Systematic overview of cost-effectiveness thresholds in ten countries across four continents.

AIM: To provide an overview of thresholds for incremental cost-effectiveness ratios (ICERs) representing willingness-to-pay (WTP) across multiple countries and insights into exemptions pertaining to the ICER (e.g., cancer). To compare ICER thresholds to individual country's estimated ability-to-pay. MATERIALS & METHODS: We included AHRQ/USA, BIQG-GOEG/Austria, CADTH/Canada, DAHTA@DIMDI/Germany, DECIT-CGATS/Brazil, HAS/France, HITAP/Thailand, IQWiG/Germany, LBI-HTA/Austria, MSAC/Australia, NICE/England/Wales and SBU/Sweden. ICER thresholds were derived from systematic literature/website search/expert surveys. WTP was compared with ATP using Spearman's rank correlation. RESULTS: Two general and explicitly acknowledged thresholds (England/Wales, Thailand), implicit thresholds in six countries and different ICER thresholds/decision-making rules in oncology were identified. Correlation between WTP and ability-to-pay was moderate. DISCUSSION: Our overview supports country-specific discussions on WTP and on how to define value(s) within societies.

Systematic assessment of decision-analytic models for chronic myeloid leukemia.

BACKGROUND: Several tyrosine kinase inhibitors (TKIs) are approved for the treatment of chronic myeloid leukemia (CML). Decision-analytic modeling can help to extrapolate data from short-term clinical trials and also consider quality of life when evaluating different treatment strategies. OBJECTIVE: Our goal was to describe and analyze the structural and methodological approaches of published decision-analytic models for various treatment strategies in CML and to derive recommendations for the development of future CML models. DATA SOURCES: We performed a systematic literature search in electronic databases (MEDLINE/PreMEDLINE, EconLit, EMBASE, NHS EED, and Tuft's CEA Registry) to identify published studies evaluating CML treatment strategies using mathematical models. The search was updated in August 2013. STUDY SELECTION: The models were required to compare different treatment strategies in relation to relevant clinical and patient-relevant health outcomes [e.g., life-years gained, quality-adjusted life-years] over a defined time horizon and population. STUDY APPRAISAL AND SYNTHESIS METHODS: We used standardized forms for data extraction, description of study design, methodological framework, and data sources for each model. RESULTS: We identified 18 different decision-analytic modeling studies. Of these, 17 included economic evaluations. Modeling approaches included decision trees, Markov cohort models, state-transition models with individual (Monte Carlo) simulations, and mathematical equations. Analytic time horizons ranged from 2 years to a lifetime. Treatment strategies compared included bone marrow or stem cell transplantation, conventional chemotherapy, interferon-α, and TKIs. Only one model evaluated a second-generation TKI. Most models did not report a model validation. All models conducted deterministic sensitivity analyses and four reported a probabilistic sensitivity analysis. LIMITATIONS: Articles that were not published in English or German were not included in this review. Our literature search was restricted to published full-text articles in certain databases. Therefore, publications that met our inclusion criteria but were published in different databases, different languages, or as abstracts only may have been missed. CONCLUSIONS: While several well-designed models of CML treatment strategies exist, there remains a need for the assessment of the long-term efficacy and cost effectiveness of novel treatment options such as second-generation TKIs. Additionally, these models should be validated using independent data.

Individual health services.

BACKGROUND: The German statutory health insurance (GKV) reimburses all health care services that are deemed sufficient, appropriate, and efficient. According to the German Medical Association (BÄK), individual health services (IGeL) are services that are not under liability of the GKV, medically necessary or recommendable or at least justifiable. They have to be explicitly requested by the patient and have to be paid out of pocket. RESEARCH QUESTIONS: The following questions regarding IGeL in the outpatient health care of GKV insurants are addressed in the present report: What is the empirical evidence regarding offers, utilization, practice, acceptance, and the relation between physician and patient, as well as the economic relevance of IGeL?What ethical, social, and legal aspects are related to IGeL? FOR TWO OF THE MOST COMMON IGEL, THE SCREENING FOR GLAUCOMA AND THE SCREENING FOR OVARIAN AND ENDOMETRIAL CANCER BY VAGINAL ULTRASOUND (VUS), THE FOLLOWING QUESTIONS ARE ADDRESSED: What is the evidence for the clinical effectiveness?Are there sub-populations for whom screening might be beneficial? METHODS: The evaluation is divided into two parts. For the first part a systematic literature review of primary studies and publications concerning ethical, social and legal aspects is performed. In the second part, rapid assessments of the clinical effectiveness for the two examples, glaucoma and VUS screening, are prepared. Therefore, in a first step, HTA-reports and systematic reviews are searched, followed by a search for original studies published after the end of the research period of the most recent HTA-report included. RESULTS: 29 studies were included for the first question. Between 19 and 53% of GKV members receive IGeL offers, of which three-quarters are realised. 16 to 19% of the insurants ask actively for IGeL. Intraocular tension measurement is the most common single IGeL service, accounting for up to 40% of the offers. It is followed by ultrasound assessments with up to 25% of the offers. Cancer screening and blood or laboratory services are also frequent and represent a major proportion of the demand. The ethical, social, and legal aspects discussed in the context of IGeL concern eight subject areas: autonomous patient decisions versus obtrusion,commercialization of medicine, duty of patient information, benefit, evidence, and (quality) control, role and relation of physicians and patients,relation to the GKV, social inequality,formally correct performance. For glaucoma screening, no randomized controlled trial (RCT) is identified that shows a patient relevant benefit. For VUS three RCT are included. However, they do not yet present mortality data concerning screened and non-screened persons. VUS screening shows a high degree of over-diagnosis in turn leading to invasive interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures are necessary. CONCLUSION: IGeL are a relevant factor in the German statutory health care system. To provide more transparency, the requests for evidence-based and independent patient information should be considered. Whether official positive and negative-lists could be an appropriate instrument to give guidance to patients and physicians, should be examined. Generally, IGeL must be seen in the broader context of the discussions about the future design and development of the German health care system.

Long-term effectiveness and cost-effectiveness of screening for hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is an emerging problem in public health. In most countries, the majority of HCV infected people are yet undiagnosed. Early detection and treatment may result in better health outcomes and save costs by preventing future advanced liver disease. The evidence for long-term effectiveness and cost-effectiveness of HCV screening was systematically reviewed. METHODS: We performed a systematic literature search on long-term health-economic effects of HCV screening and included Health Technology Assessment (HTA) reports, systematic reviews, long-term clinical trials, full health economic and decision-analytic modelling studies with a sufficiently long time horizon and patient-relevant long-term outcomes such as life-years gained (LYG) or quality-adjusted life years (QALY) gained. Economic results were converted to 2005 Euros. RESULTS: Seven studies were included. Target population, HCV prevalence, study perspective, discount rate, screening and antiviral treatment mode varied. The incremental effectiveness of HCV screening and early treatment compared to no screening and standard care varied from 0.0004 to 0.066 LYG, and from 0.0001 to 0.072 QALY. Incremental cost-effectiveness and cost-utility ratios of HCV screening vs. no screening were 3900-243,700 euro/LYG and 18,300-1,151,000 euro/QALY. HCV screening seems to be cost-effective in populations with high HCV prevalence, but not in low HCV prevalence populations. CONCLUSIONS: HCV screening and early treatment have the potential to improve average life-expectancy, but should focus on populations with elevated HCV prevalence to be cost-effective. Further research on the long-term health-economic impact of HCV screening when combined with appropriate monitoring strategies in different European health care systems is needed.

HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. METHODS: Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. RESULTS: HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3-8.8 million people (1.1-1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. CONCLUSION: Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.

Progression-free survival as a surrogate endpoint in advanced breast cancer.

OBJECTIVES: Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint. METHODS: A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption. RESULTS: Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses. CONCLUSIONS: This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.