Sweden has a long history of using data as a basis to form policies in many sectors of society. The very first documented efforts to collect data and use some kind of evidence to judge health care began 350 years ago in Sweden. In 1663, the Swedish Collegium Medicorum (re-named Collegium Medicum in 1688) was established; initially to distinguish quackery from medicine, to develop a pharmacopoeia, to control the trade of poisonous drugs, and banish all swindlers who “grease people with their fake, fraudulent, and harmful medicaments”(12;20;25;26).

Health technology assessment (HTA) grew from a need recognized by researchers concerned about the effectiveness of health services. They were later joined by policy makers in search of valid information about the costs and benefits of investments in health care. The history of HTA shows that this need appeared in many countries at nearly the same time.

Objectives: This study outlines the needs and current development of the “fourth hurdle” (i.e., requirement of effectiveness and cost-effectiveness data for drug coverage policy decisions) in Hungary, describes the legal background and seeks to address some of the most important questions in this field.

Methods: The study draws on international experiences and discusses five issues that a given jurisdiction needs to consider before introducing the “fourth hurdle” for pharmaceuticals.

Results: The “fourth hurdle” is very relevant in Hungary because many existing drugs are unevaluated and many new, expensive drugs are becoming available. On the other hand, the existing resources for health technology assessment, including economic evaluation, are quite limited. All the five issues are relevant in the Hungarian setting and were helpful in determining exactly how the “fourth hurdle” should be applied.

Conclusions: The most important issue seems to be that the implementation of the “fourth hurdle” needs to be achieved in a way consistent with the limited resources for HTA in Hungary. Specifically this means that, in setting priorities for drugs to evaluate, additional criteria need to be applied. In particular, priority should be given to assessing drugs that have been evaluated in other countries, because this affords the opportunity to adapt existing studies or models to the Hungarian situation.

We describe and illustrate the use of a generalizable model for evaluating the cost-effectiveness of alternative cholesterol-lowering treatments. We combine standard incidence-based techniques for measuring the cost of illness with logistic risk functions from the Framingham Heart Study to project, for persons with known coronary risk characteristics, the likelihood of developing coronary heart disease (CHD) over a lifetime as well as a number of related outcomes, including the expected loss of years of life due to CHD, the expected lifetime direct and indirect costs of CHD, and the changes in these outcomes that would result from cholesterol-lowering treatment.

Objectives: Previous research has suggested people with impaired fasting glucose (IFG) are less likely to develop Type 2 diabetes (T2DM) if they receive prolonged structured diet and exercise advice. This study examined the within-trial cost-effectiveness of such lifestyle interventions.

Methods: Screen-detected participants with either newly diagnosed T2DM or IFG were randomized 2:1 to intervention versus control (usual care) between February and December 2009, in Norfolk (UK). The intervention consisted of group based education, physiotherapy and peer support sessions, plus telephone contacts from T2DM volunteers. We monitored healthcare resource use, intervention costs, and quality of life (EQ-5D). The incremental cost per quality-adjusted life-year (QALY) gain (incremental cost effectiveness ratio [ICER]), and cost effectiveness acceptability curves (CEAC) were estimated.

Results: In total, 177 participants were recruited (118 intervention, 59 controls), with a mean follow-up of 7 months. Excluding screening and recruitment costs, the mean cost was estimated to be £551 per participant in the intervention arm, compared with £325 in the control arm. The QALY gains were –0.001 and –0.004, respectively. The intervention was estimated to have an ICER of £67,184 per QALY (16 percent probability of being cost-effective at the £20,000/QALY threshold). Cost-effectiveness estimates were more favorable for IFG participants and those with longer follow-up (≥4 months) (ICERs of £20,620 and £17,075 per QALY, respectively).

Conclusions: Group sessions to prevent T2DM were not estimated to be within current limits of cost-effectiveness. However, there was a large degree of uncertainty surrounding these estimates, suggesting the need for further research.

Objectives: Adapting health technology assessment (HTA) reports for different contexts could reduce the need for multiple reports on the same health technology with resultant saving of time and resources. This article describes an instrument, the adaptation toolkit, which has been developed to aid in the process of adaptation of HTA reports.

Methods: The toolkit was developed by a partnership of HTA agencies and networks from across Europe. The role of the toolkit is to guide the user through the process of selecting possible relevant material from these report(s), assessing the relevance, reliability, and transferability of the material, and adapting it for the desired context.

Results: The adaptation toolkit has been developed, it comprises a collection of resources that help the user assess whether data and information in existing HTA reports should and could be adapted for their own setting. The toolkit contains two sections: a preliminary speedy sifting section and the main toolkit. The main toolkit includes five domains: (i) technology use and development, (ii) safety, (iii) effectiveness (including efficacy), (iv) economic evaluation, and (v) organizational aspects. Legal, ethical, and social aspects are beyond the scope of the toolkit. The toolkit is designed for the adaptation of evidence synthesis rather than primary research.

Conclusions: The completed current version of the toolkit contains checklists and resources to aid in the adaptation of HTA reports. This collection of resources is available for use by all HTA agencies and can be accessed at: http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf..

Objectives: In a practice setting where casting is considered the standard of care, the aim of this study was to assess the cost-effectiveness of wrist splints compared with routine casting in children with acceptably angulated distal radius greenstick or transverse fractures.

Methods: A cost-effectiveness analysis was conducted alongside a randomized controlled trial (RCT). One hundred children with acceptably angulated distal radius greenstick or transverse fractures received either a wrist splint or cast. Information on health care provider and patient and family resource use as well as productivity cost was collected. Resource use was costed using unit costs from local administrative data sources and expense diaries. Effectiveness was assessed at 6 weeks using the performance version of the Activities Scale for Kids (ASKp) questionnaire. Cost-effectiveness analysis related differential costs to differential ASKp scores.

Results: Mean total cost was $877.58 in the splint group and $950.35 in the cast group, with a mean difference of $−72.76 (standard error [SE] 45.88). Mean total healthcare cost was $670.66 in the splint group and $768.22 in the cast group, with a mean difference of $−97.56 (SE 9.24). Mean (SE) ASKp was 92.8 in the splint group and 91.4 in the cast group, with a mean difference of 1.439 (SE 1.585). Therefore, splint management was more effective and cheaper. After accounting for uncertainty, the probability of splint being cost-effective compared with cast was 94 percent for a willingness-to-pay threshold value of $0 for one-unit gain in ASKp score and exceeded 82 percent for all threshold values.

Conclusions: In this RCT, splint management was cost-effective compared with casting in children with acceptably angulated distal radius greenstick or transverse fractures. This study challenges the existing standard of care for children with this type of fracture and provides justification on clinical and economic grounds for a change in routine practice.

Italy is one of the few countries that have matured substantial experience of risk-sharing agreements so far. The first performance-based arrangement was agreed in July 2006, and as of October 2010, eighteen contracts have been in force.

The complex management of discount schemes is entirely based on Web registries run by AIFA, the Italian drug agency. The system validates each prescription and automatically requests the hospital pharmacy by e-mail to release the drug. If a patient meets nonresponder criteria, the hospital pharmacist should apply for pay-back to the manufacturer.

There are still some important question marks to address. First of all, nonresponders have to be documented by health authorities, otherwise any undocumented nonresponder will be paid as a success. Another question concerns pre-set timing. Although the scientific rationale of the nonresponder criteria for each drug has not been made public, time frames appear too short to allow a reliable assessment. Another question is whether regions, which are financially accountable in Italy for pharmaceutical expenditure, are really able to claw back refunds from manufacturers. Unfortunately here again there are no official figures, and regions do not seem yet able to quantify the amount of pay-back matured in the 4 previous years. The delayed and incomplete availability of pay-back procedures may be one explanation.

Background: Many jurisdictions delivering health care, including Canada, have developed guidance for conducting economic evaluation, often in the service of larger health technology assessment (HTA) and reimbursement processes. Like any health intervention, personalized medical (PM) interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. However, current approaches to economic evaluation to support decision making have been largely developed from population-based approaches to therapy—that is, evaluating the costs and consequences of single interventions across single populations. This raises the issue as to whether these methods, as they are or more refined, are adequate to address more targeted approaches to therapy, or whether a new paradigm for assessing value in PM is required.

Objectives: We describe specific issues relevant to the economic evaluation of diagnostics-based PM and assess whether current guidance for economic evaluation is sufficient to support decision making for PM interventions.

Methods: Issues were identified through literature review and informal interviews with national and international experts (n = 10) in these analyses. This article elaborates on findings and discussion at a workshop held in Ottawa, Canada, in January 2012.

Results: Specific issues related to better guiding economic evaluation of personalized medicine interventions include: how study questions are developed, populations are characterized, comparators are defined, effectiveness is evaluated, outcomes are valued and how resources are measured. Diagnostics-based PM also highlights the need for analyses outside of economic evaluation to support decision making.

Conclusions: The consensus of this group of experts is that the economic evaluation of diagnostics-based PM may not require a new paradigm. However, greater complexity means that existing approaches and tools may require improvement to undertake these more analyses.

Background: In the debate on improving the quality and efficiency of the United States healthcare system, comparative effectiveness research is increasingly seen as a tool for reducing costs without compromising outcomes. Furthermore, the recent American Recovery and Reinvestment Act explicitly describes a prioritization function for establishing a comparative effectiveness research agenda. However, how such a function, in terms of methods and process, would go about identifying the most important priorities warranting further research has received little attention.

Objectives: This study describes an Agency for Healthcare Research and Quality-funded pilot project to translate one current comparative effectiveness review into a prioritized list of evidence gaps and research questions reflecting the views of the healthcare decision makers involved in the pilot.

Methods: To create a prioritized research agenda, we developed an interactive nominal group process that relied on a multistakeholder workgroup scoring a list of research questions on the management of coronary artery disease.

Results: According to the group, the areas of greatest uncertainty regarding the management of coronary artery disease are the comparative effectiveness of medical therapy versus percutaneous coronary interventions versus coronary artery bypass grafting for different patient subgroups; the impact of diagnostic testing; and the most effective method of developing performance measures for providers.

Conclusions: By applying our nominal group process, we were able to create a list of research priorities for healthcare decision makers. Future research should focus on refining this process because determining research priorities is essential to the success of developing an infrastructure for comparative effectiveness research.

Though technology assessment and quality assessment have much in common, they differ significantly in emphasis. Technology assessment judges technology itself; quality assessment examines the extent to which a technology is used well in its various settings. This article explores the nature of quality assessment–including the performance of individual practitioners as they care for individual patients and the care received by communities–and examines its interrelationship with technology assessment.

Objectives: The objective of this study was to estimate the cost-effectiveness of infliximab use in patients with rheumatoid arthritis (RA) in Swedish clinical practice, based on patient-level data from the Stockholm TNF-alpha follow-up registry (STURE).

Methods: Real-world patient-level data on infliximab use from the STURE registry were implemented in a Markov cohort model, in which health states of functional status were classified according to the Health Assessment Questionnaire Disability Index (HAQ—five categories) and twenty-eight joint count Disease Activity Score (DAS28). The transition probabilities between HAQ and DAS28 states during treatment, as well as discontinuation rates were modeled based on data from the registry for patients using infliximab as their first-line biological treatment. The transition probabilities in the comparator arm, that is, disease progression without biologic treatment, as well as mortality rates, costs, and utilities were based on published literature. The analysis had a societal cost perspective.

Results: Infliximab was associated with an incremental gain in quality-adjusted life-years of 1.02 and an incremental cost of €23,264 per patient compared with progression without biologic treatment, producing an incremental cost-effectiveness ratio (ICER) of €22,830 (SEK211,136 or US$31,230). Sensitivity analyses of input parameters and model assumptions produced ICERs in the range from €18,000 to €47,000.

Conclusions: Results from base-case and sensitivity analyses fell well below established benchmarks for cost-effectiveness in Sweden. The results, therefore, indicated that infliximab treatment for RA has provided good societal value for money in Swedish clinical practice, compared with a scenario of no biological treatment.

Objectives: To identify and assess the effects of general practitioner and patient characteristics on global adherence to pharmacotherapeutic guidelines.

Methods: In a cross-sectional study in the northern Netherlands, a two-level multilevel model was applied to patients (n=269,067) in 190 practices with a total of 251 general practitioners. The dependent variable was the global adherence to pharmacotherapeutic guidelines as a measure of good prescribing in a general practice setting.

Results: The mean global adherence was 82%. Two general practice variables, organization form and degree of urbanization influenced the global adherence, whereas all patient variables (age and gender) and the patient-related prescription characteristics (costs, volume, different ATC-codes) were significant predictors for the global adherence. The total explained variance was 28%.

Conclusions: Patient characteristics have a greater influence on prescribing behavior than general practitioner characteristics.We thank the health care insurance organization (Regionaal Ziekenfonds Groningen [RZG]) for supplying the data set. We also thank Eddie Bruin from the health care insurance organization for his assistance with data collection and Tom Snijders for data analysis and statistical advice.

The pragmatism in health care has made health technology assessment (HTA) restrict its scope to a particular set of problems, c.q. methods. The “multidisciplinary and comprehensive nature” of HTA, as the concept is presented in certain definitions, is lacking. Health care is also dominated by a positivistic-rationalistic approach of evaluation. In contrast, social studies of evaluations learn that a major difference has to be made between scientific research on (potential) impact of a technology and valuing these effects. In this contribution, we will discuss how the positivistic scientific bias of current HTA practice can be made up with other research traditions. More specifically, we focus on the question of how social scientists and particularly how qualitative research can contribute to HTA, complementary to positivistic studies of evidence and efficacy.

Clnical trial randomization schemes to control patient characteristics that can influence clinical response are not sufficient to control for their effects on operational efficiency and cost within the provider institution. This variation can result in biased economic findings when patients are allowed to select a provider themselves.

Practice guidelines are rapidly becoming preferred decision-making resources in medicine, as advances in technology and pharmaceutics continue to expand. An evidence-based approach to the development of practice guidelines serves to anchor healthcare policy to scientific documentation, and in conjunction with practitioner opinion can provide a powerful and practical clinical tool. Three sources of information are essential to an evidence-based approach: a) an exhaustive literature synthesis; b) meta-analysis; and c) consensus opinion. The systematic merging of evidence from these sources offers healthcare providers a scientifically supportable document that is flexible enough to deal with clinically complex problems. Evidence-based practice guidelines, in conjunction with practice standards and practice advisories, are invaluable resources for clinical decision making. The judicious use of these documents by practitioners will serve to improve the efficiency and safety of health care well.

Objectives: The purpose of the study is to reassess the cost-effectiveness of hormone replacement therapy (HRT) based on new medical evidence found in the Women's Health Initiative (WHI). Within a model framework using an individual state transition model, the cost-effectiveness of 50- to 60-year-old women with menopausal symptoms is assessed based on a societal perspective in Sweden.

Methods: The model has a 50-year time horizon divided into a cycle length of 1 year. The model consists of the following disease states: coronary heart disease, stroke, venous thromboembolic events, breast cancer, colorectal cancer, hip fracture, vertebral fracture, and wrist fracture. An intervention is modeled by its impact on the disease risks during and after the cessation of therapy. The model calculates costs and quality-adjusted life years (QALYs) with and without intervention. The resulting cost per QALY gained is compared with the value of a QALY gained, which is set to SEK 600,000. The model requires data on clinical effects, risks, mortality rates, quality of life weights, and costs valid for Sweden.

Results: The cost-effectiveness ratios are estimated at approximately SEK 10,000, which is below the threshold value of cost-effectiveness. On the condition that HRT increases the quality of life weight more than 0.013 units, the therapy is cost-effective.

Conclusions: In conclusion, given the new evidence in WHI, there is still a high probability that HRT is a cost-effective strategy for women with menopausal symptoms.

Objectives: Health Technology Assessment (HTA) needs to address the challenges posed by high cost, effective technologies, expedited regulatory approaches, and the opportunities provided by collaborative real-world evaluation of technologies. The Health Technology Assessment International (HTAi) Policy Forum met to consider these issues and the implications for evidence production to inform HTA. This paper shares their discussion to stimulate further debate.

Methods: A background paper, presentations, group discussions, and stakeholder role play at the 2015 HTAi Policy Forum meeting informed this paper.

Results: HTA has an important role to play in helping improve evidence production and ensuring that the health service is ready to adopt effective technologies. It needs to move from simply informing health system decisions to also working actively to align stakeholder expectations about realistic evidence requirements. Processes to support dialogue over the health technology life cycle need to be developed that are mindful of limited resources, operate across jurisdictions and learn from past processes. Collaborations between health technology developers and health systems in different countries should be encouraged to develop evidence that will inform decision making. New analytical techniques emerging for real-world data should be harnessed to support modeling for HTA.

Conclusions: A paradigm shift (to “Health Innovation System 2.0”) is suggested where HTA adopts a more central, proactive role to support alignment within and amongst stakeholders over the whole life cycle of the technology. This could help ensure that evidence production is better aligned with patient and health system needs and so is more effective and efficient.

The use of economic evaluation in decision making appears to have increased over the past few years and economic evaluation is looked upon as another measure to help contain costs and improve efficiency in an evidence-based decision-making environment. Following the examples of Australia and the Canadian Province of Ontario, four European Union (EU) countries (Finland, the Netherlands, Portugal, and the United Kingdom) have recently introduced economic evaluation guidelines. In addition to the Australian and Canadian guidelines, which constitute a hurdle to reimbursement, the paradigm that seems to be evolving in the four EU countries follows a similar route. Finland and the Netherlands seem to be moving toward the notion of a fourth hurdle to reimbursement, whereas the National Institute for Clinical Excellence in England and Wales was in principle meant to influence practice, although in reality this essentially acts as a hurdle to reimbursement, requiring a different data set to that used by regulatory authorities. Whereas the Portuguese guidelines were developed to assist in preparing economic submissions to support reimbursement decisions, they are unclear about when such evidence will be required and also discuss the dissemination of economic evidence to broader audiences. The introduction of these guidelines poses a number of challenges to policy makers, the implications of which are analyzed in the paper: a) to ensure that economic evaluations are carried out scientifically without industrial or political bias; b) to define an acceptable methodology that would increase their credibility; and c) to address certain practical issues ranging from deciding how to use economic evaluations in policy making to setting up new institutions or improving the coordination and dissemination of evidence. The variation in the use of economic evaluation guidelines in the four EU countries highlights the differences in national pharmaceutical policies and is in line with policy makers' continuous attempts to contain costs. While the paper critically discusses the guidelines, it also points out that a series of methodologic issues need to be addressed if economic criteria are to be introduced in policy making with the aim to improve resource allocation. The paper concludes that economic evaluation as a discipline is beginning to impact on policy, whereas the consistent use of economic evaluation results is, in principle, being adopted by policy makers but needs to go a step further to reach practitioners.