Biosimilar Granulocyte Colony-Stimulating Factor Uptakes in the EU-5 Markets: A Descriptive Analysis

Background

Biosimilars are copies of biological reference medicines. Unlike generics (copies of chemical molecules), biologics are complex, expensive and complicated to produce. The knowledge of the factors affecting the competition following patent expiry for biologics remains limited.

Objectives

The aims of this study were to analyse the EU-5 Granulocyte-Colony Stimulating Factor (G-CSF) markets and to determine the factors affecting the G-CSF biosimilar uptakes, particularly that of biosimilar prices relative to originators.

Methods

Data on medicine volumes, values, and ex-manufacturer prices for all G-CSF categories were provided by IMS Health. Volumes were calculated in defined daily doses (DDD) and prices in Euros per DDD. In the EU-5 countries, there is 5 years of experience with biosimilar G-CSFs (2007–2011).

Results

Two G-CSF market profiles exist: (1) countries with a high retail market distribution, which are the largest G-CSF markets with low global G-CSF biosimilar uptakes (5.4 % in France and 8.5 % in Germany in 2011); and (2) countries with a dominant hospital channel, which are the smallest markets with higher G-CSF biosimilar uptakes (12.4 % in Spain and 20.4 % in the UK). The more the decisions are decentralized, the more their uptakes are high. The price difference between G-CSF biosimilars and their reference plays a marginal role at a global level (price differences of +13.3 % in the UK and ?20.4 % in France).

Conclusion

The competition with G-CSF biosimilars varies significantly between EU-5 countries, probably because of G-CSF distribution channel differences. Currently, this competition is not mainly based on prices, but on local political options to stimulate tendering between them and recently branded second- or third-generation products.     

Drug costs developments after patent expiry of enalapril, fluoxetine and ranitidine

Background

In order to increase price competition, government regulations focus on controlling drug costs. Drug costs after patent expiry are an area of particular interest because the substitution of branded medication with generics represents an opportunity for lowering drug costs. However, drug costs may not decrease after patent expiry, because of a lack of price competition and different national pricing systems.

Aim

The aim of this study was to investigate the trends in the use of generics after patent expiry for enalapril, fluoxetine and ranitidine and the subsequent changes, if any, in the costs of these medications.

Methods

A drug-utilisation study was performed using data from a large sample of Dutch pharmacies. Both volumes (measured as defined daily doses [DDD] per 1000 population) as well as drug costs (calculated per DDD) prior to and after patent expiry were calculated. Costs per DDD were compared using trend-line analysis. In addition, the relative market shares of the different trade channels (branded, parallel imported and generic) were compared before and after patent expiry.

Results

The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine.

Conclusions

Despite relatively high reimbursement prices for generics in the Netherlands, this example from the Dutch pharmaceutical market demonstrates the benefit of generic substitution for containing pharmaceutical costs, which contrasts with concerns raised by the Dutch government.     

Demand for outpatient healthcare

Background

Price, income and health status are likely to affect the demand for healthcare in developing countries, and their quantitative effects are unclear in the literature. Some studies report that prices are not important determinants, while others conclude that prices are important determinants of the demand for healthcare. Knowledge of the extent to which price, income and health status affect the demand for healthcare is crucial for the design of effective health policy in developing countries.

Objective

To examine the role of monetary and non-monetary price, income, and a variety of individual- and household-specific characteristics on the demand for healthcare in rural India.

Methods

Utilizing micro data from the 52nd round of India’s National Sample Survey, a variable choice set based on geographical location, price, income and the severity of illness was constructed to reflect the underlying true choice-generating process in rural India. Nested multinomial logit models were estimated and simulations with respect to prices and income were conducted to estimate price and income elasticities.

Results

Contrary to many earlier studies on the demand for healthcare in developing countries, it was found that prices and income were statistically significant determinants of the choice of healthcare provider by individuals in rural India. Demand for healthcare was found to be price and income inelastic, corroborating the findings from other developing countries. Distance to formal healthcare facilities negatively affected the demand for outpatient healthcare, an effect that was mitigated as access to transportation improved. Age, sex, healthy days, educational status of the household members and the number of children and adults living in the household also affected the choice of healthcare provider in rural India.

Conclusions

After controlling for a number of sociodemographic factors, it was found that prices, income and distance are statistically significant determinants of the provider chosen by individuals; nevertheless, the demand for healthcare is price and income inelastic in rural India.     

Target patient population: how does the regulatory and reimbursement view differ? Insights from the German IQWiG

Aim

This systematic review compares European HTA-agencies (Health Technology Assessment-agencies) for the evaluation of submitted reimbursement dossiers and the acceptance of the by regulatory authorities proven indications (slicing procedure).

Subjects and methods

A Europe-wide literature search and Internet survey from 2000 to 2012 was applied. For 10 market leaders and 4 drugs which were approved in 2009 or 2010, the approved indications were compared to the indications which were eligible for reimbursement in Germany, the United Kingdom (UK) and France.

Results

A slicing procedure could be found for 5 applications (drugs) in UK and France and for 6 applications (out of 14) in Germany. Three drugs out of 16 were referred to a fixed price group. The position of the regulatory authorities remained unchanged for eight compounds. As a final result, it is obvious that indications will be cut off (slicing), market authorizations modified and comparators changed. Scientific reasons are not published.

Conclusion

Slicing (cutting off indications and populations) is well known in European HTA bodies but is applied only in a minority of submissions, which has resulted in a decrease of the population and reimbursement rate. A harmonization process between HTA agencies and regulatory authorities should be initiated.     

Cost of illness and drivers of cost in atrial fibrillation in Sweden and Germany

Background

Atrial fibrillation (AF) is an important public health problem in European countries. AF is associated with increased morbidity and mortality, e.g. from heart failure and thromboembolic events. Little data have previously been presented regarding the costs of treatment in patients with AF.

Objective

To estimate total direct and indirect costs in patients with AF in Sweden and Germany, and to identify determinants of total costs.

Methods

A cross-sectional observational study was conducted through surveys to patients and their treating physician in primary care and in hospital outpatient cardiology departments in Sweden and Germany. A total of 922 patients with AF as diagnosed in clinical practice were enrolled and completed the study. Data were collected on medical history, treatment, medical and non-medical resource use, and employment status. Costs (year 2005 values) were calculated by multiplying resources used with prices specific for Sweden and Germany, respectively.

Results

Total annual costs per patient were €7241 in Sweden and €5586 in Germany. Slightly less than 70% of total costs were judged as being AF related in both countries. Costs of AF-related medication were about 2% of total costs in both countries. In a generalized regression model, costs were found to increase with age, but were lower in patients aged >65 years than in those aged ≤65 years, due to the absence of indirect costs in older patients. Costs were highest in patients with persistent AF and lowest in those with permanent AF. Co-morbidities with a significant influence on costs included coronary heart disease, cerebrovascular disease, heart failure and asthma.

Conclusions

Current costs in AF patients are driven by the consequences of AF, while costs for specific treatments for AF are low. The addition of new, effective and safe treatment options could potentially reduce overall healthcare costs in AF.     

Firm- and Drug-Specific Patterns of Generic Drug Payments by US Medicaid Programs: 1991–2008

Background

The entry of generic drugs into markets previously monopolized by patented, branded drugs often represents large potential savings for healthcare payers in the USA.

Objectives

Our objectives were to describe and explain the trends in drug reimbursement by public Medicaid programmes post-generic entry for as many drug markets and for as long a time period as possible.

Methods

The data were the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. Quarterly utilization and expenditure data from 1991 to 2008 were extracted for 83 drugs, produced by 229 firms, that experienced initial generic entry between 1992 and 2004. A relative ‘price’ for a specific drug, firm and quarter was constructed as Medicaid reimbursement per unit (e.g. tablet, capsule or vial) divided by average reimbursement per unit for the branded drug the year before entry. Fixed-effects models controlling for time-, firm- and drug-specific differences were estimated to explain reimbursement.

Results

Twelve quarters after generic entry, 18 % of drugs had average per-unit reimbursement less than 50 % of the original branded-drug reimbursement. For each additional firm manufacturing the drug, reimbursement per unit, relative to the pre-generic-entry branded-drug reimbursement, was estimated to fall by 17 (p < 0.01) and 3 (p < 0.01) percentage points for generic and branded-drug companies, respectively. Each additional quarter post-generic entry brought a 2 (p < 0.01) percentage point drop in relative reimbursement.

Conclusions

State Medicaid programmes generally have been able to obtain relief from high drug prices following patent expirations for many branded-drug medications by adjusting reimbursement following the expanded competition in the pharmaceutical market.     

Do Higher-Priced Generic Medicines Enjoy a Competitive Advantage Under Reference Pricing?

Background: In many countries with generic reference pricing, generic producers and distributors compete by means of undisclosed discounts offered to pharmacies in order to reduce acquisition costs and to induce them to dispense their generic to patients in preference over others. Objective: The objective of this article is to test the hypothesis that under prevailing reference pricing systems for generic medicines, those medicines sold at a higher consumer price may enjoy a competitive advantage. Method: Real transaction prices for 179 generic medicines acquired by pharmacies in Spain have been used to calculate the discount rate on acquisition versus reimbursed costs to pharmacies. Two empirical hypotheses are tested: the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical presentations for which there are more generic competitors; and, the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical forms for which the consumer price has declined less in relation to the consumer price of the brand drug before generic entry (higher-priced generic medicines). Results: An average discount rate of 39.3% on acquisition versus reimbursed costs to pharmacies has been observed. The magnitude of the discount positively depends on the number of competitors in the market. The higher the ratio of the consumer price of the generic to that of the brand drug prior to generic entry (i.e. the smaller the price reduction of the generic in relation to the brand drug), the larger the discount rate. Conclusions: Under reference pricing there is intense price competition among generic firms in the form of unusually high discounts to pharmacies on official ex-factory prices reimbursed to pharmacies. However, this effect is highly distorting because it favours those medicines with a higher relative price in relation to the brand price before generic entry.     

Palliative treatment of colorectal cancer in Germany: cost of care and quality of life

Introduction

To estimate the costs of palliative care for colorectal cancer (CRC) from the perspective of German statutory health insurance and to measure the patients’ quality of life (QoL) for a 2-year time period.

Methods

A prospective observational multicentre study was carried out to estimate the direct costs of care over a 2-year period. Case report forms, medical records, and claims data were all applied to document medical and resource usage data in real-world settings. QoL was measured by using the Short Form-12 Health Survey.

Results

In total 101 patients (mean age 67.09 ± 11.13 years, 68 % male) from 12 different settings were included. The mean costs per patient during the 1st and 2nd years were calculated to be 42,361€ and 32,023€, respectively. Highest mean costs were calculated for the second quarter, which reached an amount of 12,900€ (95 % CI: 11,127€–14,673€). Mean physical summary scores and mean mental summary scores were 41.8 and 49.7, respectively.

Discussion

This is the first study assessing the costs of palliative care and the quality of life of patients with CRC in real-world health-care delivery in Germany. It could be shown that CRC treatment represents an enormous economic burden to the German health-care system. Increased efforts in promoting effective and efficient treatment options, or performance-based medication reimbursement schemes, might be helpful in reducing the costs.     

What is required to evaluate the impact of pharmaceutical reference pricing?

Objective

To describe empirical studies evaluating the impact of reference pricing (RP) interventions in pharmaceutical markets in order to discuss the requirements for these evaluations.

Methods

Ten studies were included in this review. For each study, the nature of the intervention, the nature of the data available, the nature of the question to be answered and the requirements of the evaluation method were examined through a questionnaire. The most frequently used evaluation method was the conventional before-after estimator, and only three studies used the difference-in-differences method.

Results

Nine studies evaluated a therapeutic RP system and one evaluated a generic RP system. All of the papers reported how the reference price level was established, but only one study directly reported the updating frequency and criteria of the RP system. In four studies, details of simultaneous interventions were not reported. There is no paper providing evidence on overall social welfare impact. Four papers estimated the impact of intervention on the consumer price of drugs covered by the RP system. Only one provided information about the impact on the price of related drugs not covered by the system. Three studies included an outcome variable for the use of health services. The impact of RP intervention on the level of competition in the market for those medicines covered by the system was reported in only three of ten papers.

Discussion/conclusion

Despite the rigorous effort made to evaluate the impact of RP policies in some countries, several limitations may affect both their internal validity (the nature of the data available, statistical problems common to non-experimental data, etc.) and their external validity (heterogeneity in the nature of the intervention).     

Social/economic costs and health-related quality of life in patients with Prader-Willi syndrome in Europe

Objective

The aim of this study was to determine the economic burden from a societal perspective and health-related quality of life (HRQOL) of patients with Prader-Willi syndrome (PWS) in Europe.

Methods

We conducted a cross-sectional study of patients with PWS from Spain, Bulgaria, Hungary, Germany, Italy, the UK, Sweden and France. Data on demographic characteristics, healthcare resource utilisation, informal care, labour productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire.

Results

A total of 261 patients completed the questionnaire. The average annual costs ranged from € 3937 to € 67,484 between countries; the reference year for unit prices was 2012. Direct healthcare costs ranged from € 311 to € 18,760, direct non-healthcare costs ranged from € 1269 to € 44,035, and loss of labour productivity ranged from € 0 to € 2255. Costs were also shown to differ between children and adults. The mean EQ-5D index score for adult PWS patients ranged between 0.40 and 0.81 and the mean EQ-5D visual analogue scale score ranged between 51.25 and 90.00.

Conclusion

The main strengths of this study lie in our bottom-up approach to costing and in the evaluation of PWS patients from a broad societal perspective. This type of analysis is very scarce in the international literature on rare diseases in comparison with other illnesses. We conclude that PWS patients incur considerable societal costs and experience substantial deterioration in HRQOL.

     

Global spending on orphan drugs in France, Germany, the UK, Italy and Spain during 2007

Background

Orphan drugs are indicated for the treatment of rare diseases which, in the EU, are defined as those with a prevalence of <5 per 10 000 inhabitants. Characteristically, these diseases negatively affect health-related quality of life and may be life threatening. The EU has passed legislation to encourage pharmaceutical companies to invest in research programmes into rare diseases, with the aim of developing new, safe and effective orphan drugs.

Objectives

To describe the status of orphan drugs in five countries in the EU (France, Germany, the UK, Italy and Spain), estimate the mean annual cost per patient and indication of these orphan drugs, and determine the associated cost of these drugs in comparison with overall spending on drugs in each country (year 2007 values).

Methods

The analysis was limited solely to costs of orphan drugs with sales data available for 2007. The mean annual cost per patient was estimated using recommended regimens for maintenance dose and duration from the summary of product characteristics. Likewise, the ratio between annual costs per patient for treatment of each disease and its prevalence was calculated. Sales data were available for at least one of the countries studied for 38 of the 44 orphan drugs authorized by the European Medicines Agency. Only 21 products had data available for all five countries studied.

Results

Germany was the country with access to the largest number of orphan drugs (36), followed by the UK (34), Spain (28), France (27) and Italy (25). The mean annual cost per patient and indication of the 38 orphan drugs on the market ranged widely from €331 to €337 501. It appears that orphan drugs indicated to treat diseases with a prevalence of <2 per 10 000 inhabitants have higher annual per-patient costs than those indicated to treat diseases with a higher prevalence. The percentage of total drug spending accounted for by orphan drugs in 2007 was 1.7% in France, 2.1% in Germany, 1.0% in the UK, 1.5% in Italy and 2.0% in Spain, with an average overall percentage of 1.7% for these five countries.

Conclusions

In 2007, spending on orphan drugs in five European countries was acceptable in terms of the percentage of these countries’ overall drug expenditure. Mean annual costs per patient of orphan drugs varied widely, with costs being related to the prevalence of the disease for which the product is indicated.     

Reducing uncertainty in value-based pricing using evidence development agreements

Background

Value-based pricing (VBP), whereby prices are set according to the perceived benefits offered to the consumer at a time when costs and benefits are characterized by considerable uncertainty and are then reviewed ex post, is a much discussed topic in pharmaceutical reimbursement. It is usually combined with coverage with evidence development (CED), a tool in which manufacturers are granted temporary reimbursement but are required to collect and submit additional health economic data at review. Many countries, including the UK, are signalling shifts in this direction. Several countries, including Sweden, have already adopted this approach and offer good insight into the benefits and pitfalls in actual practice.

Objective

To describe VBP reimbursement decision making using CED in actual practice in Sweden.

Methods

Decision making by The Dental and Pharmaceutical Benefits Agency (TLV) in Sweden was reviewed using a case study of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in the treatment of advanced Parkinson’s disease (PD) with severe motor fluctuations.

Results

The manufacturer of Duodopa® applied for reimbursement in late 2003. While the proper economic data were not included in the submission, TLV granted reimbursement until early 2005 to provide time for the manufacturer to submit a formal economic evaluation. The re-submission with economic data was considered inadequate to judge cost effectiveness, so TLV granted an additional extension of reimbursement until August 2007, at which time conclusive data were expected. The manufacturer initiated a 3-year, prospective health economic study and a formal economic model. Data from a pre-planned interim analysis of the data were loaded into the model and the cost-effectiveness ratio was the basis of the next re-submission. TLV concluded that the data were suitable for making a definite decision and that the drug was not cost effective, deciding to discontinue reimbursement for any new patients (current patients were unaffected). The manufacturer continued to collect data and to improve the economic model and re-submitted in 2008. New data and the improved model resulted in reduced uncertainty and a lower cost-effectiveness ratio in the range of Swedish kronor (SEK)430 000 per QALY gained in the base-case analysis, ranging up to SEK900 000 in the most conservative sensitivity analysis, resulting in reimbursement being granted.

Discussion

The case of Duodopa® provides excellent insight into VBP reimbursement decision making in combination with CED and ex post review in actual practice. Publicly available decisions document the rigorous, time-consuming process (four iterations were required before a final decision could be reached). The data generated as part of the risk-sharing agreement proved correct the initial decision to grant limited coverage despite lack of economic data. Access was provided to 100 patients while evidence was generated.

Conclusions

Economic appraisal differs from clinical assessment, and decision makers benefit from analysis of naturalistic, actual practice data. Despite reviewing the initial trial-based, ‘piggy-back’ economic analysis, TLV was uncertain of the cost effectiveness in actual practice and deferred a final decision until observational data from the DAPHNE study became available. Second, acceptance of economic modelling and use of temporary reimbursement conditional on additional evidence development provide a mechanism for risk sharing between TLV and manufacturers, which enabled patient access to a drug with proven clinical benefit while necessary evidence to support claims of cost effectiveness could be generated.     

Antiretrovirals for low income countries: an analysis of the commercial viability of a highly competitive market

Background

The price of antiretroviral drugs (ARVs) in low income countries declined steadily in recent years. This raises concerns about the commercial viability of the market of ARVs in low income countries.

Methods

Using 2 costing scenarios, we modeled the production cost of the most commonly used ARVs in low income countries in 2010 and 2012, and assessed whether, at the median price paid by low income countries, their manufacturers would still make profits. By interviews we consulted 11 generic manufacturers on the current state of the ARV market, and on what would be required to ensure their continued commitment to supply ARVs to low income countries.

Results

Using the lowest prices for active pharmaceutical ingredients (API) quoted to WHO, and applying published assumptions about the production cost of ARVs, our baseline estimate was that Indian generic manufacturers would have made profits on only 1 out of 13 formulations of ARVs in both 2010 and 2012, and publicly owned manufacturers would have made profits on 5 and 3 out of 13 formulations in 2010 and 2012, respectively. We needed to assume a 20% and a 40% lower API cost for our model to predict that publicly owned and Indian manufacturers, respectively, would make profits on the sale of the majority of their ARVs. Between 2010 and 2012, we estimate that - across the ARV portfolio - the gross profit on sales of ARVs to low income countries decreased with between 6% and 7% of their sales price. Generic manufacturers consider that current prices are unsustainable. They suggested amendments to the tender procedures, simplified regulatory procedures, improved forecasting, and simplification of the ARV guidelines as critical improvements to maintain a viable ARV market.

Conclusions

While recent price decreases indicate that there is still space for price reduction, our estimate that gross profit margin on sales decreased by 6 to 7% between 2010 and 2012 lends credibility to assertions by generic manufacturers that the ARV market in low income countries is under considerable price pressure. This might create problems for the quality and/or the continued supply of ARVs to low income countries.     

Cost effectiveness of preventive screening programmes for type 2 diabetes mellitus in Germany

Background

As in several other industrialized countries, Germany’s statutory health insurance (SHI) is facing rising healthcare costs as well as the challenges caused by a double-aging society. The early detection and prevention of chronic diseases is considered a possible way to reduce the impact of these developments. However, controversy surrounds the costs and effects in terms of medical and financial outcomes of such programmes.

Objective

To examine the cost effectiveness of screening for type 2 diabetes mellitus (T2DM) from the perspective of the German SHI. The screening programme was compared with the current status quo (i.e. diagnosis of T2DM in routine clinical care or after the occurrence of the first clinical symptoms). Prevention strategies after diagnosis of pre-diabetes encompassed lifestyle and metformin interventions.

Methods

Effects of introducing screening for T2DM were assessed based on a Markov Monte Carlo microsimulation model. In contrast to a cohort model, this approach easily allows for detailed subgroup analysis accounting for the different characteristics of the general German population that would be targeted by the screening programme. Assessed endpoints included quality of life, lifetime costs, age at diabetes diagnosis, and incidence and age at occurrence of diabetes-related complications such as myocardial infarction, stroke, renal failure and blindness.

Results

Screening for T2DM was cost effective in the general population by all commonly applied standards (€562.54 per QALY for lifestyle intervention, €325.44 per QALY for prevention with metformin [year 2006 values]) and even cost saving in the subgroup diagnosed with pre-diabetes and treated preventively. Occurrence of diabetes-related adverse events was reduced significantly and life expectancy was increased compared with no screening.

Conclusions

These results suggest that early detection and disease prevention may be cost effective in the long term. However, additional political measures are necessary to support implementation, as the German SHI is currently lacking the necessary long-term incentives to support preventive screening programmes.     

Social/economic costs and health-related quality of life in patients with histiocytosis in Europe

Objective

The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with histiocytosis in Europe.

Methods

We conducted a cross-sectional study of patients with histiocytosis from France, Germany, Italy, Spain, Bulgaria, the UK, and Sweden. Data on demographic characteristics, health resource utilisation, informal care, loss of labour productivity and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire.

Results

A total of 134 patients (35 France, 32 Germany, 30 Italy, 24 Spain, 7 Bulgaria, 4 UK and 2 Sweden) completed the questionnaire. The average annual costs ranged from € 6832 to € 33,283 between countries, the year of reference being 2012. Estimated direct healthcare costs ranged from € 1698 to € 18,213; direct nonhealthcare costs ranged from € 2936 to € 17,622 and labour productivity losses ranged from € 1 to € 8855. The mean EQ-5D score for adult histiocytosis patients was estimated at between 0.32 and 0.85, and the mean EQ-5D visual analogue scale score was estimated at between 50.00 and 66.50.

Conclusion

The main strengths of this study lie in our bottom-up approach to costing and in the evaluation of histiocytosis patients from a broad perspective (societal costs). This type of analysis is very scarce in international literature for rare diseases in comparison with other illnesses. We conclude that histiocytosis patients incur considerable societal costs and experience substantial deterioration in HRQOL.

     

The impact of post-procedural complications on reimbursement,length of stay and mechanical ventilation among patients undergoing transcatheter aortic valve implantation in Germany

Background

The impact of various post-procedural complications after transcatheter aortic valve implantation (TAVI) on resource use and their consequences in the German reimbursement system has still not been properly quantified.

Methods

In a retrospective observational study, we use data from the German DRG statistic on patient characteristics and in-hospital outcomes of all isolated TAVI procedures in 2013 (N = 9147). The impact of post-procedural complications on reimbursement, length of stay and mechanical ventilation was analyzed using both unadjusted and risk-adjusted linear and logistic regression analyses.

Results

A total of 235 (2.57%) strokes, 583 (6.37%) bleeding events, 474 (5.18%) cases of acute kidney injury and 1428 (15.61%) pacemaker implantations were documented. The predicted reimbursement of an uncomplicated TAVI procedure was €33,272, and bleeding events were associated with highest additional reimbursement (€12,839, p < 0.001), extra length of stay (14.58 days, p < 0.001), and increased likelihood of mechanical ventilation for more than 48 h (OR 17.91, p < 0.001). A more moderate complication-related impact on resource use and reimbursement was found for acute kidney injury (additional reimbursement: €5963, p < 0.001; extra length of stay: 7.92 days, p < 0.001; ventilation >48 h: OR 6.93, p < 0.001) as well as for stroke (additional reimbursement: €4125, p < 0.001; extra length of stay: 4.68 days, p < 0.001; ventilation >48 h: OR 5.73, p < 0.001). Pacemaker implantations, in contrast, were associated with comparably small increases in reimbursement (€662, p = 0.006) and length of stay (3.54 days, p = 0.006) and no impaired likelihood of mechanical ventilation more than 48 h (OR 1.22, p = 0.156). Interestingly, these complication-related consequences remain mostly unchanged after baseline risk-adjustment.

Conclusions

Post procedural complications such as bleeding events, acute kidney injuries and strokes are associated with increased resource use and substantial amounts of additional reimbursement in Germany, which has important implications for decision making outside of the usual clinical sphere.

     

Orphan drugs policies: a suitable case for treatment

Context

Current orphan drug policies are unsatisfactory when viewed from almost all perspectives. Patients find that, although therapies are available for many rare conditions, access to care is sometimes restricted. Pharmaceutical manufacturers have responded to the incentives for research embodied in orphan drug legislation, only to find that funds are not made available to pay for therapies once developed. Those funding health care find that most orphan drugs do not justify funding based on standard value for money criteria, yet that they face political problems if they fail to provide funding for therapy.

Methods

A literature review was conducted in order to determine the precise nature of the problems and to suggest potential solutions.

Results

Current orphan drug policies are not fit for the purpose and initiatives need to be taken in the areas of (1) clarifying society’s views about the priority to be given to orphan drugs, (2) revising the arrangements for pricing and reimbursement of orphan drugs, (3) defining the priorities for research into rare diseases and (4) developing ‘joined up’ policies to deal with these issues.

Conclusions

Without changes in the current policies, pharmaceutical companies will eventually cease responding to the incentives to develop orphan drugs, because they will increasingly be uncertain whether the drugs, if developed, will be reimbursed.     

Cost effectiveness of implantable cardioverter-defibrillators for primary prevention in a belgian context

Background

Implantable cardioverter-defibrillator (ICD) therapy was traditionally applied in patients who survived a cardiac arrest or who experienced a symptomatic ventricular tachyarrhythmia. Its use in primary prevention (i.e. in patients who have yet to experience a serious arrhythmic event, but who are considered at high risk for sudden cardiac death) has become more common, and policy makers question whether ICD therapy should be reimbursed in these instances.

Objective

To assess the cost effectiveness of primary prevention ICD therapy versus conventional therapy from the perspective of the Belgian health insurance system.

Method

A lifetime 1-month cycle Markov model was constructed and populated with clinical and effectiveness data from the SCD-HeFT study and real-world Belgian cost data expressed in year 2005 values. Probabilistic modelling and sensitivity analyses were performed.

Results

ICD therapy results in 1.22 life-years gained (LYG) or 1.03 QALYs gained. The lifetime cost-effectiveness and cost-utility ratios were €59 989 (95% CI 35 873, 113 518) per LYG and €71 428 (95% CI 40 225, 134 623) per QALY gained, respectively. A cost-effectiveness ratio <€50 000 per QALY gained was obtained in 15.5% of 1000 simulations. Increasing the service life of the device from 5 to 7 years would improve the cost effectiveness to €57 229 (95% CI 32 568, 106 410) per QALY gained.

Conclusions

ICD therapy may not be judged cost effective for the primary prevention of death in patients with a SCD-HeFT profile in the Belgian context using current technology and patient selection. A combination of price reductions and increased service life of the device may alter this conclusion.     

Annual direct and indirect costs attributable to nocturia in Germany,Sweden, and the UK

Objective

Our aim was to estimate the prevalence-based cost of illness imposed by nocturia (≥2 nocturnal voids per night) in Germany, Sweden, and the UK in an average year.

Methods

Information obtained from a systematic review of published literature and clinicians was used to construct an algorithm depicting the management of nocturia in these three countries. This enabled an estimation of (1) annual levels of healthcare resource use, (2) annual cost of healthcare resource use, and (3) annual societal cost arising from presenteeism and absenteeism attributable to nocturia in each country.

Results

In an average year, there are an estimated 12.5, 1.2, and 8.6 million patients ≥20 years of age with nocturia in Germany, Sweden, and the UK, respectively. In an average year in each country, respectively, these patients were estimated to have 13.8, 1.4, and 10.0 million visits to a family practitioner or specialist, ~91,000, 9000, and 63,000 hospital admissions attributable to nocturia and 216,000, 19,000, and 130,000 subjects were estimated to incur a fracture resulting from nocturia. The annual direct cost of healthcare resource use attributable to managing nocturia was estimated to be approximately €2.32 billion in Germany, 5.11 billion kr (€0.54 billion) in Sweden, and £1.35 billion (€1.77 billion) in the UK. The annual indirect societal cost arising from both presenteeism and absenteeism was estimated to be approximately €20.76 billion in Germany and 19.65 billion kr (€2.10 billion) in Sweden. In addition, in the UK, the annual indirect cost due to absenteeism was an estimated £4.32 billion (€5.64 billion).

Conclusions

Nocturia appears to impose a substantial socioeconomic burden in all three countries. Clinical and economic benefits could accrue from an increased awareness of the impact that nocturia imposes on patients, health services, and society as a whole.