Evaluation of two family-based intervention programs for children affected by rare disease and their families - research network (CARE-FAM-NET): study protocol for a rater-blinded, randomized, controlled, multicenter trial in a 2x2 factorial design.

BACKGROUND: Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. METHODS/DESIGN: The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents' as well as the children's perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. DISCUSSION: This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family's Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov : NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021.

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. OBJECTIVES: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology-specifically economic evaluation methods-in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. METHODS: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. RESULTS: Three key topics were identified and prioritised for discussion-uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. CLASSIFICATION CODE: I.

[Health Science Research with Primary Care Routine Data From Electronic Patient Records: the BeoNet Registry]. / Gesundheitswissenschaftliche Forschung mit primärärztlichen Routinedaten der elektronischen Patientenakte: das BeoNet-Register.

Reliable current information is needed for daily patient care and the health system, but comprehensive data, especially from primary care, are scarce and/or hard to access. The BeoNet Register-Database (BNR) aims to depict quality of medical care in Germany using routine data and with no additional documentation or costs for GPs. Registry design, data structure and database use will be demonstrated using chronic obstructive lung disease (COPD) as an example. The BNR is moving through pilot- and roll-out phases. Participating practices provide standardized information about (1) master data (2) practice profile (3) infrastructure and documentation systems. The routinely documented data will be pseudonymized before transmission via standardized secure interfaces to the registry database. Practices can participate in studies in cooperation with BNR if informed consent is obtained from the patients. The registry data will be linked with questionnaires on health care utilization, quality of life and disease-specific parameters. Researchers and physicians can access quasi anonymized data in specific datasets extracted from the registry. Regular automatic data quality checks and feedback from GPs, patients and researchers enhance the quality of the registry. Performance and data analysis are continuously optimized. The data security concept has been approved and ethical approval is on hand. GPs, pediatricians and pneumologists from Hanover, Munich and Heidelberg participated in the pilot phase. The registry database currently holds 98497 patient IDs and related information. BNR contains more than the standard billing data collected by health insurers. The data are applicable to a wide range of health practices, health care and economics and disease development questions. Questionnaires have been generated, tested and are being distributed. First descriptive analyses of prevalence, age and gender have been performed. Quality and validity checks have been implemented. 2016 marks the roll-out phase of the BNR. Further recruitment of practices throughout Germany, data linkage with additional questionnaires, recruitment of patients for health care research projects, quality checks and data analysis of disease-specific costs and health-related quality of life in COPD are progressing with the overall aim of improving pulmonary healthcare strategies. The floor is now open for retro- and prospective cross-sectional and longitudinal studies.

[Priority setting and rationing of pharmaceuticals - an experimental analysis of discussion processes]. / Priorisierung und Rationierung von Arzneimittel ­ eine experimentelle Analyse von Diskussionsprozessen.

BACKGROUND/OBJECTIVE: In the face of rising expenditure among statutory sickness funds in Germany it is necessary to start a discussion about priority setting in the healthcare system. For a long time this issue has been avoided in healthcare debates. As a result, normative directives are still missing, which can lead to priority setting among healthcare providers in daily healthcare practice. Prioritization can be conducted at three different levels: at the government (macro), the institutional (meso), and the patient (micro) level. Surveys about societal preferences for different criteria exist; however, specifications on their respective weighting in the situation of approval and reimbursement of pharmaceuticals (meso) are missing. For this reason, the present study analyzed the implementation and weighting of the criteria for priority setting at the meso level, taking values and experiences of the participants into account. METHOD: Six qualitative focus groups were carried out with representatives from the fields of medicine, ethics, public health and economics. During the discussions four fictitious drugs for the treatment of different lung diseases were prioritized based on guidelines. The discussion processes were analyzed according to Bohnsack's documentary method. RESULTS: The criteria "quality of life", "life expectancy" and "other patient-relevant outcomes" were discussed in relation to each other. The evaluation of change in patient-relevant outcomes was difficult to perform for non-medical participants. The second argument concerned the criteria "costs", disease severity and "number of patients". Costs were given less weight, but were often used to support other criteria. Other challenges in reaching a consensus included emerging role conflicts between profession and personal opinion, and the transfer of the discussion to a different level of decision-making. DISCUSSION: In the discussions the problem of prioritizing did not arise from different preferences for prioritization criteria, but from the weighting of the criteria. The operationalization of the criteria seemingly depends on the decision-making situation, the participants' personal connection with the relevant disease and on the correspondence between evidence and personal experiences.

[Evaluation of family doctor-centred health care in Germany based on AOK Rheinland/Hamburg claims data]. / Evaluation der hausarztzentrierten Versorgung in Deutschland anhand von GKV-Routinedaten der AOK Rheinland/Hamburg.

BACKGROUND: Health insurance funds in Germany are obliged to offer family doctor-centred health care models (Hausarztzentrierte Versorgung, "HzV"). The participation is voluntary for the insured persons. Participants agree to utilise outpatient specialist care only if their family doctor or general practitioner ("gatekeeper") refers them to a specialist. The aim of this programme is to both strengthen the role of general practitioners and to avoid unnecessary specialist visits and double examinations. Moreover, the quality of care should increase and costs decrease. There is a controversial debate among health politicians whether these objectives can be achieved with current HzV contracts. Therefore, the aim of this project was to conduct an economic evaluation of family doctor-centred health care compared with the standard of care. METHODS: The analysis covered continuously insured adult HzV participants, who have been enrolled in the contract offered by a large German sickness fund (AOK Rheinland/Hamburg) since 2011. In addition, the analysis contained data of a control group which was three times larger than the intervention group. Logistic regression analysis with relevant characteristics (social demographics, health care utilisation, cost, and Charlson Comorbidity Index) of participants and non-participants was conducted to assess the likelihood of participation in the HzV contract. With the subsequent propensity score matching, differences in the characteristics between the control and the intervention group were compensated for the base year 2010 in order to be able to evaluate the influence of the HzV contract in subsequent years. Study objectives were to analyse differences in costs as well as utilisation of services between HzV participants and the control group. RESULTS: The intervention group consisted of 25,201 HzV participants with an average age of 49.5 years [SD: 17.9]. 54.4% of them were female. The HzV participants showed significantly higher costs compared to the control group in the first and in the second year after enrolment. Drug costs in the first year added up to an average of 499 EUR [SD: 2,021] compared to 477 EUR [SD: 2,050] in the control group. In the second year, the drug costs were 544 EUR [SD: 2,758] in the intervention group and 522 EUR [SD: 2,341] in the control group. In addition, the analysis showed a higher number of specialist referrals issued by general practitioners in the intervention group. However, the length of stay in hospitals was shown to be decreasing for HzV participants. DISCUSSION: The higher costs and use of services indicate a higher morbidity (Charlson Comorbidity Index and in comparison to the German population) of HzV participants. The cost level increases in both groups, but within the group of HzV participants, the relative cost increase in the second year was lower than in the control group. The results of this study demonstrate that family doctor-centred health care is assumed to be more efficient in the long term. With regard to the objective of these contracts, quality improvement may not be achievable at the same time as cost savings. As our data set cannot distinguish between changes of patient behaviour and physician behaviour, the results of our study need to be interpreted with caution.

Valuation of the EQ-5D-5L with composite time trade-off for the German population - an exploratory study.

BACKGROUND: The EuroQol Group has extended the severity levels of the EQ-5D from three to five (EQ-5D-5L). There are valuation studies worldwide planned in order to convert the EQ-5D-5L health states into a single preference-based summary score based on country-specific value sets of social health status preference valuations. The EuroQol Group developed an internationally standardised EQ-5D-5L valuation protocol. Based on the experiences of the first wave of valuation studies applying the protocol, a number of modifications to the implementation of composite time trade-off (cTTO) were proposed and tested in an exploratory study in Germany. METHODS: The aim of the study is to test the improved EQ-5D-5L valuation protocol 1.1 and the implementation of three modifications: (1) introduction of ranking task, (2) separating time trade-off (TTO) tasks for health states "Better Than Dead"(BTD)/"Worse Than Dead" (WTD), (3) allow for removal of problematic valuations from the cTTO data (the feedback module). Data were collected in computer assisted personal interviews with 200 members of the German general public. RESULTS: In comparison to the first wave of valuation studies a higher data quality can be observed in both study arms: increasing number of WTD valuations, reduced inconsistencies for health state 55555 as well as higher values for mild health states. Comparing both study arms, mean observed cTTO value for severity 6 is higher in the test arm. The proportion of inconsistent cTTO responses is lower in the test arm than in the control arm and is further reduced by the feedback module. The ranking task prolongs the interview without the desired effect. CONCLUSIONS: Both study arms yielded higher data quality in comparison to the first wave of EQ-5D-5L valuation studies. The valuation protocol combined with an intensive interviewer training and close data monitoring showed a high feasibility and acceptability to the respondents of the general population as well as the interviewers in Germany. Based on the results of this study and other countries, the separation of TTO tasks for health states BTD/WTD and the feedback module will be implemented in the valuation study for the EQ-5D-5L for Germany.

Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

BACKGROUND: In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (<2 years old) vaccination with a 13-valent pneumococcal conjugate vaccine (PCV13) in comparison with a 10-valent pneumococcal conjugate vaccine (PCV10) for the prevention of pneumococcal disease in Germany. METHODS: A population-based Markov model was developed to estimate the impact of PCV13 and PCV10 on invasive pneumococcal disease (IPD), non-invasive pneumonia (PNE), and acute otitis media (AOM) over a time horizon of 50 years. The model included the effects of the historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. CONCLUSIONS: Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

Cost analysis of whole genome sequencing in German clinical practice.

OBJECTIVES: Whole genome sequencing (WGS) is an emerging tool in clinical diagnostics. However, little has been said about its procedure costs, owing to a dearth of related cost studies. This study helps fill this research gap by analyzing the execution costs of WGS within the setting of German clinical practice. METHODOLOGY: First, to estimate costs, a sequencing process related to clinical practice was undertaken. Once relevant resources were identified, a quantification and monetary evaluation was conducted using data and information from expert interviews with clinical geneticists, and personnel at private enterprises and hospitals. This study focuses on identifying the costs associated with the standard sequencing process, and the procedure costs for a single WGS were analyzed on the basis of two sequencing platforms-namely, HiSeq 2500 and HiSeq Xten, both by Illumina, Inc. In addition, sensitivity analyses were performed to assess the influence of various uses of sequencing platforms and various coverage values on a fixed-cost degression. RESULTS: In the base case scenario-which features 80 % utilization and 30-times coverage-the cost of a single WGS analysis with the HiSeq 2500 was estimated at €3858.06. The cost of sequencing materials was estimated at €2848.08; related personnel costs of €396.94 and acquisition/maintenance costs (€607.39) were also found. In comparison, the cost of sequencing that uses the latest technology (i.e., HiSeq Xten) was approximately 63 % cheaper, at €1411.20. CONCLUSIONS: The estimated costs of WGS currently exceed the prediction of a 'US$1000 per genome', by more than a factor of 3.8. In particular, the material costs in themselves exceed this predicted cost.

Comparison of different approaches applied in Analytic Hierarchy Process - an example of information needs of patients with rare diseases.

BACKGROUND: The Analytic Hierarchy Process (AHP) is increasingly used to measure patient priorities. Studies have shown that there are several different approaches to data acquisition and data aggregation. The aim of this study was to measure the information needs of patients having a rare disease and to analyze the effects of these different AHP approaches. The ranking of information needs is then used to display information categories on a web-based information portal about rare diseases according to the patient's priorities. METHODS: The information needs of patients suffering from rare diseases were identified by an Internet research study and a preliminary qualitative study. Hence, we designed a three-level hierarchy containing 13 criteria. For data acquisition, the differences in outcomes were investigated using individual versus group judgements separately. Furthermore, we analyzed the different effects when using the median and arithmetic and geometric means for data aggregation. A consistency ratio ≤0.2 was determined to represent an acceptable consistency level. RESULTS: Forty individual and three group judgements were collected from patients suffering from a rare disease and their close relatives. The consistency ratio of 31 individual and three group judgements was acceptable and thus these judgements were included in the study. To a large extent, the local ranks for individual and group judgements were similar. Interestingly, group judgements were in a significantly smaller range than individual judgements. According to our data, the ranks of the criteria differed slightly according to the data aggregation method used. CONCLUSIONS: It is important to explain and justify the choice of an appropriate method for data acquisition because response behaviors differ according to the method. We conclude that researchers should select a suitable method based on the thematic perspective or investigated topics in the study. Because the arithmetic mean is very vulnerable to outliers, the geometric mean and the median seem to be acceptable alternatives for data aggregation. Overall, using the AHP to identify patient priorities and enhance the user-friendliness of information websites offers an important contribution to medical informatics.

Benefit assessment in Germany: implications for price discounts.

BACKGROUND: The 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. OBJECTIVES: The aim of this evaluation is to identify factors influencing the results of the AMNOG price negotiation process. METHODS: The 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). RESULTS: Until 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. CONCLUSIONS: Although 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.

Applying the Analytic Hierarchy Process in healthcare research: A systematic literature review and evaluation of reporting.

BACKGROUND: The Analytic Hierarchy Process (AHP), developed by Saaty in the late 1970s, is one of the methods for multi-criteria decision making. The AHP disaggregates a complex decision problem into different hierarchical levels. The weight for each criterion and alternative are judged in pairwise comparisons and priorities are calculated by the Eigenvector method. The slowly increasing application of the AHP was the motivation for this study to explore the current state of its methodology in the healthcare context. METHODS: A systematic literature review was conducted by searching the Pubmed and Web of Science databases for articles with the following keywords in their titles or abstracts: "Analytic Hierarchy Process," "Analytical Hierarchy Process," "multi-criteria decision analysis," "multiple criteria decision," "stated preference," and "pairwise comparison." In addition, we developed reporting criteria to indicate whether the authors reported important aspects and evaluated the resulting studies' reporting. RESULTS: The systematic review resulted in 121 articles. The number of studies applying AHP has increased since 2005. Most studies were from Asia (almost 30%), followed by the US (25.6%). On average, the studies used 19.64 criteria throughout their hierarchical levels. Furthermore, we restricted a detailed analysis to those articles published within the last 5 years (n = 69). The mean of participants in these studies were 109, whereas we identified major differences in how the surveys were conducted. The evaluation of reporting showed that the mean of reported elements was about 6.75 out of 10. Thus, 12 out of 69 studies reported less than half of the criteria. CONCLUSION: The AHP has been applied inconsistently in healthcare research. A minority of studies described all the relevant aspects. Thus, the statements in this review may be biased, as they are restricted to the information available in the papers. Hence, further research is required to discover who should be interviewed and how, how inconsistent answers should be dealt with, and how the outcome and stability of the results should be presented. In addition, we need new insights to determine which target group can best handle the challenges of the AHP.

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

BACKGROUND AND OBJECTIVES: The 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. METHODS: Analyses 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. RESULTS: In 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. DISCUSSION: This 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.

EGFR mutation status and first-line treatment in patients with stage III/IV non-small cell lung cancer in Germany: an observational study.

INTRODUCTION: EGFR mutations confer sensitivity to EGFR tyrosine kinase inhibitors (TKI) in advanced non-small cell lung cancer (NSCLC). We investigated the clinicopathologic characteristics associated with EGFR mutations and their impact on real-world treatment decisions and outcomes in Caucasian patients with advanced NSCLC. METHODS: REASON (NCT00997230) was a noninterventional multicenter study in patients (≥18 years) with stage IIIb/IV NSCLC, who were candidates for EGFR mutation testing and first-line systemic treatment, but not eligible for surgery or radiotherapy. Patients were followed up according to normal clinical practice and assessed for primary (correlation of mutation status with baseline characteristics) and secondary endpoints (first-line treatment decision). RESULTS: Baseline data were obtained for 4,200 patients; 4,196 fulfilled the inclusion criteria; EGFR mutations were detected in 431 patients; no EGFR mutations were detected in 3,590 patients; mutation status was not evaluable in 175 patients. In multivariate analysis, the odds of EGFR mutations were significantly higher (P < 0.0001) in females versus males (odds ratio: 1.85; 95% confidence interval, 1.48-2.32), never-smokers versus smokers (3.64; 2.91-4.56), and patients with adenocarcinoma versus other histologic subtypes (2.94; 2.17-4.08). The most commonly prescribed first-line systemic treatments were: EGFR-TKIs in EGFR mutation-positive NSCLC (56.6%) and combination chemotherapy in EGFR mutation-negative NSCLC (78.5%). CONCLUSIONS: This represents the largest dataset for EGFR mutations in Caucasian patients and shows EGFR mutations to be most prevalent in females with adenocarcinoma who had never smoked. IMPACT: These findings add to our understanding of the prognostic and predictive factors of NSCLC, supporting future improved treatment selection.

Potential cost-effectiveness and benefit-cost ratios of adult pneumococcal vaccination in Germany.

BACKGROUND: Invasive (IPD, defined as detection of pneumococci in sterile body fluids like meningitis or bacteremic pneumonia) and non-invasive Streptococcus pneumoniae infections (i.e. non-bacteremic pneumonia, otitis media) in adults are associated with substantial morbidity, mortality and costs. In Germany, Pneumococcal polysaccharide vaccination (PPV23) is recommended for all persons >60 years and for defined risk groups (age 5-59). The aim of this model was to estimate the potential cost-effectiveness and benefit-cost ratios of the adult vaccination program (18 years and older), considering the launch of the pneumococcal conjugate vaccine for adults (PCV13). METHODS: A cross-sectional steady state Markov model was developed to estimate the outcomes of PCV13, PPV23 vaccination schemes and 'no vaccination'. Conservative assumptions were made if no data were available for PCV13 and PPV23 respectively. The effectiveness of individual pneumococcal vaccination in adults was adjusted for expected indirect effects due to the vaccination in infants. Data on incidences, effectiveness and costs were derived from scientific literature and publicly available databases. All resources used are indicated. Benefit-cost ratios and cost-effectiveness were evaluated from the perspective of the German Statutory Health Insurance as well as from social perspective. RESULTS: Under the assumption that PCV13 has a comparable effectiveness to PCV7, a vaccination program with PCV13 revealed the potential to avoid a greater number of yearly cases and deaths in IPD and pneumonia in Germany compared to PPV23. For PCV13, the costs were shown to be overcompensated by monetary savings resulting from reduction in the use of health care services. These results would render the switch from PPV23 to PCV13 as a dominant strategy compared to PPV23 and 'no vaccination'. Given the correctness of the underlying assumptions every Euro spent on the PCV13 vaccination scheme yields savings of 2.09 € (social perspective: 2.16 €) compared to PPV23 and 1.27 € (social perspective: 1.32 €) compared to 'no vaccination', respectively. CONCLUSIONS: Results of the model indicate that the health economic benefit of immunizing adults with PCV13 can be expected to outperform the sole use of PPV23, if the effectiveness of PCV13 is comparable to the effectiveness of PCV7.

Stereotactic radiosurgery for the treatment of brain metastases.

BACKGROUND: The objective of this systematic review was to summarise the current evidence concerning radiosurgical treatment (SRS) of newly diagnosed brain metastasis and to compare SRS as a single or additional treatment to treatment alternatives with regard to medical effectiveness and safety. METHODS: A structured search of electronic databases was performed to identify relevant publications from 2002 through 2007. Studies targeting patients with brain metastases were included. Standardised quality assessment and data extraction were performed. RESULTS: Of 1496 publications, 16 studies were included. The mean survival in most studies was less than 12 months. There was evidence that SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in patients with single metastasis, this resulted in improved survival. There was inconclusive evidence when comparing SRS to WBRT, Neurosurgery (NS) or Hypofractionated Radiotherapy (HCSRT). The Quality of life (Qol) was not investigated. CONCLUSION: SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in certain patients, this resulted in improved survival. Methodologically rigorous studies are therefore warranted to investigate further treatment options, and in view of the poor prognosis, to investigate Qol and neurological functioning.

[Comparative cost analysis of outpatient and inpatient rehabilitation for cardiac diseases]. / Kostenvergleichsanalyse der ambulanten und stationären kardiologischen Rehabilitation.

PURPOSE: : To examine costs of inpatient and outpatient rehabilitation for cardiac disorders from the perspective of a major statutory health insurance fund in Germany. METHODS: : A nationwide database from a major health insurance fund in Germany was used to evaluate all rehabilitation cases in 2005. In addition to all direct cost domains of the rehabilitation itself, costs incurred in the preceding and the following year for hospital treatment, drugs and physical therapy were analyzed. A cost-cost analysis in different institutional settings was chosen for the cost comparison of in- and outpatient rehabilitation. To minimize the influence of possible confounders, a statistical control system was implemented. RESULTS: : Mean costs were 2,006 Euros for inpatient rehabilitation and 1,502 Euros for outpatient rehabilitation. No systematic differences were identified between in- and outpatient rehabilitation in costs for drugs and physical therapy in the year preceding and the year directly following the rehabilitation. The costs for hospital treatment in the year before rehabilitation were higher in inpatient rehabilitation, whereas in the year after rehabilitation no differences between in- and outpatient rehabilitation were seen. CONCLUSION: : Assuming comparable medical outcome, outpatient rehabilitation seems to pose a superior alternative compared to inpatient rehabilitation from an economic perspective. Hence, from the perspective of the statutory health insurance, fostering a higher market share of outpatient rehabilitation may add to a better allocation of overall health-care resources.

Medical effectiveness and safety of conventional compared to laparoscopic incisional hernia repair: a systematic review.

BACKGROUND: Incisional hernias are a common complication following abdominal surgery and represent about 80% of all ventral hernia. In uncomplicated postoperative follow-up they develop in about 11% of cases and in up to 23% of cases with wound infections or other forms of wound complications. While conventional mesh repair has been the standard of care in the past, the use of laparoscopic surgery is increasing. It therefore remains uncertain which technique should be recommended as the standard of care. OBJECTIVES: To compare the medical effectiveness and safety of conventional mesh and laparoscopic incisional hernia repair. METHODS: A structured literature search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI) was conducted. English and German literature published until August 2005 was included and their methodological quality assessed. RESULTS: The search identified 17 relevant publications and included 15 studies for final assessment. Among those were one meta-analysis, one randomized clinical trial (RCT) ,and 13 cohort studies. All studies suffered from significant methodological limitations, such as differences in baseline characteristics between treatment groups, small case numbers, and the lack of adjustment for relevant confounders. Overall, medical effectiveness and safety were similar for both surgical approaches. However, there was a trend towards lower recurrence rates, length of hospital stay, and postoperative pain as well as decreased complication rates for the laparoscopic repair in the majority of studies. The impact of the technique of mesh implantation and mesh fixation as well as the impact of certain patient-related factors was not systematically assessed in any of the studies. CONCLUSION: No conclusive differences could be identified between the operative techniques. There was, however, some evidence for a trend towards similar or slightly improved outcomes associated with the laparoscopic procedure. There remains an urgent need for high-quality prospective studies to evaluate this question conclusively.