Cost-effectiveness of a multidimensional post-discharge disease management program for heart failure patients-economic evaluation along a one-year observation period.

OBJECTIVE: This study aimed to assess the cost-effectiveness of the telemedically assisted post-discharge management program (DMP) HerzMobil Tirol (HMT) for heart failure (HF) patients in clinical practice in Austria. METHODS: We conducted a cost-effectiveness analysis along a retrospective cohort study (2016-2019) of HMT with a propensity score matched cohort of 251 individuals in the HMT and 257 in the usual care (UC) group and a 1-year follow-up. We calculated the effectiveness (hospital-free survival, hospital-free life-years gained, and number of avoided rehospitalizations), costs (HMT, rehospitalizations), and the incremental cost-effectiveness ratio (ICER). We performed a nonparametric sensitivity analysis with bootstrap sampling and sensitivity analyses on costs of HF rehospitalizations and on costs per disease-related diagnosis (DRG) score for rehospitalizations. RESULTS: Base-case analysis showed that HMT resulted in an average of 42 additional hospital-free days, 40 additional days alive, and 0.12 avoided hospitalizations per patient-year compared with UC during follow-up. The average HMT costs were EUR 1916 per person. Mean rehospitalization costs were EUR 5551 in HMT and EUR 6943 in UC. The ICER of HMT compared to UC was EUR 4773 per life-year gained outside the hospital. In a sensitivity analysis, HMT was cost-saving when "non-HF related costs" related to the DMP were replaced with average costs. CONCLUSIONS: The economic evaluation along the cohort study showed that the HerzMobil Tirol is very cost-effective compared to UC and cost-saving in a sensitivity analysis correcting for "non-HF related costs." These findings promote a widespread adoption of telemedicine-assisted DMP for HF.

Health assessment of harbour porpoises (PHOCOENA PHOCOENA) from Baltic area of Denmark, Germany, Poland and Latvia.

Harbour porpoise (Phocoena phocoena), the only resident cetacean species of the Baltic Sea is formed of two subpopulations populations, occurring in the western Baltic, Belt Seas and Kattegat and the Baltic Proper, respectively. Harbour porpoises throughout these areas are exposed to a large number of human activities causing direct and indirect effects on individuals, that might also harm this species on a population level. From Latvia, Poland, Germany and Denmark 385 out of 1769 collected dead harbour porpoises were suitable for extensive necropsy. The animals were collected between 1990 and 2015 and were either by-caught or found dead on the coastline. Following necropsies, histopathological, microbiological, virological and parasitological investigations were conducted. Females and males were equally distributed among the 385 animals. Most animals from the different countries were juveniles between 3 months and 3 years old (varying between 46.5 and 100% of 385 animals per country). The respiratory tract had the highest number of morphological lesions, including lungworms in 25 to 58% and pneumonia in 21 to 58% of the investigated animals. Of those with pneumonia 8 to 33% were moderate or severe. The alimentary, hearing, and haematopoietic systems had inflammatory lesions and parasitic infections with limited health impact. 45.5 to 100% of the animals from the different countries were known by-caught individuals, of which 20 to 100% varying between countries had netmarks. Inflammatory lesions, especially in the respiratory tract were found in higher numbers when compared to control populations in areas with less human activities such as arctic waters. The high number of morphological changes in the respiratory tract and of bycatches especially among immature animals before reaching sexual maturity is of serious concern, as well as the low number of adult animals among the material. Data on health status and the causes of death are valuable for management. A next step in this regard will combine data from health and genetic investigations in order to detect differences between the two populations of the Baltic.

Improved two-stage estimation to adjust for treatment switching in randomised trials: g-estimation to address time-dependent confounding.

In oncology trials, control group patients often switch onto the experimental treatment during follow-up, usually after disease progression. In this case, an intention-to-treat analysis will not address the policy question of interest - that of whether the new treatment represents an effective and cost-effective use of health care resources, compared to the standard treatment. Rank preserving structural failure time models (RPSFTM), inverse probability of censoring weights (IPCW) and two-stage estimation (TSE) have often been used to adjust for switching to inform treatment reimbursement policy decisions. TSE has been applied using a simple approach (TSEsimp), assuming no time-dependent confounding between the time of disease progression and the time of switch. This is problematic if there is a delay between progression and switch. In this paper we introduce TSEgest, which uses structural nested models and g-estimation to account for time-dependent confounding, and compare it to TSEsimp, RPSFTM and IPCW. We simulated scenarios where control group patients could switch onto the experimental treatment with and without time-dependent confounding being present. We varied switching proportions, treatment effects and censoring proportions. We assessed adjustment methods according to their estimation of control group restricted mean survival times that would have been observed in the absence of switching. All methods performed well in scenarios with no time-dependent confounding. TSEgest and RPSFTM continued to perform well in scenarios with time-dependent confounding, but TSEsimp resulted in substantial bias. IPCW also performed well in scenarios with time-dependent confounding, except when inverse probability weights were high in relation to the size of the group being subjected to weighting, which occurred when there was a combination of modest sample size and high switching proportions. TSEgest represents a useful addition to the collection of methods that may be used to adjust for treatment switching in trials in order to address policy-relevant questions.

Two-stage estimation to adjust for treatment switching in randomised trials: a simulation study investigating the use of inverse probability weighting instead of re-censoring.

BACKGROUND: Treatment switching is common in randomised trials of oncology treatments, with control group patients switching onto the experimental treatment during follow-up. This distorts an intention-to-treat comparison of the treatments under investigation. Two-stage estimation (TSE) can be used to estimate counterfactual survival times for patients who switch treatments - that is, survival times that would have been observed in the absence of switching. However, when switchers do not die during the study, counterfactual censoring times are estimated, inducing informative censoring. Re-censoring is usually applied alongside TSE to resolve this problem, but results in lost longer-term information - a major concern if the objective is to estimate long-term treatment effects, as is usually the case in health technology assessment. Inverse probability of censoring weights (IPCW) represents an alternative technique for addressing informative censoring but has not before been combined with TSE. We aim to determine whether combining TSE with IPCW (TSEipcw) represents a valid alternative to re-censoring. METHODS: We conducted a simulation study to compare TSEipcw to TSE with and without re-censoring. We simulated 48 scenarios where control group patients could switch onto the experimental treatment, with switching affected by prognosis. We investigated various switching proportions, treatment effects, survival function shapes, disease severities and switcher prognoses. We assessed the alternative TSE applications according to their estimation of control group restricted mean survival (RMST) that would have been observed in the absence of switching up to the end of trial follow-up. RESULTS: TSEipcw performed well when its weights had a low coefficient of variation, but performed poorly when the coefficient of variation was high. Re-censored analyses usually under-estimated control group RMST, whereas non-re-censored analyses usually produced over-estimates, with bias more serious when the treatment effect was high. In scenarios where TSEipcw performed well, it produced low bias that was often between the two extremes associated with the re-censoring and non-recensoring options. CONCLUSIONS: Treatment switching adjustment analyses using TSE should be conducted with re-censoring, without re-censoring, and with IPCW to explore the sensitivity in results to these application options. This should allow analysts and decision-makers to better interpret the results of adjustment analyses.

Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate 'counterfactual' (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes, treatment effect changes over time, survival function shapes, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival that would be observed in the absence of switching, up to the end of trial follow-up. We found that analyses which re-censored usually produced negative bias (i.e. underestimating control group restricted mean survival and overestimating the treatment effect), whereas analyses that did not re-censor consistently produced positive bias which was often smaller in magnitude than the bias associated with re-censored analyses, particularly when the treatment effect was high and the switching proportion was low. The RPSFTM with re-censoring generally resulted in increased bias compared to the other methods. We believe that analyses should be conducted with and without re-censoring, as this may provide decision-makers with useful information on where the true treatment effect is likely to lie. Incorporating re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects.

Cost effectiveness of personalized treatment in women with early breast cancer: the application of OncotypeDX and Adjuvant! Online to guide adjuvant chemotherapy in Austria.

A Breast Cancer Outcomes model was developed at the ONCOTYROL research center to evaluate personalized test-treatment strategies in Austria. The goal was to evaluate the cost-effectiveness of a new 21-gene assay (ODX) when used in conjunction with the Adjuvant! Online (AO) decision aid to support personalized decisions about use of adjuvant chemotherapy in early-stage breast cancer patients in Austria. We applied a validated discrete-event-simulation model to a hypothetical cohort of 50 years old women over a lifetime horizon. The test-treatment strategies of interest were defined using three-letter acronyms. The first (second, third) letter indicates whether patients with a low (intermediate, high) risk according to AO were tested using ODX (Y yes, N no). The main outcomes were life-years gained, quality-adjusted life-years (QALYs), costs and cost effectiveness. Robustness of the results was tested in sensitivity analyses. Results were compared to a Canadian analysis conducted by the Toronto Health Economics and Technology Assessment Collaborative (THETA). Five of eight strategies were dominated (i.e., more costly and less effective: NNY, NYN, YNN, YNY, YYN). The base-case analysis shows that YYY (ODX provided to all patients) is the most effective strategy and is cost effective with an incremental cost-effectiveness ratio of 15,700 EUR per QALY gained. These results are sensitive to changes in the probabilities of distant recurrence, age and costs of chemotherapy. The results of the base-case analysis were comparable to the THETA results. Based on our analyses, using ODX in addition to AO is effective and cost effective in all women in Austria. The development of future genetic tests may require alternative or additional test-treatment strategies to be evaluated.

The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review.

BACKGROUND: Generic drugs are considered therapeutically equivalent to their original counterparts and lower in acquisition costs. However, the overall impact of generic substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated. OBJECTIVE: To test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies. METHODS: We performed a systematic literature review in Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine clinical or economic outcomes of GS. After standardized data extraction, reported outcomes were categorized as supporting or rejecting the hypotheses. Each reported outcome was assessed and accounted for supporting and opposing GS. One publication could provide multiple outcome comparisons. RESULTS: We included 40 studies across ten therapeutic areas. Fourteen studies examined patients on de novo therapy; 24 studies investigated maintenance drug therapy, and two studies considered both settings. Overall, 119 outcome comparisons were examined. Of 97 clinical outcome comparisons, 67% reported no significant difference between generic drugs and their off-patent counterparts. Of 22 economic comparisons, 64% suggested that GS increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major differences among studies that investigated clinical outcomes with de novo or maintenance therapy. CONCLUSION: The review suggests that clinical effects are similar after GS. However, economic savings are not guaranteed. More systematic research comparing clinical and economic outcomes with or without GS is needed to inform policy on the use of generic substitution.

Decision-analytic modeling studies: An overview for clinicians using multiple myeloma as an example.

PURPOSE: The purpose of this study was to provide a clinician-friendly overview of decision-analytic models evaluating different treatment strategies for multiple myeloma (MM). METHODS: We performed a systematic literature search to identify studies evaluating MM treatment strategies using mathematical decision-analytic models. We included studies that were published as full-text articles in English, and assessed relevant clinical endpoints, and summarized methodological characteristics (e.g., modeling approaches, simulation techniques, health outcomes, perspectives). RESULTS: Eleven decision-analytic modeling studies met our inclusion criteria. Five different modeling approaches were adopted: decision-tree modeling, Markov state-transition modeling, discrete event simulation, partitioned-survival analysis and area-under-the-curve modeling. Health outcomes included survival, number-needed-to-treat, life expectancy, and quality-adjusted life years. Evaluated treatment strategies included novel agent-based combination therapies, stem cell transplantation and supportive measures. CONCLUSION: Overall, our review provides a comprehensive summary of modeling studies assessing treatment of MM and highlights decision-analytic modeling as an important tool for health policy decision making.

Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

Consideration of international generic distribution policies on patient outcomes in the United States and Germany.

Generic substitution of narrow therapeutic index drugs can have unintended consequences. Generic switching is often driven by cost incentives, regulations and supply, but may raise concerns about equal bioavailability, therapeutic equivalence and about possible confusion for the patient. Integrated systems of care with active management of patient behaviors, including adherence, may minimize the impact of switching. This article is intended to present policy drivers and potential consequences of generic switching and the role of pharmacist education in minimizing patient risk using warfarin and the pharmaceutical distribution systems of the United States and Germany as examples.

Economic outcomes of sequences which include monoclonal antibodies against vascular endothelial growth factor and/or epidermal growth factor receptor for the treatment of unresectable metastatic colorectal cancer.

BACKGROUND: Patients with unresectable, metastatic colorectal cancer with wild type Kirsten ras mutational status are eligible for sequential treatments which include monoclonal antibodies as first line (1L), second line (2L), or third line (3L) regimens. OBJECTIVE: To compare the economic outcomes of different sequences which include monoclonal antibodies for the treatment of unresectable metastatic colorectal cancer. METHODS: Individual drug regimens for 1L, 2L, and 3L treatments were compiled according to the clinical studies in the Summary of Product Characteristics for monoclonal antibodies. They were combined into plausible treatment sequences. Health outcomes were approximated using additive median PFS benefit, and economic outcomes were calculated with a treatment sequencing costing tool. Limitations of the analysis include the clinical trial data sources, cost assumptions, and the additive PFS approach. RESULTS: Seventeen sequences were evaluated. Results of the analysis show that sequences including 1L anti-EGFRs generally have relatively low-to-medium health outcomes at the highest comparative sequence costs compared to sequences including 2L anti-EGFRs, which have lower health outcomes at the lowest cost. Sequences including 3L anti-EGFRs (sequential bevazicumab-based 1L and 2L) have the highest health outcomes, with potential cost savings of €5972-€11,676 if replacing 2L anti-EGFRs or an additional cost of €5909-€12,708 if replacing 1L anti-EGFR regimens. CONCLUSION: Clinical sequences consisting of 1L and 2L line bevacizumab followed by 3L anti-EGFR potentially yield the greatest health outcomes associated with a reasonable trade-off in additional cost when replacing 1L anti-EGFRs and are potentially cost-saving if replacing 2L anti-EGFRs, per patient per lifetime. To maximize health outcomes, optimal sequences include anti-EGFRs as 3L regimen, with an approximately equivalent trade-off in costs between the most costly (anti-EGFR 2L) and least costly (anti-EGFR 1L) sequences.

[Direct and indirect costs of fractures due to osteoporosis in Austria]. / Direkte und indirekte Kosten von osteoporotisch bedingten Frakturen in Österreich.

OBJECTIVES: We examined the financial burden of osteoporosis in Austria. METHODS: We took both direct and indirect costs into consideration. Direct costs encompass medical costs such as expenses for pharmaceuticals, inpatient and outpatient medical care costs, as well as other medical services (e.g., occupational therapies). Non-medical direct costs include transportation costs and medical devices (e.g., wheel chairs or crutches). Indirect costs refer to costs of productivity losses due to absence of work. Moreover, we included costs for early retirement and opportunity costs of informal care provided by family members. While there exist similar studies for other countries, this is the first comprehensive study for Austria. For our analysis, we combined data of official statistics, expert estimates as well as unique patient surveys that are currently conducted in the course of an international osteoporotic fracture study in Austria. RESULTS: Our estimation of the total annual costs in the year 2008 imposed by osteoporosis in Austria is 707.4 million €. The largest fraction of this amount is incurred by acute hospital treatment. Another significant figure, accounting for 29% of total costs, is the opportunity cost of informal care. CONCLUSIONS: The financial burden of osteoporosis in Austria is substantial. Economic evaluations of preventive and therapeutic interventions for the specific context of Austria are needed to inform health policy decision makers.

Cost-effectiveness of primary HPV screening for cervical cancer in Germany--a decision analysis.

OBJECTIVES: To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. METHODS: A Markov-model for HPV-infection and cervical cancer was developed for the German health care context, and applied to evaluate various screening strategies that differ by screening interval and test algorithms, including HPV-testing alone or in combination with cytology. German clinical, epidemiological, and economic data, and test accuracy data from international meta-analyses were used. Outcomes predicted included the reduction in cervical cancer cases and deaths, life expectancy and discounted incremental cost-effectiveness ratios (ICER). The analysis was performed from the perspective of the healthcare system adopting a 3% annual discount rate for costs and outcomes. Extensive sensitivity analyses were performed. RESULTS: HPV-based screening is more effective than cytology alone. It results in a 71-97% reduction in cervical cancer cases as compared to 53-93% for cytology alone. The ICER range from 2600 Euro/LYG (cytology, 5-year-interval) to 155,500 Euro/LYG (annual HPV-testing starting at age 30 years, cytology age 20-29 years). Annual cytology alone, the current recommended screening strategy in Germany, is dominated by HPV-strategies. Increasing the age at screening initiation from 20 to 25 years does not result in a relevant loss in effectiveness but results in lower costs. CONCLUSIONS: Based on our analyses, HPV-based cervical cancer screening is more effective than cytology alone and could be cost-effective if performed at intervals of two years or longer. In the German context, an optimal screening strategy may be biennial HPV screening starting at age 30 years preceded by biennial cytology for women aged 25-29 years. Longer screening intervals may be considered in low-risk women with good screening adherence and in populations with low HPV-incidence.

[Perinatal mortality by mother's country of origin in Tyrol 2000-2008]. / Perinatale Mortalität nach Herkunftsland der Mutter in Tirol 2000-2008.

INTRODUCTION: This study analyses for the first time the Tyrolean perinatal mortality stratified by the country of origin of the mother. Data of the Tyrolean birth registry were evaluated from 2000-2008. The aim of our study was to analyse differences in perinatal mortality according to the country of origin of the mother. METHODS: 58 787 single births were assessed between the years 2000-2008. Mothers with similar experiences of how to access the health-care system were aggregated into 5 groups: (1) "Tyrol/Austria", (2) "western Europe/West", (3) "former Yugoslavia/eastern Europe", (4) "Turkey" and (5) "other countries". The odds ratio for perinatal mortality according to the country of origin of the mother was calculated in a multivariate model. The following independent variables were included: age of mother at birth, parity, housewife during pregnancy, week of gestation at the first check-up visit, smoking, preterm delivery and weight of the newborn. RESULTS: The number of mothers of Tyrolean/Austrian origin decreased over the years by 2% whereas the number of mothers from Western Europe/West increased by 3%. The other migration groups remained constant or were slightly decreased. In the multivariate model; the perinatal mortality [odds ratio (CI)] was for the subgroups "Turkey" 1.06 (0.61-1.83) and for "western Europe/West" 1.09 (0.64-1.86), and therefore almost identical with the reference subgroup "Tyrol/Austria" (OR=1); the perinatal mortality was significantly increased with 2.14 (1.37-3.34) for the subgroup "former Yugoslavia/eastern Europe and for the subgroup "other countries" 2.54 (1.21-5.36). The variables "age under 18 years" OR 1.99 (0.80-4.93) and "mulitpara" OR 1.30 (0.96-1.74) were not significantly increased. Significantly increased was "preterm delivery" OR 4.53 (2.80-7.33) and "low birthweight" (<1 500 g) OR 53.60 (32.02-89.73) and 1 500 to 2 499 g OR 4.85 (2.96-7.96). There are considerable differences comparing the odds ratios between the 5 subgroups for perinatal mortality. The subgroups "Turkey" and "western Europe/West" have a similar odds ratio compared to the reference group "Tyrol/Austria". The subgroups "former Yugoslavia" and "other countries" have a significantly increased perinatal mortality (OR 2-2.5). CONCLUSION: The good outcome of the mothers from "Turkey" can be seen as similar to the "Latina paradoxon", which means a better outcome of pregnancy and birth of mothers from "Turkey", even though they are more comparable with other migrant groups in some risk factors, such as a lower socioeconomic standard, late check-ups, language difficulties and cultural factors. A single case analysis would be necessary to examine the exact causes.

Benefit, risks and cost-effectiveness of screening for abdominal aortic aneurysm.

PURPOSE: Abdominal aortic aneurysms (AAA) cause a considerable number of deaths. A ruptured AAA is associated with a mortality rate of 80%. The purpose of this study was to summarize the current evidence from published health economic models for the long-term effectiveness and cost-effectiveness of screening programs for AAA. MATERIALS AND METHODS: Medical, economic and health technology assessment (HTA) databases were systematically searched for cost-effectiveness models up to October 2007. Only models with a lifetime time horizon of evaluating AAA screening in men over 65 years were included in the review. Study data were extracted, standardized and summarized in evidence tables and cost-effectiveness plots. RESULTS: We reviewed 8 cost-effectiveness models published between 1993 and 2007 comparing AAA screening and lack of screening in men over 60. One model yielded a loss of life-years at additional costs. The remaining seven models yielded gains in life expectancy ranging from 0.02 to 0.28LYs. Gains in quality-adjusted life expectancy reported by six of the seven models ranged from 0.015 to 0.059 QALYs. Incremental costs ranged from 96 to 721 Euros. Incremental cost-effectiveness ratios (ICER) ranged from 1443 to 13 299 Euros per LY or QALY gained. CONCLUSION: Based on our analysis, the introduction of a screening program to identify AAA will probably gain additional life years and quality of life at acceptable extra costs. The target population for a screening program should be men 65 years and older.

Long-term effectiveness and cost-effectiveness of antiviral treatment in hepatitis C.

We systematically reviewed the evidence for long-term effectiveness and cost-effectiveness of antiviral treatment in patients with chronic hepatitis C. We performed a systematic literature search on the long-term effectiveness and cost-effectiveness of AVT in hepatitis C (1990-March 2007), and included health technology assessment (HTA) reports, systematic reviews, long-term clinical trials, economic studies conducted alongside clinical trials and decision-analytic modelling studies. All costs were converted to 2005euro. Antiviral therapy with peginterferon plus ribavirin in treatment-naïve patients with chronic hepatitis C was the most effective (3.6-4.7 life years gained [LYG]) treatment and was reasonably cost-effective (cost-saving to 84 700euro/quality adjusted life years [QALY]) when compared to interferon plus ribavirin. Some results also suggest cost-effectiveness (below 8400euro/(QALY) of re-treatment in nonresponders/relapsers. Results for patients with persistently normal alanine aminotransferase (ALT) levels or with special co-morbidities (e.g. HIV) or risk profiles were rare. We conclude that antiviral therapy may prolong life, improve long-term health-related quality-of-life and be reasonably cost-effective in treatment-naïve patients with chronic hepatitis C as well as in former relapsers/nonresponders. Further research is needed in patients with specific co-morbidities or risk profiles.

The cost-effectiveness of testing for hepatitis C in former injecting drug users.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). DATA SOURCES: Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. REVIEW METHODS: A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. RESULTS: Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around pounds sterling 760,000 more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around pounds sterling 70,000. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of pounds sterling 20,084. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as pounds sterling 16,514 per QALY. The probabilistic sensitivity analysis shows that, if NHS policy makers view pounds sterling 30,000 per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At pounds sterling 20,000 per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of pounds sterling 30,000 per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (pounds sterling 20,000 per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around pounds sterling 15,000 per QALY. Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below pounds sterling 30,000 for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of pounds sterling 19 million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising, since the point estimates for differences in utility between states and across the arms of the model are small. CONCLUSIONS: Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly.