Since 1977, the Consensus Development Program of the Office of Medical Applications of Research (OMAR), part of the National Institutes of Health (NIH), has sponsored more than 50 consensus development conferences (CDCs) on the safety and efficacy of important biomedical technologies. The aim of these conferences, described fully elsewhere (4), is to inform the health care community, and to some extent the public, of the status of emerging biomedical technologies and the need for change in the use of existing health-related technologies. OMAR has therefore, worked diligently to publicize conference findings among these audiences. Further, OMAR has sought to improve the effectiveness of these transfer activities by conducting assessments of the impact of CDCs on their primary audience, U.S. physicians.

Do we have the will, the power of innovation, to lift ourselves above our own creations and control them? This is the central question of modern medicine, a question which for some time has dominated current discourse in health care and which gave rise in the early 1970s to the field of technology assessment. The technologic armory that has been developed over the past one and a half centuries is vast, formidable, and expanding. Its presence must be reckoned with, and to do this we must begin by understanding our relationship to it.

Objective: A basic issue in randomized controlled trials (RCTs) is whether we can safely assume comparability between groups at baseline with respect to all potentially important prognostic factors. In other words, did randomization work sufficiently well? In small trials balanced allocation procedures are employed, whereas in large-scale trials simple randomization will do. The question is: When should balancing be considered?

Methods: We performed a simulation study in which we varied the number of categories in the prognostic factors and the number of patients.

Results: Simulation showed that, in all instances, a balancing procedure almost always led to perfect or almost perfect balance, while the imbalance with simple randomization was larger. To study the effect of balanced and random allocation on subgroup analyses in our OME trial, we compared the quotient of the width of the confidence intervals (CI). The widest CI in random allocation over the 13 hospitals was on average 13% wider than in balanced allocation.

Conclusion: Investigators should always consider balanced allocation, especially in categories with a low number of patients and when subgroup analysis over many categories is requested.

Objectives: Recently, we developed a diagnostic rule for the diagnosis and treatment of children with meningeal signs. This rule may provide the physician with a rationale to decide on the use of diagnostic and treatment procedures in these children and to improve their care. In this study, we estimated cost savings of the rule compared with current practice.

Methods: Routine care data of 360 children visiting the emergency department of the Sophia Children's Hospital with meningeal signs between 1988 and 1998 were used. Costs of diagnostic tests and treatment were estimated by using financial accounts of an academic and a general pediatric hospital. The number of procedures actually performed and the resulting cost estimates (i.e. unit costs×volume) were compared with the estimated figures after application of the decision rule.

Results: The population of children with meningeal signs comprised 99 with bacterial meningitis (27%), 36 with another serious bacterial infection (10%), and 225 with a self-limiting disease (63%). Application of the rule would reduce lumbar punctures by 12% and hospitalizations for empirical treatment by 15% with the same diagnostic accuracy as current practice. Cost savings were estimated at €292 per patient (relative reduction 10%) and were mainly achieved in the treatment course (€259).

Conclusions: A diagnostic decision rule for children with meningeal signs has the potential to improve the appropriate use of medical resources, to be cost-effective, and to ascertain the absence of bacterial meningitis earlier.

Objectives: Decision analysis is commonly used to perform economic evaluations of new pharmaceuticals. The outcomes of such studies are often reported as an incremental cost per quality-adjusted life year (QALY) gained with the new agent. Decision analysis can also be used in the context of estimating drug cost before market entry. The current study used neurokinin-1 (NK-1) receptor antagonists, a new class of antiemetics for cancer patients, as an example to illustrate the process using an incremental cost of $Can20,000 per QALY gained as the target threshold.

Methods: A decision model was developed to simulate the control of acute and delayed emesis after cisplatin-based chemotherapy. The model compared standard therapy with granisetron and dexamethasone to the same protocol with the addition of an NK-1 before chemotherapy and continued twice daily for five days. The rates of complete emesis control were abstracted from a double-blind randomized trial. Costs of standard antiemetics and therapy for breakthrough vomiting were obtained from hospital sources. Utility estimates characterized as quality-adjusted emesis-free days were determined by interviewing twenty-five oncology nurses and pharmacists by using the Time Trade-Off technique. These data were then used to estimate the unit cost of the new antiemetic using a target threshold of $Can20,000 per QALY gained.

Results: A cost of $Can6.60 per NK-1 dose would generate an incremental cost of $Can20,000 per QALY. The sensitivity analysis on the unit cost identified a range from $Can4.80 to $Can10.00 per dose. For the recommended five days of therapy, the total cost should be $Can66.00 ($Can48.00–$Can100.00) for optimal economic efficiency relative to Canada's publicly funded health-care system.

Conclusions: The use of decision modeling for estimating drug cost before product launch is a powerful technique to ensure value for money. Such information can be of value to both drug manufacturers and formulary committees, because it would facilitate negotiations for optimal pricing in a given jurisdiction.

Objectives: The clinical assessment efficiency of the CAGE questionnaire for alcohol abuse based on diagnostic accuracy has not been fully established to date because of the varied and inconclusive gold standards used as diagnostic criteria. CAGE has also been highlighted to miss almost half of the risk-drinkers due to the use of inadequetly set criteria for the positive recognition of alcohol abuse. This study aims to establish the diagnostic accuracy of CAGE at different treatment settings.

Methods: A hybrid of the receiver operating characteristic (ROC) and the Taguchi method was used, as this approach proved to evaluate the diagnostic performance and accuracy in hypothetical clinical settings. Data were used from three cross-clinical treatment settings, i.e., general medicine outpatients, medical inpatients, and psychiatric inpatients, and analyzed by means of a step-wise application of managable number of statistical indices such as the area under the ROC curve (AUC), leveling factor (p′), and signal-to-noise ratios (S/N; standardized S/N [SS/N]).

Results: The selected settings yielded similar AUCs but portrayed different trade-offs on the ROC curves signaling the presence of different critical CAGE scores. Analysis of the sensitivity and specificity data of i, ii, iii by p′, S/N, SS/N and their dependent relation resulted in the critical CAGE scores of 1,1, and 2; and high diagnostic accuracy levels of 76.84 percent, 86 percent, and 76.84 percent, respectively.

Conclusions: By setting these critical CAGE scores as the minimum detection levels of alcohol abuse, early intervention before the onset of serious alcohol-related problems is possible. This will decrease the health-care costs of the patient and, in addition, reduce the psychological and social burdens inherent to alcohol abuse both on the patient and society. Having its critical scores reliably identified and diagnostic accuracy fully determined, CAGE can now improve the detection rate of problem drinking individuals substantially.

Objectives: Since 2002, the treatment with cholinesterase inhibitors (CHEIs) for Alzheimer's disease (AD) has been paid for by the public health system of the Brazilian Ministry of Health for any patient that fulfills clinical criteria established by an evidence-based guideline developed and published by the Ministry. The aim of this study was to evaluate compliance of prescription patterns to the national guideline for use of CHEIs’ in the southern Brazilian state of Rio Grande do Sul.

Methods: We created a regional expert-committee reference center to review all prescriptions of CHEIs and to send feedback to physicians whenever prescriptions without compliance to the guideline were noted. One thousand three hundred ninety-nine (1,399) CHEI prescriptions presented to the public health system from 2005 to 2007 were evaluated by an expert team of neurologists and psychiatrists. Clinical history, performance on mental status screening by Mini Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), laboratory results, and neuroimaging findings were evaluated in relation to the adherence to the national guideline's recommendations. If the prescription was rejected because of lack of adherence to the criteria of the guideline, a written response was sent by the expert committee to physicians concerning the request.

Results: The majority of the requests (n = 1,044; 75 percent) did not meet the AD guideline's criteria, either for diagnosis or for treatment, and were not granted. A diagnostic mistake was evident in 64.3 percent of cases. Findings of vascular or Parkinson's dementia or severe AD were the main reasons for rejection. Rivastigmine was the most prescribed cholinesterase inhibitor, used in 86 percent of cases. Of note was the reduction in the number of CHEIs prescriptions in the years following this intervention.

Conclusions: The public health strategy of using expert-review of prescriptions and their compliance to national guideline revealed a low rate of rational use of CHEIs for dementia. Such a strategy is relevant for protecting patients from unproven medical interventions and for reducing waste of resources.

Objectives: Current health technology assessment (HTA) is not well equipped to assess complex technologies as insufficient attention is being paid to the diversity in patient characteristics and preferences, context, and implementation. Strategies to integrate these and several other aspects, such as ethical considerations, in a comprehensive assessment are missing. The aim of the European research project INTEGRATE-HTA was to develop a model for an integrated HTA of complex technologies.

Methods: A multi-method, four-stage approach guided the development of the INTEGRATE-HTA Model: (i) definition of the different dimensions of information to be integrated, (ii) literature review of existing methods for integration, (iii) adjustment of concepts and methods for assessing distinct aspects of complex technologies in the frame of an integrated process, and (iv) application of the model in a case study and subsequent revisions.

Results: The INTEGRATE-HTA Model consists of five steps, each involving stakeholders: (i) definition of the technology and the objective of the HTA; (ii) development of a logic model to provide a structured overview of the technology and the system in which it is embedded; (iii) evidence assessment on effectiveness, economic, ethical, legal, and socio-cultural aspects, taking variability of participants, context, implementation issues, and their interactions into account; (iv) populating the logic model with the data generated in step 3; (v) structured process of decision-making.

Conclusions: The INTEGRATE-HTA Model provides a structured process for integrated HTAs of complex technologies. Stakeholder involvement in all steps is essential as a means of ensuring relevance and meaningful interpretation of the evidence.

Objectives: Despite recent development of health technology assessment (HTA) methods, there are still methodological gaps for the assessment of complex health technologies. The INTEGRATE-HTA guidance for effectiveness, economic, ethical, socio-cultural, and legal aspects, deals with challenges when assessing complex technologies, such as heterogeneous study designs, multiple stakeholder perspectives, and unpredictable outcomes. The objective of this article is to outline this guidance and describe the added value of integrating these assessment aspects.

Methods: Different methods were used to develop the various parts of the guidance, but all draw on existing, published knowledge and were supported by stakeholder involvement. The guidance was modified after application in a case study and in response to feedback from internal and external reviewers.

Results: The guidance consists of five parts, addressing five core aspects of HTA, all presenting stepwise approaches based on the assessment of complexity, context, and stakeholder involvement. The guidance on effectiveness, health economics and ethics aspects focus on helping users choose appropriate, or further develop, existing methods. The recommendations are based on existing methods’ applicability for dealing with problems arising with complex interventions. The guidance offers new frameworks to identify socio-cultural and legal issues, along with overviews of relevant methods and sources.

Conclusions: The INTEGRATE-HTA guidance outlines a wide range of methods and facilitates appropriate choices among them. The guidance enables understanding of how complexity matters for HTA and brings together assessments from disciplines, such as epidemiology, economics, ethics, law, and social theory. This indicates relevance for a broad range of technologies.

Cost-effectiveness analysis has much conceptual attractiveness in priority setting but is not used to its full potential to assist policy-makers on making choices in health in developed or in developing countries. We call for a shift away from present economic evaluation activities—that tend to produce ad hoc and incomparable economic evaluation studies and, therefore, add little to the compendium of knowledge of cost-effectiveness of health interventions in general—toward a more systematic approach. Research efforts in economic evaluation should build on the foundations of cost-effectiveness research of the past decades to arrive at an informative methodology useful for national policy-makers. This strategy means that governments should steer sectoral cost-effectiveness analysis to obtain systematic and comprehensive information on the economic attractiveness of a set of new and current interventions, using a standardized methodology and capturing interactions between interventions. Without redirecting the focus of economic evaluation research, choosing in health care bears the risk to remain penny-wise but pound-foolish.

Objectives: Developing a search strategy for use in a systematic review is a time-consuming process requiring construction of detailed search strings using complicated syntax, followed by iterative fine-tuning and trial-and-error testing of these strings in online biomedical search engines.

Methods: Building upon limitations of existing online-only search builders, a user-friendly computer-based tool was created to expedite search strategy development as part of production of a systematic review.

Results: Search Builder 1.0 is a Microsoft Excel®-based tool that automatically assembles search strategy text strings for PubMed (www.pubmed.com) and Embase (www.embase.com), based on a list of user-defined search terms and preferences. With the click of a button, Search Builder 1.0 automatically populates the syntax needed for functional search strings, and copies the string to the clipboard for pasting into Pubmed or Embase. The offline file-based interface of Search Builder 1.0 also allows for searches to be easily shared and saved for future reference.

Conclusions: This novel, user-friendly tool can save considerable time and streamline a cumbersome step in the systematic review process.

Objectives: The healthcare transformation program in Turkey has shown its success with improvements in important health indicators, increased access to healthcare services and expansion of coverage to all citizens. Turkey has been relatively able to bear the burdens associated with this due to rapid economic growth. The need for health technology assessment (HTA) was believed as a result of the expansion of coverage, pressure of new technologies, and increased expenditures. This study outlines the background and current formalization of HTA and shares the current use of HTA in decision making, while summarizing the transformation of the Turkish healthcare system for developing a high-quality, equal, and accessible care system.

Methods: We reviewed and analyzed policy changes in the Turkish healthcare system, universal health coverage, healthcare expenditures, and pricing and reimbursement policies to identify the changes leading to HTA. We reviewed existing HTA functions in Turkey and outlined their activities. Finally, we outlined a set of major challenges for HTA in Turkey over the next decade.

Results: HTA was formalized in Turkey in 2012–2013 with three national HTA structures and one hospital-based HTA unit. These functions currently run independent from each other. There are three major challenges in this country for HTA in the next decade: clarification of the assessment scope and methods, building a strong supporting system for HTA, and defining the role of HTA in the future vision of Turkish healthcare policy.

Conclusion: HTA, despite challenges, has a good opportunity to develop further with clear action plans and strong political will.

Objectives: The aim of this study was to evaluate the direct costs of type 2 diabetes mellitus patients treated in a Brazilian public hospital.

Methods: This was an exploratory retrospective cost-of-illness study with quantitative approach, using medical records of patients treated in a public hospital (2012–14), with at least one consultation over a period of 12 months. Data on patient's profile, exams, number of consultations, medications, hospitalizations, and comorbidities were collected. The cost per patient per year (pppy) was calculated as well as the costs related to glycated hemoglobin (HbA1c) values, using thresholds of 7 and 8 percent.

Results: Data of 726 patients were collected with mean age of 62 ± 11 years (68.3 percent female). A total of 67.1 percent presented HbA1c > 7 percent and 44.9 percent > 8 percent. The median cost of diabetes was United States dollar (USD) 197 pppy. The median costs of medication were USD 152.49 pppy, while costs of exams and consultations were USD 40.57 pppy and 8.70 pppy, respectively. Thirty-eight patients (4 percent) were hospitalized and presented a median cost of 3,656 per patient per hospitalization with a cost equivalent to 53.1 percent of total expenses. Total costs of patients with HbA1c ≤ 7 percent were lower for this group and also costs of medications and consultations, whereas for patients with HbA1c ≤ 8 percent, only total costs and costs of medications were lower when compared with HbA1c > 8 percent patients.

Conclusions: Medications and hospitalizations were the major contributor of diabetes expenses. Preventing T2DM, or reducing its complications through adequate control, may help avoid the substantial costs related to this disease.

Objectives: The primary objective of this study was to determine the extent to which international standards on transparency and quality are met by the health technology assessment (HTA) process in Poland. A secondary objective is to describe the outcomes of the HTA process and their associated factors.

Methods: All published online HTA appraisal and meeting proceedings on pharmaceutical products in 2008 were reviewed using a score card developed from international checklists recommended by INAHTA and ECHTA.

Results: The sixty-nine reports reviewed showed that five of nine transparency standards and six of eight quality standards were usually met by the HTA reports. Areas for improvement for transparency include inputs from external stakeholders, availability of English summaries, conclusions, implications of results, and suggested program of action. Areas of improvement for quality include appropriateness of target population and comparator/s, sufficiency of evidence on efficacy and safety, methodological rigor, economic model assumptions, and adaptation to the Polish setting. A consideration of the ethical and social consequences to the healthcare system must also be strengthened.

Conclusions: The study demonstrates that the incorporation and implementation of the HTA appraisal process in Poland has been successful. HTA appraisal reports in Poland have considered most of the international standards of transparency and quality. Recommendations for both HTA users and doers are forwarded for the improvement of the HTA process in the Polish setting.