Background: Several countries have developed policy frameworks allowing timely access to promising health technologies on the condition that additional evidence is generated. However, an important barrier to evidence generation is the lack of structured collaboration among health technology assessment (HTA) agencies.

Objectives: One of the aims of Work Package 7 (WP7) of the European network for Health Technology Assessment (EUnetHTA) Project was to determine the types of structured collaboration that could facilitate evidence generation and to develop a Web-based toolkit to support such collaboration.

Methods: Collaboration modalities were defined by all WP7 Partners. Initial emphasis was on information sharing. Standardized forms for information sharing were developed and tested. An information technology development phase followed with the creation of the Web-based toolkit (Web site).

Results: Three levels of collaboration were agreed on: (i) sharing information, (ii) coordinated action, and (iii) joint action. The Web site allows access to structured and standardized forms for requesting information, posting information in response to a request, and posting information spontaneously. An online database contains all of the information requested or posted. Pilot tests on twenty-one promising technologies were satisfactory.

Conclusions: This new Web site for sharing information on evidence generation should help countries reach robust decisions on the timely adoption of promising health technologies. It will only become fully operational if EUnetHTA Partners supply relevant, accurate, and updated information, and regularly use the Web site.

From the perspectives of coverage and reimbursement, heart transplantation has been a serious concern of policymakers in the U.S. since 1980, the year it was decided that a comprehensive study was required before the Health Care Financing Administration (HCFA), the federal agency responsible for the administration of the Medicare program, would be able to decide the status of the procedure (14;15;30;35). It was well acknowledged that the issues surrounding this decision were complex and that initial attempts to resolve the underlying coverage issue seemed to be too narrowly construed. It was at this time that the late Patricia Roberts Harris, then Secretary of the Department of Health and Human Services (DHHS), declared that DHHS would require new technologies to pass muster on the basis of their “social consequences” before “financing their wide distribution” (30). In a very special sense, although not appreciated at the time, a new era of health care technology assessment was ushered in, as Harris proclaimed that the then-conceived study of heart transplantation should serve as the “prototype” of technology assessment.

Objectives: Hospital-based health technology assessment (HTA) has become increasingly important in Brazil due to its strategic importance to promote adoption, incorporation, dissemination, and disinvestment of technologies. A strategy to foster hospital-based HTA was implemented in 2009 by creating hospital-based HTA nuclei (NATS) at university hospitals and other strategic hospitals.

Methods: Between 2011 and 2012, we interviewed board members in twenty-three NATS located in all geographic regions of Brazil to assess their general characteristics, scientific output, and challenges.

Results: Of the total, 65 percent of the NATS belonged to teaching institutions, with 44 percent associated with federal universities. The bulk of their output was in the form of mini-HTA reports. Centers in the Southeast and South of Brazil had the highest production compared with other regions. Lack of expertise and low levels of advanced training were identified as limiting factors in the majority of centers.

Conclusions: The experience of the initial twenty-three NATS could be considered positive and has led to the creation of new ones around Brazil. Regional disparities in workload, production, and technical training should be targeted by new policies toward hospital-based HTA in Brazil. The limits and possibilities for intensifying the strategy relate to continuous investment in priority studies, which simultaneously, allow professionals who work in hospitals to receive continued education and produce relevant HTA work in a timely manner.

The paper presents a set of principles that cover the broad scope of HTA from formulation of the question to effects on the decision-making process. It also provides goals for HTA programs to aim for in producing assessments. The principles are supported by material that includes illustrations from the experience of several programs. The authors have had long contact with the field and are well able to authoritatively discuss a range of methodological and other topics. The paper includes a range of views and details that are relevant to those involved with HTA.

Objectives: The cost-effectiveness of opportunistic nuchal translucency ultrasound screening in pregnancy was compared with alternative screening strategies for trisomy 21 in Australia.

Methods: A decision analytic model was used of various pregnancy screening strategies based on a systematic review of the literature on the effectiveness of nuchal translucency ultrasound and serum screening and costs based on current reimbursement fees. The model included the likelihood and cost of terminations after diagnostic testing and the associated risk of fetal loss. All prices are in 2001 Australian dollars.

Results: With a twenty percentage point difference in detection rate, the incremental cost for a combination of nuchal translucency and serum screening with age in the first trimester compared with maternal serum screening in the second trimester was $105,484 per extra case detected and $374,779 per live trisomy 21 birth avoided. Serum screening in the second trimester had an incremental cost per extra case detected of between $61,700 and $117,100 per extra live birth avoided when compared with no screening.

Conclusions: The cost-effectiveness of ultrasound screening for trisomy 21 would appear to be more attractive if it were done at the same time as current dating ultrasound. Any funding mechanism for screening should take this strategy into account by incorporating, as far as possible, provision of nuchal translucency screening into existing services provided in early pregnancy.

Objectives: The aim of this study was to evaluate the cost-effectiveness of alemtuzumab (CAMPATH-1H) compared with conventional chemotherapy in people with T-cell prolymphocytic leukemia (T-PLL).

Methods: We developed a decision-analytic model to assess the costs and benefits of alemtuzumab or conventional therapy based on their effects on quality of life of patients. The main outcome was the incremental cost-effectiveness ratio incorporating costs per additional quality-adjusted life-year (QALY) gained over lifetime. Due to the limited data available, a large number of assumptions had to be made to construct the cost-utility model. One-way, multi-way, and probabilistic sensitivity analyses (PSA) were conducted to explore the impact of these uncertainties. Expected values of perfect information were also calculated for four specific scenarios.

Results: Depending on different key assumptions made, the PSA suggested distinct conclusions using a willingness-to-pay threshold of 30,000 GBP per QALY gained. Using this threshold, the probability that alemtuzumab would be cost-effective varies from 0 percent to 53 percent for the four modeled scenarios. Population expected value of perfect information analysis suggests that resolving the parameter uncertainty in the analysis for people with T-PLL in the United Kingdom would have considerable value—up to 5.3 million euro.

Conclusions: Alemtuzumab appears more likely to be cost-effective if used earlier in the course of T-PLL and where it replaces the use of multiple alternative therapies. However, cost-effectiveness is highly uncertain and future research is clearly justified. Nevertheless, our analysis demonstrates the feasibility of considering the cost-effectiveness of an agent despite the presence of significant uncertainty to provide appropriate assessment information to policy makers.

Objectives: Acute otitis media (AOM) is one of the most common diseases of childhood, representing a major disease burden on the society. New evidence-based guidelines for AOM, focusing on children under 7 years of age, were introduced in Finland in 1999. The aim of this study was to evaluate the cost-effectiveness of implementing those guidelines in Finland.

Methods: A 5-year prospective trial was conducted in thirty community primary healthcare centers in Finland. All AOM patients between 0 and 6 years of age visiting the study health centers for the first time, for this episode of illness, during 1 week in November 1998 (n = 579) and November 2002 (n = 369) were included in this study. The outcome measure was the percentage of symptom-free patients.

Results: The mean direct cost of an AOM episode per patient stayed almost the same after implementing the guidelines, €152 in 1998 and €150 in 2002. After implementing the guidelines, the percentage of symptom-free patients was 10 percentage points higher than before the guidelines. The treatment after the implementation of the guidelines, thus, was a dominant strategy.

Conclusions: Implementing the guidelines to the treatment of AOM in children was associated with extra health benefits at slightly lower direct costs and, thus, is a dominant strategy. The focus of this study was on the short-term effects of the treatment; including long-term effects in the analysis might affect the results.

Two retrospective cohorts of patients who had undergone a primary total hip replacement (THR) were studied in Japan and England. We analyzed information from hospital case notes and self-administered questionnaires. THR was highly effective in both countries, with significant improvements in morbidity and health status. There were, however, important differences in clinical management and outcome. Japanese patients were more likely to be treated under regional anesthesia by means of an anterior/anterolateral incision, to be transfused, to have a prosthesis implanted without cement, and to stay longer in the hospital. A higher rate of serious in-hospital complications occurred in England, mostly due to the high frequency of hypotension. The incidences of minor complications were consistent with known differences in risks between the two countries. The persistent postoperative perception of limping reported by the English patients was unexpected.

Objective: The aim of this report was to describe the history of health technology assessment (HTA) in the Netherlands.

Methods: This article is a descriptive review from two people who have been very much involved in the events described and is based on review of relevant policy documents and Web sites.

Results: HTA has been progressively developed in the Netherlands since (at least) the early 1980s. Beginning in 1985, there were progressive attempts to expand and institutionalized HTA in the Netherlands healthcare system. These attempts were generally successful, but did not result in a national agency for HTA. An important development in HTA in the Netherlands was a special fund (Ontwikkelingsgeneeskunde) designed to support prospective HTAs with the main purpose of affecting insurance coverage decisions. The administration of this fund moved progressively to broaden the subjects chosen for analysis to include such subjects as chronic illness and disability. A more-or-less hidden conflict developed in the question of the leadership and orientation of this fund, with the result that it was largely moved to a more research-oriented and less policy-oriented site.

Conclusions: The situation today is that HTA is visible and is used by the government in policy decisions, especially in the areas of prevention and screening. In addition, HTA is influential in insurance coverage decision making, especially in the field of pharmaceuticals. The principles of HTA and evidence-based medicine are generally familiar to physicians and other clinicians, however, the influence of HTA on clinical and administrative decisions is less than in some other countries.

Objectives: The aim of this study was to evaluate utilization trends of the diagnostic imaging examinations during the past decade in a university hospital in Turkey.

Methods: Patient registries of a university hospital were used for the years 1995 and 2003. The data set consisted of patients' admissions, social security status, and diagnostic imaging tests.

Results: When compared with 1995 data, the total number of diagnostic imaging examinations and patient admissions increased 65.9 percent and 81.6 percent, respectively, in the year 2003. Although the total number of diagnostic imaging tests decreased 9.0 percent, there was a 145.4 percent increase in magnetic resonance imaging (MRI) examinations. Nevertheless, radiological diagnostic procedures consisted of 12.8 percent of the total hospital revenues in 1995 and 9.4 percent in 2003.

Conclusions: This study shows that approximately one third of inpatients underwent MRI and computed tomography examinations in 2003. The utilization rates of diagnostic imaging procedures, especially new technologies, need to be considered carefully with respect to appropriateness of procedures and planning of services.

Collecting descriptive data on patterns of recovery from a disabling condition could provide a baseline for assessing treatment methods and for monitoring the progress of individual patients. An illustrative study of patients recovering from stroke is presented and the strengths and weaknesses of such studies are discussed.

The National Institutes of Health (NIH) has always carefully limited its responsibilities to biomedical research and knowledge development, including clinical trials, dissemination of results of research, and training. Ten years ago, NIH undertook to examine its possible role in the evaluation of medical technologies.

In 1976, the U.S. Congress became alarmed over the increase in health care costs: in particular, that a number of expensive technologies, such as coronary artery bypass surgery and electronic fetal monitoring, had entered the delivery system without adequate study of their safety, efficacy, cost, or other implications. At the time, there was no formal structure or forum in either the executive branch of the government or in the private sector for seeking a consensus that a medical innovation was actually safe, beneficial, and ready to be transferred into the health care delivery system. Similarly, there was no structured process through which the parties who comprise the delivery system could meet with representatives of the research community to examine the medical-scientific issues surrounding a given innovation along with cost and cost- effectiveness, ethics, and other societal issues of importance to the system.

Objectives: The aim of this study was to evaluate cost effectiveness of coronary artery bypass graft (CABG) versus percutaneous coronary intervention (PCI) with stenting from Iran society perspective.

Methods: A retrospective study was carried out to estimate the annual cost and health related quality of life (HRQoL) of 109 patients who underwent coronary revascularization (PCI [n = 75] and CABG [n = 34]). A Markov model has been developed to determine the cost effectiveness of CABG compared with PCI. We used the model to calculate lifetime costs, life-years (LYs), and quality-adjusted life-years (QALYs) of each strategy. We also used probabilistic sensitivity analysis to test model robustness.

Results: We found that discounted QALY lived per person in CABG versus PCI group in 5 years, 10 years, and lifetime time horizon were (3.8 ± 0.13 versus 3.88 ± 0.14), (6.4 ± 0.23 versus 6.33 ± 0.22), and (8.74 ± 0.29 versus 8.33 ± 0.27), respectively. The estimated medical cost of CABG and PCI per patient in 5 years, 10 years, and lifetime time horizon were (USD 6,819 ± 765 versus 9,011 ± 1,816), (USD 8,852 ± 1,348 versus 12,034 ± 2,375), and (USD 14,037± 4,201 versus 18,798 ± 5,821), respectively. The incremental cost-effectiveness ratio results showed CABG is a dominate alternative in 10 years and lifetime time horizon.

Conclusions: This study demonstrated that despite higher initial cost and lower HRQoL, CABG is a cost-effective revascularization strategy compared with PCI for patients with multivessel coronary artery disease in long-term.

Objectives: The aim of this study was to review, systematically and critically, evidence used to derive estimates of cost-effectiveness of human immunodeficiency virus (HIV) screening.

Methods: A systematic review was conducted. Searched were three main electronic bibliographic databases from 1993 to 2008 using key words including HIV, mass screening, HAART, economic evaluation, cost-effectiveness analysis, modeling. We included studies of sexually transmitted HIV infection in both sexes, including studies comparing diagnostic testing protocols and partner notification. Outcomes included were cases of HIV infection detected, deterioration to the AIDS state, secondary transmission of HIV, the quality-adjusted life-years/survival, costs, and cost-effectiveness of HIV screening.

Results: Eighty-four papers were identified; ten of which were formal economic evaluations, one cost study, three effectiveness studies, and three systematic reviews of HIV prevention programs. The predominant assertion was that HIV screening is cost-effective; methodological problems, such as the preponderance of static models which are inappropriate for infectious diseases, varying perspectives from which the studies were analyzed, and arbitrary threshold incremental cost-effectiveness ratio levels, limited the validity of these findings, and their usefulness in informing health policy decisions.

Conclusions: The majority of published economic evaluations are based on inappropriate static models. This flaw renders the results of these studies as inconclusive and the purported cost-effectiveness of HIV screening debatable. The results of this review could form a basis for consideration of further research and analysis by health economists into the cost-effectiveness of HIV screening.

Objectives: The aim of this study was to provide a brief, 7-year history of health technology assessment (HTA) implementation in Croatia through national and international activities.

Methods: We used retrospective descriptive analysis of key documents related to the legal framework, process of decision making, and HTA. Analysis of the Agency's plan for and experience with the implementation of a transparent HTA process in Croatia was performed by addressing seven key components of the HTA implementation scorecard framework. The main challenges and facilitating factors were also assessed.

Results: HTA is not yet fully implemented in Croatia. The main challenges are the insufficient legal framework, limited human and financial resources, and limited stakeholder involvement. Facilitating factors are active international collaboration and education through EUnetHTA and the International Society for Pharmacoeconomics and Outcomes Research and production of national and international HTA reports.

Conclusions: The HTA process is not yet sustainable in Croatia and HTA reports are still not mandatory for reimbursement/investment or disinvestment decision processes. There are still barriers to overcome.

Objectives: This article reports a cost-effectiveness analysis of targeted screening for abdominal aortic aneurysm (AAA). A major emphasis was on the estimation of distributions of costs and effectiveness.

Methods: We performed a Monte Carlo simulation using C programming language in a PC environment. Data on survival and costs, and a majority of screening probabilities, were from our own empirical studies. Natural history data were based on the literature.

Results: Each screened male gained 0.07 life-years at an incremental cost of FIM 3,300. The expected values differed from zero very significantly. For females, expected gains were 0.02 life-years at an incremental cost of FIM 1,100, which was not statistically significant. Cost-effectiveness ratios and their 95% confidence intervals were FIM 48,000 (27,000–121,000) and 54,000 (22,000–∞) for males and females, respectively. Sensitivity analysis revealed that the results for males were stable. Individual variation in life-year gains was high.

Conclusions: Males seemed to benefit from targeted AAA screening, and the results were stable. As far as the cost-effectiveness ratio is considered acceptable, screening for males seemed to be justified. However, our assumptions about growth and rupture behavior of AAAs might be improved with further clinical and epidemiological studies. As a point estimate, females benefited in a similar manner, but the results were not statistically significant. The evidence of this study did not justify screening of females.

Objectives: Ipilimumab is the first licensed immune checkpoint inhibitor for treatment of melanoma. The promising results of the registration clinical study need confirmation in real practice and its clinical success comes together with a relevant budget impact due to the high price of this drug. The aim of this work is to describe a new model of economical sustainability of ipilimumab developed in an Italian reference center for melanoma treatment.

Methods: This retrospective, observational, and monocentric study was carried out at the Veneto Institute of Oncology. Ipilimumab was administered to fifty-seven patients with advanced melanoma. Overall survival, progression free survival, and toxicity were evaluated. A local management procedure was evaluated together with the cost-saving strategies implemented by the Italian Medicines Agency (AIFA).

Results: We demonstrated that the use of ipilimumab for metastatic melanoma in real practice had an efficacy and toxicity similar to that reported in the literature. In this scenario, our management model (centralization of compounding + drug-day) permitted savings up to the 11.1 percent of the gross cost for the drug (calculated assuming that no cost saving procedures were applied) while the policy of cost containment designed by AIFA produced an additional 6.2 percent of savings.

Conclusions: In real practice conditions, the centralized administration of ipilimumab allows to replicate the results of clinical studies and in the meantime to contain the cost associated with this drug. The local strategy of management can be readily applied to most of the high cost drugs compounded in the hospital pharmacy. Impact of findings on practice: (i) We describe a new model of economic sustainability (drug-day, centralization of compounding, payback systems) of an expensive and innovative drug, ipilimumab, for treatment of melanoma within an Italian cancer center. (ii) This pivotal study demonstrated that a cost containment strategy is feasible and it needs the cooperation of all healthcare providers (oncologists, pharmacists, nurses, and technicians) to guarantee the full efficiency of the process.

Recent experience with COVID-19 has reminded us of the importance of scientific progress in enabling pharmaceutical innovation. Developing novel therapies is a highly risky but rewarding process: it not only produces innovative drugs, but also valuable scientific knowledge that benefits the community of innovators. This paper examines whether the existing reward system for pharmaceutical research and development (R&D) leads to socially optimal levels of scientific knowledge generation and sharing, with a particular focus on the value of failures in the pharmaceutical R&D efforts. We first outline a conceptual approach based on the idea that pharmaceutical R&D efforts produce both medicines and scientific knowledge, and illustrate this with some examples of how failures may generate information beneficial to concurrent and subsequent R&D efforts. We then summarize the relatively small literature on failures in pharmaceutical R&D and their impact on R&D decision making. Lastly, we discuss several market-based and nonmarket-based policy approaches that can address potential shortcomings in the current reward system which may lead to suboptimal R&D and knowledge sharing.

The availability of new vaccines for pediatric use provides an unprecedented opportunity to prevent serious infectious diseases and their associated morbidity and mortality. However, each new product entails the need for additional injections that could become so numerous as to discourage the administration of new vaccines. This challenge can be overcome by mixing individual vaccines before delivery such that multiple vaccines are administered as single combination vaccines. Technical, clinical, manufacturing, regulatory and marketing issues relative to combination vaccines in general are the major challenges for ongoing and future development.