Sickness Funds Research Articles

PHP222 - Advanced Therapy Medicinal Products (Atmps) In Europe 8 Years On: What Is The Path To Market Access So Far?

To examine the current EU5 market access landscape for ATMPs. Assessed the regulatory path, HTA assessments and funding mechanisms for ATMPs with EMA approval as of May 2016. Eight ATMPs are EMA approved as of May 2016. Of these, one was suspended (matrix-induced autologous chondrocyte implantation) and another withdrawn (sipuleucel-T). Germany: All ATMPs need to be authorised by the Paul Ehrlich Institute (PEI). Furthermore, the GBA could classify an ATMP as a procedure rather than a drug thereby bypassing AMNOG (e.g. autologous human corneal epithelial cells). The two ATMPs assessed under AMNOG (alipogene tiparvovec and sipuleucel-T), were both assigned “non-quantifiable additional benefit”. Talimogene laherparepvec is currently undergoing assessment with a final decision expected in mid-Dec 2016. Currently, alipogene tiparvovec is a hospital use only drug with reimbursement negotiated by the hospital and sickness funds on a case by case basis. In France, HAS assessed only two ATMPs (autologous cultured chondrocytes and alipogene tiparvovec) with reimbursement not being granted for either. Autologous cultured chondrocytes is the only ATMP that hospitals in Italy can currently import while it is available for hospital use only in Spain. Preliminary UK recommendation for autologous cultured chondrocytes and matrix-induced autologous chondrocyte implantation was for use in research only. Draft guidance on talimogene laherparepvec issued by NICE in March 2016 did not recommend use in melanoma. No other ATMP is currently routinely commissioned. All EMA approved ATMPs to date have faced EU5 market access challenges, with Germany being particularly complex. HTA assessments have been unfavourable largely due to the uncertainty with available data and – possibly – costs. The ATMP landscape is beginning to form and evolve. It will need to solidify for AMTPs to be viable for the companies seeking to market them and the patients who will benefit.

PRS17 - Burden of Non-Tuberculous Mycobacterial Pulmonary Disease In Germany Based on Sick Fund Data Analysis

PRS17 - Burden of Non-Tuberculous Mycobacterial Pulmonary Disease In Germany Based on Sick Fund Data Analysis

Comparing routine administrative data with registry data for assessing quality of hospital care in patients with myocardial infarction using deterministic record linkage

BackgroundAssessment of quality of care in patients with myocardial infarction (MI) should be based on data that effectively enable determination of quality. With the need to simplify measurement techniques, the question arises whether routine data can be used for this purpose. We therefore compared data from a German sickness fund (AOK) with data from the Berlin Myocardial Infarction Registry (BMIR).MethodsWe included patients hospitalised for treatment of MI in Berlin from 2009-2011. We matched 2305 patients from AOK and BMIR by using deterministic record linkage with indirect identifiers. For matched patients we compared the frequency in documentation between AOK and BMIR for quality assurance variables and calculated the kappa coefficient (KC) as a measure of agreement.ResultsThere was almost perfect agreement in documentation between AOK and BMIR data for matched patients for: catheter laboratory (KC: 0.874), ST elevation MI (KC: 0.826), diabetes (KC: 0.818), percutaneous coronary intervention (KC: 0.860) and hospital mortality (KC: 0.952). The remaining variables compared showed moderate or less than moderate agreement (KC < 0.6), and were grouped in Category II with less frequent documentation in AOK for risk factors and aspects of patients’ history; in Category III with more frequent documentation in AOK for comorbidities; and in Category IV for medication at and after hospital discharge.ConclusionsRoutine data are primarily collected and defined for reimbursement purposes. Quality assurance represents merely a secondary use. This explains why only a limited number of variables showed almost perfect agreement in documentation between AOK and BMIR. If routine data are to be used for quality assessment, they must be constantly monitored and further developed for this new application. Furthermore, routine data should be complemented with registry data by well-established methods of record linkage to realistically reflect the situation – also for those quality-associated variables not collected in routine data.

Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark

ObjectiveTo analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. MethodsInsurance claims data on anti-diabetic drug prescriptions in primary care in Germany and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug prescriptions register and one large statutory sickness fund in Germany. ResultsTZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had a significant impact on utilisation, reducing the number of DDD per 1000 insurees per day by −0.0105 in Denmark and −0.0312 in Germany (p-values<0.05). For pioglitazone, neither of the drug warnings had a significant effect on utilisation. ConclusionThe impact of EMA drug warnings differed across countries and might be mediated by information released through national reimbursement bodies and physician associations. Increasing complexity of new drugs and modified approval procedures require a strengthening of information exchange between drug regulation bodies and physicians to ensure patient safety.

Measuring customer preferences in the German statutory health insurance.

This paper investigates consumer preferences in the German statutory health insurance market. It further aims to test whether preferences differ by age and health status. Evidence is provided by a discrete choice experiment conducted in 2014 using the six most important attributes in sickness fund competition and ten random generated choice sets per participant. Price is found to be the most important attribute followed by additional benefits, managed care programmes, and distance to nearest branch. Other positive attributes of sickness funds are found to balance out a higher price, which would allow a sickness fund to position itself as high quality. However, significant differences in preferences were found between age and health status group. In particular, compromised health is associated with higher preference for illness-related additional benefits and less distance to the lowest branch, but lower preference for a lower price. Based on these differences, a distinct sickness fund offer could be constructed that would allow passive risk selection.

German cooperation-network 'equity in health'-health promotion in settings.

In 2003, the German Federal Centre for Health Education (BZgA) initiated the national Cooperation-Network (CN) 'Equity in Health'. The CN is constantly increasing in size and scope, supporting setting approaches aimed at reducing health inequalities. A detailed description of the CN has not yet been available in English. The CN comprises a total of 66 institutional cooperation partners. Information concerning the structure and activities can be found on a special website. Coordination Centres (CC) have been established in the 16 federal states, for the coordination of all state-specific activities. Funding for the CN and CC is provided by the BZgA, the German statutory sickness funds and by the state-specific ministries of health. These partners also support the continuous quality improvement, which is based on the good-practice criteria developed by the Advisory Committee of the CN. In 2011, the 'Municipal Partner Process (MPP)' has been launched, specifically supporting local partners and integrated life-course approaches focussing on children. In 2015, the focus has been widened to include all age-groups. In July 2015, a new national health law concerning health promotion and prevention has been ratified by the federal Parliament, with a focus on reducing health inequalities. Currently, the details of its implementation are discussed on a nationwide basis. The CN has long advocated for such a law, and today the CN is a well-accepted partner providing concepts, methods and a strong and long-standing network. The article closes with future challenges faced by the CN.

A Comparative Analysis of the Health System Financing in Poland and Selected Countries

IntroductionHealthcare is a very important and, at the same time, difficult element of each state's policy. For many countries, the issue of financing the healthcare system is a delicate matter and one of the basic economic and social issues. Nevertheless, decisions concerning the sources and principles of healthcare financing influence the quality of the entire system (Hady and Lesniowska, 2013, p. 1).The development of medical technologies, as well as the introduction of new generations of drugs, cause that currently there are opportunities of effectively treating cases which until recently were beyond doctors' reach. Another problem which is connected with the functioning of systems of health care is ageing population observed practically in all developed countries as well as new challenges connected with it. These circumstances cause that maintaining domestic systems of health services is generating higher and higher costs (Kujawska, 2015, p. 113).Every health system is aimed at satisfying the specific health needs of the population.Health systems can be described using models of service delivery, financing, and economic policy. Much of the literature depicts health delivery systems in terms of a national health system, social insurance or private insurance model. Within each model, there are various forms of financing including general taxation, specific taxation, and private financing (Kulesher, Forrestal, 2014, p. 127).The cost of delivering health care imposes a large, and often growing, burden in nearly all countries. Increasingly, health care decision-makers are being asked to improve performance by containing expenditures while maintaining steady improvements in access and quality (Anell and Willis, 2000, p. 770).This article presents a comparative analysis of the health system financing in Poland and selected countries: The Netherlands, Germany, United Kingdom, USA. Analysis will cover the period from 2011 to 2013. Data deriving from the OECD Health Data database were used.1.Characteristics of Foreign Health SystemsTraditional models of health systems are treated as benchmarks describing the desired and ideal shape of the system. They represent a collection of potentially possible solutions from which one can choose those best suited in specific conditions. There are three health systems defined in literature:- model of national health service, also known as the Beveridge model,- social insurance system, the so-called Bismarck model,- the system of non-regulated insurance market, the so-called residual model.Britain's National Helath Service (NHS) came into existence on 5 July 1948. It was the first health system in any western society to offer free medical care to the entire population. It was, furthermore, the first comprehensive system to be based not on the insurance principle, with entitlement following contributions, but on the national provision of services available to everyone (Fincham, 2011, p. 27).The Bismarck model of health care structure, financing, and delivery is named in honor of Prussian Chancellor Otto von Bismarck, who unified Germany in the 19th century the system incorporates sickness funds which are jointly financed by employers and employees via payroll deductions. In this instance, the Bismarc model represent what is available to employees via employer-sponsored health insurance coverage. The major difference in the German system is that the sickness funds companies are not profit-generating entities. These sickness fund companies do not make o profit (Fincham, 2011, p. 29).A model of private health insurance in which access to benefits is conditioned on having a private insurance policy. Monies allotted to financing the benefits derive from private insurance premiums, health service manufacturers are private entities (Lyszczarz, 2014, p. 92).The European Union Member States and the United States built their health systems on the basis of these models. …

Benefit assessment in Germany: implications for price discounts.

BackgroundThe AMNOG regulation, introduced in 2011 in Germany, changed the game for new drugs. Now, the industry is required to submit a dossier to the GBA (the central decision body in the German sickness fund system) to show additional benefit. After granting the magnitude of the additional benefit by the GBA, the manufacturer is entitled to negotiate the reimbursement price with the GKV-SV (National Association of Statutory Health Insurance Funds). The reimbursement price is defined as a discount on the drug price at launch. As the price or discount negotiations between the manufacturers and the GKV-SV takes place behind closed doors, the factors influencing the results of the negotiation are not known.ObjectivesThe aim of this evaluation is to identify factors influencing the results of the AMNOG price negotiation process.MethodsThe analysis was based on a dataset containing detailed information on all assessments until the end of 2015. A descriptive analysis was followed by an econometric analysis of various potential factors (benefit rating, size of target population, deviating from appropriate comparative therapy and incorporation of HRQoL-data).ResultsUntil December 2015, manufacturers and the GKV-SV finalized 96 negotiations in 193 therapeutic areas, based on assessment conducted by the GBA. The GBA has granted an additional benefit to 100/193 drug innovations. Negotiated discount was significantly higher for those drugs without additional benefit (p = 0.030) and non-orphan drugs (p = 0.015). Smaller population size, no deviation from recommended appropriate comparative therapy and the incorporation of HRQoL-data were associated with a lower discount on the price at launch. However, neither a uni- nor the multivariate linear regression showed enough power to predict the final discount.ConclusionsAlthough the AMNOG regulation implemented binding and strict rules for the benefit assessment itself, the outcome of the discount negotiations are still unpredictable. Obviously, negotiation tactics, the current political situation and soft factors seem to play a more influential role for the outcome of the negotiations than the five hard and known factors analyzed in this study. Further research is needed to evaluate additional factors.

Cost-Utility Analysis of Telemonitoring Interventions for Patients with Chronic Obstructive Pulmonary Disease (COPD) in Germany.

Chronic obstructive pulmonary disease (COPD) poses major challenges for health care systems. Previous studies suggest that telemonitoring could be effective in preventing hospitalisations and hence reduce costs. The aim was to evaluate whether telemonitoring interventions for COPD are cost-effective from the perspective of German statutory sickness funds. A cost-utility analysis was conducted using a combination of a Markov model and a decision tree. Telemonitoring as add-on to standard treatment was compared with standard treatment alone. The model consisted of four transition stages to account for COPD severity, and a terminal stage for death. Within each cycle, the frequency of exacerbations as well as outcomes for 2015 costs and quality adjusted life years (QALYs) for each stage were calculated. Values for input parameters were taken from the literature. Deterministic and probabilistic sensitivity analyses were conducted. In the base case, telemonitoring led to an increase in incremental costs (€866 per patient) but also in incremental QALYs (0.05 per patient). The incremental cost-effectiveness ratio (ICER) was thus €17,410 per QALY gained. A deterministic sensitivity analysis showed that hospitalisation rate and costs for telemonitoring equipment greatly affected results. The probabilistic ICER averaged €34,432 per QALY (95% confidence interval 12,161-56,703). We provide evidence that telemonitoring may be cost-effective in Germany from a payer's point of view. This holds even after deterministic and probabilistic sensitivity analyses.

Follow Your Heart: Survival Chances and Costs after Heart Attacks-An Instrumental Variable Approach.

To determine the effect of heart attack patients' access to intensive treatment on mortality and costs. Administrative data of 4,920 patients with acute myocardial infarction from the Austrian Social Security Database and the Upper Austrian Sickness Fund for the period 2002-2011. As treatment intensity in a hospital largely depends on whether it has a catheterization laboratory, we explore the effects of patients' initial admission to such specialized percutaneous coronary intervention (PCI) hospitals. To account for the nonrandom selection of patients into hospitals, we exploit individuals' place of residence as a source of exogenous variation in an instrumental variable framework. We find that the initial admission to PCI hospitals increases patients' survival chances substantially. The effect on 3-year mortality is -9.5 percentage points. Subgroup analysis shows the strongest effects in relative terms for patients below the age of 65. We do not find significant effects on long-term inpatient costs and only marginal increases in outpatient costs. Our findings suggest that place of residence affects the access of patients to invasive heart attack treatment and therefore their chance of survival. We conclude that that providing more patients immediate access to PCI hospitals should be beneficial.

Quantifying low-value services by using routine data from Austrian primary care.

Open debates about the reduction of low-value services, unnecessary diagnostic tests and ineffective therapeutic procedures and initiatives like "Choosing Wisely "in the USA and Canada are still absent in Austria. The objectives of this study are: (i) to establish a list of ineffective or low-value services possibly provided in Austrian primary care, (ii) to explore how many of these services are quantifiable using routine data and (iii) to estimate the number of affected beneficiaries and avoidable costs arising from the provision of these services. In May 2014, we identified low-value care services relevant for primary care in Austria. For our analysis we used routine data sets from the Austrian health insurance. All analysis refer to the insured population of the Lower Austrian Sickness Fund (n = 1 168 433) in the year 2013. (i) We found 453 low-value services possibly offered in Austrian primary care. (ii) Only 34 (7.5%) services were quantifiable using routine data. (iii) In the year 2013, these 34 services were provided to at least 246 131 beneficiaries and the estimated avoidable costs arising were at least 11.38 million Euros. This accounts for 1.2% of overall spending of the Lower Austrian Sickness Fund for drugs and services provided by primary care doctors in the year 2013. The absence of a homogeneous, transparent and accessible coding system for diagnosis in Austrian primary care restrained our assessment. However, our study findings illustrate the potential utility and limitations of using claims-based measures to identify low-value care.

(210) Prescribed pain medication before and after total joint replacement of hip or knee in Germany – a sickness fund analysis

(210) Prescribed pain medication before and after total joint replacement of hip or knee in Germany – a sickness fund analysis

Forgone care among chronically ill patients in Germany—Results from a cross-sectional survey with 15,565 individuals

The decision not to seek health care although one feels that care is needed (forgone care), is influenced by various factors. Within the study “Responsiveness in ambulatory care” 15,565 chronically ill (coronary heart disease and/or type 2 diabetes) patients in Germany were surveyed in 2013. The survey included questions on forgone care, perceived discrimination when seeking care, net-income, subjective health status and subjective socioeconomic status (subSES). Survey data were linked on patient-level with administrative claims data by a German sickness fund. We applied multivariate binomial logistic regression analyses to assess the association between age, sex, comorbidities, living area, subjective health status, subSES, experienced discrimination, net-equivalent income and reported forgone care. The majority in the sample are men (71.4%), the average age is 69.4 (SD: 10.2) years and 14.1% reported forgone care. In the multivariate model, we find that younger age, female gender, perceived discrimination, depression, and a poor subjective health status increase the odds of reporting forgone care. Overall, our results suggest that a negative experience with the health care system, i.e. perceived discrimination/unfair treatment, are strong predictors of forgone care among the chronically ill.

Current trends in the management of glioblastoma in a French University Hospital and associated direct costs.

Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma (GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5-ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours.

Depression-related treatment and costs in Germany: Do they change with comorbidity? A claims data analysis

BackgroundExisting diverse bottom-up estimations of direct costs associated with depression in Germany motivated a detailed patient-level analysis of depression-related treatment (DRT), -costs (DRC) and Comorbidity. MethodsA large sickness fund’s claims data was used to retrospectively identify patients aged 18–65 years with new-onset depression treatment between January 1st and February 15th 2010, and follow them until December 31st 2010, describe DRT, estimate associated DRC, and predict DRC with a generalised linear model. ResultsA total of 18,139 patients were analysed. Mean direct DRC were €783. Predictors of DRC regarding psychiatric comorbidities were: “Delusion, psychotic disorders and personality disorders” (DRC-ratio 1.72), “Alcohol/drug addiction” (1.82), “abuse of alcohol/drugs” (1.57). Predictors of DRC regarding medical comorbidities were: “Rheumatoid arthritis” (0.77), “atherosclerosis” (0.65), “pregnancy” (0.66), and “Osteoarthritis” (1.87). Of all patients, 60.8% received their most intense/specialised DRT from a general practitioner, a medical specialist (23.7%), a psychotherapist (8.0%), a medical specialist and psychotherapist (2.9%), or in hospital (4.6%). Serious psychiatric comorbidity nearly tripled depression-related hospitalisation rates. LimitationsSeasonal affective disorder and missing psychiatric outpatient clinic data must be considered. ConclusionsEstimated DRC are significantly below the assessment of the German national guideline. Differing definitions of observation period and cost attribution might explain differing German DRC results. Signs of hospital psychiatric comorbidity bias indicate overestimation of hospital DRC. Identified associations of DRC with certain medical diseases in older adults warrant further research. Up to one quarter of patients with severe depression diagnosis might lack specialist treatment.

Cash Benefits for Sickness and Maternity in Selected States of the European Union and Austerity Measures

The paper introduces the results of the research focused on cash benefits for sickness and maternity in selected Member States of the European Union during the financial crisis and concerns the economic and demographic data. The aim was to determine whether and to what extent the expected austerity measures touched the monitored social area. For the paper we studied the situation from 2009 to 2014, especially in relation to employees and employers. Regarding the methods of the research, the authors gathered the data obtained from the relevant legal, statistical and other printed documents as well as the documents from the website of the European Union, relevant national ministries, social insurance companies, sickness funds and similar institutions. They undertook a legal, economic and demographic data analysis and consequently its comparisons as well as the final evaluation.

Costs and treatment patterns of incident ADHD patients - a comparative analysis before and after the initial diagnosis.

Background and objectivesThe costs and treatment patterns of attention deficit hyperactivity disorder (ADHD) are subjects of health services research in Germany and worldwide. Previous publications focused mainly on prevalent patients and thus research gaps were identified regarding costs and treatment patterns of incident patients before and after the first diagnosis.MethodsAnalyses were conducted using claims data obtained from a large German sickness fund (Techniker Krankenkasse). Inclusion criteria consisted of patients with at least two secured outpatient or one inpatient ADHD diagnosis in 2007. Incidence was ensured by defining a baseline period without ADHD-diagnosis in 2006. In addition to diseaserelated cost analyses compared to a control group including age group comparisons, comorbidities, the proportion of multimodal treatment and medication treatment patterns were described.ResultsIn total, 9083 newly diagnosed ADHD patients were identified (73 % male; mean age: 12.9 years (SD: 10.3)). The mean total cost of ADHD patients during the year after the first diagnosis exceeded the mean total cost of the year before by 976 € (Differencein-Difference-estimator: 1006 €). Our analyses have shown that 10 % of ADHD patients have been treated with multimodal therapy. In addition, 11 % of the investigated ADHD population have received methylphenidate or atomoxetine preceeding the date of diagnosis in the relevant observation period.DiscussionThis study provides important insights into the costs as well as the treatment patterns of incident ADHD patients. ADHD-related costs and medications can be identified prior to the date of the first ADHD diagnosis. Although, multimodal therapy is presented as an optimal treatment option by many international guidelines and experts, its proportion for treatment is low (10 %).Further research is necessary to identify reasons for the low proportion of multimodal therapy and (cost-)effectiveness has to be evaluated in comparison to other treatment options. In addition, ADHD-related costs could be identified before the first diagnosis is documented. The reasons for medication prior to diagnosis have to be further investigated.

Community-acquired pneumonia (CAP) hospitalizations and deaths: is there a role for quality improvement through inter-hospital comparisons?

To assess between-hospital variations in standardized in-hospital mortality ratios of community-acquired pneumonia (CAP), and identify possible leads for quality improvement. We used an administrative database to estimate standardized in-hospital mortality ratios for 111 Belgian hospitals, by carrying out a set of hierarchical logistic regression models, intended to disentangle therapeutic attitudes and biases. To facilitate the detection of false-negative/positive results, we added an inconclusive zone to the funnel plots, derived from the results of the study. Data quality was validated by comparison with (i) alternative data from the largest Belgian Sickness Fund, (ii) published German hospital data and (iii) the results of an on-site audit. All Belgian hospital discharge records from 2004 to 2007. A total of 111 776 adult patients were admitted for CAP. Risk-adjusted standardized in-hospital mortality ratios. Out of the 111 hospitals, we identified five and six outlying hospitals, with standardized mortality ratios of CAP consistently on the extremes of the distribution, as providing possibly better or worse care, respectively, and 18 other hospitals as having possible quality weaknesses/strengths. At the individuals' level of the analysis, adjusted odds ratios showed the paramount importance of old age, comorbidity and mechanical ventilation. The data compared well with the different validation sources. Despite the limitations inherent to administrative data, it seemed possible to establish inter-hospital differences in standardized in-hospital mortality ratios of CAP and to identify leads for quality improvement. Monitoring is needed to assess progress in quality.

The diffusion of generics after patent expiry in Germany

To identify the influences on the diffusion of generics after patent expiry, we analyzed 65 generic entries using prescription data of a large German sickness fund between 2007 and 2012 in a sales model. According to theory, several elements are responsible for technology diffusion: (1) time reflecting the rate of adaption within the social system, (2) communication channels, and (3) the degree of incremental innovation, e.g., the modifications of existing active ingredient's strength. We investigated diffusion in two ways: (1) generic market share (percentage of generic prescriptions of all prescriptions of a substance) and, (2) generic sales quantity (number of units sold) over time. We specified mixed regression models. Generic diffusion takes considerable time. An average generic market share of about 75% was achieved not until 48months. There was a positive effect of time since generic entry on generic market share (p<0.001) and sales (p<0.001). Variables describing the communication channels and the degree of innovation influenced generic market share (mostly p<0.001), but not generic sales quantity. Market structure, e.g., the number of generic manufacturers (p<0.001) and prices influenced both generic market share and sales. Imperfections in generic uptake through informational cascades seem to be largely present. Third-party payers could enhance means to promote generic diffusion to amplify savings through generic entry.

A population-based analysis of the risk of drug interaction between clarithromycin and statins for hospitalisation or death.

BackgroundClarithromycin, known as a potent inhibitor of the cytochrome P450 isoenzyme CYP3A, may increase the plasma concentration of statins metabolized by this pathway; therefore, increase the risk of interaction with statins in reference to pharmacokinetic studies. This study aimed to characterize whether the concomitant use of a statin with clarithromycin is associated with serious outcomes among adult persons.MethodsHealth claims data of adult persons in the Regional Sickness Fund of Burgenland, Austria, who filled a prescription for clarithromycin between July 1, 2009 and June 30, 2012 were reviewed retrospectively. We assumed that the risk of hospitalisation increases acutely with the indication for taking an antibiotic, whereas statin use can be considered a chronic exposure with a low constant effect on hospitalisation. When defining the population as persons taking clarithromycin and the use of statins as the exposure we could achieve a comparable effect in both groups from the acute condition on hospitalisation. Therefore, we defined exposed patients as those who had overlapping treatment with a statin and unexposed controls as those who had filled a prescription for clarithromycin without concomitant statin therapy. Outcome was defined as a composite of hospital admission or death within 30 days after starting clarithromycin. We used generalised linear regression to model an association between outcome and exposure to statins.ResultsAmong 28,484 prescriptions of clarithromycin, 2317 persons were co-exposed to statins. Co-administration of CYP3A4 metabolized statins and clarithromycin was associated with a 2.11 fold increased risk of death or hospitalisation (95 % confidence interval [CI]: 1.79–2.48). This effect was explained by age, evidence of cardiovascular disease, diabetes mellitus and utilization of other antibiotics (multivariable adjusted risk ratio: 1.02, 95 % CI: 0.85–1.22). The sensitivity analyses did not change the significance of effect.ConclusionsThe risk for hospitalisation or death in persons receiving clarithromycin increases with age and cardiovascular disease but is not causally associated with statin-clarithromycine co-administration.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0134-y) contains supplementary material, which is available to authorized users.