Preferences as fairness judgments: a critical review of normative frameworks of preference elicitation and development of an alternative based on constitutional economics.

Preference elicitation is widely used within health economic evaluations to inform coverage decisions. However, coverage decisions involve questions of social justice and it is unclear what role empirical evidence about preferences can play here. This study reviews the prevalent normative frameworks for using population-based preference elicitation and the criticisms they face, and proposes an alternative based on constitutional economics. The frameworks reviewed include a supposedly value-neutral framework of preferences as predictors of choice, preference utilitarian frameworks that aim to maximize preference satisfaction, and substantive consequentialist frameworks that aim to maximize happiness, health, or capabilities. The proposed alternative implements the idea that indices of social value are tools for conflict resolution, rather than tools for maximization. Preference elicitation is used for validating values generated by multi-criteria decision analysis results within representative processes of stakeholder deliberation.

The impact of switching from single-use to reusable healthcare products: a transparency checklist and systematic review of life-cycle assessments.

BACKGROUND: Replacing single-use products with reusable ones may reduce the environmental impact of healthcare. This study aimed to broadly assess the environmental effects of that substitution. METHODS: A systematic review of comparative cradle-to-grave life-cycle assessments (LCAs) of single-use and reusable healthcare products was conducted. The main outcomes assessed were changes in the environmental impact that resulted after switching from single-use to reusable products. As no standardized transparency checklist was available, one was developed here using DIN ISO 14040/14044. The final checklist included 22 criteria used to appraise the included studies. RESULTS: After screening, 27 studies were included in the analysis. The healthcare products were assigned to four categories: invasive medical devices, non-invasive medical devices, protection equipment and inhalers. The outcomes revealed a reduction in mean effect sizes for all environmental impacts except water use. Non-invasive medical devices have greater relative mitigation potential than invasive devices. On average, information on 64% of the transparency checklist items was reported. Gaps included the reporting of data quality requirements. CONCLUSIONS: Switching to reusable healthcare products is likely to reduce most impacts on the environment except water use, but the effect size differs among product categories. Possible study limitations include location bias, no systematic search of the grey literature and small samples for some impacts. This study's strengths are its approach to product categories and developed transparency catalogue. This catalogue could be useful to inform and guide a future process towards creating a standardized transparency checklist for the systematic reviews of LCAs.

Reporting Quality of Discrete Event Simulations in Healthcare-Results From a Generic Reporting Checklist.

OBJECTIVES: The aims of this study were to formulate a generic reporting checklist for healthcare-related discrete event simulation (DES) studies and to critically appraise the existing studies. METHODS: Based on the principles of accessibility and generality, assessment items were derived from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)-Society for Medical Decision Making (SMDM) Task Force reports. The resulting checklist was applied to all 211 DES studies identified in a previous review. The proportion of fulfilled checklist items served as an indicator of reporting quality. A logistic regression was conducted to investigate whether study characteristics (eg, publication before or after the publication of the ISPOR-SMDM reports) increased the likelihood of fulfilling more than the mean number of items fulfilled by the appraised DES studies. RESULTS: An 18-item checklist was formulated covering model conceptualization, parameterization and uncertainty assessment, validation, generalizability, and stakeholder involvement. The reporting quality of the DES models fluctuated around the mean of 63.7% (SD 11.0%) over the period studied. A modest nonsignificant improvement in reporting quality was found after the publication of the ISPOR-SMDM reports (64.5% vs 62.9%). Items with the lowest performance were related to predictive validation (2.8% of studies), cross validation (8.5%), face validity assessment (26.5%), and stakeholder involvement (27.5%). Models applied to health economic evaluation (HEE), country under study, and industry sponsorship were significantly associated with the odds of achieving above-average reporting quality. CONCLUSIONS: The checklist is applicable across various model-based analyses beyond HEEs. Adherence to the ISPOR-SMDM guidelines should be improved, particularly regarding model validation.

MCDA-based deliberation to value health states: lessons learned from a pilot study.

BACKGROUND: Health economists have shown a growing interest in deliberation and multi-criteria decision analysis (MCDA) as possible pathways to transparently integrate value judgments in cost-utility analyses. In line with these developments, this study piloted a consensus process to derive a German value set for the Short-Form Six-Dimension (SF-6D). In a conference setting, a group was tasked to deliberate on scores and weights for the SF-6D from the perspective of a self-determined and independent life. METHODS: The one-day consensus conference was based on a deliberative process in combination with the MCDA method MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique). According to MACBETH, participants were asked to qualitatively rate pairwise comparisons of SF-6D health states. The scoring within each dimension was conducted in parallel group sessions. Final agreement on the scores as well as weights for the SF-6D dimensions were derived in a subsequent plenary assembly. Results were analyzed using the software M-MACBETH and qualitative content analysis. RESULTS: A total of 34 participants were recruited. While each of the 6 small groups presented a consented score, the plenary assembly reached consensus on all dimensions apart from pain. Concerning dimension weights, some participants favored prioritizing pain and mental health. Others disputed that trade-offs between dimensions and thus assigning weights were not acceptable in a context where this may involve withholding care from someone. As a consequence, no consensus on a value set was reached. Participants identified the group size of the plenary session and the applied weighting procedure as main obstacles to the process. CONCLUSIONS: This pilot study presents a consensus-based approach for valuing health-related quality of life. However, further research is needed on deliberative processes that yield quantifiable results. Future conferences should explore smaller group sizes, longer durations of the deliberative process and alternatives to the additive value function applied in MACBETH.

Evaluation as institution: a contractarian argument for needs-based economic evaluation.

BACKGROUND: There is a gap between health economic evaluation methods and the value judgments of coverage decision makers, at least in Germany. Measuring preference satisfaction has been claimed to be inappropriate for allocating health care resources, e.g. because it disregards medical need. The existing methods oriented at medical need have been claimed to disregard non-consequentialist fairness concerns. The aim of this article is to propose a new, contractarian argument for justifying needs-based economic evaluation. It is based on consent rather than maximization of some impersonal unit of value to accommodate the fairness concerns. MAIN TEXT: This conceptual paper draws upon contractarian ethics and constitution economics to show how economic evaluation can be viewed as an institution to overcome societal conflicts in the allocation of scarce health care resources. For this, the problem of allocating scarce health care resources in a society is reconstructed as a social dilemma. Both disadvantaged patients and affluent healthy individuals can be argued to share interests in a societal contract to provide technologies which ameliorate medical need, based on progressive funding. The use of needs-based economic evaluation methods for coverage determination can be interpreted as institutions for conflict resolution as far as they use consented criteria to ensure the social contract's sustainability and avoid implicit rationing or unaffordable contribution rates. This justifies the use of needs-based evaluation methods by Pareto-superiority and consent (rather than by some needs-based value function per se). CONCLUSION: The view of economic evaluation presented here may help account for fairness concerns in the further development of evaluation methods. This is because it directs the attention away from determining some unit of value to be maximized towards determining those persons who are most likely not to consent and meeting their concerns. Following this direction in methods development is likely to increase the acceptability of health economic evaluation by decision makers.

Manual Compression versus Vascular Closing Device for Closing Access Puncture Site in Femoral Left-Heart Catheterization and Percutaneous Coronary Interventions: A Retrospective Cross-Sectional Comparison of Costs and Effects in Inpatient Care.

OBJECTIVES: To compare complication rates, length of hospital stay, and resulting costs between the use of manual compression and a vascular closing device (VCD) in both diagnostic and interventional catheterization in a German university hospital setting. METHODS: A stratified analysis according to risk profiles was used to compare the risk of complications in a retrospective cross-sectional single-center study. Differences in costs and length of hospital stay were calculated using the recycled predictions method, based on regression coefficients from generalized linear models with gamma distribution. All models were adjusted for propensity score and possible confounders, such as age, sex, and comorbidities. The analysis was performed separately for diagnostic and interventional catheterization. RESULTS: The unadjusted relative risk (RR) of complications was not significantly different in diagnostic catheterization when a VCD was used (RR = 0.70; 95% confidence interval [CI] 0.22-2.16) but significantly lower in interventional catheterization (RR = 0.44; 95% CI 0.21-0.93). Costs were on average €275 lower in the diagnostic group (95% CI -€478.0 to -€64.9; P = 0.006) and around €373 lower in the interventional group (95% CI -€630.0 to -€104.2; P = 0.014) when a VCD was used. The adjusted estimated average length of stay did not differ significantly between the use of a VCD and manual compression in both types of catheterization. CONCLUSIONS: In interventional catheterization, VCDs significantly reduced unadjusted complication rates, as well as costs. A significant reduction in costs also supports their usage in diagnostic catheterization on a larger scale.

The cost-effectiveness of UGT1A1 genotyping before colorectal cancer treatment with irinotecan from the perspective of the German statutory health insurance.

BACKGROUND: The evidence concerning the cost-effectiveness of UGT1A1*28 genotyping is ambiguous and does not allow drawing valid conclusions for Germany. This study evaluates the cost-effectiveness of UGT1A1 genotyping in patients with metastatic colorectal cancer undergoing irinotecan-based chemotherapy compared to no testing from the perspective of the German statutory health insurance. MATERIAL AND METHODS: A decision-analytic Markov model with a life time horizon was developed. No testing was compared to two genotype-dependent therapy strategies: 1) dose reduction by 25%; and 2) administration of a prophylactic G-CSF growth factor analog for homozygous and heterozygous patients. Probability, quality of life and cost parameters used in this study were based on published literature. Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Strategy 1 dominated all remaining strategies. Compared to no testing, it resulted in only marginal QALY increases (0.0002) but a cost reduction of €580 per patient. Strategy 2 resulted in the same health gains but increased costs by €10 773. In the probabilistic analysis, genotyping and dose reduction was the optimal strategy in approximately 100% of simulations at a threshold of €50 000 per QALY. Deterministic sensitivity analysis shows that uncertainty for this strategy originated primarily from costs for irinotecan-based chemotherapy, from the prevalence of neutropenia among heterozygous patients, and from whether dose reduction is applied to both homozygotes and heterozygotes or only to the former. CONCLUSION: This model-based synthesis of the most recent evidence suggests that pharmacogenetic UGT1A1 testing prior to irinotecan-based chemotherapy dominates non-personalized colon cancer care in Germany. However, as structural uncertainty remains high, these results require validation in clinical practice, e.g. based on a managed-entry agreement.

Costs of conservative management of early-stage prostate cancer compared to radical prostatectomy-a claims data analysis.

BACKGROUND: Due to widespread PSA testing incidence rates of localized prostate cancer increase but curative treatment is often not required. Overtreatment imposes a substantial economic burden on health care systems. We compared the direct medical costs of conservative management and radical therapy for the management of early-stage prostate cancer in routine care. METHODS: An observational study design is chosen based on claims data of a German statutory health insurance fund for the years 2008-2011. Three hundred fifty-three age-matched men diagnosed with prostate cancer and treated with conservative management and radical prostatectomy, are included. Individuals with diagnoses of metastases or treatment of advanced prostate cancer are excluded. In an excess cost approach direct medical costs are considered from an insured community perspective for in- and outpatient care, pharmaceuticals, physiotherapy, and assistive technologies. Generalized linear models adjust for comorbidity by Charlson comorbidity score and recycled predictions method calculates per capita costs per treatment strategy. RESULTS: After follow-up of 2.5 years per capita costs of conservative management are €6611 lower than costs of prostatectomy ([-9734;-3547], p < 0.0001). Complications increase costs of assistive technologies by 30% (p = 0.0182), but do not influence any other costs. Results are robust to cost outliers and incidence of prostate cancer diagnosis. The short time horizon does not allow assessing long-term consequences of conservative management. CONCLUSIONS: At a time horizon of 2.5 years, conservative management is preferable to radical prostatectomy in terms of costs. Claims data analysis is limited in the selection of comparable treatment groups, as clinical information is scarce and bias due to non-randomization can only be partly mitigated by matching and confounder adjustment.

USING CLAIMS DATA FOR EVIDENCE GENERATION IN MANAGED ENTRY AGREEMENTS.

OBJECTIVES: This study assesses the use of routinely collected claims data for managed entry agreements (MEA) in the illustrative context of German statutory health insurance (SHI) funds. METHODS: Based on a nonsystematic literature review, the data needs of different MEA were identified. A value-based typology to classify MEA on the basis of these data needs was developed. The typology is oriented toward health outcomes and utilization and costs, key components of a new technology's value. For each MEA type, the suitability of claims data in establishing evidence of the novel technology's value in routine care was systematically assessed. Assessment criteria were data availability, completeness, timeliness, confidentiality, reliability, and validity. RESULTS: Claims data are better suited to MEA addressing uncertainty regarding the utilization and costs of a novel technology in routine care. In schemes where safety aspects or clinical effectiveness are assessed, the role of claims data is limited because clinical information is not included in sufficient detail. CONCLUSIONS: The suitability of claims data depends on the source of uncertainty and, in consequence, the outcome measures chosen in the agreements. In all schemes, the validity of claims data should be judged with caution as data are collected for billing purposes. This framework may support manufacturers and payers in selecting the most suitable contract type and agreeing on contract conditions. More research is necessary to validate these results and to address remaining medical, economic, legal, and ethical questions of using claims data for MEA.

Economic evaluation of genetic screening for Lynch syndrome in Germany.

PURPOSE: Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. METHODS: We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically. RESULTS: On average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was [euro ]77,268, [euro ]253,258, and [euro ]4,188,036 per life-year gained, respectively. CONCLUSION: The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.

Challenges of translating genetic tests into clinical and public health practice.

Research in genetics and genomics has led to an expanding list of molecular genetic tests, which are increasingly entering health care systems. However, the evidence surrounding the benefits and harms of these tests is frequently weak. Here we present the main challenges to the successful translation of new research findings about genotype-phenotype associations into clinical practice. We discuss the means to achieve an accelerated translation research agenda that is conducted in a reasonable, fair and efficient manner.

Early decision-analytic modeling - a case study on vascular closure devices.

BACKGROUND: As economic considerations become more important in healthcare reimbursement, decisions about the further development of medical innovations need to take into account not only medical need and potential clinical effectiveness, but also cost-effectiveness. Already early in the innovation process economic evaluations can support decisions on development in specific indications or patient groups by anticipating future reimbursement and implementation decisions. One potential concept for early assessment is value-based pricing. METHODS: The objective is to assess the feasibility of value-based pricing and product design for a hypothetical vascular closure device in the pre-clinical stage which aims at decreasing bleeding events. A deterministic decision-analytic model was developed to estimate the cost-effectiveness of established vascular closure devices from the perspective of the Statutory Health Insurance system. To identify early benchmarks for pricing and product design, three strategies of determining the product's value are explored: 1) savings from complications avoided by the new device; 2) valuation of the avoided complications based on an assumed willingness-to-pay-threshold (the efficiency frontier approach); 3) value associated with modifying the care pathways within which the device would be applied. RESULTS: Use of established vascular closure devices is dominated by manual compression. The hypothetical vascular closure device reduces overall complication rates at higher costs than manual compression. Maximum cost savings of only about €4 per catheterization could be realized by applying the hypothetical device. Extrapolation of an efficiency frontier is only possible for one subgroup where vascular closure devices are not a dominated strategy. Modifying care in terms of same-day discharge of patients treated with vascular closure devices could result in cost savings of €400-600 per catheterization. CONCLUSIONS: It was partially feasible to calculate value-based prices for the novel closure device which can be used to inform product design. However, modifying the care pathway may generate much more value from the payers' perspective than modifying the device per se. Manufacturers should thus explore the feasibility of combining reimbursement of their product with arrangements that make same-day discharge attractive also for hospitals. Due to the early nature of the product, the results are afflicted with substantial uncertainty.

The cost-utility of open prostatectomy compared with active surveillance in early localised prostate cancer.

BACKGROUND: There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. METHODS: A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. RESULTS: With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of €6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of €96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. CONCLUSION: AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients' valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences.

Accounting for planetary boundaries in health economic evaluation.

INTRODUCTION: Health economic evaluation (HEE) provides guidance for decision-making in the face of scarcity but ignores ecological scarcities as long as they involve external costs only. Following the imperative to account for planetary health, this study explores how this blind spot can be addressed. AREAS COVERED: The study is based on a critical review of relevant work, particularly in the fields of HEE and life cycle assessment (LCA). LCA can provide information on a technology's environmental impacts which can be accounted for on both the effect and cost sides of HEE. Cost-benefit analyses can incorporate environmental impacts in case vignettes used for eliciting consumers' willingness to pay. Existing LCA impact models can be used to estimate human health risks associated with environmental impacts and add them to the health benefits in cost-utility analyses. Many jurisdictions offer lists of shadow prices that can be used to incorporate environmental impacts on the cost side of HEE. Also, environmental impacts can be reported in a disaggregated manner. EXPERT OPINION: Accounting for planetary boundaries is likely to become a key field of methodological innovation in HEE. Decision relevance is likely to be highest for technologies with similar cost-effectiveness but different ecological impacts.

Carbon footprint of healthcare systems: a systematic review of evidence and methods.

OBJECTIVE: Given the demand for net-zero healthcare, the carbon footprint (CF) of healthcare systems has attracted increasing interest in research in recent years. This systematic review investigates the results and methodological transparency of CF calculations of healthcare systems. The methodological emphasis lies specifically on input-output based calculations. DESIGN: Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. DATA SOURCES: PubMed, Web of Science, EconBiz, Scopus and Google Scholar were initially searched on 25 November 2019. Search updates in PubMed and Web of Science were considered until December 2023. The search was complemented by reference tracking within all the included studies. ELIGIBILITY CRITERIA: We included original studies that calculated and reported the CF of one or more healthcare systems. Studies were excluded if the specific systems were not named or no information on the calculation method was provided. DATA EXTRACTION AND SYNTHESIS: Within the initial search, two independent reviewers searched, screened and extracted information from the included studies. A checklist was developed to extract information on results and methodology and assess the included studies' transparency. RESULTS: 15 studies were included. The mean ratio of healthcare system emissions to total national emissions was 4.9% (minimum 1.5%; maximum 9.8%), and CFs were growing in most countries. Hospital care led to the largest relative share of the total CF. At least 71% of the methodological items were reported by each study. CONCLUSIONS: The results of this review show that healthcare systems contribute substantially to national carbon emissions, and hospitals are one of the main contributors in this regard. They also show that mitigation measures can help reduce emissions over time. The checklist developed here can serve as a reference point to help make methodological decisions in future research reports as well as report homogeneous results.

What is personalized medicine: sharpening a vague term based on a systematic literature review.

BACKGROUND: Recently, individualized or personalized medicine (PM) has become a buzz word in the academic as well as public debate surrounding health care. However, PM lacks a clear definition and is open to interpretation. This conceptual vagueness complicates public discourse on chances, risks and limits of PM. Furthermore, stakeholders might use it to further their respective interests and preferences. For these reasons it is important to have a shared understanding of PM. In this paper, we present a sufficiently precise as well as adequate definition of PM with the potential of wide acceptance. METHODS: For this purpose, in a first step a systematic literature review was conducted to understand how PM is actually used in scientific practice. PubMed was searched using the keywords "individualized medicine", "individualised medicine", "personalized medicine" and "personalised medicine" connected by the Boolean operator OR. A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing the search terms in title or abstract were screened for definitions. Definitions were extracted; according to the means/ends distinction their elements were assigned to the corresponding category. To reduce complexity of the resulting list, summary categories were developed inductively from the data using thematic analysis. In a second step, six well-known criteria for adequate definitions were applied to these categories to derive a so-called precising definition. RESULTS: We identified 2457 articles containing the terms PM in title or abstract. Of those 683 contained a definition of PM and were thus included in our review. 1459 ends and 1025 means were found in the definitions. From these we derived the precising definition: PM seeks to improve stratification and timing of health care by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics. CONCLUSIONS: Our definition includes the aspects that are specific for developments labeled as PM while, on the other hand, recognizing the limits of these developments. Furthermore, it is supported by the quantitative analysis of PM definitions in the literature, which suggests that it it is widely acceptable and thus has the potential to avoid the above mentioned issues.

A Transparency Checklist for Carbon Footprint Calculations Applied within a Systematic Review of Virtual Care Interventions.

Increasing concerns about climate change imply that decisions on the digitization of healthcare should consider evidence about its carbon footprint (CF). This study aims to develop a transparency catalogue for reporting CF calculations, to compare results, and to assess the transparency (reporting quality) of the current evidence of virtual care (VC) intervention. We developed a checklist of transparency criteria based on the consolidation of three established standards/norms for CF calculation. We conducted a systematic review of primary studies written in English or German on the CF of VC interventions to check applicability. Based on our checklist, we extracted methodological information. We compared the results and calculated a transparency score. The checklist comprises 22 items in the aim, scope, data and analysis categories. Twenty-three studies out of 1466 records were included, mostly addressing telemedicine. The mean transparency score was 38% (minimum 14%, maximum 68%). On average, 148 kg carbon dioxide equivalents per patient were saved. Digitization may have co-benefits, improving care and reducing the healthcare CF. However, the evidence for this is weak, and CF reports are heterogeneous. Our transparency checklist may serve as a reference for developing a standard to assess the CF of virtual and other healthcare and public health services.

The role of health technology assessment in coverage decisions on newborn screening.

OBJECTIVES: The role and impact of health technology assessment (HTA) in health policy has been widely discussed. Researchers have started to analyze how decisions on coverage of new technologies are made. Although the involvement of HTA may be an indicator of a well established decision process, this hypothesis requires validation. Also, it is not known whether HTA involvement is associated with other characteristics of decision making like participation or transparency. The primary objective of this study was to develop and test statements on the association between the publication of an HTA and coverage decision making for newborn screening tests in European Union countries. METHODS: Five statements were defined on the relative role of HTA during the steps of decision processes: trigger, participation, publication, assessment, and appraisal. For this purpose, data on twenty-two decision processes in the area of newborn screening across Europe were analyzed, defined as a coverage decision for a given disorder in a specific country. Decision processes were compared by whether the decision was accompanied by the publication of an HTA report. To test differences, nonparametric statistical tests were used. RESULTS: The decision steps of trigger, participation and publication differed between the HTA and the non-HTA groups. No clear association between HTA and assessment methods in coverage decision making was identified. CONCLUSIONS: It appeared that there is an association between HTA and coverage decision processes that are more explicit, inclusive, and transparent. It is unclear whether HTA is associated with formal evidence reviews and economic evaluations.

The cost-effectiveness of screening for hereditary hemochromatosis in Germany: a remodeling study.

OBJECTIVE: Genetic tests for hereditary hemochromatosis (HH) are currently included in the German ambulatory care reimbursement scheme but only for symptomatic individuals and the offspring of HH patients. This study synthesizes the most current evidence to examine whether screening in the broader population is cost-effective and to identify the best choice of initial and follow-up screening tests. METHODS: A probabilistic decision-analytic model was constructed to calculate cost per life year gained (LYG) for HH screening among male Caucasians aged 30. Three strategies were considered in both the general population and male offspring of HH patients: phenotypic (transferrin saturation, TS), genotypic (C282Y mutation), and sequential (genotype if TS is elevated) screening. RESULTS: The incremental cost-effectiveness of sequential screening among male offspring, sequential population-wide screening, and genotypic screening is 41000, 124000, and 161000 Eero/LYG, respectively. All other strategies were subject to simple or extended dominance. The results are subject to high uncertainty. The most influential parameters in the deterministic one-way sensitivity analysis are discounting of life years gained and the adherence of patients to preventive phlebotomy. DISCUSSION: The current German policy of only screening at-risk individuals is consistent with health economic decision making based on typically accepted thresholds. However, conducting the DNA test after the first elevated TS result is more cost-effective than waiting for a second TS result as recommended by the German guidelines. Further empirical work regarding adherence to long-term prevention recommendations and explicit and well-justified guidance for the choice of discount rates in German economic evaluation are needed.

Systematic review of economic evaluations of human cell-derived wound care products for the treatment of venous leg and diabetic foot ulcers.

BACKGROUND: Tissue engineering is an emerging field. Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of diabetic foot and venous leg ulcers for both patients and health care systems. However, they frequently are very costly. Based on a systematic review of the literature, this study assesses the cost-effectiveness of these growth factors and tissue-engineered artificial skin for treating chronic wounds. METHODS: On the basis of an extensive explorative search, an appropriate algorithm for a systematic database search was developed. The following databases were searched: BIOSIS Previews, CRD databases, Cochrane Library, EconLit, Embase, Medline, and Web of Science. Only completed and published trial- or model-based studies which contained a full economic evaluation of growth factors and bioengineered skin substitutes for the treatment of chronic wounds were included. Two reviewers independently undertook the assessment of study quality. The relevant studies were assessed by a modified version of the Consensus on Health Economic Criteria (CHEC) list and a published checklist for evaluating model-based economic evaluations. RESULTS: Eleven health economic evaluations were included. Three biotechnology products were identified for which topical growth factors or bioengineered skin substitutes for the treatment of chronic leg ulceration were economically assessed: (1) Apligraf, a bilayered living human skin equivalent indicated for the treatment of diabetic foot and venous leg ulcers (five studies); (2) Dermagraft, a human fibroblast-derived dermal substitute, which is indicated only for use in the treatment of full-thickness diabetic foot ulcers (one study); (3) REGRANEX Gel, a human platelet-derived growth factor for the treatment of deep neuropathic diabetic foot ulcers (five studies). The studies considered in this review were of varying and partly low methodological quality. They calculated that due to shorter treatment periods, fewer complications and fewer inpatient episodes the initial cost of the novel biotechnology products may be offset, making the treatment cost-effective or even cost-saving. The results of most studies were sensitive to initial costs of the products and the evidence of effectiveness. CONCLUSION: The study results suggest that some growth factors and tissue-engineered artificial skin products feature favourable cost-effectiveness ratios in selected patient groups with chronic wounds. Despite the limitations of the studies considered, it is evident that health care providers and coverage decision makers should take not only the high cost of the biotechnology product but the total cost of care into account when deciding about the appropriate allocation of their financial resources. However, not only the cost-effectiveness but first of all the effectiveness of these novel biotechnology products deserve further research.