Objectives: To apply the Theory of Constraints (TOC) to the Evidence-based Practice Center (EPC) process.

Methods: Participants in the EPC process were interviewed, and the technical contracting literature was reviewed. Undesirable effects (UDEs) that might occur in the EPC process were identified and, in a TOC Current Reality Tree (CRT), a fundamental UDE was selected and tracked back to potential root causes, focusing on the core “constraint.” The resulting draft CRT was presented at an EPC directors' meeting and finalized. From possible solutions obtained from interviews and literature, a Future Reality Tree (FRT) was constructed.

Results: Three UDEs were identified and that a report is not used was deemed fundamentally undesirable. Nine root causes were identified, and using the CRT, a core constraint emerged: EPC partner does not know how to conceptualize and articulate needs, objectives, and specifications. Two change strategies (“injections”) appeared to address the core constraint: establish an ongoing relationship between partners, EPC, and Agency for Healthcare Research and Quality early in the process, and use a changes clause; in a FRT the injections lead to the positive outcome—the production of a successful EPC report that meets partner needs and, therefore, will be used.

Conclusions: As with any complex enterprise, the EPC needs to engage in self-reflection and active improvement to maximize its value. The development of technical reports intended to inform decision making represents a complicated area, involving a network of interrelated processes. Using the TOC permitted us to understand process failures; results serve as a guide to improvement.

The Dutch healthcare system is not a single overall plan, but has evolved from a constantly changing mix of institutions, regulations, and responsibilities. The resulting system provides high-quality care with reasonable efficiency and equal distribution over the population. Every Dutch citizen is entitled to health care. Health insurance is provided by a mix of compulsory national insurance and public and private insurance schemes. Hospitals generally have a private legal basis but are heavily regulated. Supraregional planning of high-tech medical services is also regulated. Hospitals function under fixed, prospective budgets with regulation of capital investments. Independent general practitioners serve a gatekeeper role for specialist and hospital services and are paid by capitation or fee for service. Specialists are paid by fee for service. All physicians' fees are controlled by the Ministry of Economic Affairs. Coverage of benefits is an important method of controlling the cost of services. There is increasing concern about health care quality. Health technology assessment (HTA) has become increasingly visible during the last 15 years. A special national fund for HTA, set up in 1988, has led to many formal and informal changes. HTA has evolved from a research activity into policy research for improving health care on the national level. In 1993 the government stated formally that enhancing effectiveness in health care was one of its prime targets and that HTA would be a prime tool for this purpose. The most important current issue is coordination of HTA activities, which is now undertaken by a new platform representing the important actors in health care and HTA.

Objectives: To describe health technology assessment (HTA) and policies concerning three screening procedures in Sweden.

Methods: The main source of information was reports from the Swedish Council for Technology Assessment in Health Care (SBU) and other governmental reports, supplemented by the professional literature.

Results: Prevention is emphasized in the healthcare services of Sweden. Specifically, screening is encouraged and supported when it is deemed beneficial. Sweden has a strong orientation toward evidence-based health care and HTA. Since its inauguration in 1987, SBU has fostered the use of HTA in making policy and clinical decisions in Sweden. Government policy in Sweden is to encourage services that are beneficial and cost-effective and discourages services that are not. Screening is no exception to this general rule. The three cases examined in this paper—mammography screening, PSA screening, and routine ultrasound screening in pregnancy—have all been formally assessed in Sweden. Assessments have been an integral part of policy making concerning these and other preventive measures. Mammography screening has been widely implemented. However, as in other countries, screening is often carried out in an opportunistic fashion, so that PSA screening, in particular, is carried out more in Sweden than can be justified by the evidence.

Conclusions: Mammography screening is promoted and is completely available to the target group. PSA screening is discouraged, but not with complete success. Ultrasound in pregnancy is widely used, not because of good evidence of impact on mortality and morbidity among newborns, but because it increases the detection rate of congenitally malformed fetuses and because of evidence of positive effects on the management and planning of deliveries, as well as because of psychological and ethical implications of the technology. HTA is an important part of health policy making in Sweden.

Objectives: The study evaluates the costs of systemic lupus erythematosus (SLE) and the budget impact due to the introduction of belimumab in the Italian setting.

Methods: Adaptation to the Italian setting of a budget impact model with a time horizon of 4 years (year 0 without belimumab, years 1–3 with belimumab) to compare treatment, administration, and clinical monitoring costs of standard therapy and of the alternative scenario in which belimumab is administered in addition to the standard therapy to the subgroup of patients selected according to the label approved by the European Medicines Agency. The model takes also into account the costs of flares.

Results: Over 3 years, belimumab is able to prevent cumulatively 1,111 severe flares and 3,631 nonsevere flares with a total saving for the Italian National Health System (NHS) of approximately €6.2 million. Budget impact ranges from €4.4 million in the first year to €20.3 million in the third year.

Conclusions: The decrease in the number of flare partially counterbalances the costs of the new technology (impact attenuation of approximately 16 percent). These data elucidate the importance to control and monitor the disease progression and to prevent exacerbations, which are the major causes of the increase in costs paid by the NHS and by the society. The financial impact could be replicate on a regional basis, to inform local decision makers. Further developments are possible as the model does not consider the additional clinical and economic benefits of reduced damage accrual and slowed disease progression.

Orphan drug products generally are used in treating or preventing rare diseases. The small number of patients available for study may create special problems in the evaluation of these products. This paper examines some of the special problems that are associated with the design and implementation of studies to evaluate the safety and efficacy of orphan drugs. The U.S. Food and Drug Administration (FDA) has not established special criteria for evaluating orphan drugs per se, but the FDA has been flexible in evaluating drug products that present special problems, especially when these products are for treatment of serious of life-threatening illnesses. The FDA and other U.S. governmental agencies also have taken steps to promote the development and availability of drugs for rare diseases, including making these products available to patients who are in need, even before the drugs have full FDA marketing approval.

The intensive care unit (ICU), one of the great achievements of modern medicine, is both a set of technologies and a space with a special function. This essay traces the evolution of the ICU's crucial technologies, and how the space bearing this name was carved out in the hospital. Ethical, legal, and social developments, an important part of this story, are incorporated in it.

Recent advances in genetic identification and characterization of a number or hereditary disorders have led to increased possibilities for genetic testing and screening. The context and methods of screening are important given that identification of otherwise healthy persons as being presymptomatic or at increased risk for genetic diseases may have serious consequences for their future lifestyle, employment, and insurability. This article examines general principles for genetic screening, including goals, delivery issues, and professional and lay responses to screening and counseling, and recommends areas in which social psychological research on screening is needed.

The long-term health sequelae for women from assisted reproductive technology (ART) have not been studied extensively. There are a number of reasons that women's health may be compromised after ART procedures, including the consequences of the increased incidence of multiple births, operative deliveries, and preterm infants, the possible adverse effects of the drug regimens used for ovarian stimulation, and the instrumentation involved in ART procedures. In this paper we review the existing literature in these areas. It emphasizes the effects of the drugs used for ovarian stimulation, and in particular the incidence of cancer among women who have undergone ART. The review indicates that there is cause for concern about the long-term effects on women from ART treatments. It highlights the lack of research undertaken in almost all areas related to women's long-term health after ART. In the area of ART and cancer, it draws attention to the lack of conclusive evidence in relation to the posited association between fertility treatments and cancer, resulting from the limited number of very large studies and the need for longer follow-up periods. We make a number of recommendations regarding further research that is needed to address the current shortcomings in the published literature.

Increasingly, health technology assessment (HTA) is used to aid decisions on the reimbursement of pharmaceuticals or recommendations for their use. The pharmaceutical industry seeks to work in partnership with HTA agencies; however, this presents a number of challenges. Clinical trials will need to include appropriate measures that capture economic and patient benefits as well as relevant clinical endpoints, and the industry will want to seek international harmonization of the many guidelines for economic evaluation. The problem of demonstrating cost-effectiveness of a product before it is available for use must be addressed, possibly by conditional reimbursement to allow collection of real world evidence. It is also important that reimbursement decision makers minimize bias, play fair, and adhere to the written rules they issue. If the industry fairly demonstrates the value of a product using the best available evidence, HTA agencies should be transparent in the rationale for their recommendations.

There is a wide panorama of disorders in the newborn infant where neonatal intensive care has been proven effective in reducing mortality. Although modern neonatal intensive care can be very costly, shortand simple interventions for support and resuscitation still can be highly beneficial. In reviewing the field of neonatal intensive careduring the 1980s, it becomes evident that a major challenge for the future will be to apply physiological principles of great and provenvaluefor the newborn baby to more simple devices. Only thereby canthe technology of neonatal care defined as a complex of actions–not only equipment and techniques–become justified for future generations.

The purpose of this study was to determine how horizon-scanning organizations can encourage the implementation of recommendations contained in their early warning messages about emerging health technologies. We reviewed the conclusions of the EUR-ASSESS Project Subgroup report on dissemination and impact, an overview of systematic reviews of interventions to promote implementation of research findings by health care professionals, and various Cochrane Effective Practice and Organisation of Care Group protocols and reviews. The evidence on the effectiveness of different implementation strategies aimed at distinct target groups is of variable quality. There is some evidence from rigorous study designs on the effectiveness of strategies designed to influence the behavior of health care professionals; the quality of the evidence relating to policy makers and the general public is more limited. Horizon-scanning organizations can improve the likelihood of their recommendations being acted upon by developing active implementation strategies based on the best available evidence, establishing links with key groups, and directing early warning messages at specific target audiences. Given the relative lack of good quality evidence, it is important that implementation strategies be rigorously evaluated to determine their effectiveness.

Patterns of the diffusion of laparoscopic cholecystectomy in Canadian hospitals were determined by a telephone survey of 153 randomly selected hospitals over two years. Results were analyzed by region, hospital size, and type of hospital. Laparoscopic cholecystectomy has diffused very quickly compared with other technologies, before any comprehensive evaluation to consider its potential impact could take place.

Objectives: Made available since 2002, transcatheter aortic valve implantation (TAVI) is a minimally invasive new intervention which can provide significant survival improvement to patients with aortic stenosis. However, TAVI is expensive and currently not reimbursed by many governments. Some governments and institutions have been conducting health technology assessments (HTAs) to inform their reimbursement decisions. The aim of the present study is to review HTAs that have relied on a cost-effectiveness analysis to inform reimbursement decisions of TAVI.

Methods: A systematic literature review was conducted among published literature as well as reports released by HTA agencies. Predetermined inclusion and exclusion criteria, following the Preferred Reporting System for Systematic Reviews and Meta-Analysis guidelines, were used to select relevant HTAs. The selected papers were assessed against the Consolidated Health Economic Evaluation Reporting Standards.

Results: HTAs on TAVI from three countries were available for this review: Canada, Belgium, and the United Kingdom. All three HTAs used the Placement of Aortic Transcatheter Valve (PARTNER) trial data with Markov models to estimate the incremental cost effectiveness ratio. The three HTAs recommended conditional reimbursement for TAVI for otherwise inoperable patients. The HTAs did not use clear methods to estimate the health-related utility which ultimately affected their cost-effectiveness results. The UK HTA showed the best value for money (US$20,416 per quality-adjusted life-year).

Conclusion: All studies found TAVI to be more costly and less effective for high-risk patients suitable for surgery, whereas TAVI was consistently found to be cost effective for otherwise inoperable patients.

Objectives: Economic evaluation (EE) is an accepted element of decision making and priority setting in healthcare. As the number of published EEs grows, so does the number of systematic reviews (SRs) of EEs. Although search methodology makes an important contribution to SR quality, search methods in reviews of EEs have not been evaluated in detail. We investigated the resources used to identify studies in recent, published SRs of EEs, and assessed whether the resources reflected recommendations.

Methods: We searched MEDLINE for SRs of EEs published since January 2013 and extracted the following from eligible reviews: databases searched, health technology assessment (HTA) sources searched, supplementary search techniques used. Results were compared against the minimum search resources recommended by National Institute for Health and Care Excellence (NICE) (MEDLINE, Embase, NHS EED, EconLit) for economic evidence for single technology appraisals, and resource types suggested in the summary of current best evidence from SuRe Info (economic databases, general databases, HTA databases, HTA agency Web pages, gray literature).

Results: Sixty-five SRs met the inclusion criteria; data were extracted from forty-two. Five reviews (12 percent) met or exceeded the NICE recommended resources. Nine reviews (21 percent) searched at least four of the five types of resource recommended by SuRe Info. Five reviews (12 percent) searched all five. Twenty-three reviews (55 percent) did not meet the NICE recommendations or four of five of the SuRe Info recommended resource types. Search reporting was frequently unclear or incorrect.

Conclusions: Searches conducted for the majority of recently published SRs of EEs do not meet two published approaches.

Background: Uncertainty about the applicability of controlled trial findings is an increasing concern for clinicians and policy decision makers. This study aimed to determine whether information reported in studies included in systematic reviews was adequate enough to assess their applicability.

Methods: We used the databases of four recently conducted systematic reviews on the comparative efficacy and safety of second-generation antidepressants, inhaled corticosteroids, Alzheimer's drugs, and targeted immune modulators. We developed and pilot-tested a questionnaire to assess the adequacy of reporting with respect to seven previously validated criteria of study design that distinguish explanatory from pragmatic studies. For each of the 137 included studies, two reviewers independently assessed the adequacy of reporting.

Results: Overall, only 12 percent of the included studies provided sufficient information to reliably distinguish explanatory from pragmatic studies. The areas with the greatest lack of reporting were the setting of the study, methods of adverse event assessment, and sample size considerations to determine a minimally important difference from a patient perspective.

Conclusions: Substantial shortcomings in reporting exist in aspects of study design important to determine whether a study is applicable to specific populations of interest.

Background and Objectives: Horizon scanning systems need to handle a wide range of sources to identify new or emerging health technologies. The objective of this study is to develop a validated Medline bibliographic search strategy (PubMed search engine) to systematically identify new or emerging health technologies.

Methods: The proposed Medline search strategy combines free text terms commonly used in article titles to denote innovation within index terms that make reference to the specific fields of interest. Efficacy was assessed by running the search over a period of 1 year (2009) and analyzing its retrieval performance (number and characteristics). For comparison purposes, all article abstracts published during 2009 in six preselected key research journals and eight high impact surgery journals were scanned. Sensitivity was defined as the proportion of relevant new or emerging technologies published in key journals that would be identified in the search strategy within the first 2 years of publication.

Results: The search yielded 6,228 abstracts of potentially new or emerging technologies. Of these, 459 were classified as new or emerging (383 truly new or emerging and 76 new indications). The scanning of 12,061 journal abstracts identified 35 relevant new or emerging technologies. Of these, twenty-nine were located within the Medline search strategy during the first 2 years of publication (sensitivity = 83 percent).

Conclusions: The current search strategy, validated against key journals, has demonstrated to be effective for horizon scanning. Even though it can require adaptations depending on the scope of the horizon scanning system, it could serve to simplify and standardize scanning processes.