In this theme section on early awareness and alert (EAA) systems and activities, we are pleased to present a series of articles covering the structure of EAA systems, their development and integration into decision making for the adoption and use of new and emerging health technologies, and the methods used by current networks, systems, and organizations.

Health systems are challenged continuously to provide the highest quality universal health care within their means. While for 30 years, health technology assessment (HTA) has contributed to the process of evidence-informed decision making and the managed entry of new technologies, its remit has not expanded to include assessment of technologies currently in use, as a means of managing their use and potentially their exit. We propose that health technology reassessment (HTR) become standard practice, an integral part of all health technology assessment agencies, and that we develop standardized models and methodologies for reassessment drawing from what we have learned from HTA.

Background: Health systems face rising patient expectations and economic pressures; decision makers seek to enhance efficiency to improve access to appropriate care. There is international interest in the role of HTA to support decisions to optimize use of established technologies, particularly in “disinvesting” from low-benefit uses.

Methods: This study summarizes main points from an HTAi Policy Forum meeting on this topic, drawing on presentations, discussions among attendees, and an advance background paper.

Results and Conclusions: Optimization involves assessment or re-assessment of a technology, a decision on optimal use, and decision implementation. This may occur within a routine process to improve safety and quality and create “headroom” for new technologies, or ad hoc in response to financial constraints. The term “disinvestment” is not always helpful in describing these processes. HTA contributes to optimization, but there is scope to increase its role in many systems. Stakeholders may have strong views on access to technology, and stakeholder involvement is essential. Optimization faces challenges including loss aversion and entitlement, stakeholder inertia and entrenchment, heterogeneity in patient outcomes, and the need to demonstrate convincingly absence of benefit. While basic HTA principles remain applicable, methodological developments are needed better to support optimization. These include mechanisms for candidate technology identification and prioritization, enhanced collection and analysis of routine data, and clinician engagement. To maximize value to decision makers, HTA should consider implementation strategies and barriers. Improving optimization processes calls for a coordinated approach, and actions are identified for system leaders, HTA and other health organizations, and industry.

Objectives: The aim of this study was to determine how evidence from systematic review (SR) is perceived and negotiated by expert stakeholders in considering a technology for potential disinvestment.

Methods: An evidence-informed stakeholder engagement examined results from a diagnostic accuracy SR of vitamin B12 and folate tests. Pathologists deliberated around the SR findings to generate an informed contribution to future policy for the funding of B12 and folate tests. Deliberations were transcribed and subject to qualitative analysis.

Results: Pathologists did not engage with findings from the SR in depth; rather they sought to contest the terms of the problem driving the review and attempted to reframe it. Pathologists questioned the usefulness of SR outcomes given the variable definitions of B12 deficiency and deferred addressing disinvestment options specifically pertaining to B12 testing. However, folate testing was proffered as a potential disinvestment candidate, based upon pathologists' definition of “appropriate” evidence beyond the bounds of the SR.

Conclusions: The value of SR to informing disinvestment deliberations by expert stakeholders may be a function of timing as well as content. Engagement of stakeholders in co-produced evidence may be required at two levels: (i) Early in the synthesis phase to help shape the SR and harmonize expert views with the available evidence (including gaps); (ii) Collaboration in primary research to fill evidence-gaps thus supporting evidence-based disinvestment. Without this, information asymmetry between clinically engaged experts and decision makers may preclude the collaborative, informed, and technical discussions required to generate productive policy change.

Objectives: Obsolescence is a natural phase of the lifecycle of health technologies. Given increasing cost of health expenditures worldwide, health organizations have little choice but to engage in health technology reassessment (HTR); a structured, evidence-based assessment of the medical, social, ethical, and economic effects of a technology, currently used within the healthcare system, to inform optimal use of that technology in comparison to its alternatives. This research was completed to identify and summarize international HTR initiatives for non-drug technologies.

Methods: A systematic review was performed using the terms disinvestment, obsolescence, obsolete technology, ineffective, reassessment, reinvestment, reallocation, program budgeting, and marginal analysis to search PubMED, MEDLINE, EMBASE, and CINAHL until November 2011. Websites of organizations listed as members of INAHTA and HTAi were hand-searched for gray literature. Documents were excluded if they were unavailable in English, if the title/abstract was irrelevant to HTR, and/or if the document made no mention of current practices. All citations were screened in duplicate with disagreements resolved by consensus.

Results: Sixty full-text documents were reviewed and forty were included. One model for reassessment was identified; however, it has never been put into practice. Eight countries have some evidence of past or current work related to reassessment; seven have shown evidence of continued work in HTR. There is negligible focus on monitoring and implementation.

Conclusions: HTR is in its infancy. Although health technology reassessments are being conducted, there is no standardized approach. Future work should focus on developing and piloting a comprehensive methodology for completing HTR.

Background: A randomized controlled trial has shown that supervised, facility-based exercise training is effective in improving glycemic control in type 2 diabetes. However, these programs are associated with additional costs. This analysis assessed the cost-effectiveness of such programs.

Methods: Analysis used data from the Diabetes Aerobic and Resistance Exercise (DARE) clinical trial which compared three different exercise programs (resistance, aerobic or a combination of both) of 6 months duration with a control group (no exercise program). Clinical outcomes at 6 months were entered for individual patients into the UKPDS economic model for type 2 diabetes adapted for the Canadian context. From this, expected life-years, quality-adjusted life-years (QALYs) and costs were estimated for all patients within the trial.

Results: The combined exercise program was the most expensive ($40,050) followed by the aerobic program ($39,250), the resistance program ($38,300) and no program ($31,075). QALYs were highest for combined (8.94), followed by aerobic (8.77), resistance (8.73) and no program (8.70). The incremental cost per QALY gained for the combined exercise program was $4,792 compared with aerobic alone, $8,570 compared with resistance alone, and $37,872 compared with no program. The combined exercise program remained cost-effective for all scenarios considered within sensitivity analysis.

Conclusions: A program providing training in both resistance and aerobic exercise was the most cost-effective of the alternatives compared. Based on previous funding decisions, exercise training for individuals with diabetes can be considered an efficient use of resources.

Objectives: Order sets are widely used in hospitals to enter diagnosis and treatment orders. To determine the effectiveness of order sets in improving guideline adherence, treatment outcomes, processes of care, efficiency, and cost, we conducted a systematic review of the literature.

Methods: A comprehensive literature search was performed in various databases for studies published between January 1, 1990, and April 18, 2009. A total of eighteen studies met inclusion criteria. No randomized controlled trials were found.

Results: Outcomes of the included studies were summarized qualitatively due to variations in study population, intervention type, and outcome measures. There were no important inconsistencies between the results reported by studies involving different types of order sets. While the studies generally suggested positive outcomes, they were typically of low quality, with simple before-after designs and other methodological limitations.

Conclusions: The benefits of order sets remain eminently plausible, but given the paucity of high quality evidence, further investigations to formally evaluate the effectiveness of order sets would be highly valuable.

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: Immune thrombocytopenia (ITP) causes increased platelet destruction and suboptimal platelet production, increasing risk of bleeding. This analysis uses a Bayesian metaregression model to indirectly compare effectiveness of the thrombopoietin mimetics romiplostim and eltrombopag for increasing platelet counts, and contrasts the results with those of non-Bayesian approaches.

Methods: Ten databases were searched during 2010. Placebo-controlled trials of 24 weeks’ duration were included. An indirect comparison was undertaken using Bayesian metaregression, which includes all trials in a single model. This was compared with previous analyses in which data for each intervention were combined using simple pooling, logistic regression or meta-analysis, followed by indirect comparison of pooled values using the Bucher method.

Results: Two trials of romiplostim and one of eltrombopag were included. The indirect evidence suggests romiplostim significantly improves overall platelet response compared with eltrombopag. Bayesian metaregression gave an odds ratio (OR) for eltrombopag versus romiplostim of 0.11 (95 percent credible interval 0.02–0.66); p values and Bayesian posterior probabilities ranged from 0.01 to 0.05 for all analyses. There was no significant difference in durable platelet response in any of the analyses, although the direction of effect favored romiplostim (OR = 0.15; 95 percent credible interval, 0.01–1.88); p values and Bayesian posterior probabilities ranged from 0.08 to 0.40 across analyses. Results were relatively consistent between analyses.

Conclusions: Bayesian metaregression generated similar results to other indirect comparison methods, and may be considered the most robust as it incorporates all data in a single model and accounts appropriately for parameter uncertainty.

Background: Total thyroidectomy (TT) can be performed either with the traditional technique or using the ultrasound scalpel. Here, the use of the ultrasound scalpel is investigated in order to assess cost-effectiveness from an hospital, third party payer and societal perspective.

Methods: A randomized controlled trial was conducted at the University Hospital A. Gemelli in Rome. Data refer to 198 patients, randomized to either surgery with the ultrasound scalpel (n = 96) or traditional (n = 102) and followed for 3 months after hospital discharge. Operation time (OT) and resource consumption were recorded. Main clinical outcome investigated was quality of life (evaluated with EQ-5D).

Results: A shorter operation time (traditional: 76.36 vs ultrasound: 54.16 minutes, p < 0.001) was observed. 3 months after surgery, differences in QoL were significant (0.91 vs 0.84, p = 0.002). Concerning the hospital perspective, ultrasound scalpel allows savings of 119 EUR per patient. From a societal perspective, ultrasound scalpel is also related to lower medical resource consumption during a 3 month follow-up after discharge (traditional: 129.03 EUR vs ultrasound: 107.82 EUR) and lower non-medical resource utilization (transport/hotels costs traditional:535.51 EUR vs ultrasound: 342.77 EUR. No statistical difference was found in productivity losses up to 3 months (traditional: 377.71 EUR vs ultrasound: 385.51 EUR).

Conclusion: Allowing an overall saving of 325.36 EUR per patient, Ultrasound scalpel should be adopted for TT procedures in the “A.Gemelli” University hospital.

Objectives: The news media plays a central role in providing information regarding new medical technologies and exerts an influence on their social perception, understanding, and assessments. This study, therefore, analyzes how healthcare robotics are portrayed in the German print news media. It examines whether the risks and opportunities of new medical technologies are presented in a balanced manner and investigates whether or not print media coverage of these technologies is affected by science-fiction discourse, in which robots appear mostly as a threat to humans.

Methods: Ten years of German print media coverage (2000–2010) have been studied by means of systematic, standardized content analysis.

Results: Reporting focuses predominantly on beneficial advancements in medical practice and the advantages of robotics for patients, medical staff, and society. The results show that the dominant relationship between robots and humans that is transmitted in print media in medical contexts is positive, with robots mostly portrayed as assistants, colleagues, or even friends. Only a small number of articles report ethical questions and risks.

Conclusions: In contrast to science-fiction discourse, the German print media provides a positive picture of robotics to the lay public.

Background: In 2008 the Danish National Board of Health launched an information campaign aimed at introducing mini-HTA as a management and decision support tool for the municipalities. Today (January 2012), mini-HTA is still not used regularly in the municipalities.

Aim: The aim of this study was to evaluate the latent attitudes toward mini-HTA among ninety-three participants in five voluntary workshops on mini-HTA held in the period of May 2008 to February 2009.

Methods: In a questionnaire including three open questions respondents were asked to state their perception of what mini-HTA could be used for in the municipality, the main barriers for using mini-HTA, and what could make it easier to implement mini-HTA. Answers were analyzed qualitatively and quantitatively using binary coding and statistical examination of patterns in form of R-factor analysis.

Results: The four significant latent attitudes were a general acceptance of HTA-principles, a derived need for a political/managerial decision to use mini-HTA in the municipality, worries about barriers in the medium run, and worries about barriers in the short run.

Conclusions: A national information campaign to support the uptake of mini-HTA in local health-care institutions was insufficient in the Danish municipalities and should have been supplemented with a strategy to secure local political/managerial willingness to use mini-HTA and the removal of short- and medium-term barriers. The implementation of local HTA should not just be seen as a question of how to increase the use of evidence in decision-making, but as a matter of reforming local decision processes.

Objectives: High-quality clinical evidence is most often lacking when novel high-risk devices enter the European market. At the same time, a randomized controlled trial (RCT) is often initiated as a requirement for obtaining market access in the US. Should coverage in Europe be postponed until RCT data are available? We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the US, and with medicines, where appropriate.

Methods: The literature and regulatory documents were checked. Representatives from industry, Competent Authorities, Notified Bodies, Ethics Committees, and HTA agencies were consulted. We also discuss patient safety and the transparency of information.

Results: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. Patients in Europe can thus have earlier access to a potentially lifesaving device, but at the risk of insufficiently documented efficacy and safety. Variations in the stringency of clinical reviews, both at the level of Notified Bodies and Competent Authorities, do not guarantee patient safety. We tried to document the design of premarket trials in Europe and number of patients exposed, but failed as this information is not made public. Furthermore, the Helsinki Declaration is not followed with respect to the registration and publication of premarket trials.

Conclusions: For innovative high-risk devices, new EU legislation should require the premarket demonstration of clinical efficacy and safety, using an RCT if possible, and a transparent clinical review, preferably centralized.

Objectives: When a new health technology has been approved by a health system, it is difficult to guarantee that it is going to be efficiently adopted, adequately used, and that effectiveness, safety, and consumption of resources and costs are in line with what was expected in preliminary investigations. Many governmental institutions promote the idea that efficient mechanisms should be established aimed at developing and incorporating continuous evidence into health technologies management. The purpose of this article is to stimulate the discussion on systematic post-introduction observation of health technologies.

Methods: Literature review and input of HTA experts.

Results: The study addresses the key issues related to post-introduction observation and presents a summary of the guide commissioned by the Spanish Ministry of Health, Social Policy and Equality to the Galician HTA agency for the prioritization and implementation of systematic post-introduction observation in Spain. The manuscript describes the prioritization tool developed as part of this project and discusses the main aspects of protocol development, observation implementation, and assessment of results.

Conclusions: The observation of prioritized health technologies after they are introduced in standard clinical practice can provide useful information for health organizations. However, implementing the observation of health technologies can require specific policy frameworks, commitment from different stakeholders, and dedicated funding.

Background: Mental illness constitutes a large proportion of the burden of disease in Zambia. Yet mental health services at the primary care level are either provided in a fragmented manner or are lacking altogether.

Methods: A literature review focused on terms including mental health and primary care and strategic options were analyzed.

Results: From the analysis, two options were considered for integrating mental health into primary health care. An incremental option would start with a pilot project introducing mental health services into primary care with a well-designed evaluation before scaling up. One key advantage of this option is that it is possible to make improvements in the plan, if needed, before scaling up. A comprehensive option would entail introducing mental health services into primary care in all nine provinces of Zambia. In this option, scaling up could occur more rapidly than an incremental approach.

Conclusions: Strategies to implement either option must address several barriers, including insufficient funding for mental health services, inadequate mental health indicators, lack of general public awareness of and social stigma attached to mental illnesses and mental health care not being perceived as cost-effective or affordable.

Objectives: Early awareness and alert (EAA) activities are increasingly recognized to be an important component of the health technology assessment (HTA) process. Sharing information on methods used in this discipline is vital to ensure the development of sustainable systems. The objectives of this study is to outline the approach taken to share the different methods that members of the EuroScan International Network use by producing a methods toolkit; and to provide an overview of the similarities and differences in methods adopted by EAA systems.

Methods: A Delphi technique was used to develop the methods toolkit. Structured questionnaires were used to identify the sources used in the identification of emerging technologies and to determine the methods used by agencies to carry out EAA activities.

Results: A methods toolkit incorporating guidance on all of the stages described by EuroScan members was produced. The toolkit and an accompanying checklist presents users with different methods that can be adopted to suit their needs. The comparative analysis demonstrates that different methods are being used by EAA systems dependent on resources available and customer requirements. Differences in identification, filtration, prioritization, and assessment are apparent along with the role of collaborators in these processes.

Conclusions: The methods used by EAA systems are not homogeneous resulting in a toolkit constructed on the basis of “one size doesn't fit all.” Methods in this discipline are developing continually to accommodate changes in health systems and the HTA world. Differences between agencies and the sharing of ideas and experiences enable EAA agencies to adapt to these developments.

Objectives: The aim of this study was to assess the accuracy of the English National Horizon Scanning Centre (NHSC) in identifying and filtering pharmaceutical developments using end user and international collaborator databases of emerging technologies as proxies for new drugs of likely significance to health services and/or patients.

Methods: We used the NHSC information system and the list of National Institute for Health and Clinical Excellence (NICE) technology appraisals to estimate the false positive rate for NHSC identification, filtration, and reporting. We assessed the sensitivity of NHSC identification and filtration of pharmaceuticals for NICE technology appraisals from 1999 to the end of December 2010, and for pharmaceuticals entered into the EuroScan International Network database.

Results: We estimate that overall NHSC identification, filtration and reporting had a positive predictive value of 0.39 (95 percent CI, 0.36 to 0.43) and a false positive rate of 60 percent. Using NICE appraisals and EuroScan's database as proxies for pharmaceuticals of significance, we estimate the NHSC sensitivity over the 10-year period at 0.92 (95 percent CI, 0.89 to 0.95) and 0.89 (95 percent CI, 0.82 to 0.96) respectively.

Conclusions: Our results suggest that the NHSC has performed well in terms of sensitivity over the past decade, but that the false positive rate of 60 percent may indicate that the filtration criteria for pharmaceuticals could be tightened for increased efficiency. Future evaluations of EAA systems should include an element of external review and explore the level of accuracy acceptable to funders and customers of such systems.

Objectives: The aim of this study was to briefly describe the current state of early awareness and alert (EAA) activities and systems in four Latin-American countries (Argentina, Brazil, Colombia, and Mexico).

Methods: Key informants were selected and completed an open questionnaire that included the following domains: current state of EAA activities and systems in each country, potential role for EAA systems in the health system, and future EAA projects that are currently being considered.

Results: In all four countries, health technology assessment (HTA) processes are used to prioritize the use of health resources, albeit at varying degrees and with different mechanisms and methodologies. EAA activities are still limited and there are virtually no institutions or units with specific functions explicitly devoted to EAA activity. However, most countries have developed some initial forms of EAA systems. Being in its initial stages there is no clear differentiation between these early awareness activities and other HTA functions, and no specific methodologies or processes are used to anticipate the emergence of new technologies. Consequently, early evaluation of technologies generally occurs in a reactive manner, after they have been introduced in the market and under the pressure of different stakeholders.

Conclusions: There is growing awareness that the early identification and assessment of emerging technologies should be an integral part of HTA and the decision-making process. Many initiatives are currently focusing on building partnerships between the various regulatory bodies involved in the incorporation of technologies at national levels. It is reasonable to foresee that EAA activities will continue to develop and expand in the region.

Objectives: The aim of this study was to establish a national Early Awareness and Alert (EAA) system for the identification and assessment of new and emerging health technologies in Italy.

Methods: In 2008, Agenas, a public body supporting Regions and the Ministry of Health (MoH) in health services research, started a project named COTE (Observatory of New and Emerging Health Technologies) with the ultimate aim of implementing a national EAA system. The COTE project involved all stakeholders (MoH, Regions, Industry, Universities, technical government bodies, and Scientific Societies), in defining the key characteristics and methods of the EAA system. Agreement with stakeholders was reached using three separate workshops.

Results: During the workshops, participants shared and agreed methods for identification of new and emerging health technologies, prioritization, and assessment. The structure of the Horizon Scanning (HS) reports was discussed and defined. The main channels for dissemination of outputs were identified as the EuroScan database, and the stakeholders’ Web portals. During the final workshop, Agenas presented the first three HS reports produced at national level and proposed the establishment of a permanent national EAA system.

Conclusions: The COTE Project created the basis for a permanent national EAA system in Italy. An infrastructure to enable the stakeholders network to grow was created, methods to submit new and emerging health technologies for possible evaluation were established, methods for assessment of the technologies selected were defined, and the stakeholders involvement was delineated (in the identification, assessment, and dissemination stages).

Canada has a highly decentralized health care system with 13 provinces and territories delivering health care within their own respective jurisdictions. Decisions regarding which innovative health technologies to adopt are often driven by the unique health care priorities of each jurisdiction's population. To understand these needs, the Canadian Agency for Drugs and Technologies in Health's (CADTH's) Early Awareness Service has expanded its activities. In addition to proactively scanning the horizon for new and emerging health technologies, the Early Awareness Service also scans the horizon for national and jurisdictional health policy issues. This paper looks at CADTH's process for identifying and monitoring policy issues at a national and jurisdictional level.

CADTH's Early Awareness Service delivers timely information on emerging health care concerns and technologies that may affect health care finances, facilities, operations, and patient care. The identification of important policy issues can help determine which new and emerging technologies will have the most significant impact on the health care system. The information that CADTH scans can also be used to help decision-makers prepare for potential developments and events that may have an impact on health care systems.

By improving its capability to identify and share policy issues across and within jurisdictions, CADTH is better situated to provide information that can be used by policy-makers to help them plan and anticipate for the introduction of new technologies and future developments affecting the unique health care needs of their jurisdictions.