Economic Evaluation for Pricing and Reimbursement of New Drugs in Spain: Fable or Desideratum?

BACKGROUND: The economic evaluation of healthcare technologies has become in many countries a basic tool for reimbursement, pricing and purchasing decisions. OBJECTIVE: The objective of this article is to examine the institutional, legal, and political factors that have impeded the application of economic evaluation and the criterion of efficiency in the process of pricing and reimbursement of new medicines in Spain. METHODS: Narrative description of the current institutional framework for the use of economic evaluation in pricing and reimbursement in Spain, legal and policy framework in the field of evaluation of new medicines, and stakeholder initiatives and policies related to the use of economic evaluation outside of the pricing and reimbursement process. RESULTS: Spain has an institutional framework created and established over the last years that could have facilitated a formal use of economic evaluation in the process of pricing and reimbursement. Nevertheless, the real use of economic evaluation at the central or regional level is still unknown, although application of the efficiency criterion, linking to cost-effectiveness, has been clearly required by Spanish laws and regulations at the national level. We highlight a certain degree of moral hazard from the central government that is not directly responsible for the budget impact of reimbursement and pricing decisions. There are currently a number of ongoing initiatives in the field of economic evaluation by various agents, but they remain uncoordinated. CONCLUSIONS: Poor governance at the highest level of decision making is the main reason for the lack of interest in economic evaluation. A profound political change, supported by transparency and accountability, is required before the criterion of efficiency can be fully considered in the process of pricing and reimbursement of new medicines in Spain.

Free prescriptions for low-income pensioners? The cost of returning to free-of-charge drugs in the Spanish National Health Service.

This study estimated the impact of reducing a capped low coinsurance rate for outpatient medicines to nil for low-income pensioners and disabled individuals in the Valencian Community (Spain). This reduction was implemented in January 2016 as a regional reform which modified the national cost-sharing reform adopted in July 2012. The impact of this intervention on the number of monthly prescriptions dispensed between July 2012 and December 2018 was estimated using two different approaches of the synthetic control method, the classical method and the method based on Bayesian structural time series. The estimates from both methods were similar, showing significant overall increases of 6.34% and 6.70% [95% credible interval: 4.05, 9.47], respectively in the number of prescriptions dispensed in this region. These results are similar to those of the previous studies indicating that reducing price from a small amount to zero discontinuously boosts demand. This evidence indicates that the impact of this intervention on the budget of the regional health service is far greater than the amount of the subsidy in the public budget. These results are useful for making accurate budgetary projections for similar eliminations of charges for low-income pensioners in the Spanish National Health Service.

Free Medicines Thanks to Retirement: Impact of Coinsurance Exemption on Pharmaceutical Expenditures and Hospitalization Offsets in a national health service.

This paper examines the impact of coinsurance exemption for prescription medicines applied to elderly individuals in Spain after retirement. We use a rich administrative dataset that links pharmaceutical consumption and hospital discharge records for the full population aged 58 to 65 years in January 2004 covered by the public insurer in a Spanish region, and we follow them until December 2006. We use a difference-in-differences strategy and exploit the eligibility age for Social Security to control for the endogeneity of the retirement decision. Our results show that this uniform exemption increases the consumption of prescription medicines on average by 17.5%, total pharmaceutical expenditure by 25% and the costs borne by the insurer by 60.4%, without evidence of any offset effect in the form of lower short term probability of hospitalization. The impact is concentrated among consumers of medicines for acute and other non-chronic diseases whose previous coinsurance rate was 30% to 40%. Copyright © 2015 John Wiley & Sons, Ltd.

How efficient are referral hospitals in Uganda? A data envelopment analysis and tobit regression approach.

BACKGROUND: Hospitals represent a significant proportion of health expenditures in Uganda, accounting for about 26 % of total health expenditure. Improving the technical efficiency of hospitals in Uganda can result in large savings which can be devoted to expand access to services and improve quality of care. This paper explores the technical efficiency of referral hospitals in Uganda during the 2012/2013 financial year. METHODS: This was a cross sectional study using secondary data. Input and output data were obtained from the Uganda Ministry of Health annual health sector performance report for the period July 1, 2012 to June 30, 2013 for the 14 public sector regional referral and 4 large private not for profit hospitals. We assumed an output-oriented model with Variable Returns to Scale to estimate the efficiency score for each hospital using Data Envelopment Analysis (DEA) with STATA13. Using a Tobit model DEA, efficiency scores were regressed against selected institutional and contextual/environmental factors to estimate their impacts on efficiency. RESULTS: The average variable returns to scale (Pure) technical efficiency score was 91.4 % and the average scale efficiency score was 87.1 % while the average constant returns to scale technical efficiency score was 79.4 %. Technically inefficient hospitals could have become more efficient by increasing the outpatient department visits by 45,943; and inpatient days by 31,425 without changing the total number of inputs. Alternatively, they would achieve efficiency by for example transferring the excess 216 medical staff and 454 beds to other levels of the health system without changing the total number of outputs. Tobit regression indicates that significant factors in explaining hospital efficiency are: hospital size (p < 0.01); bed occupancy rate (p < 0.01) and outpatient visits as a proportion of inpatient days (p < 0.05). CONCLUSIONS: Hospitals identified at the high and low extremes of efficiency should be investigated further to determine how and why production processes are operating differently at these hospitals. As policy makers gain insight into mechanisms promoting hospital services utilization in hospitals with high efficiency they can develop context-appropriate strategies for supporting hospitals with low efficiency to improve their service and thereby better address unmet needs for hospital services in Uganda.

Predictors of primary health care pharmaceutical expenditure by districts in Uganda and implications for budget setting and allocation.

BACKGROUND: There is need for the Uganda Ministry of Health to understand predictors of primary health care pharmaceutical expenditure among districts in order to guide budget setting and to improve efficiency in allocation of the set budget among districts. METHODS: Cross sectional, retrospective observational study using secondary data. The value of pharmaceuticals procured by primary health care facilities in 87 randomly selected districts for the Financial Year 2011/2012 was collected. Various specifications of the dependent variable (pharmaceutical expenditure) were used: total pharmaceutical expenditure, Per capita district pharmaceutical expenditure, pharmaceutical expenditure per district health facility and pharmaceutical expenditure per outpatient department visit. Andersen's behaviour model of health services utilisation was used as conceptual framework to identify independent variables likely to influence health care utilisation and hence pharmaceutical expenditure. Econometric analysis was conducted to estimate parameters of various regression models. RESULTS: All models were significant overall (P < 0.01), with explanatory power ranging from 51 to 82%. The log linear model for total pharmaceutical expenditure explained about 80% of the observed variation in total pharmaceutical expenditure (Adjusted R(2) = 0.797) and contained the following variables: Immunisation coverage, Total outpatient department attendance, Urbanisation, Total number of government health facilities and total number of Health Centre IIs. The model based on Per capita Pharmaceutical expenditure explained about 50% of the observed variation in per capita pharmaceutical expenditure (Adjusted R(2) = 0.513) and was more balanced with the following variables: Outpatient per capita attendance, percentage of rural population below poverty line 2005, Male Literacy rate, Whether a district is characterised by MOH as difficult to reach or not and the Human poverty index. CONCLUSIONS: The log-linear model based on total pharmaceutical expenditure works acceptably well and can be considered useful for predicting future total pharmaceutical expenditure following observed trends. It can be used as a simple tool for rough estimation of the potential overall national primary health pharmaceutical expenditure to guide budget setting. The model based on pharmaceutical expenditure per capita is a more balanced model containing both need and enabling factor variables. These variables would be useful in allocating any set budget to districts.

Differential costs for the non-adult ADHD population in Catalonia.

Attention-Deficit/Hyperactivity Disorder (ADHD) is young children's most common mental health disorder. We aim to provide causal estimates of the differential costs for the non-adult population with ADHD. We used longitudinal administrative data covering the non-adult population over five years and different healthcare providers (general practitioners, hospitalisations and emergency departments, visits to mental healthcare centres-day-care or hospitals) of 1,101,215 individuals in Catalonia (Spain). We also include the consumption of pharmaceuticals and cognitive therapies. We instrumented ADHD diagnosis by the probability of being diagnosed by the most visited healthcare provider based on individual monthly visits to the provider in which this visit was related to ADHD and the density of professionals in the different mental health providers. After using matching procedures to include a proper control group, we estimated two-part and finite mixture models. Our results indicate that ADHD children and adolescents displayed 610€ higher annual health direct costs compared to not diagnosed counterparts. We provide average costs disentangling the sample by age boundaries, gender, and comorbidities to offer values for cost-effective analyses and incremental costs after diagnosis, which is around 400€. A significant differential annual direct health cost for the non-adult population with ADHD is determined, which will be helpful for cost-effectiveness analysis and complete cost-of-illness studies.

What is the social cost of injured people in traffic collisions? An assessment for Catalonia.

BACKGROUND: Traffic collisions are an important public health problem worldwide, in terms of mortality, morbidity, and economic burden. The goal of this study is to estimate the social cost of injured people in traffic collisions in Catalonia in the year 2007. METHODS: We performed a cost-of-illness analysis, under the perspective of the healthcare system, the public sector, and the society, using a 1-year time horizon. In Catalonia, during 2007, there were a total of 26,063 collisions with victims, which translates into 34,565 non-mortal victims and 521 deaths. As direct costs, all healthcare costs (primary care, acute hospital care, emergency care, ambulances and transport, long-term care, and specialized care); costs of adaptation to disability, disability benefits, material costs, and administrative costs; and costs of police, fire-fighters, and road assistance have been included. As indirect costs, productivity losses as a result of hospital and long-term institutionalization as well as productivity losses from work sick leave and productivity losses of carers have been taken into account. RESULTS: From the perspective of the healthcare system, the cost of the injured people in traffic collisions was 31,803,024.03€ in 2007; from the perspective of the public sector, it was 134,047,059.27€ (up to 1,463,645,407.13€ in the sensitivity analysis) and 144,043,238.88€ (up to 1,558,926,995.12€ in the sensitivity analysis) from the perspective of the society. The cost per injured person ranged from 3,855.38€ from the perspective of the healthcare system to 17,461.90€ from the perspective of the society (up to 188,983.76€ in the sensitivity analysis). CONCLUSIONS: The importance of the costs of injured people in traffic collisions is an argument more-besides the epidemiologic and social impact-to start off preventive policies.

Inequity and benefit incidence analysis in healthcare use among Syrian refugees in Egypt.

BACKGROUND: The Syrian conflict has created the worst humanitarian refugee crisis of our time, with the largest number of people displaced. Many have sought refuge in Egypt, where they are provided with the same access to healthcare services as Egyptian citizens. Nevertheless, in addition to the existing shortcomings of the Egyptian health system, many obstacles specifically limit refugees' access to healthcare. This study looks to assess equity across levels of care after observing services utilization among the Syrian refugees, and look at the humanitarian dilemma when facing resource allocation and the protection of the most vulnerable. METHODS: A cross-sectional survey was used and collected information related to access and utilization of outpatient and inpatient health services by Syrian refugees living in Egypt. We used concentration index (CI), horizontal inequity (HI) and benefit incidence analysis (BIA) to measure the inequity in the use of healthcare services and distribution of funding. We decomposed inequalities in utilization, using a linear approximation of a probit model to measure the contribution of need, non-need and consumption influential factors. RESULTS: We found pro-rich inequality and horizontal inequity in the probability of refugees' outpatient and inpatient health services utilization. Overall, poorer population groups have greater healthcare needs, while richer groups use the services more extensively. Decomposition analysis showed that the main contributor to inequality is socioeconomic status, with other elements such as large families, the presence of chronic disease and duration of asylum in Egypt further contributing to inequality. Benefit incidence analysis showed that the net benefit distribution of subsidies of UNHCR for outpatient and inpatient care is also pro-rich, after accounting for out-of-pocket expenditures. CONCLUSION: Our results show that without equitable subsidies, poor refugees cannot afford healthcare services. To tackle health inequities, UNHCR and organisations will need to adapt programmes to address the social determinants of health, through interventions within many sectors. Our findings contribute to assessments of different levels of accessibility to healthcare services and uncover related sources of inequities that require further attention and advocacy by policymakers.

The impact of taxing sugar-sweetened beverages on cola purchasing in Catalonia: an approach to causal inference with time series cross-sectional data.

Sugar-sweetened beverage (SSB) taxes related to the quantity of sugar have appeared as a popular regulatory tool around the world during the last decade showing important variations in their implementation and impact. We evaluated the impact of a new SSB tax implemented in Catalonia since May 1, 2017 on the purchased quantities and penetration rates of taxed and untaxed cola beverages. We use aggregate time series of cola beverages purchases in all 17 Spanish Autonomous Communities before and after the implementation of the SBB tax in Catalonia, from January 2013 to June 2019. A comparison between two different types of causal inference methods was conducted: a two-way fixed effects difference in differences model and a modified synthetic control model. Regular cola purchases decreased 12.1% and their penetration rate decreased by 1.27 points during the two post-intervention years using the preferred model. Diet cola purchases increased 17.0% and their penetration rate also increased by 1.65 points. Only regular cola results were robust to all placebo test checks. The SSB tax implemented in Catalonia in 2017 significantly reduced the volume and penetration rates of regular colas with no robust evidence for the substitution effect on diet colas.

The Effect of Changes in Cost Sharing on the Consumption of Prescription and Over-the-Counter Medicines in Catalonia.

Many universal health care systems have increased the share of the price of medicines paid by the patient to reduce the cost pressure faced after the Great Recession. This paper assesses the impact of cost-sharing changes on the propensity to consume prescription and over-the-counter medicines in Catalonia, a Spanish autonomous community, affected by three new cost-sharing policies implemented in 2012. We applied a quasi-experimental difference-in-difference method using data from 2010 to 2014. These reforms were heterogeneous across different groups of individuals, so we define three intervention groups: (i) middle-income working population-co-insurance rate changed from 40% to 50%; (ii) low/middle-income pensioners-from free full coverage to 10% co-insurance rate; (iii) unemployed individuals without benefits-from 40% co-insurance rate to free full coverage. Our control group was the low-income working population whose co-insurance rate remained unchanged. We estimated the effects on the overall population as well as on the group with long-term care needs. We evaluated the effect of these changes on the propensity to consume prescription or over-the-counter medicines, and explored the heterogeneity effects across seven therapeutic groups of prescription medicines. Our findings showed that, on average, these changes did not significantly change the propensity to consume prescription or over-the-counter medicines. Nonetheless, we observed that the propensity to consume prescription medicines for mental disorders significantly increased among unemployed without benefits, while the consumption of prescribed mental disorders medicines for low/middle-income pensioners with long-term care needs decreased after becoming no longer free. We conclude that the propensity to consume medicines was not affected by the new cost-sharing policies, except for mental disorders. However, our results do not preclude potential changes in the quantity of medicines individuals consume.

Estimation of the Clinical and Economic Impact of an Improvement in Adherence Based on the Use of Once-Daily Single-Inhaler Triple Therapy in Patients with COPD.

Background: Adherence to treatment is key to achieve desired outcomes. In COPD, adherence is generally suboptimal and is impaired by treatment complexity. Objective: To estimate the clinical and economic impact of an improvement in treatment adherence due to an increased use of once-daily single-inhaler triple therapy (SITT) in patients with COPD. Patients and Methods: A 7-state Markov model with monthly cycles was developed. Patients with moderate-to-very severe COPD, for whom triple therapy is indicated, were included. Outcomes and costs were estimated and compared for two scenarios: current distribution of adherent patients treated with multiple inhaler triple therapies (MITT) vs a potential scenario where patients shifted to once-daily SITT. In the potential scenario, adherence improvement due to once-daily SITT attributes was estimated. Costing was based on the Spanish National Health System (NHS) perspective (€2019). A 3-year time horizon was defined considering a 3% discount rate for both costs and outcomes. Results: A target population of 185,111 patients with moderate-to-very severe COPD currently treated with MITT was estimated. A 20% increase in the use of once-daily SITT in the potential scenario raised adherence up to 52%. This resulted in 6835 exacerbations and 532 deaths avoided, with 775 LYs and 594 QALYs gained. Total savings reached €7,082,105. Exacerbation reduction accounted for 61.8% (€4,378,201) of savings. Conclusion: Increasing the use of once-daily SITT in patients with moderate-to-very severe COPD treated with triple therapy would be associated with an improvement in adherence, a reduction of exacerbations and deaths, and cost savings for the Spanish NHS.

Price Models for Multi-indication Drugs: A Systematic Review.

BACKGROUND: Marketing of new and existing drugs with new indications used alone or in combination is increasing. OBJECTIVE: To identify the advantages and disadvantages of indication-based pricing (IBP) systems for such drugs from the standpoint of economic theory, practical applications and international experiences. METHODS: We conducted a systematic review of published articles and reports using six bibliographic databases: PubMed, ASCO, Scopus, DARE, HTA and NHS EED. We also conducted a search of gray literature in Google Scholar. The same search terms were used as in Towse et al. (The debate on indication-based pricing in the U.S. and five major European countries. OHE Consulting Report, London, 2018). Articles and reports published from 1 January 2000 to 30 September 2018 were included. RESULTS: A total of 26 studies met the inclusion criteria. There are three main types of IBP: different brands with different prices for each indication, an averaged single price for all indications and a single price with differential discounts. The studies indicate that IBP systems are premised on the idea that charging a different price for different indications reflects the differences in their value and in social willingness to pay for each one and for the investment in R&D based on the indication's incremental clinical benefit. Some argue that a uniform price reduces access and increases the price for lower-value indications, while others contend that if IBP sets prices at the maximum threshold of social willingness to pay for each indication, all surplus is transferred to the producer and consumer surplus is reduced to zero. No practical applications of pure IBP were found. Single pricing for drugs is the most prevalent approach. The system that most closely approximates an IBP model consists of agreements that are generally confidential and linked to risk-sharing agreements. CONCLUSIONS: There are no applications of pure IBP systems and their practical consequences are therefore unknown. More economic theory-based assessments of the pros and cons of IBP and studies different from reviews are needed to capture their intricacies and specificities.

[What is an efficient health intervention in Spain in 2020?] / ¿Qué es una intervención sanitaria eficiente en España en 2020?

Fifteen years ago, Gaceta Sanitaria published the article entitled "What is an efficient health technology in Spain?" The growing interest in setting the price of new technologies based on the value they provide to health systems and the experience accumulated by the countries in our environment make it opportune to review what constitutes an efficient health intervention in Spain in 2020. Cost-effectiveness analysis continues to be the reference method to maximize social health outcomes with the available resources. The interpretation of its results requires establishing reference values that serve as a guide on what constitutes a reasonable value for the health care system. Efficiency thresholds must be flexible and dynamic, and they need to be updated periodically. Its application should be based on and transparency, and consider other factors that reflect social preferences. Although setting thresholds is down to political decision-makers, in Spain it could be reasonable to use thresholds of 25,000 and 60,000 Euros per QALY. However, currently, in addition to determining exact figures for the threshold, the key question is whether the Spanish National Health System is able and willing to implement a payment model based on value, towards achieving gradual financing decisions and, above all, to improve the predictability, consistency and transparency of the process.

Economic evaluations of massive HPV vaccination: within-study and between study variations in incremental cost per QALY gained.

OBJECTIVE: We describe the heterogeneity of the estimates of the incremental cost per quality-adjusted year of life (QALY) within and between cost-utility studies of the human papillomavirus (HPV) vaccine. METHOD: We searched for articles in English published in peer-reviewed journals that perform cost-utility analyses to evaluate the addition of HPV vaccine to 12-year-old girls to existing cervical cancer screening practices. Fifteen studies were selected according to our inclusion and exclusion criteria. RESULTS: There are large within-study variations in estimates of the cost per QALY gained. The most influential source of uncertainty is the duration of the vaccine protection. Between-study variations are mainly due to three causes: methodological differences, assumptions, and local conditions in the application area. We find large variations between studies for a given country. DISCUSSION: Economic evaluation models are increasingly sophisticated, but scientific treatment of epidemiological and market uncertainty does not compensate for the lack of basic information. CONCLUSIONS: The large disparities in cost per QALY estimates of massive vaccination programs around the world may be attributed to several critical sources (unavoidable and avoidable) of uncertainty. An asset of economic evaluation is the ability to highlight the areas of research that could be undertaken to reduce uncertainty.

[From the therapeutic utility to the added therapeutic value and the incremental cost-effectiveness ratio]. / De la utilidad de los medicamentos al valor terapéutico añadido y a la relación coste-efectividad incremental.

From the social perspective, the concepts of therapeutic utility and degree of innovation of new drugs should be referred to their social added value in relation to the available treatment alternatives and the added costs that they imply; that is, to their incremental cost-effectiveness ratio. The analytic elements highlighting this approach are: 1) the dimensions of the social value of the medication that should go beyond the conventional outcomes measures to also incorporate measures of health related quality of life, patient and family comfort and convenience, healthcare consumption avoided and productive losses avoided; 2) the relative or incremental character of this value that should be quantified in front of previous alternatives -not versus placebo- and under conditions of real use; and 3) the incremental costs that bears the administration of the new medication. The incremental cost-effectiveness ratio is the appropriate approach for decisions about coverage of a treatment by the public insurer, the price that he is willing to pay for the drug, and the clinical situations and patient groups in which it is recommended. The incremental cost-effectiveness analysis and the use of an indicative threshold of the maximum cost that the society is willing to pay for one additional "quality adjusted life year" are the essential elements of this approach, which doesn't require to fix the price of the new medications at the threshold of the willingness to pay.

Effectiveness and cost-effectiveness of Improving clinicians' diagnostic and communication Skills on Antibiotic prescribing Appropriateness in patients with acute Cough in primary care in CATalonia (the ISAAC-CAT study): study protocol for a cluster randomised controlled trial.

BACKGROUND: Despite their marginal benefit, about 60% of acute lower respiratory tract infections (ALRTIs) are currently treated with antibiotics in Catalonia. This study aims to evaluate the effectiveness and efficiency of a continuous disease-focused intervention (C-reactive protein [CRP]) and an illness-focused intervention (enhancement of communication skills to optimise doctor-patient consultations) on antibiotic prescribing in patients with ALRTIs in Catalan primary care centres. METHODS/DESIGN: A cluster randomised, factorial, controlled trial aimed at including 20 primary care centres (N = 2940 patients) with patients older than 18 years of age presenting for a first consultation with an ALRTI will be included in the study. Primary care centres will be identified on the basis of socioeconomic data and antibiotic consumption. Centres will be randomly assigned according to hierarchical clustering to any of four trial arms: usual care, CRP testing, enhanced communication skills backed up with patient leaflets, or combined interventions. A cost-effectiveness and cost-utility analysis will be performed from the societal and national healthcare system perspectives, and the time horizon of the analysis will be 1 year. Two qualitative studies (pre- and post-clinical trial) aimed to identify the expectations and concerns of patients with ALRTIs and the barriers and facilitators of each intervention arm will be run. Family doctors and nurses assigned to the interventions will participate in a 2-h training workshop before the inception of the trial and will receive a monthly intervention-tailored training module during the year of the trial period. Primary outcomes will be antibiotic use within the first 6 weeks, duration of moderate to severe cough, and the quality-adjusted life-years. Secondary outcomes will be duration of illness and severity of cough measured using a symptom diary, healthcare re-consultations, hospital admissions, and complications. Healthcare costs will be considered and expressed in 2021 euros (year foreseen to finalise the study) of the current year of the analysis. Univariate and multivariate sensitivity analyses will be carried out. DISCUSSION: The ISAAC-CAT project will contribute to evaluate the effectiveness and efficiency of different strategies for more appropriate antibiotic prescribing that are currently out of the scope of the actual clinical guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03931577.

Influence of bacterial resistances on the efficiency of antibiotic treatments for community-acquired pneumonia.

The objective of this paper is to perform a cost-effectiveness analysis of the oral antibiotics used in Spain for the ambulatory treatment of community-acquired pneumonia. Our analysis takes into account the influence of bacterial resistances on the cost-effectiveness ratio of antibiotic alternatives from the viewpoint of the public insurer. A deterministic decision analysis model is used to simulate the impact of treatment alternatives on both patients' health and resource consumption. Amoxicillin 1 g may be the most efficient therapy for treating typical pneumonia, as long as the physician is able to discriminate clinically the aetiology of the process with a high degree of reliability. However, for those pathological pictures in which the aetiology cannot be discriminated clinically, and for those in which the consequences of incorrect diagnosis are serious according to clinical criteria, moxifloxacin is the most effective and efficient option.

[Advances and experiences in economic evaluation of medicines: a complementary view]. / Evaluación económica de medicamentos: experiencias y vías de avance. Una visión complementaria.

This article presents a complementary view of the latest experiences and advances in the economic evaluation of medicines in the Spanish market. The European context and recent normative changes seem to favour the incorporation of economic evaluation of medicines as a basic tool in the decision-making process of public funding of drugs. However, some doubts remain about whether government support for economic evaluation of medicines will be open and explicit and about the role that regional decision-makers and other health actors will play in this process.

Non-healthcare costs of hepatitis C: a systematic review.

INTRODUCTION: There is an increasing interest in the indirect (or non-healthcare) costs of hepatitis C virus (HCV). Areas covered: Systematic review of original studies on the non-healthcare costs of HCV published in English or Spanish between January 2000 and March 2017. 19 studies addressing non-healthcare cost of HCV were included in the analysis. All studies but one contain treatments with monotherapy or dual therapy prior to the recent introduction of innovative and highly effective direct acting antivirals (DAAs). Five studies estimate the incremental non-healthcare cost of HCV with a control group, which is regarded as high-quality methodology. The incremental annual non-healthcare costs of HCV in untreated patients compared with non-HCV patients are €4,209 in the US, and taking data from 5 European countries costs range from €280 in the UK to €659 in France. Expert commentary: Available studies may be underestimating the true burden of non-healthcare costs for HCV as they are all partial studies, mainly including absenteeism and premature mortality estimates. Moreover, there is a need for studies addressing non-healthcare costs of HCV in settings where new treatments with DAAs have been implemented, as they are probably changing the current and future burden of the disease.