Pinchon-Riviere and colleagues have made an extremely timely contribution that addresses the thorny issues of innovative, high-cost medicines, global health disparities, and the growing interest and application of HTA in low- and middle-income countries.

Background: Rapid on site evaluation (ROSE) allows immediate processing and interpretation of the aspirate in the procedural suite. It improves diagnostic yield and lowers patient care costs. There are limited data on its cost-effectiveness with endobronchial ultrasound (EBUS).

Methods: We developed an economic model with two arms, no ROSE (our current practice) and simulated ROSE. To simulate ROSE, a cytopathologist retrospectively identified the first diagnostic slide in each case. Using a decision analytic modeling technique under a hospital diagnostic unit perspective, the benefits of simulated ROSE were estimated as cost-savings. The model input was estimated from actual data, consulting experts, and the literature. The benefits were estimated as cost savings per patient and for the province of Alberta per year. Due to differences in the procedure, sarcoidosis and cancer patients were analyzed separately. The costs are shown in 2012 Canadian dollars, CAD.

Results: In our model without ROSE, the procedure cost/patient was CAD 646.00(USD 523.32) for cancer and CAD 1,170.00 (USD 947.73) for sarcoidosis. With simulated ROSE cost savings of CAD 63.00(37.00 to 89.00) [USD 51.04(29.97 to 72.10)], CAD 544.00(490.00 to 598.00) [USD 440.65(397.05 to 484.44)] for cancer and sarcoidosis, respectively. Extrapolating this to provincial data, our model estimates that EBUS with ROSE would lead to savings of CAD 50,000.00(30,000 to 71,000) [USD 40,501.24 (24,300.75 to 57,531.34)] for cancer and CAD 109,000.00 (87,000 to 130,000) [USD 88,337.07 (70,546.45 to 105,313.04) for sarcoidosis.

Conclusion: The use of ROSE with EBUS is cost saving. The projected savings were CAD 50,000.00 (USD 40,501.24) and CAD 109,000.00(USD 88,337.07) in cancer and sarcoidosis, respectively, for the province of Alberta, Canada.

In this issue, Facey and colleagues have eloquently summarized the product of the February 2015 HTAi Policy Forum discussion—the need for health technology assessment (HTA) to shift from a historically reactive role in both evaluating current evidence and requesting additional evidence generation to a more proactive role engaging with stakeholders to ensure that evidence produced is appropriate for any given intervention at different stages of the clinical development program. This makes logical a priori sense, of course, as proactive and engaged discussion is always superior to reactive and potentially adversarial interaction.

All evaluation exercises involve ethical values, as they require some conception of the “good life.” Evaluation of health technologies is no exception. Because there is no consensus about what is a good life, we have to devise decision-making procedures in which citizens with different opinions are heard and treated fairly (1). The purpose of health technology assessment (HTA) is to offer useful input into this process so as to increase the quality of the deliberations and of the resulting decisions. How to bring ethical values into this process?

Objectives: Many of the currently used health technologies have never been systematically assessed or are misused, overused or superseded. Therefore, they may be ineffective. Active identification of ineffectiveness in health care is gaining importance to facilitate best care for patients and optimal use of limited resources. The present research analyzed processes and experiences of programs for identifying ineffective health technologies. The goal of this study was to elucidate factors that facilitate implementation.

Methods: Based on an overview article, a systematic literature search and unsystematic hand-search were conducted. Further information was gained from international experts.

Results: Seven programs were identified that include identification, prioritization and assessment of ineffective health technologies and dissemination of recommendations. The programs are quite similar regarding their goals, target groups and criteria for identification and prioritization. Outputs, mainly HTA reports or lists, are mostly disseminated by means of the internet. Top–down and bottom–up programs both have benefits in terms of implementation of recommendations, either as binding guidelines and decisions or as nonbinding information for physicians and other stakeholders. Crucial facilitators of implementation are political will, transparent processes and broad stakeholder involvement focusing on physicians.

Conclusions: All programs can improve the quality of health care and enable cost reduction in supportive surrounding conditions. Physicians and patients must be continuously involved in the process of evaluating health technologies. Additionally, decision makers must support programs and translate recommendations into concrete actions.

Background: Relative effectiveness has become a key concern of health policy. In Europe, this is because of the need for early information to guide reimbursement and funding decisions about new medical technologies. However, ways that effectiveness (does it work?) and efficacy (can it work?) might differ across health systems are poorly understood.

Methods: This study proposes an analytical framework, drawing on production function theory, to systematically identify and quantify the determinants of relative effectiveness and sources of variation between populations and healthcare systems. We consider how methods such as stochastic frontier analysis and data envelopment analysis using a Malmquist productivity index could in principle be used to generate evidence on, and improve understanding about, the sources of variation in relative effectiveness between countries and over time.

Results: Better evidence on factors driving relative effectiveness could: inform decisions on how to best use a new technology to maximum effectiveness; establish the need if any for follow-up post-launch studies, and provide evidence of the impact of new health technologies on outcomes in different healthcare systems.

Conclusions: The health production function approach for assessment of relative effectiveness is complementary to traditional experimental and observational studies, focusing on identifying, collecting, and analyzing data at the national level, enabling comparisons to take place. There is a strong case for exploring the use of this approach to better understand the impact of new medicines and devices for improvements in health outcomes.

Objectives: Differential pricing, based on countries’ purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA).

Methods: A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country.

Results: Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA.

Conclusions: Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

Objectives: International guidelines recommend annual mammography after early breast cancer, but there is no randomized controlled trial evidence to support this schedule over any other. Given that not all women have the same risk of recurrence, it is possible that, by defining different risk profiles, we could tailor mammographic schedules that are more effective and efficient.

Methods: A discrete event simulation model was developed to describe the progression of early breast cancer after completion of primary treatment. Retrospective data for 1,100 postmenopausal women diagnosed with early breast cancer in South Australia from 2000 to 2008 were used to calibrate the model. Women were divided into four prognostic subgroups based on the Nottingham Prognostic Index of their primary tumor. For each subgroup, we compared the cost-effectiveness of three different mammographic schedules for two different age groups.

Results: Annual mammographic follow-up was not cost-effective for most postmenopausal women. Two yearly mammography was cost-effective for all women with excellent prognosis tumors; and for women with good prognosis tumors if high compliance rates can be achieved. Annual mammography for 5 years and 2 yearly surveillance thereafter (a mixed schedule) may be cost-effective for 50- to 69-year-old women with moderate prognosis tumors, and for women aged 70–79 years with poor prognosis tumors. For younger women with poor prognosis tumors, annual mammography is potentially cost-effective.

Conclusions: Our results suggest that mammographic follow-up could be tailored according to risk of recurrence. If validated with larger datasets, this could potentially set the stage for personalized mammographic follow-up after breast cancer.

Objectives: The objective of this study was to explore barriers and facilitators influencing the integration of ethical considerations in health technology assessment (HTA).

Methods: The study consisted of two complementary approaches: (a) a systematic review of the literature; and (b) an eighteen-item online survey that was distributed to fifty-six HTA agencies affiliated with the International Network of Agencies for Health Technology Assessment.

Results: The review identified twenty-six relevant articles. The most often cited barriers in the literature were: scarcity, heterogeneity and complexity of ethical analysis methods; challenges in translating ethical analysis results into knowledge that is useful for decision makers; and lack of organizational support in terms of required expertise, time and financial resources. The most frequently cited facilitators included: usage of value-based appraisal methods, stakeholder and public engagement, enhancement of practice guidelines, ethical expertise, and educational interventions.

Representatives of twenty-six (46.5 percent) agencies from nineteen countries completed the survey. A median of 10 percent (interquartile range, 5 percent to 50 percent) of the HTA products produced by the agencies was reported to include an assessment of ethical aspects. The most commonly perceived barriers were: limited ethical knowledge and expertise, insufficient time and resources, and difficulties in finding ethical evidence or using ethical guidelines. Educational interventions, demand by policy makers, and involvement of ethicists in HTA were the most commonly perceived facilitators.

Conclusions: Our results emphasize the importance of simplification of ethics methodology and development of good practice guidelines in HTA, as well as capacity building for engaging HTA practitioners in ethical analyses.

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.

Objectives: Although the clinical benefits of endovenous thermal ablation are widely recognized, few studies have evaluated the health economic implications of different treatments. This study compares 6-month clinical outcomes and cost-effectiveness of endovenous laser ablation (EVLA) compared with radiofrequency ablation (RFA) in the setting of a randomized clinical trial.

Methods: Patients with symptomatic primary varicose veins were randomized to EVLA or RFA and followed up for 6 months to evaluate clinical improvements, health related quality of life (HRQOL) and cost-effectiveness.

Results: A total of 131 patients were randomized, of which 110 attended 6-month follow-up (EVLA n = 54; RFA n = 56). Improvements in quality of life (AVVQ and SF-12v2) and Venous Clinical Severity Scores (VCSS) achieved at 6 weeks were maintained at 6 months, with no significant difference detected between treatment groups. There were no differences in treatment failure rates. There were small differences in favor of EVLA in terms of costs and 6-month HRQOL but these were not statistically significant. However, RFA is associated with less pain at up to 10 days.

Conclusions: EVLA and RFA result in comparable and significant gains in quality of life and clinical improvements at 6 months, compared with baseline values. EVLA is more likely to be cost-effective than RFA but absolute differences in costs and HRQOL are small.

Objectives: Assessment of ethical aspects of a technology is an important component of health technology assessment (HTA). Nevertheless, how the implementation of ethical assessment in HTA is to be organized and adapted to specific regulatory and organizational settings remains unclear. The objective of this study is to present a framework for systematic identification of ethical aspects of health technologies. Furthermore, the process of developing and adapting the framework to a specific setting is described.

Methods: The framework was developed based on an inventory of existing approaches to identification and assessment of ethical aspects in HTA. In addition, the framework was adapted to the Swedish legal and organizational healthcare context, to the role of the HTA agency and to the use of non-ethicists. The framework was reviewed by a group of ethicists working in the field as well as by a wider set of interested parties including industry, interest groups, and other potential users.

Results: The framework consists of twelve items with sub-questions, short explanations, and a concluding overall summary. The items are organized into four different themes: the effects of the intervention on health, its compatibility with ethical norms, structural factors with ethical implications, and long term ethical consequences of using the intervention.

Conclusions: In this study, a framework for identifying ethical aspects of health technologies is proposed. The general considerations and methodological approach to this venture will hopefully inspire and present important insights to organizations in other national contexts interested in making similar adaptations.

Background: Pharmaceuticals’ relative effectiveness has come to the fore in the policy arena, reflecting the need to understand how relative efficacy (what can work) translates into added benefit in routine clinical use (what does work). European payers and licensing authorities assess value for money and post-launch benefit–risk profiles, and efforts to standardize assessments of relative effectiveness across the European Union (EU) are under way. However, the ways that relative effectiveness differs across EU healthcare settings are poorly understood.

Methods: To understand which factors influence differences in relative effectiveness, we developed an analytical framework that treats the healthcare system as a health production function. Using evidence on breast cancer from England, Spain, and Sweden as a case study, we investigated the reasons why the relative effectiveness of a new drug might vary across healthcare systems. Evidence was identified from a literature review and national clinical guidance.

Results: The review included thirteen international studies and thirty country-specific studies. Cross-country differences in population age structure, deprivation, and educational attainment were consistently associated with variation in outcomes. Screening intensity appeared to drive differences in survival, although the impact on mortality was unclear.

Conclusions: The way efficacy translates into relative effectiveness across health systems is likely to be influenced by a range of complex and interrelated factors. These factors could inform government and payer policy decisions on ways to optimize relative effectiveness, and help increase understanding of the potential transferability of data on relative effectiveness from one health system to another.

Objectives: Local health technology assessment (HTA) to determine whether new health technologies should be adopted is now a common practice in many healthcare organizations worldwide. However, little is known about hospital-based HTA activities in France. The objective of this study was to explore hospital-based HTA activities in French university hospitals and to provide a picture of organizational approaches to the assessment of new and innovative medical devices.

Methods: Eighteen semi-structured interviews with hospital pharmacists were conducted from October 2012 to April 2013. Six topics were discussed in depth: (i) the nature of the institution concerned; (ii) activities relating to innovative medical devices; (iii) the technology assessment and decision-making process; (iv) the methodology for technology assessment; (v) factors likely to influence decisions and (vi) suggestions for improving the current process. The interview data were coded, collated and analyzed statistically.

Results: Three major types of hospital-based HTA processes were identified: medical device committees, innovation committees, and “pharmacy & management” processes. HTA units had been set up to support medical device and innovation committees for technology assessment. Slow decision making was the main limitation to both these committee-based approaches. As an alternative, “pharmacy & management” processes emerged as a means of rapidly obtaining a formal assessment.

Conclusions: This study provides an overview of hospital-based HTA initiatives in France. We hope that it will help to promote hospital-based HTA activities in France and discussions about ways to improve and harmonize practices, through the development of national guidelines and/or a French mini-HTA tool, for example.

With an increasing awareness that active engagement between policy decision makers, HTA agencies, regulators and payers with industry in the premarket space is needed, a disruptive comprehensive approach is described which moves the evidentiary process exclusively into this space. Single harmonized studies pre-market to address regulatory and coverage needs and expectations are more likely to be efficient and less costly and position evidence to drive rather than test innovation. An example of such a process through the MaRS EXCITE program in Ontario, Canada, now undergoing proof of concept, is briefly discussed. Other examples of dialogue between decision makers and industry pre-market are provided though these are less robust than a comprehensive evidentiary approach.

Objectives: The aim of this study was to identify and discuss appropriate approaches to integrate ethical inquiry in health technology assessment (HTA).

Methods: The key question is how ethics can be integrated in HTA. This is addressed in two steps: by investigating what it means to integrate ethics in HTA, and by assessing how suitable the various methods in ethics are to be integrated in HTA according to these meanings of integration.

Results: In the first step, we found that integrating ethics can mean that ethics is (a) subsumed under or (b) combined with other parts of the HTA process; that it can be (c) coordinated with other parts; or that (d) ethics actively interacts and changes other parts of the HTA process. For the second step, we found that the various methods in ethics have different merits with respect to the four conceptions of integration in HTA.

Conclusions: Traditional approaches in moral philosophy tend to be most suited to be subsumed or combined, while processual approaches being close to the HTA or implementation process appear to be most suited to coordinated and interactive types of integration. The article provides a guide for choosing the ethics approach that appears most appropriate for the goals and process of a particular HTA.

Objectives: The Carpentier-Edwards pericardial (CEP) prostheses are the type of bioprostheses most used worldwide. Although they were designed to minimize the rate of valve deterioration and reoperation, their clinical superiority over other prostheses models still lacks confirmation. The objective of this study was to evaluate its effectiveness.

Methods: We performed a systematic review and meta-analysis in the PubMed, Embase, Cochrane, and Lilacs databases. Operative mortality, overall mortality and reoperation rates after heart valve surgery were compared between the use of CEP and other cardiac prostheses. Two independent reviewers screened studies for inclusion and extracted the data. Disagreements were resolved by consensus. The GRADE criterion was used to assess the evidence quality.

Results: A total of twenty-eight studies were selected, including 19,615 individuals. The studies presented a high heterogeneity and low quality of evidence what limited the reliability of the results. The pooled data from the selected studies did not demonstrate significant differences between CEP and porcine, pericardial or stentless prostheses regarding operative mortality, overall mortality and reoperation rates. However, the pooled data from 3 observational trials pointed out a higher risk for reoperation after valve replacement using CEP prostheses against mechanical prostheses (OR 4.92 [95 percent confidence interval 2.43–9.96]).

Conclusions: The current data present in the literature still does not support a clinical advantage for the use of CEP prostheses over other bioprostheses. The quality of the studies in the literature is limited and further studies are needed to address if CEP prostheses will have a clinical advantage over other prostheses.

Objectives: Medical technology is a large and expanding industry. Introducing new medical devices is important but several challenges exist in implementing the optimal method of evaluation. Both objective and subjective measures can be used for evaluation. The former is the mainstay of evaluation, yet subjective assessment is often the basis for the introduction of new medical technology. The aim of this study was to determine the interaction and concordance between objective and subjective assessment of new medical technology.

Methods: This study used both objective performance measures and subjective user perceptions in the evaluation of a new medical device designed to improve the accuracy of gravity-assisted delivery of intravenous fluids, compared with the current, widely used “roller-clamp” device. The concordance of objective and subjective assessments was evaluated using comparative analysis.

Results: Objective assessment of the accuracy of intravenous fluid delivery revealed no difference between the two devices (p = .636). Subjective assessment revealed that the new device was perceived to be significantly more accurate (p = .001). This lack of concordance can be partially explained by both device and demand characteristics.

Conclusions: This case study reveals a significant discordance between the objective and subjective assessments. It provides some explanation for why new medical devices are adopted without objective evidence of benefit. This phenomenon has been termed “persuasive design” and its influence should be controlled for in the evaluation, purchase and introduction of new medical devices. This should help reduce the risk and associated cost of premature introduction.

Objectives: The aim of this study was to predict the potential impact of the introduction of implantation of polyurethane scaffold for the treatment of partial meniscal lesions in the South Korean healthcare system.

Methods: The horizon scanning process was used to select a target technology and assess its potential impacts on patients and the Korean healthcare system. We identified and filtered research-phase health technologies that are not listed yet in Korean, but appear promising. After a process of prioritization, we chose the implantation of polyurethane scaffolds as a target technology. Then, through the procedures of assessment and peer review, we analyzed current evidence and its predicted potential impacts.

Results: There were eight studies included in the review: one prospective cohort and seven case-series studies. Six revealed significant improvements in function and pain relief. Of the six studies, which reported safety endpoints, four stated no major postoperative complications related to scaffold, and two reported adverse events and serious adverse events such as pain, joint swelling, et cetera. We also included the potential impact of this technology based on the experts’ consultation. They all agreed that it would satisfy the diverse needs of patients and fulfill clinical needs. However, the majority of related clinical studies were based on short-term follow-up observations without any validation process involving comparison with control groups.

Conclusions: Through a horizon scanning activity, we found that the implantation of polyurethane scaffolds is a promising technology to resolve articular cartilage defects; however, long-term evidence with comparison groups for safety and effectiveness is required.

Objectives: The AIFA (Agenzia Italiana del Farmaco—Italian Medicines Agency) Monitoring Registries track the eligibility of patients and the complete flow of treatments, guaranteeing appropriateness in use of pharmaceutical products, according to approved indications.

Methods: This study describes the Italian pharmaceutical context and the aims and functioning of AIFA Monitoring Registries, focusing on the applications to the Managed Entry Agreements (MEAs) and HTA approaches.

Results: The AIFA Monitoring Registries System has been operational in Italy since 2005. In 2012, the system became part of the NHS Information Technology system, aiming at enhancing appropriate use of pharmaceuticals and efficiency of the administrative activity. Currently, seventy-six medicines are monitored through the system, corresponding to fifty-eight therapeutic indications; individual treatments recorded are more than 515,000, for a population of approximately 505,000 patients. For each monitored product, patients eligible for treatment are registered in the specific therapeutic indication dynamic monitoring database to collect epidemiologic and clinical data, including data on the safety profile, and ex-post information missing at first evaluation stage.

Conclusions: AIFA Monitoring Registries allow the evaluation of the pharmaceuticals’ performance in clinical practice and may promote innovation and quicker access to medicines at affordable prices, for the benefit of patients.