Introduction: Spontaneous adverse drug events (ADE) reporting is the main source of data for assessing the risk/benefit of drugs available in the pharmaceutical market. However, its major limitation is underreporting, which hinders and delays the signal detection by Pharmacovigilance (PhV).

Objectives: To identify the techniques of educational intervention (EI) for promotion of PhV by health professionals and to assess their impact.

Methods: A systematic review was performed in the PUBMED, PAHO, LILACS and EMBASE databases, from November/2011 to January/2012, updated in March/2013. The strategy search included the use of health descriptors and a manual search in the references cited by selected papers.

Results: 101 articles were identified, of which 16 met the inclusion criteria. Most of these studies (10) were conducted in European hospitals and physicians were the health professionals subjected to most EI (12), these studies lasted from one month to two years. EI with multifaceted techniques raised the absolute number, the rate of reporting related to adverse drug reactions (ADR), technical defects of health technologies, and also promoted an improvement in the quality of reports, since there was increased reporting of ADR classified as serious, unexpected, related to new drugs and with high degree of causality.

Conclusion: Multifaceted educational interventions for multidisciplinary health teams working at all healthcare levels, with sufficient duration to reach all professionals who act in the institution, including issues related to medication errors and therapeutic ineffectiveness, must be validated, with the aim of standardizing the Good Practice of PhV and improve drug safety indicators.

Objectives: The aim of this study was to describe a current practical approach of priority setting of health technology assessment (HTA) research that involves multi-criteria decision analysis and a deliberative process.

Methods: Criteria related to HTA prioritization were identified and grouped through a systematic review and consultation with a selection committee. Criteria were scored through a pair-wise comparison approach. Criteria were pruned based on the average weights obtained from consistent (consistency index < 0.2) responders and consensus. HTA proposals are ranked based on available information and a weighted criteria score. The rank, along with additional contextual information and discussion among committee members, is used to achieve consensus on HTA research priorities.

Results: Six of eleven criteria represented > 75 percent of the weight behind committee member decisions to conduct an HTA. These criteria were disease burden, clinical impact, alternatives, budget impact, economic impact, and available evidence. Since May 2006, committees have considered 102 proposals at sixteen biannual in-person advisory committee meetings. These have selected twenty-nine research priorities for the HTA program.

Conclusions: The approach works well and was easy to implement. Feedback from committee members has been positive. This approach may assist HTA and other research agencies in better priority setting by informing the selection of the most important and policy-relevant topics in the presence of a wide variety of research proposals. This may in turn lead to efficiently allocating resources available for HTA research.

A case study design was used to determine the reliance on technology assessment of decisionmakers in hospitals, health maintenance organizations (HMOs), and third-party payers. Thirty different organizations were contacted and semistructured interviews conducted. The study found that hospitals, HMOs, and insurers are conducting technology assessments, but the form and sophistication of these analyses range widely. Hospitals are particularly focused on traditional financial analyses (“prudent purchasing”) with the exception of pharmacy committees, which generally conduct more sophisticated socio-economic analyses. HMOs and insurers conduct outcome assessments for coverage of expensive or controversial technologies but exclude economics. Technology assessment will become increasingly important in resource allocation decision making and it is in the interest of technology providers to foster better information, a more comprehensive assessment process, and a more efficient assessment system.

This study analyzes opportunity costs for the treatment of end-stage renal disease. Kidney transplantation remains the most cost-effective treatment for uremia and is one of the most cost-effective technologies in health care. Improved survival of grafts and increased numbers of transplants have the potential to reduce costs for dialysis programs. To support organ donation activities, the public and concerned health professionals should be informed about the opportunity cost of “unnecessary” dialysis. These resources could be reallocated from dialysis to other programs. Among patients in dialysis, a more common use of chronic ambulatory peritoneal dialysis instead of institution-based hemodialysis would greatly increase cost-utility and further reduce the program costs of renal replacement therapy.

The objective of this paper is to illustrate the advantages of the Bayesian approach in quantifying, presenting, and reporting scientific evidence and in assisting decision making. Three basic components in the Bayesian framework are the prior distribution, likelihood function, and posterior distribution. The prior distribution describes analysts' belief a priori; the likelihood function captures how data modify the prior knowledge; and the posterior distribution synthesizes both prior and likelihood information. The Bayesian approach treats the parameters of interest as random variables, uses the entire posterior distribution to quantify the evidence, and reports evidence in a “probabilistic” manner. Two clinical examples are used to demonstrate the value of the Bayesian approach to decision makers. Using either an uninformative or a skeptical prior distribution, these examples show that the Bayesian methods allow calculations of probabilities that are usually of more interest to decision makers, e.g., the probability that treatment A is similar to treatment B, the probability that treatment A is at least 5% better than treatment B, and the probability that treatment A is not within the “similarity region” of treatment B, etc. In addition, the Bayesian approach can deal with multiple endpoints more easily than the classic approach. For example, if decision makers wish to examine mortality and cost jointly, the Bayesian method can report the probability that a treatment achieves at least 2% mortality reduction and less than $20,000 increase in costs. In conclusion, probabilities computed from the Bayesian approach provide more relevant information to decision makers and are easier to interpret.

Objectives: The aim of this study was to develop and apply an instrument to map the level of health technology assessment (HTA) development at country level in selected countries. We examined middle-income countries (Argentina, Brazil, India, Indonesia, Malaysia, Mexico, and Russia) and countries well-known for their comprehensive HTA programs (Australia, Canada, and United Kingdom).

Methods: A review of relevant key documents regarding the HTA process was performed to develop the instrument which was then reviewed by selected HTAi members and revised. We identified and collected relevant information to map the level of HTA in the selected countries. This was supplemented by information from a structured survey among HTA experts in the selected countries (response rate: 65/385).

Results: Mapping of HTA in a country can be done by focusing on the level of institutionalization and the HTA process (identification, priority setting, assessment, appraisal, reporting, dissemination, and implementation in policy and practice). Although HTA is most advanced in industrialized countries, there is a growing community in middle-income countries that uses HTA. For example, Brazil is rapidly developing effective HTA programs. India and Russia are at the very beginning of introducing HTA. The other middle-income countries show intermediate levels of HTA development compared with the reference countries.

Conclusions: This study presents a set of indicators for documenting the current level and trends in HTA at country level. The findings can be used as a baseline measurement for future monitoring and evaluation. This will allow a variety of stakeholders to assess the development of HTA in their country, help inform strategies, and justify expenditure for HTA.

Objectives: The objective of this study was to examine and explain the differential international diffusion of six health innovations.

Methods: A retrospective diffusion study was undertaken of sildenafil, cyclooxygenase-II (COX II) inhibitors, beta interferon, verteporfin, deep brain stimulators, and drug-eluting coronary stents in ten countries—Australia, Canada, Denmark, France, The Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. We plotted diffusion curves of daily defined doses per quarter, vials or implants per million population, and examined the association between diffusion and five key variables.

Results: Canada, Switzerland, and Sweden are generally high users of new technologies; Spain, Denmark, and particularly the United Kingdom are low users. Almost all countries experienced rapid adoption of sildenafil with diffusion to a similar level; there was variable adoption and diffusion of COX II inhibitors, verteporfin, and interferon beta; drug-eluting stents penetrated the market in a similar way in all but one country; and two countries had very different adoption patterns for deep brain stimulators. Above average health spending and the presence of health technology assessment (HTA) or other guidance reports are consistently associated with increased diffusion. Early warning activity and a national coverage decision being taken are more likely to be associated with a reduced diffusion.

Conclusions: The significant differences in diffusion between different countries are not consistent with a neat evidence-based world. The tools available to policy makers to control diffusion (early warning systems, HTA, and a fourth hurdle) play some part in influencing diffusion but need close scrutiny of how successfully they operate.

Objectives: The aim of this study was to assess if the use of Markov modeling (MM) or discrete event simulation (DES) for cost-effectiveness analysis (CEA) may alter healthcare resource allocation decisions.

Methods: A systematic literature search and review of empirical and non-empirical studies comparing MM and DES techniques used in the CEA of healthcare technologies was conducted.

Results: Twenty-two pertinent publications were identified. Two publications compared MM and DES models empirically, one presented a conceptual DES and MM, two described a DES consensus guideline, and seventeen drew comparisons between MM and DES through the authors’ experience. The primary advantages described for DES over MM were the ability to model queuing for limited resources, capture individual patient histories, accommodate complexity and uncertainty, represent time flexibly, model competing risks, and accommodate multiple events simultaneously. The disadvantages of DES over MM were the potential for model overspecification, increased data requirements, specialized expensive software, and increased model development, validation, and computational time.

Conclusions: Where individual patient history is an important driver of future events an individual patient simulation technique like DES may be preferred over MM. Where supply shortages, subsequent queuing, and diversion of patients through other pathways in the healthcare system are likely to be drivers of cost-effectiveness, DES modeling methods may provide decision makers with more accurate information on which to base resource allocation decisions. Where these are not major features of the cost-effectiveness question, MM remains an efficient, easily validated, parsimonious, and accurate method of determining the cost-effectiveness of new healthcare interventions.

This article discusses data that might be used for measuring quality of care, for health care administrative purposes, and for tracking the use of technologies. The advantages and limitations of administrative data banks for research purposes and some process-of-care and outcome analysis are noted. Three important obstacles to their use—reliability of diagnosis and service information, unique patient identifiers, and provider identifiers—are discussed briefly.

Objectives: The aim of this study was to investigate how the societal perspective is conceptualized in economic evaluations and to assess how intersectoral costs and benefits (ICBs), that is, the costs and benefits pertaining to sectors outside the healthcare sector, impact their results.

Methods: Based on a search in July 2015 using PubMed, Embase, CINAHL, and PsychINFO, a systematic literature review was performed for economic evaluations which were conducted from a societal perspective. Conceptualizations were assessed in NVivo version 11 using conventional and directed content analysis. Trial-based evaluations in the fields of musculoskeletal and mental disorders were analyzed further, focusing on the way ICBs impact the results of economic evaluations.

Results: A total of 107 studies were assessed, of which 74 (69.1 percent) provided conceptualizations of the societal perspective. These varied in types of costs included and in descriptions of cost bearers. Labor productivity costs were included in seventy-two studies (67.3 percent), while only thirty-eight studies (35.5 percent) included other ICBs, most of which entailed informal care and/or social care costs. ICBs within the educational and criminal justice sectors were each included five times. Most of the trial-based evaluations analyzed further (n = 21 of 28) reported productivity costs. In nine, these took up more than 50 percent of total costs. In several studies, criminal justice and informal care costs were also important.

Conclusions: There is great variety in the way the societal perspective is conceptualized and interpreted within economic evaluations. Use of the term “societal perspective” is often related to including merely productivity costs, while other ICBs could be relevant as well.

The consensus development conference method developed by the National Institutes of Health in the United States has been adopted and modified by a number of countries. Based on published articles and communication with representatives from each country, we examined whether the organization and conduct of these conferences in nine countries (United States, Canada, Denmark, Finland, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom) enhanced or detracted from achieving the stated conference goals and objectives. We conclude that improvements in the process by which consensus conferences are conducted may be warranted. More scientific methods for synthesizing literature, such as meta-analysis, should be used in developing inputs for the conference panel. Formalizing the decision-making processes through polling or other methods that allow for structured disagreement with parts of a consensus statement would potentially expand the range and type of issues that can be addressed in such conferences. Finally, countries should consider having the consensus statement written over a longer period of time than the traditional overnight session, which seems unlikely to promote clear thinking.

Objectives: As an initiative of the International Network of Agencies for Health Technology Assessment (INAHTA), a checklist for assessment reports was developed as a means of improving transparency and consistency in HTA.

Methods: Preparation of a summary of key elements in HTA reports, drawing on experience in preparation of such documents, information from guidelines for HTA, and individual assessments. Review by INAHTA agencies and modification of the summary to reflect the consensus.

Results: The resulting checklist includes 17 questions, with supporting detail. General areas covered include preliminary information, why and how the assessment has been prepared, the results of the assessment, implications of the results, and conclusions.

Conclusions: The checklist is intended to be considered by those preparing or using an HTA report. It reflects the views of INAHTA members and is seen as a mechanism to improve the standard of HTA reports, being complementary to the more detailed guidelines on how to conduct assessments.

Background: Health technology reassessment (HTR) is “a structured, evidence-based assessment of the clinical, social, ethical, and economic effects of a technology currently used in the healthcare system, to inform optimal use of that technology in comparison to its alternatives.” The purpose of this study is to describe the key themes in the context of current HTR activities and propose a way forward for this newly emerging field.

Methods: Data were gathered from a workshop held as part of the 2012 Canadian Agency for Drugs and Technology in Health (CADTH) symposium. The workshop consisted of two panel presentations followed by discussion; data gathered, including presentations and rich audience discussion transcripts, were analyzed for key themes emerging in the field of HTR using constant comparative analysis.

Results: The language chosen to describe HTR will set the tone for engagement. The identification of champions at multiple levels and political will are essential. Key lessons from international experience are: disinvestment is difficult, focus on clinical areas not specific technologies, identify clear goals of the HTR agenda. Six key themes were identified to move the HTR agenda forward: emphasize integration over segregation, focus on development of HTR methods and processes, processes are context-specific but lessons must be shared, build capacity in synergistic interdisciplinary fields, develop meaningful stakeholder engagement, strengthen postimplementation monitoring and evaluation.

Conclusions: To move this field forward, we must continue to build on international experiences with a focus on developing novel methodological approaches to generating, incorporating, and implementing evidence into policy and practice.

Objectives: In many economic evaluations and reimbursement decisions, quality-adjusted life-years (QALYs) are used as a measure of benefit to assess effectiveness of novel therapies, often based on the EQ-5D 3-level questionnaire. As only five dimensions of physical and mental well-being are reflected in this tool, significant aspects of the patient experience may be missed. We evaluate the use of the EQ-5D as a measurement of clinical change across a wide range of disorders from dermatological (acne) to life-threatening (metastatic cancers).

Methods: We analyze published studies on the psychometric properties of the EQ-5D 3-level questionnaire, extracting information on the Visual Analogue Scale versus Index score, Standardized Response Mean, and Effect Size. These are compared with ranges generally accepted to represent good responsiveness in the psychometric literature.

Results: We find that only approximately one in five study populations report subjective health state valuation of patients within 5 percent of the score attributed by the EQ-5D index, and more than 40 percent of studies report unacceptable ceiling effects. In the majority of studies, responsiveness of the EQ-5D index was found to be poor to moderate, based on Effect Size (63 percent poor–moderate) and Standardized Response Mean (72 percent poor–moderate).

Conclusions: We conclude that the EQ-5D index does not adequately reflect patient health status across a range of conditions, and it is likely that a significant proportion of the subjective patient experience is not accounted for by the index. This has implications for economic evaluations of novel drugs based on evidence generated with the EQ-5D.

Objectives: This study investigated the direct medical resource use and cost, informal care cost, and indirect cost associated with breast cancer in different states of the disease in normal clinical practice.

Methods: A retrospective database analysis was used to estimate direct medical resource use and cost, and a patient questionnaire was used to evaluate informal care and work capacity in different states of breast cancer.

Results: For patients younger than 65 years of age, the first year after a primary diagnosis total cost amounted to 280,000 SEK ($39,000) and the first year after a local or contralateral recurrence total cost was 351,000 SEK ($48,900). The second and following years after primary breast cancer or recurrence had substantially lower total cost, amounting to 94,000 SEK ($13,000). For patients with metastatic disease, the annual total cost was estimated to 334,000 SEK ($46,500). For patients older than 65 years of age, the total cost for the first year after a primary diagnosis amounted to 80,000 SEK ($11,200) and the total cost for the first year after a local or contralateral recurrence was 92,000 SEK ($12,900). The total cost for the second and following years after primary breast cancer or recurrence was estimated to 18,000 SEK ($2,600), and the total annual cost for patients with metastatic was 122,000 SEK ($17,000).

Conclusions: Both direct medical costs and indirect cost vary substantially between disease states. For patients under 65 year of age, indirect costs accounted for more than 50 percent of the total cost.

Objectives: Congenital heart defects (CHD) are an important cause of death and morbidity in early childhood, but the effectiveness of alternative newborn screening strategies in preventing the collapse or death—before diagnosis—of infants with treatable but life-threatening defects is uncertain. We assessed their effectiveness and efficiency to inform policy and research priorities.

Methods: We compared the effectiveness of clinical examination alone and clinical examination with either pulse oximetry or screening echocardiography in making a timely diagnosis of life-threatening CHD or in diagnosing clinically significant CHD. We contrasted their cost-effectiveness, using a decision-analytic model based on 100,000 live births, and assessed future research priorities using value of information analysis.

Results: Clinical examination alone, pulse oximetry, and screening echocardiography achieved 34.0, 70.6, and 71.3 timely diagnoses per 100,000 live births, respectively. This finding represents an additional cost per additional timely diagnosis of £4,894 and £4,496,666 for pulse oximetry and for screening echocardiography. The equivalent costs for clinically significant CHD are £1,489 and £36,013, respectively. Key determinants of cost-effectiveness are detection rates and screening test costs. The false-positive rate is very high with screening echocardiography (5.4 percent), but lower with pulse oximetry (1.3 percent) or clinical examination alone (.5 percent).

Conclusions: Adding pulse oximetry to clinical examination is likely to be a cost-effective newborn screening strategy for CHD, but further research is required before this policy can be recommended. Screening echocardiography is unlikely to be cost-effective, unless the detection of all clinically significant CHD is considered beneficial and a 5 percent false-positive rate acceptable.

Objectives: While strategies for enhancing the dissemination and impact of Health Technology Assessment (HTA) are now being increasingly examined, the characteristics of HTA production have received less attention.

Methods: This study presents the results of a content analysis of the HTA documents (n=187) produced by six Canadian agencies from 1995 to 2001, supplemented by interviews with chief executive officers and researchers (n=40). The goal of this analysis was to characterize the agencies' portfolios and to analyze the challenges these agencies face in responding to the increased demand for HTA.

Results: On average, thirty HTA products were issued annually by the agencies. While the bulk of documents produced were full HTA reports (76 percent), two agencies showed significant diversification in their products. Three agencies in particular actively supported the publication of results in scientific journals. Three agencies showed evidence of adapting to different institutional environments by specializing in certain areas (drugs, health services). Overall, a significant portion of the agencies' HTAs contained data on costs (37 percent) and effectiveness (48 percent), whereas ethical and social issues were rarely addressed (17 percent). Most agencies addressed issues and outcomes that did not strictly fall under the typical definition of HTA but that increased the “contextualization” of their findings.

Conclusions: Our discussion highlights four paradoxes and reflects further on challenges raised by the coordination of HTA within large countries and among European states. This study concludes that HTA is being redefined in Canada as HTA agencies offer a more contextualized informational basis, an approach that may prove more compatible with the increased demand for HTA.

Previously, our group—the International Working Group for HTA Advancement—proposed a set of fifteen Key Principles that could be applied to health technology assessment (HTA) programs in different jurisdictions and across a range of organizations and perspectives. In this commentary, we investigate the extent to which these principles are supported and used by fourteen selected HTA organizations worldwide. We find that some principles are broadly supported: examples include being explicit about HTA goals and scope; considering a wide range of evidence and outcomes; and being unbiased and transparent. Other principles receive less widespread support: examples are addressing issues of generalizability and transferability; being transparent on the link between HTA findings and decision-making processes; considering a full societal perspective; and monitoring the implementation of HTA findings. The analysis also suggests a lack of consensus in the field about some principles—for example, considering a societal perspective. Our study highlights differences in the uptake of key principles for HTA and indicates considerable room for improvement for HTA organizations to adopt principles identified to reflect good HTA practices. Most HTA organizations espouse certain general concepts of good practice—for example, assessments should be unbiased and transparent. However, principles that require more intensive follow-up—for example, monitoring the implementation of HTA findings—have received little support and execution.