Economic and social cost of epilepsy in Poland: 5-year analysis.

INTRODUCTION: Epilepsy affects nearly 50 million people around the world. As a common and chronic disease generates a high cost burden for healthcare system and patients. AIM: We aimed to determine the most current direct and indirect costs of epilepsy in Poland from the social perspective for the years 2014-2018, to analyze the changes of expenditures over time, indicate trends and to determine key cost-drivers. MATERIAL AND METHODS: Direct and indirect costs using a top-down approach were estimated based on the public institutions' data for the ICD-10 codes G40 and G41. Direct costs included pharmacotherapy, hospitalizations, outpatient specialist care and rehabilitation. A human capital approach was used to estimate loss of productivity due to sick leaves and long-term inability to work. RESULTS: Annual total direct and indirect costs related to epilepsy accounted for EUR 410 million in 2014 and decreased in subsequent years to EUR 361 million in 2018. The indirect costs were dominant (76-83% of total costs) and in the majority related to the long-term absenteeism (87-92% of total indirect costs). In 2014-2018, patients with epilepsy generated EUR 341 million to EUR 282 million of indirect costs. Annual direct costs for patients with epilepsy were EUR 69 million in 2014 and increased to EUR 80 million in 2018. The biggest expenses were the costs of drugs (> 50%) and hospitalizations (~ 40%). CONCLUSIONS: Epilepsy is an expensive disorder in terms of consumption of resources and social costs. Decision-makers should take it under special consideration.

Indirect Costs of Rheumatoid Arthritis Depending on Type of Treatment-A Systematic Literature Review.

The economic burden of rheumatoid arthritis (RA) on society is high. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of therapy. Biological DMARDs are reported to prevent disability and improve quality of life, thus reducing indirect RA costs. We systematically reviewed studies on the relationship between RA and indirect costs comparing biological treatment with standard care. Studies, economic analyses, and systematic reviews published until October 2018 through a MEDLINE search were included. A total of 153 non-duplicate citations were identified, 92 (60%) were excluded as they did not meet pre-defined inclusion criteria. Sixty-one articles were included, 17 of them (28%) were reviews. After full-text review, 28 articles were included, 11 of them were reviews. Costs associated with productivity loss are substantial; in several cases, they may represent over 50% of the total. The most common method of estimation is the Human Capital method. However, certain heterogeneity is observed in the method of estimating, as well as in the resultant figures. Data from included trials indicate that biological therapy is associated with improved labor force participation despite an illness, in which the natural course of disease is defined by progressive work impairment. Use of biological DMARDs may lead to significant indirect cost benefits to society.

Policies for biosimilar uptake in Europe: An overview.

BACKGROUND: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. OBJECTIVES: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. METHODS: An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. RESULTS: In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. CONCLUSIONS: Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future.

BACKGROUND: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. OBJECTIVE: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. METHODS: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). RESULTS: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. CONCLUSION: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.

[The costs of asthma in Poland in 2012]. / Koszty astmy w Polsce w 2012 roku.

UNLABELLED: The costs incurred for treatment of patients with asthma are an important part of health care in the budget of each country. The aim of the study was to evaluate the direct and indirect costs of asthma in Poland. The study was based on questionnaires completed by professionals--allergists and pneumonologists of 13 centers in which is conducted the diagnosis and treatment of asthma. MATERIALS AND METHODS: The costs of asthma were determined from the payer perspective (NHF) and from the perspective of social security (ZUS). The study evaluated the direct costs of one patient with asthma in 2012, and indirect costs, as measured by human capital or friction costs. The study involved 128 people, including 84 women and 44 men, mean age 51.04+/11.41 years. RESULTS: Among the most frequent concomitant diseases: allergic rhinitis (93.75%), gastro-oesophageal reflux (38.54%), urticaria (16.67%), atopic dermatitis (21.88%) were present. The average monthly cost of drugs in 2012 amounted to PLN 251.32 (61.29 EURO, 2012 EURO 1 year=4.1 PLN), including patient,s copayment amounted to PLN 65.48 (EUR 15.97). The study showed that the direct cost per patient was 3240,88 PLN (790,46 EURO,). The Indirect cost, calculated using the human capital was for an average PLN 17,579.18 (4287.6 EURO) per patient, and using the method of friction costs was PLN 5974.06 (EUR 1,457.2). CONCLUSIONS: Estimating the cost of the disease often depends on the adopted method of analysis, but in the study group, a significant advantage of the indirect costs of the disease was observed. The effectiveness of the treatment of asthma in Poland should also be aimed at reducing the indirect costs of illness.

Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.

BACKGROUND: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. OBJECTIVE: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. METHODOLOGY: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. RESULTS: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. CONCLUSION: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

Altered tissue electrical properties in women with breast cancer--preliminary observations.

INTRODUCTION AND OBJECTIVES: In the United States, breast cancer (BC) is the most common non-skin cancer. In Poland, it is estimated that the number of new breast cancer cases affects about 13,500 women each year. There are many methods for nutritional status assessment. One of them is bioimpedance analysis (BIA). Direct bioimpedance measures (resistance, reactance, phase angle (PA)) determined by bioelectrical impedance analysis (BIA) detectf changes in tissue electrical properties. The study was conducted to investigate whether there are any tissue electrical differences in patients with breast cancer. MATERIALS AND METHODS: The direct bioimpedance measures determined by bioelectrical impedance analysis (BIA) were performed on 34 patients with BC and 34 healthy volunteers. The measurements were made with ImpediMed bioimpedance analysis SFB7 BioImp v1.55 (Pinkenba Qld 4008, Australia). RESULTS: Reactance and resistance at 50 kHz was found to be significantly greater in patients with BC than in the control group (53.59° ± 1.53 vs. 47.26° ± 1.25, respectively, p=0.0031; 603.24° ± 15.38 ohm vs. 515.87° ± 11.48 ohm, respectively, p=0.00004). CONCLUSION: Pre-surgical patients diagnosed with BC have altered tissue electrical properties. Further observations of a larger patient group would be valuable to calculate survival, validate the prognostic significance of PA, and monitor nutritional and therapeutic interventions in this patient population.

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs.

BACKGROUND: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. OBJECTIVE: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. METHODOLOGY: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. RESULTS: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. CONCLUSION: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

'HTA for Crisis': sharing experiences during the 7th EBHC Symposium.

The Central and Eastern European Society of Technology Assessment in Health Care was founded in Krakow, Poland in 2003. On October 8th and 9th, the 7th symposium took place titled 'HTA for Crisis'. This meeting was attended by over 250 decision makers, evidence-based specialists, healthcare managers, commercial company personnel and experts. The symposium was principally divided into four main themes: insurance in times of crisis; importance of pricing of health services in times of crisis; managing welfare benefits in times of crisis and Health Technology Assessment in crisis-laden countries. The symposium finished by debating potential ways forward for healthcare systems in times of crisis.

[Health economics of inhibitor bypassing agents in haemophilia A-activated prothrombin complex concentrate (aPCC) and recombinant activated factor VIIa (rFVIIa)]. / Ekonomika terapii lekami omijajacymi w hemofilii A powiklanej inhibitorem--aktywowane koncentraty zespolu protrombiny (aPCC) a rekombinowany aktywowany czynnik VII (rfVIIa).

UNLABELLED: Haemophilia A is a sex-linked recessive genetic disorder associated with haemorrhagic diathesis due to reduced plasma activity of coagulation factor VIII, i.e., below 50% of the normal value (< 0.5 IU/ ml). The treatment of haemophilia A-Inhibitor patients is bidirectional. Major issues with treatment are inhibitor eradication and control of haemorrhage. The aim of the analysis was to evaluate costs and effects of the use of aPCC and rFVIIa in haemophilia A-inhibitor patients in on-demand treatment, perioperative prophylaxis and long-term prophylaxis. MATERIALS AND METHODS: The cost analysis was performed from the payer's perspective for all treatment schemes. Dosage and duration of treatment were obtained from a systematic review of clinical trials, Summary of Product Characteristics and clinical practice guidelines. Analysis was conducted in accordance with the AHTAPol (Agency for Health Technology Assessment in Poland) guidelines. RESULTS: The use of aPCC in on-demand treatment of children and adults during one day or one episode of bleeding (irrespective of the intensity of bleeding: from mild to severe) reduced the payer's expenditures in comparison to the use of rFVIIa. The use of aPCC in perioperative prophylaxis of children and adults during minor and major surgical interventions and implantations of central venous access devices was associated with savings for the payer in comparison to the use of rFVIIa, irrespectively of dosage of both drugs. Break even point analysis showed that the use of aPCC in long-term prophylaxis may be less expensive than the use of aPCC in on-demand treatment if bleedings last for 2.5 days or more. Sensitivity analysis showed that assumptions concerning body weight of patients significantly influence expenses of the public payer. However, the use of aPCC was associated with lower costs than the use of rFVIIa, irrespectively of the patients' body weight. CONCLUSIONS: In order to demonstrate the actual size of expenditures on treatment of haemophilia A-Inhibitor patients, collection of data concerning real clinical practice in Poland is required.

Review articles, systematic reviews and meta-analyses: which can be trusted?

A large number of scientific articles published every year requires from practicing physicians the ability to choose among them and to use secondary studies, such as guidelines, review articles, meta-analyses and systematic reviews. The aim of this article was to discuss basic differences between meta-analyses and systematic reviews. Meta-analysis is a mathematical method of pooling the results of several or more studies; a meta-analysis may be based on a systematic review, but this is not always the case. A systematic review is a multistage process aimed at the identification of all reliable evidence regarding a specific clinical problem. Systematic reviews make it possible to objectively address particular issues according to the current state of clinical knowledge and therefore constitute a reliable basis for clinical decision-making. An appropriate systematic review should include: 1) a defined clinical question, 2) pre-specified inclusion and exclusion criteria, 3) complex search for medical evidence sources according to a search strategy, 4) critical evaluation of reliability of identified clinical trials, 5) qualitative or quantitative data synthesis and 6) evidence based conclusions. These simple criteria, formulated by Cook et al. more than 10 years ago, allow to differentiate between a reliable systematic review and a "quasi-systematic" one, as well as between a reliable meta-analysis based on a systematic review and a potentially misleading meta-analysis without a systematic review.

Generic olanzapine: health authority opportunity or nightmare?

Pressures to contain pharmaceutical expenditure have led to increased prescribing and dispensing of generic drugs in addition to low prices for generics. Atypical antipsychotics are prescribed for schizophrenia leading to resource pressures with their higher acquisition costs than typical antipsychotics. Drug costs can be reduced once multiple sources are available. However, this must be balanced against possible efficacy, safety and compliance concerns given the high cost of relapses for patients with schizophrenia. Generic clozapine has been launched. There was an increase in relapse rates with early formulations in the USA. However, this has not been the case with more recent formulations. Despite this, there could be patient and physician concerns when additional generic atypicals, such as olanzapine are available, reducing potential savings. A retrospective survey of patients prescribed Zyprexa((R)), generic olanzapine or both, over an extensive period was undertaken in Poland to help address these concerns given the difficulties with conducting randomized clinical trials with generics in complex situations. The survey showed similar effective doses of olanzapine in all groups. Relapse rates were similar in patients before and after switching to generic olanzapine, and no untoward side effects were seen in any patient prescribed generic olanzapine. Consequently, generic olanzapine should be welcomed with savings redirected to improving compliance or funding new premium priced drugs that can reduce relapses in refractory patients. This should give reassurance to health authorities to continue their reforms where pertinent to optimize resources by increasing availability of generics.