Cost-Effectiveness of Targeted Genetic Testing for Breast and Ovarian Cancer: A Systematic Review.

BACKGROUND: Targeted genetic testing is a tool to identify women at increased risk of gynaecological cancer. OBJECTIVE: This systematic review evaluates the results and quality of cost-effectiveness modeling studies that assessed targeted genetic-based screen-and-treat strategies to prevent breast and ovarian cancer. METHODS: Using MEDLINE and databases of the Centre for Reviews and Dissemination, we searched for health economic modeling evaluations of targeted genetic-based screen-and-treat strategies to prevent inheritable breast and ovarian cancer (until August 2020). The incremental cost-effectiveness ratios (ICERs) were compared. Methodological variations were addressed by evaluating the model conceptualizations, the modeling techniques, parameter estimation and uncertainty, and transparency and validation of the models. Additionally, the reporting quality of each study was assessed. RESULTS: Eighteen studies met our inclusion criteria. From a payer perspective, the ICERs of (1) BRCA screening for high-risk women without cancer ranged from dominating the no test strategy to an ICER of $21 700/quality-adjusted life years (QALY). In studies that evaluated (2) BRCA cascade screening (ie, screening of women with cancer plus their unaffected relatives) compared with no test, the ICERs were between $6500/QALY and $50 200/QALY. Compared with BRCA alone, (3) multigene testing in women without cancer had an ICER of $51 800/QALY (one study), while for (4) multigene-cascade screening the ICERs were $15 600/QALY, $56.500/QALY, and $69 600/QALY for women in the United Kingdom, Norway, and the United States, respectively (2 studies). More recently published studies showed a higher methodological and reporting quality. CONCLUSIONS: Targeted BRCA or multiple gene screening is likely to be cost-effective. Methodological variations could be decreased by the development of a reference model, which may serve as a tool for validation of present and future cost-effectiveness models.

A cross-sectional analysis of health literacy: patient- versus family doctor-reported and associations with self-efficacy and chronic disease.

BACKGROUND: Adequate health literacy (HL) levels contribute to good health outcomes and successful disease self-management in patients with chronic disease. Hence, it is essential that family doctors recognize patients with inadequate HL in need of additional support. This study had two aims: (1) to assess and compare patient self-reported versus family doctor-rated HL estimates, and (2) to explore associations between patient-reported HL, self-efficacy and chronic diseases. METHODS: Participants in this cross-sectional survey were recruited through general practices in North Rhine-Westphalia, Germany. Patient self-reported HL was measured using the European Health Literacy Survey-16. Family doctor-rated HL was measured with an adapted version of this instrument. Using crosstabulations patient-reported and family doctor-rated HL estimates were compared for 346 patient-family doctor pairs. Associations between HL, self-efficacy and chronic disease were investigated using regression analyses. RESULTS: Patient-reported and family doctor-rated HL estimates were concordant in 38% of all cases. On average family doctors rated their patients' HL lower than patients rated their own HL. The lower average family doctor ratings were more pronounced when patients were older, male and had more than one chronic disease. Female family doctors rated HL of male patients lower than their male colleagues. Patient reported HL had a significant positive association with self-efficacy. Mediation analysis provided support that self-efficacy acts as mediator between HL and the number of chronic diseases. CONCLUSIONS: Our study findings indicate a significant discrepancy between patients' self-reported HL and externally rated HL by family doctors. A more systematic utilization of HL screeners might help reduce this discrepancy. At the same time, consideration should be given to enhancing communication training for family doctors and addressing critical HL skills in patient education.

Parental views on acute otitis media (AOM) and its therapy in children--results of an exploratory survey in German childcare facilities.

BACKGROUND: Acute otitis media (AOM) is one of the main reasons for medical consultation and antibiotic use during childhood. Although 80% of AOM cases are self-limiting, antibiotic prescription is still high, either for physician- or for parent-related factors. This study aims to identify parental knowledge about, beliefs and attitudes towards, and experiences with AOM and its therapy and thus to gain insights into parents' perspectives within the German health care system. METHODS: An exploratory survey was conducted among German-speaking parents of children aged 2 to 7 years who sent their children to a childcare facility. Childcare facilities were recruited by convenience sampling in different urban and rural sites in Germany, and all parents with children at those facilities were invited to participate. Data were evaluated using descriptive statistical analyses. RESULTS: One-hundred-thirty-eight parents participated. Of those, 75.4% (n = 104) were AOM-experienced and 75.4% (n = 104) had two or more children. Sixty-six percent generally agree that bacteria cause AOM. 20.2% generally agree that viruses cause AOM. 30.5% do not generally agree that viruses cause AOM. Eight percent generally agree that AOM resolves spontaneously, whereas 53.6% do not generally agree. 92.5% generally (45.7%) and partly (42.8%) agree that AOM needs antibiotic treatment. With respect to antibiotic effects, 56.6% generally agree that antibiotics rapidly relieve earache. 60.1% generally agree that antibiotics affect the gastrointestinal tract and 77.5% generally agree that antibiotics possibly become ineffective after frequent use. About 40% generally support and about 40% generally reject a "wait-and-see" strategy for AOM treatment. Parental-reported experiences reveal that antibiotics are by far more often prescribed (70.2%) than actively requested by parents (26.9%). CONCLUSIONS: Parental views on AOM, its therapy, and antibiotic effects reveal uncertainties especially with respect to causes, the natural course of the disease and antibiotic effects on AOM. These results indicate that more evidence-based information is needed if parents' health literacy in the treatment of children with AOM is to be enhanced. The discrepancy between reported parental requests for antibiotics and reported actual prescriptions contradicts the hypothesis of high parental influence on antibiotic use in AOM.

Testing a single item screener to support family doctors in identifying patients with limited health literacy: convergent validity of the SILS and the HLS-EU-Q16.

BACKGROUND: Low health literacy (HL) is associated with reduced disease self-management skills, worse health outcomes, an increased number of hospitalizations, more frequent use of the emergency room and less utilization of preventive services. To support patients with low HL it is crucial to identify affected patients. HL is a multidimensional construct, which covers different skills and abilities to make informed health decisions. Validated brief screening tools to assess health-literacy-related skills or abilities in primary care settings are currently not available in German. This study aimed to validate a single item screener developed in the US for the German primary care setting. METHODS: Our study used cross-sectional data from a survey among mainly chronically ill patients (n = 346) conducted in family practices in the state of North Rhine-Westphalia. We explored the convergent validity between a single item literacy screener (SILS) and the HLS-EU-Q16. The SILS measures functional HL by asking patients about their need for help when reading information materials. The HLS-EU-Q16 is a multidimensional HL measure frequently used for research purposes in Germany. Associations between the two instruments were examined using Spearman's correlations and regression analyses. The diagnostic performance of the SILS relative to the HLS-EU-Q16 was assessed using receiver operator curves (ROC). RESULTS: The SILS had a statistically significant correlation with the HLS-EU-Q16 (Spearman ρ: 0.35) and explained 26% of its total variance. Stratified analyses of the convergent validity between both instruments by age, sex, migration background, education level and chronic disease status showed moderate statistically significant correlations in all subgroups (range: 0.223 to 0.428). With an area under the curve of 0.66, the receiver operator curve indicated a satisfactory diagnostic performance of the SILS relative to the HLS-EU-Q16. CONCLUSIONS: The SILS provided an acceptable initial assessment of HL limitations among a heterogeneous population of mainly chronically ill patients in a primary care setting. With only one item, the SILS can be a short and effective tool for routine use in primary care and specialized care settings. Future research should test the SILS in other populations and pilot applications of the SILS in routine care.

Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol.

​INTRODUCTION: Randomised controlled trials (RCTs) have shown a positive effect of early integration of palliative care (EIPC) in various advanced cancer entities regarding patients' quality of life (QoL), survival, mood, caregiver burden and reduction of aggressiveness of treatment near the end of life. However, RCTs investigating the positive effect of EIPC for patients suffering from glioblastoma multiforme (GBM) are lacking. After modelling work identifying the specific needs of GBM patients and their caregivers, the aim of this study is to investigate the impact of EIPC in this particular patient group. ​METHODS AND ANALYSIS: The recruitment period of this multicenter RCT started in May 2019. GBM patients (n=214) and their caregivers will be randomly assigned to either the intervention group (receiving proactive EIPC on a monthly basis) or the control group (receiving treatment according to international standards and additional, regular assessment of QoL ('optimised' standard care)).The primary outcome is QoL assessed by subscales of the Functional Assessment of Cancer Therapy for brain tumour (FACT-Br) from baseline to 6 months of treatment. Secondary outcomes are changes in QoL after 12 (end of intervention), 18 and 24 months (end of follow-up), the full FACT-Br scale, patients' palliative care needs, depression/anxiety, cognitive impairment, caregiver burden, healthcare use, cost-effectiveness and overall survival. ​ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the local ethics committees of the University Clinics of Cologne, Aachen, Bonn, Freiburg and Munich (LMU). Results of the trial will be submitted for publication in a peer-reviewed, open access journal and disseminated through presentations at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00016066); Pre-results.

Sex differences in treatment patterns of six chronic diseases: an analysis from the German statutory health insurance.

OBJECTIVE: The goal of this study was to investigate gender-specific differences in prevalence, healthcare costs, and treatment patterns in the German Statutory Health Insurance (SHI). METHODS: The study analyzed administrative claims data of over 26 million insured with respect to prevalence and cost of illness of six chronic diseases. Insured were identified using the ATC code for medication prescription and ICD-9 code for diagnosis. The influences of gender, age, and comorbidity on cost differences were analyzed via multivariate regression analysis. RESULTS: Adjusted for age and comorbidity, gender had a significant influence on both hospital and medication spending. Hospital costs on average were 17.1% (95% CI 14.1; 20.2) higher for men compared with women. Medication spending for men exceeded that for women on average by 13.8% (95% CI 10.9; 16.7). The diagnoses with the highest prevalence were hypertension and heart failure. Women had a higher prevalence of diabetes, coronary artery disease (CAD), heart failure, and hypertension. Medication costs were higher for men in three of five diagnoses and comparable for two diagnoses (diabetes and asthma). Women received more medication prescriptions than men, but on average prescriptions for men were 14%-26% more expensive than prescriptions for women. Regarding treatment patterns men were treated with different drug classes in cardiovascular disease (CVD) compared with women. Total medication spending stratified by diagnosis was highest for diabetes. CONCLUSIONS: Gender differences for costs and prescribing patterns for chronic diseases vary disease specifically, but generally men had higher inpatient costs and more expensive medication prescriptions, whereas women had higher numbers of prescriptions.

Applying GRADE Criteria to Clinical Inputs to Cost-Effectiveness Modeling Studies.

BACKGROUND: Concerns have been raised about the use of clinical data in cost-effectiveness models. The aim of this analysis was to evaluate the appropriate use of data on clinical effectiveness in cost-effectiveness modeling studies that were published between 2001 and 2015. METHODS: Assessors rated 72 modeling studies obtained from three therapeutic areas by applying criteria defined by the Grading of Recommendations Assessment, Development and Evaluation group for assessing the quality of clinical evidence: selection of clinical data (publication bias), imprecision, indirectness, inconsistency (i.e., heterogeneity), and study limitations (risk of bias). For all parameters included in the analyses, potential changes over time were assessed. RESULTS: Although three out of four modeling studies relied on randomized controlled trials, more than 60% of the modeling studies were based on clinical data with a high or unclear risk of bias, in more than 80%, a risk of publication bias was found, and in about 30%, evidence was based on indirect clinical evidence, having significantly increased over the years. Study limitations were inadequately described in more than one third of the studies. However, less than 10% of clinical studies showed inconsistency or imprecision in study results. CONCLUSION: Despite the fact that the majority of economic evaluations are based on precise and consistent randomized controlled trials, their results are often affected by limitations arising from methodological shortcomings in the underlying data on clinical efficacy. Modelers and assessors should be more aware of aspects surrounding the quality of clinical evidence as considered by the Grading of Recommendations Assessment, Development and Evaluation group.

Patients' preferences in periodontal disease treatment elicited alongside an IQWiG benefit assessment: a feasibility study.

BACKGROUND AND PURPOSE: The German Institute for Quality and Efficiency in Health Care (IQWiG) previously tested two preference elicitation methods in pilot projects and regarded them as generally feasible for prioritizing outcome-specific results of benefit assessment. The present study aimed to investigate the feasibility of completing a discrete choice experiment (DCE) within 3 months and to determine the relative importance of attributes of periodontal disease and its treatment. PATIENTS AND METHODS: This preference elicitation was conducted alongside the IQWiG benefit assessment of systematic treatments of periodontal diseases. Attributes were defined based on the benefit assessment, literature review, and patients' and periodontologists' interviews. The DCE survey was completed by patients with a history of periodontal disease. Preferences were elicited for the attributes "tooth loss within next 10 years", "own costs for treatment, follow-up visits, re-treatment", "complaints and symptoms", and "frequency of follow-up visits". Patients completed a self-administered questionnaire including 12 choice tasks. Data were analyzed using a random parameters logit model. The relative attribute importance was calculated based on level ranges. RESULTS: Within 3 months, survey development, data collection among 267 patients, data analysis, and provision of a study report could be completed. The analysis showed that tooth loss (score 0.73) was the most important attribute in patients' decisions, followed by complaints and symptoms (0.22), frequency of follow-up visits (0.02), and costs (0.03) (relative importance scores summing up to 1). CONCLUSION: A preference analysis performing a DCE can be generally feasible within 3 months; however, a good research infrastructure and access to patients is required. Outcomes used in benefit assessments might need to be adapted to be used in preference analyses.

[Disability Pension and Productivity Loss in Schizophrenia - An Empirical Analysis of the Financial Burden in Germany]. / Erwerbsminderung bei Schizophrenie ­ eine empirische Analyse der Folgelasten.

Objective Quantification of the economic burden for society and the German Statutory Pension Insurance due to early retirement in schizophrenia. Methods Based on empirical data of the German Statutory Pension Insurance, productivity losses were calculated using the human capital approach. Results The total expenditures of the German Statutory Pension Insurance due to pension payments for schizophrenic insurants amounted to €â€Š450 million. Total indirect costs due to morbidity and mortality were estimated at €â€Š2,3 million. Average indirect costs per patient ranged between €â€Š17 000 - 28 000, depending on rates for discounting and inflation. Conclusion Regarding substantial economic consequences, preventive measures and therapeutic procedures should aim to prevent reduction in earning capacity and to promote occupational reintegration of schizophrenic patients.

Patients' Preferences for Outcome, Process and Cost Attributes in Cancer Treatment: A Systematic Review of Discrete Choice Experiments.

INTRODUCTION: As several studies have been conducted to elicit patients' preferences for cancer treatment, it is important to provide an overview and synthesis of these studies. This study aimed to systematically review discrete choice experiments (DCEs) about patients' preferences for cancer treatment and assessed the relative importance of outcome, process and cost attributes. METHODS: A systematic literature review was conducted using PubMed and EMBASE to identify all DCEs investigating patients' preferences for cancer treatment between January 2010 and April 2016. Data were extracted using a predefined extraction sheet, and a reporting quality assessment was applied to all studies. Attributes were classified into outcome, process and cost attributes, and their relative importance was assessed. RESULTS: A total of 28 DCEs were identified. More than half of the studies (56%) received an aggregate score lower than 4 on the PREFS (Purpose, Respondents, Explanation, Findings, Significance) 5-point scale. Most attributes were related to outcome (70%), followed by process (25%) and cost (5%). Outcome attributes were most often significant (81%), followed by process (73%) and cost (67%). The relative importance of outcome attributes was ranked highest in 82% of the cases where it was included, followed by cost (43%) and process (12%). CONCLUSION: This systematic review suggests that attributes related to cancer treatment outcomes are the most important for patients. Process and cost attributes were less often included in studies but were still (but less) important to patients in most studies. Clinicians and decision makers should be aware that attribute importance might be influenced by level selection for that attribute.

Cost-effectiveness of rituximab in addition to fludarabine and cyclophosphamide (R-FC) for the first-line treatment of chronic lymphocytic leukemia.

The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17,979 per QALY (€15,773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.

Osteoporosis in German men: a cost-of-illness study.

Costs of male osteoporosis may have increased due to population aging and change of treatment patterns. This cost-of-illness study provides a current estimate of the economic burden of male osteoporosis in Germany. Routine claims data from six German sickness funds were analyzed and extrapolated to the German statutory health insurance (SHI). For men above the age of 50 with at least one ICD-10 osteoporosis-related diagnosis or osteoporosis-related fracture in 2010, direct costs related to osteoporosis were considered based on a payer's perspective. Total direct costs attributable to osteoporosis amounted to €728 million in 2010. The majority of these costs (71%) resulted from inpatient treatment due to fractures. Patients aged 75 and older caused approximately 63% of costs. Male osteoporosis represents a non-negligible economic burden for the German health care system. Targeted prevention and promotion measures should be offered both to men and women.