Unconscious Bias among Health Professionals: A Scoping Review.

BACKGROUND: Unconscious biases are one of the causes of health disparities. Health professionals have prejudices against patients due to their race, gender, or other factors without their conscious knowledge. This review aimed to provide an overview of research on unconscious bias among health professionals and to investigate the biases that exist in different regions of the world, the health professions that are considered, and the research gaps that still exist. METHODS: We conducted a scoping review by systematically searching PubMed/MEDLINE, CINAHL, PsycINFO, PsycARTICLES, and AMED. All records were double-screened and included if they were published between 2011 and 2021. RESULTS: A total of 5186 records were found. After removing duplicates (n = 300), screening titles and abstracts (n = 4210), and full-text screening (n = 695), 87 articles from 81 studies remained. Studies originated from North America (n = 60), Europe (n = 13), and the rest of the world (n = 6), and two studies were of global scope. Racial bias was investigated most frequently (n = 46), followed by gender bias (n = 11), weight bias (n = 10), socio-economic status bias (n = 9), and mental illness bias (n = 7). Most of the studies were conducted by physicians (n = 51) and nurses (n = 20). Other health care professionals were rarely included in these studies. CONCLUSIONS: Most studies show that health professionals have an implicit bias. Racial biases among physicians and nurses in the USA are well confirmed. Research is missing on other biases from other regions and other health professions.

Estimation of Input Costs for a Markov Model in a German Health Economic Evaluation of Newer Antidepressants.

Background: Estimating input costs for Markov models in health economic evaluations requires health state-specific costing. This is a challenge in mental illnesses such as depression, as interventions are not clearly related to health states. We present a hybrid approach to health state-specific cost estimation for a German health economic evaluation of antidepressants. Methods: Costs were determined from the perspective of the community of persons insured by statutory health insurance ("SHI insuree perspective") and included costs for outpatient care, inpatient care, drugs, and psychotherapy. In an additional step, costs for rehabilitation and productivity losses were calculated from the societal perspective. We collected resource use data in a stepwise hierarchical approach using SHI claims data, where available, followed by data from clinical guidelines and expert surveys. Bottom-up and top-down costing approaches were combined. Results: Depending on the drug strategy and health state, the average input costs varied per patient per 8-week Markov cycle. The highest costs occurred for agomelatine in the health state first-line treatment (FT) ("FT relapse") with €506 from the SHI insuree perspective and €724 from the societal perspective. From both perspectives, the lowest costs (excluding placebo) were €55 for selective serotonin reuptake inhibitors in the health state "FT remission." Conclusion: To estimate costs in health economic evaluations of treatments for depression, it can be necessary to link different data sources and costing approaches systematically to meet the requirements of the decision-analytic model. As this can increase complexity, the corresponding calculations should be presented transparently. The approach presented could provide useful input for future models.

The efficiency-frontier approach for health economic evaluation versus cost-effectiveness thresholds and internal reference pricing: combining the best of both worlds?

INTRODUCTION: The efficiency-frontier approach (EFA) to health economic evaluation aims to benchmark the relative efficiency of new drugs with the incremental cost-effectiveness ratios (ICERs) of non-dominated comparators. By explicitly considering any differences in health outcomes and costs, it enhances the internal reference pricing (IRP) policy that was officially endorsed by Germany as the first country worldwide in 1989. However, the EFA has been repeatedly criticized since its official endorsement in 2009. Areas covered: This perspective aims to stimulate the debate by discussing whether the main objections to the EFA are technically valid, irrespective of national contextual factors in Germany with reservations towards using cost-per-quality-adjusted life year (QALY) thresholds. Moreover, we comparatively assessed whether the objections are truly unique to the EFA or apply equally to IRP and cost-effectiveness thresholds. Expert commentary: The plethora of objections to the EFA (n = 20) has obscured that many objections are neither technically valid nor unique to the EFA. Compared with cost-effectiveness thresholds, only two objections apply uniquely to the EFA and concern intended key properties: (1) no external thresholds are needed and (2) the EFA is sensitive to price changes of comparators. Combining these policies and developing them further are under-utilized research areas.

[Checklist for the Development and Assessment of Cost-of-Illness Studies]. / Checkliste zur Erstellung und Bewertung von Krankheitskostenstudien.

BACKGROUND: Cost-of-illness (CoI) studies are important instruments for estimating the socioeconomic burden of specified diseases. CoI studies provide important information about the cost structure of a disease, the resulting research need, approaches to improve aspects of care and, monetary consequences from different perspectives. This information can be useful for healthcare research and health policy. Due to heterogeneity of available Cost-of-Illness studies, the working group 'Health Economics' of the German Network for Healthcare Research (DNVF) in accordance with the German Society for Health Economics (DGGÖ) developed an instrument for the planning, conduct and assessment of CoI studies. METHODS: The checklist was developed based on a systematic literature search of published national and international checklists as well as guidelines and recommendations for development and assessment of CoI studies and health economic evaluations. Structure and subject matter of the generic checklist was designed, approved and, finally, examined in a pretest by the working group. RESULTS: Based on the results of the literature search (n=2 454), 58 articles were used for the identification of relevant criteria for the checklist. With respect to the results of the pretest, 6 dimensions were included in the checklist: (i) general aspects, (ii) identification of resources, (iii) description and quantification of resource consumption, (iv) valuation of resources (v) analysis and presentation of results and (vi) discussion and conclusion. In total, the 6 dimensions were operationalized through 37 items. CONCLUSION: This checklist is an initial approach to improve transparency and understanding of CoI studies in terms of the extent, structure and development of the socioeconomic burden of diseases. The checklist supports the comparability of different studies and facilitates study conception.

Preferences for antiviral therapy of chronic hepatitis C: a discrete choice experiment.

BACKGROUND: The German Institute for Quality and Efficiency in Health Care (IQWiG) uses patient-relevant outcomes to inform decision-makers. OBJECTIVE: IQWiG conducted a pilot study to examine whether discrete choice experiments (DCEs) can be applied in health economic evaluations in Germany to identify, weight, and prioritize multiple patient-relevant outcomes, using the example of antiviral therapy for chronic hepatitis C (HCV). A further objective was to contribute to a more structured approach towards eliciting and comparing preferences across key stakeholders. METHODS: In autumn 2010, a DCE questionnaire was sent to patients with chronic HCV to estimate preferences across seven outcomes ("attributes"), including treatment efficacy [sustained viral response (SVR) at 6 months], adverse effects (flu-like symptoms, gastrointestinal symptoms, psychiatric symptoms, and skin symptoms/alopecia), and measures of treatment burden (duration of therapy, frequency of injections). A linear model and an effects coded full model were applied to assess the relative importance of the attributes. RESULTS: In total N = 326 patients were included. A clear preference for SVR was shown; frequency of injections and duration of therapy shared the second rank, while psychiatric symptoms ranked third. The duration of flu-like symptoms was the least important attribute. CONCLUSION: Our findings indicate that it is possible to perform a DCE at the national level in a health technology assessment agency. The weighting of multiple outcomes allows an indication-specific and evidence-based measure to be used in health economic evaluations. In decision-making in health care, the approach generally allows for consideration of patient-relevant trade-offs regarding the benefits and harms of medical interventions.

Cost Recommendation under Uncertainty in IQWiG's Efficiency Frontier Framework.

BACKGROUND: The National Institute for Quality and Efficiency in Health Care (IQWiG) employs an efficiency frontier (EF) framework to facilitate setting maximum reimbursable prices for new interventions. Probabilistic sensitivity analysis (PSA) is used when yes/no reimbursement decisions are sought based on a fixed threshold. In the IQWiG framework, an additional layer of complexity arises as the EF itself may vary its shape in each PSA iteration, and thus the willingness-to-pay, indicated by the EF segments, may vary. OBJECTIVES: To explore the practical problems arising when, within the EF approach, maximum reimbursable prices for new interventions are sought through PSA. METHODS: When the EF is varied in a PSA, cost recommendations for new interventions may be determined by the mean or the median of the distances between each intervention's point estimate and each EF. Implications of using these metrics were explored in a simulation study based on the model used by IQWiG to assess the cost-effectiveness of 4 antidepressants. RESULTS: Depending on the metric used, cost recommendations can be contradictory. Recommendations based on the mean can also be inconsistent. Results (median) suggested that costs of duloxetine, venlafaxine, mirtazapine, and bupropion should be decreased by €131, €29, €12, and €99, respectively. These recommendations were implemented and the analysis repeated. New results suggested keeping the costs as they were. The percentage of acceptable PSA outcomes increased 41% on average, and the uncertainty associated to the net health benefit was significantly reduced. CONCLUSIONS: The median of the distances between every intervention outcome and every EF is a good proxy for the cost recommendation that would be given should the EF be fixed. Adjusting costs according to the median increased the probability of acceptance and reduced the uncertainty around the net health benefit distribution, resulting in a reduced uncertainty for decision makers.

Challenges in Cost-Effectiveness Analysis Modelling of HPV Vaccines in Low- and Middle-Income Countries: A Systematic Review and Practice Recommendations.

BACKGROUND: Low- and middle-income countries (LMICs) face a number of challenges in implementing cervical cancer prevention programmes that do not apply in high-income countries. OBJECTIVE: This review assessed how context-specific challenges of implementing cervical cancer prevention strategies in LMICs were accounted for in existing cost-effectiveness analysis (CEA) models of human papillomavirus (HPV) vaccination. METHODS: The databases of MEDLINE, EMBASE, NHS Economic Evaluation Database, EconLit, Web of Science, and the Center for the Evaluation of Value and Risk in Health (CEA) Registry were searched for studies published from 2006 to 2015. A descriptive, narrative, and interpretative synthesis of data was undertaken. RESULTS: Of the 33 studies included in the review, the majority acknowledged cost per vaccinated girl (CVG) (26 studies) and vaccine coverage rate (21 studies) as particular challenges for LMICs, while nine studies identified screening coverage rate as a challenge. Most of the studies estimated CVG as a composite of different cost items. However, the basis for the items within this composite cost was unclear. The majority used an assumption rather than an observed rate to represent screening and vaccination coverage rates. CVG, vaccine coverage and screening coverage were shown by some studies through sensitivity analyses to reverse the conclusions regarding cost-effectiveness, thereby significantly affecting policy recommendations. CONCLUSIONS: While many studies recognized aspects of the particular challenges of HPV vaccination in LMICs, greater efforts need to be made in adapting models to account for these challenges. These include adapting costings of HPV vaccine delivery from other countries, learning from the outcomes of cervical cancer screening programmes in the same geographical region, and taking into account the country's previous experience with other vaccination programmes.

Health Economics as Rhetoric: The Limited Impact of Health Economics on Funding Decisions in Four European Countries.

BACKGROUND: A response to the challenge of high-cost treatments in health care has been economic evaluation. Cost-effectiveness analysis presented as cost per quality-adjusted life-years gained has been controversial, raising heated support and opposition. OBJECTIVES: To assess the impact of economic evaluation in decisions on what to fund in four European countries and discuss the implications of our findings. METHODS: We used a protocol to review the key features of the application of economic evaluation in reimbursement decision making in England, Germany, the Netherlands, and Sweden, reporting country-specific highlights. RESULTS: Although the institutions and processes vary by country, health economic evaluation has had limited impact on restricting access of controversial high-cost drugs. Even in those countries that have gone the furthest, ways have been found to avoid refusing to fund high-cost drugs for particular diseases including cancer, multiple sclerosis, and orphan diseases. Economic evaluation may, however, have helped some countries to negotiate price reductions for some drugs. It has also extended to the discussion of clinical effectiveness to include cost. CONCLUSIONS: The differences in approaches but similarities in outcomes suggest that health economic evaluation be viewed largely as rhetoric (in D.N. McCloskey's terms in The Rhetoric of Economics, 1985). This is not to imply that economics had no impact: rather that it usually contributed to the discourse in ways that differed by country. The reasons for this no doubt vary by perspective, from political science to ethics. Economic evaluation may have less to do with rationing or denial of medical treatments than to do with expanding the discourse used to discuss such issues.

Health Economic Evaluations of Sofosbuvir for Treatment of Chronic Hepatitis C: a Systematic Review.

BACKGROUND AND OBJECTIVE: The approval of sofosbuvir offers new therapeutic options for patients suffering from chronic hepatitis C. In phase III trials, it has demonstrated significantly greater efficacy and safety in comparison with the old standard of care. In addition, it provides the first interferon-free regimen allowing treatment of patients without previous therapeutic options. A current debate regarding pricing and affordability can be attributed to high treatment costs. The objective of this review was to compare health economic evaluations of sofosbuvir for the treatment of chronic hepatitis C in terms of models, patient populations, interventions and results. METHODS: A systematic review was conducted using the data sources Medline (1946-09/2015), Embase (1974-09/2015), the Health Technology Assessment Database (September 2015) and the UK National Health Service Economic Evaluation Database (September 2015). We included health economic evaluations that measured the cost-effectiveness of sofosbuvir-based regimens compared with regimens without sofosbuvir for the treatment of adult patients infected with chronic hepatitis C. The articles were then critically appraised regarding the effectiveness data, cost data and models utilised. RESULTS: Fourteen studies were included, which analysed the cost-effectiveness of sofosbuvir in seven different countries. Differences in study characteristics were found regarding study populations, modelling and willingness-to-pay thresholds. The study results demonstrated the cost-effectiveness of the treatment combination of sofosbuvir with pegylated interferon and ribavirin in comparison with the old standard of care. Dual therapy with sofosbuvir and ribavirin was considered cost effective only in comparison with no therapy. CONCLUSION: Despite high costs, the included studies indicate that sofosbuvir-based regimens are cost effective in most patients. While the results are unequivocal with regard to sofosbuvir-based triple therapy, the cost-effectiveness of sofosbuvir-based dual therapy heavily depends on country-specific willingness to pay. Although interferon-containing triple therapy has now been replaced by newly approved direct-acting antivirals in most middle- and high-income countries, the availability of these oral treatment combinations is poor in low-income countries. Therefore, the findings of our review are still of relevance.

Methods for Health Economic Evaluation of Vaccines and Immunization Decision Frameworks: A Consensus Framework from a European Vaccine Economics Community.

BACKGROUND: Incremental cost-effectiveness and cost-utility analyses [health economic evaluations (HEEs)] of vaccines are routinely considered in decision making on immunization in various industrialized countries. While guidelines advocating more standardization of such HEEs (mainly for curative drugs) exist, several immunization-specific aspects (e.g. indirect effects or discounting approach) are still a subject of debate within the scientific community. OBJECTIVE: The objective of this study was to develop a consensus framework for HEEs of vaccines to support the development of national guidelines in Europe. METHODS: A systematic literature review was conducted to identify prevailing issues related to HEEs of vaccines. Furthermore, European experts in the field of health economics and immunization decision making were nominated and asked to select relevant aspects for discussion. Based on this, a workshop was held with these experts. Aspects on 'mathematical modelling', 'health economics' and 'decision making' were debated in group-work sessions (GWS) to formulate recommendations and/or--if applicable--to state 'pros' and 'contras'. RESULTS: A total of 13 different aspects were identified for modelling and HEE: model selection, time horizon of models, natural disease history, measures of vaccine-induced protection, duration of vaccine-induced protection, indirect effects apart from herd protection, target population, model calibration and validation, handling uncertainty, discounting, health-related quality of life, cost components, and perspectives. For decision making, there were four aspects regarding the purpose and the integration of HEEs of vaccines in decision making as well as the variation of parameters within uncertainty analyses and the reporting of results from HEEs. For each aspect, background information and an expert consensus were formulated. CONCLUSIONS: There was consensus that when HEEs are used to prioritize healthcare funding, this should be done in a consistent way across all interventions, including vaccines. However, proper evaluation of vaccines implies using tools that are not commonly used for therapeutic drugs. Due to the complexity of and uncertainties around vaccination, transparency in the documentation of HEEs and during subsequent decision making is essential.

Is There a European View on Health Economic Evaluations? Results from a Synopsis of Methodological Guidelines Used in the EUnetHTA Partner Countries.

OBJECTIVES: The objectives of this study were to review current methodological guidelines for economic evaluations of all types of technologies in the 33 countries with organizations involved in the European Network for Health Technology Assessment (EUnetHTA), and to provide a general framework for economic evaluation at a European level. METHODS: Methodological guidelines for health economic evaluations used by EUnetHTA partners were collected through a survey. Information from each guideline was extracted using a pre-tested extraction template. On the basis of the extracted information, a summary describing the methods used by the EUnetHTA countries was written for each methodological item. General recommendations were formulated for methodological issues where the guidelines of the EUnetHTA partners were in agreement or where the usefulness of economic evaluations may be increased by presenting the results in a specific way. RESULTS: At least one contact person from all 33 EUnetHTA countries (100 %) responded to the survey. In total, the review included 51 guidelines, representing 25 countries (eight countries had no methodological guideline for health economic evaluations). On the basis of the results of the extracted information from all 51 guidelines, EUnetHTA issued ten main recommendations for health economic evaluations. CONCLUSIONS: The presented review of methodological guidelines for health economic evaluations and the consequent recommendations will hopefully improve the comparability, transferability and overall usefulness of economic evaluations performed within EUnetHTA. Nevertheless, there are still methodological issues that need to be investigated further.

Reporting health care decision models: a prospective reliability study of a multidimensional evaluation framework.

The aim of this study was to evaluate the inter-rater reliability of the Phillips-checklist, a proposed framework for the quality assessment of modeling studies. Six raters evaluated nine modeling studies from three different medical specialties. Intra-class correlation (ICC) and corresponding variance components were estimated from these studies. Raters were asked to comment on their experience with the framework. While overall the mean inter-rater reliability showed no significant rater-effect (ICC = 0.69, p = 0.064), there was - presumably as a result of a lower study variability - a significant rater effect for clopidogrel only (p < 0.001). The framework allowed a more structured methodological assessment but several items remained unclear. Regarding the quality assessment of modeling studies with the proposed framework, the rater variability is similar or even higher than variability because of studies or residual effects. Several scoring items can and should be improved to ease interpretation.

Communicating the parameter uncertainty in the IQWiG efficiency frontier to decision-makers.

The Institute for Quality and Efficiency in Health Care (IQWiG) developed-in a consultation process with an international expert panel-the efficiency frontier (EF) approach to satisfy a range of legal requirements for economic evaluation in Germany's statutory health insurance system. The EF approach is distinctly different from other health economic approaches. Here, we evaluate established tools for assessing and communicating parameter uncertainty in terms of their applicability to the EF approach. Among these are tools that perform the following: (i) graphically display overall uncertainty within the IQWiG EF (scatter plots, confidence bands, and contour plots) and (ii) communicate the uncertainty around the reimbursable price. We found that, within the EF approach, most established plots were not always easy to interpret. Hence, we propose the use of price reimbursement acceptability curves-a modification of the well-known cost-effectiveness acceptability curves. Furthermore, it emerges that the net monetary benefit allows an intuitive interpretation of parameter uncertainty within the EF approach. This research closes a gap for handling uncertainty in the economic evaluation approach of the IQWiG methods when using the EF. However, the precise consequences of uncertainty when determining prices are yet to be defined.

Decision making in Germany: is health economic evaluation as a supporting tool a sleeping beauty?

For many years, the legal situation within the statutory health insurance (SHI) system in Germany has allowed for health economic evaluations. There are various reasons why health economic evaluations have played virtually no role in decision making until now: to begin with, a method for the evaluation of the relation between benefits and costs which needed to be in accordance with the legal requirements had to be developed, the outcome of which was the efficiency frontier approach. Subsequent health care reforms have led to changing objectives and strategies. Currently, price negotiations of newly launched drugs are based on an early benefit assessment of dossiers submitted by pharmaceutical manufacturers. Other reasons might be the presently very comfortable financial situation of the statutory health insurance system as well as a historically grown societal fear and discomfort towards what is perceived to be a rationing of medicinal products. For the time being, it remains open how long the German health care system can afford to continue neglecting the benefits of health economic evaluations for drug and non-drug interventions, and when it will be time to wake this sleeping beauty.