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.

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.

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.

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.

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.

Clearing up the hazy road from bench to bedside: a framework for integrating the fourth hurdle into translational medicine.

BACKGROUND: New products evolving from research and development can only be translated to medical practice on a large scale if they are reimbursed by third-party payers. Yet the decision processes regarding reimbursement are highly complex and internationally heterogeneous. This study develops a process-oriented framework for monitoring these so-called fourth hurdle procedures in the context of product development from bench to bedside. The framework is suitable both for new drugs and other medical technologies. METHODS: The study is based on expert interviews and literature searches, as well as an analysis of 47 websites of coverage decision-makers in England, Germany and the USA. RESULTS: Eight key steps for monitoring fourth hurdle procedures from a company perspective were determined: entering the scope of a healthcare payer; trigger of decision process; assessment; appraisal; setting level of reimbursement; establishing rules for service provision; formal and informal participation; and publication of the decision and supplementary information. Details are given for the English National Institute for Health and Clinical Excellence, the German Federal Joint Committee, Medicare's National and Local Coverage Determinations, and for Blue Cross Blue Shield companies. CONCLUSION: Coverage determination decisions for new procedures tend to be less formalized than for novel drugs. The analysis of coverage procedures and requirements shows that the proof of patient benefit is essential. Cost-effectiveness is likely to gain importance in future.

Health Care Costs Associated With Incident Complications in Patients With Type 2 Diabetes in Germany.

OBJECTIVE: The aim of this study is to provide reliable regression-based estimates of costs associated with different type 2 diabetes complications. RESEARCH DESIGN AND METHODS: We used nationwide statutory health insurance (SHI) data from 316,220 patients with type 2 diabetes. Costs for inpatient and outpatient care, pharmaceuticals, rehabilitation, and nonmedical aids and appliances were assessed in the years 2013-2015. Quarterly observations are available for each year. We estimated costs (in 2015 euro) for complications using a generalized estimating equations model with a normal distribution adjusted for age, sex, occurrence of different complications, and history of complications at baseline, 2012. Two- and threefold interactions were included in an extended model. RESULTS: The base case model estimated total costs in the quarter of event for the example of a 60- to 69-year-old man as follows: diabetic foot €1,293, amputation €14,284, retinopathy €671, blindness €2,933, nephropathy €3,353, end-stage renal disease (ESRD) €22,691, nonfatal stroke €9,769, fatal stroke €11,176, nonfatal myocardial infarction (MI)/cardiac arrest (CA) €8,035, fatal MI/CA €8,700, nonfatal ischemic heart disease (IHD) €6,548, fatal IHD €20,942, chronic heart failure €3,912, and angina pectoris €2,695. In the subsequent quarters, costs ranged from €681 for retinopathy to €6,130 for ESRD. CONCLUSIONS: Type 2 diabetes complications have a significant impact on total health care costs in the SHI system, not only in the quarter of event but also in subsequent years. Men and women from different age-groups differ in their costs for complications. Our comprehensive estimates may support the parametrization of diabetes models and help clinicians and policy makers to quantify the economic burden of diabetes complications in the context of new prevention and treatment programs.

Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations.

INTRODUCTION: Expert judgement has a role in model-based economic evaluations (EEs) of healthcare interventions. This study aimed to produce reporting criteria for two types of study design to use expert judgement in model-based EE: (i) an expert elicitation (quantitative) study; and (ii) a Delphi study to collate (qualitative) expert opinion. METHODS: A two-round online Delphi process identified the degree of consensus for four core definitions (expert; expert parameter values; expert elicitation study; expert opinion) and two sets of reporting criteria in a purposive sample of experts. The initial set of reporting criteria comprised 17 statements for reporting a study to elicit parameter values and/or distributions and 11 statements for reporting a Delphi survey to obtain expert opinion. Fifty experts were invited to become members of the Delphi process panel by e-mail. Data analysis summarised the extent of agreement (using a pre-defined 75 % 'consensus' threshold) on the definitions and suggested reporting criteria. Free-text comments were analysed using thematic analysis. RESULTS: The final panel comprised 12 experts. Consensus was achieved for the definitions of expert (88 %); expert parameter values (83 %); and expert elicitation study (83 %). The panel recommended criteria to use when reporting an expert elicitation study (16 criteria) and a Delphi study to collate expert opinion (11 criteria). CONCLUSION: This study has produced guidelines for reporting two types of study design to use expert judgement in model-based EE: (i) an expert elicitation study requiring 16 reporting criteria; and (ii) a Delphi study to collate expert opinion requiring 11 reporting criteria.

Using needs-based frameworks for evaluating new technologies: an application to genetic tests.

Given the multitude of newly available genetic tests in the face of limited healthcare budgets, the European Society of Human Genetics assessed how genetic services can be prioritized fairly. Using (health) benefit maximizing frameworks for this purpose has been criticized on the grounds that rather than maximization, fairness requires meeting claims (e.g. based on medical need) equitably. This study develops a prioritization score for genetic tests to facilitate equitable allocation based on need-based claims. It includes attributes representing health need associated with hereditary conditions (severity and progression), a genetic service's suitability to alleviate need (evidence of benefit and likelihood of positive result) and costs to meet the needs. A case study for measuring the attributes is provided and a suggestion is made how need-based claims can be quantified in a priority function. Attribute weights can be informed by data from discrete-choice experiments. Further work is needed to measure the attributes across the multitude of genetic tests and to determine appropriate weights. The priority score is most likely to be considered acceptable if developed within a decision process which meets criteria of procedural fairness and if the priority score is interpreted as "strength of recommendation" rather than a fixed cut-off value.

Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany.

BACKGROUND: Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. METHODS: A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. RESULTS: The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of € 200, yielding an incremental cost-effectiveness ratio (ICER) of € 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about € 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds. LIMITATIONS: The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. CONCLUSIONS: Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.

Is individualized medicine more cost-effective? A systematic review.

BACKGROUND: Individualized medicine (IM) is a rapidly evolving field that is associated with both visions of more effective care at lower costs and fears of highly priced, low-value interventions. It is unclear which view is supported by the current evidence. OBJECTIVE: Our objective was to systematically review the health economic evidence related to IM and to derive general statements on its cost-effectiveness. DATA SOURCES: A literature search of MEDLINE database for English- and German-language studies was conducted. STUDY APPRAISAL AND SYNTHESIS METHOD: Cost-effectiveness and cost-utility studies for technologies meeting the MEDLINE medical subject headings (MeSH) definition of IM (genetically targeted interventions) were reviewed. This was followed by a standardized extraction of general study characteristics and cost-effectiveness results. RESULTS: Most of the 84 studies included in the synthesis were from the USA (n = 43, 51 %), cost-utility studies (n = 66, 79 %), and published since 2005 (n = 60, 71 %). The results ranged from dominant to dominated. The median value (cost-utility studies) was calculated to be rounded $US22,000 per quality-adjusted life year (QALY) gained (adjusted to $US, year 2008 values), which is equal to the rounded median cost-effectiveness in the peer-reviewed English-language literature according to a recent review. Many studies reported more than one strategy of IM with highly varying cost-effectiveness ratios. Generally, results differed according to test type, and tests for disease prognosis or screening appeared to be more favorable than tests to stratify patients by response or by risk of adverse effects. However, these results were not significant. LIMITATIONS: Different definitions of IM could have been used. Quality assessment of the studies was restricted to analyzing transparency. CONCLUSIONS: IM neither seems to display superior cost-effectiveness than other types of medical interventions nor to be economically inferior. Instead, rather than 'whether' healthcare was individualized, the question of 'how' it was individualized was of economic relevance.

Criteria for fairly allocating scarce health-care resources to genetic tests: which matter most?

The use of genetic tests is expanding rapidly. Given limited health-care budgets throughout Europe and few national coverage decisions specifically for genetic tests, decisions about allocating scarce resources to genetic tests are frequently ad hoc and left to lower-level decision makers. This study assesses substantive ethical and economic criteria to prioritize genetic services in a reasonable and fair manner. Principles for allocating health-care resources can be classified into four categories: need-based allocation; maximizing total benefits; treating people equally; and promoting and rewarding social usefulness. In the face of scarcity, the degree of an individual's need for medical intervention is an important criterion. Also, different economic concepts of efficiency are of relevance in the theory and practice of prioritizing genetic tests. Equity concerns are most likely to be relevant in terms of avoiding undesirable inequities, which may also set boundaries to the use of efficiency as a prioritization criterion. The aim of promoting and rewarding social usefulness is unlikely to be relevant to the question of what priority a genetic test should have in clinical practice. Further work is needed to select an appropriate set of criteria; operationalize them; and assign weights before some kind of standardized priority information can be added to information sources for genetic services. Besides the substantive criteria, formal considerations like those pointed out in the framework of accountability for reasonableness need to be considered in decision making.