Health Technology Assessment as Part of a Broader Process for Priority Setting and Resource Allocation Abstract Over the last two decades, economic evaluation of health technologies has developed enormously, affirming its importance within the pursuit of efficiency in the management of health care systems. One concern that has been raised with health technology assessment (HTA) has been its operationalization within the realm of decision making. Here, we suggest a mechanism by which HTA can be understood as an input into a broader framework for priority setting and resource allocation. When HTA is seen in this light, topics that at times have had some lack of clarity, such as public engagement and disinvestment, simply become steps in the overall decision-making process.

Developing Attributes and Attribute-Levels for a Discrete-Choice Experiment: An Example for Interventions of Impulsive Violent Offenders Abstract Background Discrete-Choice Experiments (DCEs) are used to assess the strength of preferences and value of interventions, but researchers using the method have been criticised for failing to either undertake or publish the rigorous research for selecting the necessary attributes and levels. The aim of this study was to elicit attributes to inform a DCE to assess societal and offenders’ preferences for, and value of, treatment of impulsive-violent offenders. In doing so, this paper thoroughly describes the process and methods used in developing the DCE attributes and levels. Methods Four techniques were used to derive the final list of attributes and levels: (1) a narrative literature review to derive conceptual attributes; (2) seven focus group discussions (FGDs) comprising 25 participants including offenders and the general public and one in-depth interview with an offender’s family member to generate contextual attributes; (3) priority-setting methods of voting and ranking to indicate participants’ attributes of preference; (4) a Delphi method consensus exercise with 13 experts from the justice health space to generate the final list of attributes. Results Following the literature review and qualitative data collection, 23 attributes were refined to eight using the Delphi method. These were: treatment effectiveness, location and continuity of treatment, treatment type, treatment provider, voluntary participation, flexibility of appointments, treatment of co-morbidities and cost. Conclusion Society and offenders identified similar characteristics of treatment programs as being important. The mixed methods approach described in this manuscript contributes to the existing limited methodological literature in DCE attribute development.

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults Abstract Objectives In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. Methods A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. Results RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. Conclusions The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

General Trends in Prices and Prescription Patterns of Anticonvulsants in Germany between 2000 and 2017: Analysis of National and Cohort-Based Data Abstract Objective Our aim was to explore trends in price evolution and prescription volumes of anticonvulsants (AEDs, antiepileptic drugs) in Germany between 2000 and 2017. Method This study used data from annual reports on mean prescription frequency and prices of defined daily doses (DDD) of AEDs in Germany to analyze nationwide trends. Interrupted time series (ITS) analysis was employed to test for significant effects of several statutory healthcare reforms in Germany on AED price evolution. These data were compared to cohort-based prescription patterns of four German cohort studies from 2003, 2008, 2013, and 2016 that included a total of 1368 patients with focal and generalized epilepsies. Results Analysis of national prescription data between 2000 and 2017 showed that mean prices per DDD of third-generation AEDs decreased by 65% and mean prices of second-generation AEDs decreased by 36%, whereas mean prices of first-generation AEDs increased by 133%. Simultaneously, mean prescription frequency of third- generation AEDs increased by 2494%, while there was a substantial decrease in the use of first- (− 55%) and second- (− 16%) generation AEDs. ITS analysis revealed that in particular the introduction of mandatory rebates on drugs in 2003 affected prices of frequently used newer AEDs. These findings are consistent with data from cohort studies of epilepsy patients showing a general decrease of prices for frequently used AEDs in monotherapy by 62% and in combination therapies by 68%. The analysis suggests that overall expenses for AEDs remained stable despite an increase in the prescription of “newer” and “non-enzyme-inducing” AEDs for epilepsy patients. Conclusion Between 2000 and 2017, a distinct decline in AED prices can be observed that seems predominately caused by a governmentally obtained price decline of third- and second-generation drugs. These observations seem to be the result of a German statutory cost containment policy applied across all health-care sectors. The increasing use of third-generation AEDs to the disadvantage of “old” and “enzyme-inducing” AEDs reflects the preferences of physicians and patients with epilepsy and follows national treatment guidelines.

Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16) Abstract Objectives To evaluate the cost-effectiveness of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in basal–bolus regimens for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk based on the DEVOTE CV outcomes trial. Methods A microsimulation model, informed by clinical outcomes from the subgroup of patients using basal–bolus insulin therapy in DEVOTE (NCT01959529) and by the UKPDS Outcomes Model 2 risk equations, was used to model direct costs (2018 GBP) and effectiveness outcomes [quality-adjusted life years (QALYs)] with degludec versus glargine U100 over a 40-year time horizon. The model captured the development of eight diabetes-related complications, death, severe hypoglycemia and insulin dosing. This analysis was conducted from the perspective of National Health Service (NHS) England. Results Treatment with degludec versus glargine U100 in basal–bolus regimens was associated with improved clinical outcomes at a higher cost per patient [incremental cost effectiveness ratio (ICER): £14,956 GBP/QALY]. Degludec remained cost effective versus glargine U100 in all exploratory sensitivity analyses, with ICERs below the widely accepted willingness-to-pay threshold, although the result was most sensitive to assumptions regarding the persistence of treatment effects. Conclusions Our long-term modeling analysis suggested that degludec was cost effective (from the perspective of NHS England) versus glargine U100 in basal–bolus regimens for patients with T2D at high CV risk. Our findings raise important questions regarding how to model the health economics of diabetes therapies.

Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma Abstract Background The presence of lymph node (LN) metastasis is a critical prognostic factor in colorectal cancer (CRC) patients and is also an indicator for adjuvant chemotherapy. The gold standard (GS) technique for LN diagnosis and staging is based on the analysis of haematoxylin and eosin (H&E)-stained slides, but its sensitivity is low. As a result, patients may not be properly diagnosed and some may have local recurrence or distant metastases after curative-intent surgery. Many of these diagnostic and treatment problems could be avoided if the one-step nucleic acid amplification assay (OSNA) was used rather than the GS technique. OSNA is a fast, automated, standardised, highly sensitive, quantitative technique for detecting LN metastases. Objectives The aim of this study was to assess the budget impact of introducing OSNA LN analysis in early-stage CRC patients in the Spanish National Health System (NHS). Methods A budget impact analysis comparing two scenarios (GS vs. OSNA) was developed within the Spanish NHS framework over a 3-year time frame (2017–2019). The patient population consisted of newly diagnosed CRC patients undergoing surgical treatment, and the following costs were included: initial surgery, pathological diagnosis, staging, follow-up expenses, systemic treatment and surgery after recurrence. One- and two-way sensitivity analyses were performed. Results Using OSNA instead of the GS would have saved €1,509,182, €6,854,501 and €10,814,082 during the first, second and third years of the analysis, respectively, because patients incur additional costs in later years, leading to savings of more than €19 million for the NHS over the 3-year time horizon. Conclusions Introducing OSNA in CRC LN analysis may represent not only an economic benefit for the NHS but also a clinical benefit for CRC patients since a more accurate staging could be performed, thus avoiding unnecessary treatments.

A Systematic Review of Productivity in Economic Evaluations of Workplace Interventions: A Need for Reporting Criteria? Abstract Background Rheumatic and musculoskeletal diseases (RMDs) are understood to reduce levels of paid productivity. Productivity, including absenteeism and presenteeism, is arguably an important factor for consideration in economic evaluations of workplace interventions for RMDs (WPI-RMDs). Existing methods available to quantify and value absenteeism and presenteeism are heterogeneous and produce estimates that vary substantially across studies. To date, there has been no systematic summary of the reporting quality of methods used to quantify paid productivity included in economic evaluations of WPI-RMDs. Objective The aim of this systematic review was twofold. First, the review was conducted to understand if, and how, the impact of WPI-RMDs on productivity was considered and incorporated in published economic evaluations. Second, we aimed to assess the reporting quality of productivity in published economic evaluations of WPI-RMDs and determine the need for a published set of reporting guidelines for productivity. Methods This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic review published in 2008 that focused on the cost effectiveness of WPIs, with limited information on productivity, was updated from 2007 to July 2018. A global search was conducted using three online databases: MEDLINE (1946 to August 2018, week 2), EMBASE (1974 to 10 July 2018); and EconLit (1886 to July 2018). The studies were double-screened by four independent reviewers. Data extraction was conducted using a bespoke data extraction table. Results Twenty-one economic evaluations of WPI-RMDs were identified. All studies evaluated absenteeism, but only five reported on levels of presenteeism. The methods used to identify and measure absenteeism were fairly consistent; however, methods used to identify and measure presenteeism, and value absenteeism and presenteeism, varied across studies. Two studies may have potentially double-counted productivity in their economic evaluations of WPI-RMDs. The results of this systematic review identified key elements potentially useful as a starting point to inform reporting quality guidelines for productivity. Conclusions Variation in the methods used to quantify productivity and how it is reported in economic evaluations suggests the need for specific published reporting guidelines for productivity. The development of standardised reporting guidelines for the identification, measurement, and valuation of absenteeism and presenteeism in economic evaluations may help reduce variation in the methods and promote transparency.

Treatment Patterns, Overall Survival, and Total Healthcare Costs of Advanced Merkel Cell Carcinoma in the USA Abstract Background Merkel cell carcinoma (MCC) is a rare and aggressive type of cancer with poor outcomes. Objective To describe treatment patterns, overall survival, and healthcare costs associated with advanced MCC (aMCC) using data from Medicare enrollees who received an aMCC diagnosis in the USA States between 2006 and 2013. Methods Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2006 to 2013 were used to describe treatment patterns, 1- and 5-year overall survival, and total healthcare costs for the periods 12 months before aMCC diagnosis and 4–12 months afterward in patients aged ≥ 65 years. Results We identified 257 patients with an aMCC diagnosis, of whom 51% had stage IIIb disease and 49% had stage IV. Within 4 months after diagnosis, 84% of patients (n = 216) received treatment; 45% (n = 115) received surgery, 48% (n = 124) radiation therapy, and 31% (n = 80) chemotherapy. Second-line chemotherapy was administered in 33% of patients (n = 26) receiving first-line chemotherapy. Median overall survival was 27 months in patients whose aMCC was diagnosed at stage IIIb and 12 months in patients whose aMCC was diagnosed at stage IV. Median total 12-month direct healthcare costs were US$48,006 (25th–75th percentile range = US$30,594–US$69,797) per patient. Total costs were highest in patients receiving chemotherapy, either alone or combined with radiation and/or surgery (US$52,854; 25th–75th percentile range = US$34,473–US$71,987). Conclusion Most patients with aMCC received initial treatment, including surgery, radiation, and/or chemotherapy, and approximately one-third of those receiving chemotherapy received second-line chemotherapy. Total 12-month direct healthcare costs were highest in patients who received chemotherapy alone or combined with radiation and/or surgery. These poor survival results and high treatment costs highlight the need for effective new aMCC therapies.

The Economic Burden of Asthma in Greece: A Cross-Sectional Study Abstract Background The high prevalence rates of asthma worldwide and the chronic nature of the disease make asthma a major cause of morbidity, imposing a significant socio-economic burden in many countries. Specifically in Greece, the self-reported prevalence of asthma reached 9% in 2017. Objectives The objective of this study was to estimate the total management cost of asthma in Greece and its potential determinants. Methods A population-based, random-digit-dialed telephone nationwide survey was conducted to recruit patients with asthma in Greece (n = 353). A structured questionnaire was used to collect data on demographic and lifestyle characteristics, exacerbations, asthma control, medical resource utilization, and productivity loss during the past 12 months. The total annual direct cost from the societal, payer, and patient perspective as well as the indirect cost was calculated. All costs refer to the year 2017 (€). The significance level was set to α = 0.05. Results The mean (95% confidence interval) annual total cost per patient for asthma management from the societal, payer, and patient perspective was €895 (696–1105), €673 (497–861), and €151 (119–188), respectively. The direct medical cost accounted for almost 90% of the total cost, whereas only 4% was attributed to the indirect cost. The direct medical cost was mainly driven by the medication cost (48%). The total annual societal cost was statistically significantly higher in those with not well-controlled asthma (p = 0.014) and those experiencing exacerbations during the past 12 months (p < 0.001) than in their counterparts. The total annual economic burden of asthma in Greece was estimated at €727 million and €547 million from the societal and payer perspective, respectively. Conclusion Our findings indicate that asthma imposes a high economic burden on society and the healthcare system in Greece. Therefore, greater investment in interventions aimed at asthma control and prevention of acute exacerbations may reduce the overall burden of asthma in Greece.

Access and Affordability of Medicines in Malaysia: Need for a National Pricing Policy Abstract Background High medicines prices are a barrier to medicines access, and their impact is greater in developing countries. Objective This study assessed the availability, prices and affordability of medicines in public and private sectors in Malaysia to understand the pharmaceutical environment and guide policy recommendations. Methods This nationwide cross-sectional study adapted the World Health Organization/Health Action International (WHO/HAI) methodology. A total of 87 premises from both public and private sectors participated in this study. Data on 50 medicines were collected to analyze availability, prices and affordability. Medicine prices were compared against the international reference prices (IRPs), and affordability was assessed by daily income level. Results In the public sector, the average availability of generics (74.8%) was higher than that of the originator brand name products (19.4%). However, in the private sector, the availability of originator brands was higher (52.2%) than generics (49.1%). Procurement prices in the public sector were up to 1.5 times the IRPs, but up to 8.4 times in the private sector. The study also observed large price variation across medicines in the private sector. Median retail mark-ups in private hospitals (generics 166.9%; originators 51.0%) were higher than in retail pharmacies (generics 94.7%; originators 22.4%). Generics were generally affordable, but originator brands were unaffordable. Conclusion Current policies on generic medicines need to be strengthened to improve the availability and use of generics in the country. High medicine prices and large price variation in the current free market suggest that coherent pricing policies and regulations are needed to safeguard the accessibility and affordability of medicines for the people.