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Time to Entry for New Cancer Medicines: From European Union-Wide Marketing Authorization to Patient Access in Belgium, Estonia, Scotland, and Sweden.

OBJECTIVES: First, to quantify the median time from European Union (EU)-wide approval to first use (launch) for a sample of cancer medicines and number of launches in Belgium, Estonia, Scotland, and Sweden as of June 2015. Second, to assess whether longer times to launch or lack of launches affected medicines with high or low expected additional clinical benefit. Third, to identify possible determinants of the probability of a cancer medicine to be launched. METHODS: Correlation between time to launch and a set of variables hypothesized to affect launch was tested using a complementary log-log model for a sample of 46 cancer medicines that obtained EU-wide marketing authorization between 2000 and 2014. RESULTS: In median, for a sample of 24 cancer medicines that obtained marketing authorization between 2010 and 2014, the expected time from EU-wide marketing authorization to first use of a medicine was shortest in Sweden, 3.1 months, followed by Scotland (9.3 months), Belgium (14.8 months), and Estonia (27.8 months). Median times to launch were longer for the entire sample of 46 cancer medicines that obtained marketing authorization between 2000 and 2014. In the all-country model, medicines with shorter times to submission for reimbursement, local manufacturers headquarter (or local sales representative), and a Food and Drugs Administration priority review or a combination of expedited approval programs and medicines launched in Scotland and Sweden were associated with a higher hazard of launch. Longer times since EU-wide approval initially correlate with an increased hazard but as time further elapses they negatively affect the hazard of launch. CONCLUSIONS: Median times from marketing authorization to first use of cancer medicines were shorter for medicines launched between 2010 and 2014 versus sample-wide (2000-2014). In Estonia, more medicines than in the other countries were not yet launched at the end of the observation period. There was no correlation between Prescrire and European School of Medical Oncology Magnitude of Clinical Benefit Scale ratings of added clinical value and time to launch.

Drug promotional activities in Nigeria: impact on the prescribing patterns and practices of medical practitioners and the implications.

OBJECTIVE: Pharmaceutical companies spend significant amount of resources on promotion influencing the prescribing behavior of physicians. Drug promotion can negatively impact on rational prescribing, which may adversely affect the quality of patient care. However, little is known about these activities in Nigeria as the most populous country in Africa. We therefore aimed to explore the nature of encounters between Nigerian physicians and pharmaceutical sales representatives (PSRs), and how these encounters influence prescribing habits. METHODS: Cross-sectional questionnaire-based study conducted among practicing physicians working in tertiary hospitals in four regions of Nigeria. RESULTS: 176 questionnaires were completed. 154 respondents (87.5%) had medicines promoted to them in the previous three months, with most encounters taking place in outpatients' clinics (60.2%), clinical meetings (46%) and new medicine launches (17.6%). Information about potential adverse effects and drug interactions was provided in 41.5%, and 27.3% of cases, respectively. Food, in the form of lunch or dinner, was the most common form of incentive (70.5%) given to physicians during promotional activities. 61% of physicians felt motivated to prescribe the drug promoted to them, with the quality of information provided being the driving factor. Most physicians (64.8%) would agree to some form of regulation of the relationship between medical doctors and the pharmaceutical industry. CONCLUSION: Interaction between PSRs and physicians is a regular occurrence in Nigeria, influencing prescribing practices. Meals and cheap gifts were the most common items offered to physicians during their encounters with PSRs. The need for some form of regulation by professional organizations and the government was expressed by most respondents to address current concerns.

Clinical and Financial Implications of Medicine Consumption Patterns at a Leading Referral Hospital in Kenya to Guide Future Planning of Care.

Background: Medicines can constitute up to 70% of total health care budgets in developing countries as well as considerable expenditure in hospitals. Inventory management techniques can assist with managing resources efficiently. In Kenyatta National Hospital (KNH), a leading hospital in Kenya, over 30% of expenditure is currently allocated to medicines, and this needs to be optimally managed. Objective: To investigate drug consumption patterns, their costs and morbidity patterns at KNH in recent years. Methodology: Cross-sectional retrospective record review. Inventory control techniques, ABC (Always, Better, and Control), VEN (Vital, Essential, and Non-essential) and ABC-VEN matrix analyses were used to study drug expenditure patterns. Morbidity data was extracted from the Medical Records. Results: Out of an average of 811 medicine types procured annually (ATC 5), 80% were formulary drugs and 20% were non-formulary. Class A medicines constituted 13.2-14.2% of different medicines procured each year but accounted for an average of 80% of total annual drug expenditure. Class B medicines constituted 15.9-17% of all the drugs procured yearly but accounted for 15% of the annual expenditure, whilst Class C medicines constituted 70% of total medicines procured but only 5% of the total expenditure. Vital and Essential medicines consumed the highest percentage of drug expenditure. ABC-VEN categorization showed that an average of 31% of medicine types consumed an average of 85% of total drug expenditure. Therapeutic category and Morbidity patterns analysis showed a mismatch between drug expenditure and morbidity patterns in over 85% of the categories. Conclusion: Class A medicines are few but consume the largest proportion of hospital drug expenditure. Vital and essential items account for the highest drug expenditure, and need to be carefully managed. ABC-VEN categorization identified medicines where major savings could potentially be made helped by Therapeutic category and Morbidity pattern analysis. There was a high percentage of non-formulary items, which needs to be addressed. Inventory control techniques should be applied routinely to optimize medicine use within available budgets especially in low and middle income countries.

The value of innovation in decision-making in health care in Central Eastern Europe - The Sixth International Conference, 2 June 2017, Belgrade, Serbia.

The Pharmacoeconomics Section of the Pharmaceutical Association of Serbia organised a one day international conference on the value of innovation in decision-making in health care in Central and Eastern Europe. The focus of the conference was on reimbursement decisions for medicines using health technology assessment and the use of managed entry agreements (MEAs). The objectives of this conference were firstly to discuss the challenges and opportunities with the use of MEAs in Central and Eastern European countries; secondly the role of patient registries especially with outcome based schemes, and finally new approaches to improve accessibility to new medicines including better managing their entry.

The Implementation of Managed Entry Agreements in Central and Eastern Europe: Findings and Implications.

BACKGROUND: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. METHOD: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. RESULTS: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). CONCLUSIONS: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.

How Can Pricing and Reimbursement Policies Improve Affordable Access to Medicines? Lessons Learned from European Countries.

This article discusses pharmaceutical pricing and reimbursement policies in European countries with regard to their ability to ensure affordable access to medicines. A frequently applied pricing policy is external price referencing. While it provides some benchmark for policy-makers and has been shown to be able to generate savings, it may also contribute to delay in product launch in countries where medicine prices are low. Value-based pricing has been proposed as a policy that promotes access while rewarding useful innovation; however, implementing it has proven quite challenging. For high-priced medicines, managed-entry agreements are increasingly used. These agreements allow policy-makers to manage uncertainty and obtain lower prices. They can also facilitate earlier market access in case of limited evidence about added therapeutic value of the medicine. However, these agreements raise transparency concerns due to the confidentiality clause. Tendering as used in the hospital and offpatent outpatient sectors has been proven to reduce medicine prices but it requires a robust framework and appropriate design with clear strategic goals in order to prevent shortages. These pricing and reimbursement policies are supplemented by the widespread use of Health Technology Assessment to inform decision-making, and by strategies to improve the uptake of generics, and also biosimilars. While European countries have been implementing a set of policy options, there is a lack of thorough impact assessments of several pricing and reimbursement policies on affordable access. Increased cooperation between authorities, experience sharing and improving transparency on price information, including the disclosure of confidential discounts, are opportunities to address current challenges.

Determinants of utilisation differences for cancer medicines in Belgium, Scotland and Sweden.

BACKGROUND: Little comparative evidence is available on utilisation of cancer medicines in different countries and its determinants. The aim of this study was to develop a statistical model to test the correlation between utilisation and possible determinants in selected European countries. METHODS: A sample of 31 medicines for cancer treatment that obtained EU-wide marketing authorisation between 2000 and 2012 was selected. Annual data on medicines' utilisation covering the in- and out-patient public sectors were obtained from national authorities between 2008 and 2013. Possible determinants of utilisation were extracted from HTA reports and complemented by contacts with key informants. A longitudinal mixed effect model was fitted to test possible determinants of medicines utilisation in Belgium, Scotland and Sweden. RESULTS: In the all-country model, the number of indications reimbursed positively correlated with increased consumption of medicines [one indication 2.6, 95% CI (1.8-3.6); two indications 2.4, 95% CI (1.4-4.3); three indications 4.9, 95% CI (2.2-10.9); all P < 0.01], years since EU-wide marketing authorisation [1.2, 95% CI (1.02-1.4); p < 0.05], price per DDD [0.9, 95% CI (0.998-0.999), P < 0.01], and Prescrire rating [0.5, 95% CI (0.3-0.9), P < 0.05] after adjusting for time and other covariates. CONCLUSIONS: In this study, the most important correlates of increased utilisation in a sample of cancer medicines introduced in the past 15 years were: medicines coverage and time since marketing authorisation. Prices had a negative effect on consumption in Belgium and Sweden. The positive impact of financial MEAs in Scotland suggests that the latter may remove the regressive effect of list prices on consumption.

Progress in increasing affordability of medicines for non-communicable diseases since the introduction of mandatory health insurance in the Republic of Moldova.

BACKGROUND: To assess progress in improving affordability of medicines since the introduction of mandatory health insurance in the Republic of Moldova. METHOD: Using data from national health insurance, we estimate affordability of partially reimbursed medicines for the treatment of non-communicable diseases, and analyse which factors contributed to changes in affordability. RESULTS: Affordability of subsidized medicines improved over time. In 2013, it took a median of 0.84 days of income for the lowest income quintile (ranging from 0 to 3.32 days) to purchase 1 month of treatment for cardiovascular conditions in comparison to 1.85 days in 2006. This improvement however was mainly driven by higher incomes rather than deeper coverage through the reimbursement list. CONCLUSION: If mandatory health insurance is to improve affordability of medicines for the Moldovan population, more funds need to be (re-)allocated to enable higher percentage coverage of essential medicines and efficiencies need to be generated within the health system. These should include a budget reallocation between secondary and primary care, strengthening primary care to manage chronic conditions and raise population awareness, implementation of evidence-based selection and quality use of medicines in both outpatient and inpatient settings, improving monitoring and regulation of prices and the supply chain; and alignment of national treatment guidelines and clinical practice with international best practices and evidence-based medicine.

Dealing with uncertainty and high prices of new medicines: a comparative analysis of the use of managed entry agreements in Belgium, England, the Netherlands and Sweden.

Managed entry agreements are a set of instruments used to reduce the impact of uncertainty and high prices when introducing new medicines. This study develops a conceptual framework for these agreements and tests it by exploring variations in their implementation in Belgium, England, the Netherlands and Sweden and over time as well as their governance structures. Using publicly available data from HTA agencies and survey data from the European Medicines Information Network, a database of agreements implemented between 2003 and 2012 was developed. A review of governance structures was also undertaken. In December 2012 there were 133 active MEAs for different medicine-indications across the four countries. These corresponded to 110 unique medicine-indications. Over time there has been a steady growth in the number of agreements implemented, with the highest number in the Netherlands in 2012. The number of new agreements introduced each year followed a different pattern. In Belgium and England it increased over time, while it decreased in the Netherlands and fluctuated in Sweden. Only 18 (16%) of the unique medicine-indication pairs identified were part of an agreement in two or more countries. England uses mainly discounts and free doses to influence prices. The Netherlands and Sweden have focused more on addressing uncertainties through coverage with evidence development and, in Sweden, on monitoring use and compliance with restrictions through registries. Belgium uses a combination of the above. Despite similar reasons being cited for managed entry agreements implementation, only in a minority of cases have countries implemented an agreement for the same medicine-indication; when they do, a different agreement type is often implemented. Differences in governance across countries partly explain such variations. However, more research is needed to understand whether e.g. risk-perception and/or notion of what constitutes a high price differ between these countries.

The economic burden of diabetes in India: a review of the literature.

BACKGROUND: Diabetes and its complications are a major cause of morbidity and mortality in India, and the prevalence of type 2 diabetes is on the rise. This calls for an assessment of the economic burden of the disease. OBJECTIVE: To conduct a critical review of the literature on cost of illness studies of diabetes and its complications in India. METHODS: A comprehensive literature review addressing the study objective was conducted. An extraction table and a scoring system to assess the quality of the studies reviewed were developed. RESULTS: A total of nineteen articles from different regions of India met the study inclusion criteria. The third party payer perspective was the most common study design (17 articles) while fewer articles (n =2) reported on costs from a health system or societal perspective. All the articles included direct costs and only a few (n =4) provided estimates for indirect costs based on income loss for patients and carers. Drug costs proved to be a significant cost component in several studies (n =12). While middle and high-income groups had higher expenditure in absolute terms, costs constituted a higher proportion of income for the poor. The economic burden was highest among urban groups. The overall quality of the studies is low due to a number of methodological weaknesses. The most frequent epidemiological approach employed was the prevalence-based one (n =18) while costs were mainly estimated using a bottom up approach (n =15). CONCLUSION: The body of literature on the costs of diabetes and its complications in India provides a fragmented picture that has mostly concentrated on the direct costs borne by individuals rather than the healthcare system. There is a need to develop a robust methodology to perform methodologically rigorous and transparent cost of illness studies to inform policy decisions.