What are economic costs and when should they be used in health economic studies?

Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources' opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource's value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.

Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.

Background: In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe. Methods: We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation. Findings: In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. Interpretation: We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals. Funding: World Health Organization.

Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

Health and economic impact of seasonal influenza mass vaccination strategies in European settings: A mathematical modelling and cost-effectiveness analysis.

INTRODUCTION: Despite seasonal influenza vaccination programmes in most countries targeting individuals aged ≥ 65 (or ≥ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million). METHODS: We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%. RESULTS: In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At €35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels. CONCLUSION: Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings.

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection. FINDINGS: Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable. INTERPRETATION: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered. FINDINGS: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option. INTERPRETATION: A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust. RESEARCH IN CONTEXT: Evidence before this study: We searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: ("COVID-19" OR "SARS-CoV-2") AND ("priorit*) AND ("model*") AND ("vaccin*") and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history.Added-value of this study: We evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered.Implication of all the available evidence: COVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines.

The potential health and economic value of SARS-CoV-2 vaccination alongside physical distancing in the UK: a transmission model-based future scenario analysis and economic evaluation.

BACKGROUND: In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era. METHODS: We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs. FINDINGS: Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large. INTERPRETATION: Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective. FUNDING: National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation.

Optimizing Benefits of Testing Key Workers for Infection with SARS-CoV-2: A Mathematical Modeling Analysis.

BACKGROUND: Internationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates/quarantines many staff without SARS-CoV-2, while not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others. METHODS: We used a decision-analytic model for 1000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially positive tests, initially negative tests, or no re-testing. We varied all parameters, including the infection rate (0.1-20%), proportion asymptomatic (10-80%), sensitivity (60-95%), and specificity (90-100%). RESULTS: Testing all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers/1000 tests (with reductions throughout at RT-PCR sensitivity ≥65%), and absences by -0.5 to +3.6 days/test but at heightened testing needs of 989.6-1995.9 tests/1000 workers. Testing workers in household quarantine (S2) reduces absences the most by 3.0-6.9 days/test (at 47.0-210.4 tests/1000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers/1000 tests (which can be minimized when re-testing initially negative tests). CONCLUSIONS: Based on optimizing absence durations or transmission risk, our modeling suggests testing staff in household quarantine or all staff, depending on infection levels and testing capacities.

Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation.

BACKGROUND: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.

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.

Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients.

Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus.

Estimating the opportunity costs of bed-days.

Opportunity costs of bed-days are fundamental to understanding the value of healthcare systems. They greatly influence burden of disease estimations and economic evaluations involving stays in healthcare facilities. However, different estimation techniques employ assumptions that differ crucially in whether to consider the value of the second-best alternative use forgone, of any available alternative use, or the value of the actually chosen alternative. Informed by economic theory, this paper provides a taxonomic framework of methodologies for estimating the opportunity costs of resources. This taxonomy is then applied to bed-days by classifying existing approaches accordingly. We highlight differences in valuation between approaches and the perspective adopted, and we use our framework to appraise the assumptions and biases underlying the standard approaches that have been widely adopted mostly unquestioned in the past, such as the conventional use of reference costs and administrative accounting data. Drawing on these findings, we present a novel approach for estimating the opportunity costs of bed-days in terms of health forgone for the second-best patient, but expressed monetarily. This alternative approach effectively re-connects to the concept of choice and explicitly considers net benefits. It is broadly applicable across settings and for other resources besides bed-days.

Do reassessments reduce the uncertainty of decision making? Reviewing reimbursement reports and economic evaluations of three expensive drugs over time.

OBJECTIVE: To investigate the desirability and feasibility of a cyclic reimbursement process to address uncertainty accompanying initial decision making. METHODS: We performed desk research for three expensive outpatient drugs: imatinib, pegfilgrastim, and adalimumab. We analysed the evidence base at the time of decision making (T=0) and May 2011 (T=1). For T=0, public reports of the Dutch reimbursement agency were investigated regarding available clinical and economic evidence, and a systematic review was performed to retrieve additional economic evidence. For T=1, the systematic review was extended till May 2011. RESULTS: The evidence base at T=0 lacked information on clinically relevant outcomes such as mortality, morbidity, and quality of life (5/8 reports), (long-term) adverse events (2/8 reports) and experience in use (1/8 reports). One budget impact analysis and one economic evaluation were available but no pharmacoeconomic dossiers. The systematic review identified 39 cost-utility studies (of 52 economic evaluations) for T=1, characterised by methodological heterogeneity. CONCLUSIONS: Given the considerable uncertainty accompanying initial decision-making, a more cyclic reimbursement process seems feasible to reduce uncertainty regarding the therapeutical and economical value of expensive drugs. A mandatory evidence development requirement seems desirable to sufficiently meet decision makers' needs.