Scientific reports should be orderly, clear, and unambiguous. Clarity is even more important for health technology assessments (HTAs), which aim at supplying reliable and up-to-date evidence on the effectiveness, safety, and cost of healthcare interventions. Increasingly assessments also provide information about the effects of technologies on organization of care, as well as relevant legal, social, and ethical considerations.

Objectives: In a practice setting where casting is considered the standard of care, the aim of this study was to assess the cost-effectiveness of wrist splints compared with routine casting in children with acceptably angulated distal radius greenstick or transverse fractures.

Methods: A cost-effectiveness analysis was conducted alongside a randomized controlled trial (RCT). One hundred children with acceptably angulated distal radius greenstick or transverse fractures received either a wrist splint or cast. Information on health care provider and patient and family resource use as well as productivity cost was collected. Resource use was costed using unit costs from local administrative data sources and expense diaries. Effectiveness was assessed at 6 weeks using the performance version of the Activities Scale for Kids (ASKp) questionnaire. Cost-effectiveness analysis related differential costs to differential ASKp scores.

Results: Mean total cost was $877.58 in the splint group and $950.35 in the cast group, with a mean difference of $−72.76 (standard error [SE] 45.88). Mean total healthcare cost was $670.66 in the splint group and $768.22 in the cast group, with a mean difference of $−97.56 (SE 9.24). Mean (SE) ASKp was 92.8 in the splint group and 91.4 in the cast group, with a mean difference of 1.439 (SE 1.585). Therefore, splint management was more effective and cheaper. After accounting for uncertainty, the probability of splint being cost-effective compared with cast was 94 percent for a willingness-to-pay threshold value of $0 for one-unit gain in ASKp score and exceeded 82 percent for all threshold values.

Conclusions: In this RCT, splint management was cost-effective compared with casting in children with acceptably angulated distal radius greenstick or transverse fractures. This study challenges the existing standard of care for children with this type of fracture and provides justification on clinical and economic grounds for a change in routine practice.

Background: In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in “off label” patients.

Objectives: The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance.

Methods: Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy.

Results: Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features.

Conclusions: For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.

Objectives: This article examines the challenges for health technology assessment (HTA) in the light of new developments of personalized health care, focusing on European HTA perspectives.

Methods: Using the example of the Integrated Genome Research Network – Mutanom (IG Mutanom) project, with focus on personalized cancer diagnostics and treatment, we assess the scope of current HTA and examine it prospectively in the context of the translation of basic and clinical research into public health genomics and personalized health care.

Results: The approaches developed within the IG-Mutanom project are based on innovative technology potentially providing targeted therapies for cancer; making translation into clinical practice requires a novel course of action, however. New models of HTA are needed that can account for the unique types of evidence inherent to individualized targeted therapies. Using constructive health technology assessment (CTA) models is an option, but further suitable models should be developed.

Conclusions: Integrative, systems biology-based approaches toward personalized medicine call for novel assessment methods. The translation of their highly innovative technologies into the practice of health care requires the development of new HTA concepts.

Objectives: Health systems frequently make decisions regarding acquisition and use of new technologies. It is desirable to base these decisions on clinical evidence, but often these technologies are used for multiple indications and evidence of effectiveness for one indication does not prove effectiveness for all. Here, we describe two examples of evidence inventory reports that were performed for the purposes of identifying how much and what type of published clinical evidence was available for a given technology, and the contexts in which those technologies were studied.

Methods: The evidence inventory reports included literature searches for systematic reviews and health technology assessment (HTA) reports, and systematic searches of the primary literature intended to count and categorize published clinical studies. The reports did not include analysis of the primary literature.

Results: The inventory reports were completed in 3 to 4 days each and were approximately ten pages in length, including references. Reports included tables listing the number of reported studies by specific indication for use, and whether or not there were randomized trials. Reports also summarized findings of existing systematic reviews and HTA reports, when available. Committees used the inventory reports to decide for which indications they wanted a full HTA report.

Conclusions: Evidence inventory reports are a form of rapid HTA that can give decision makers a timely understanding of the available evidence upon which they can base a decision. They can help HTA providers focus subsequent reports on topics that will have the most influence on healthcare decision making.

Objectives: The aim of this study was to explore whether Bayesian reasoning can be applied to therapeutic questions in a way that is similar to its application in diagnostics.

Methods: A clinically relevant, therapeutic question was formulated in accordance with Bayesian reasoning for the clinical management of patients with newly diagnosed rheumatoid arthritis (RA). Prior probability estimates of response to drug treatment (methotrexate, MTX) were obtained from the literature. As a marker of treatment response, changes in the Health Assessment Questionnaire (HAQ) scores were assessed after three months of treatment. Likelihood ratios for this marker were calculated on the basis of data from a clinical registry, using changes in the Disease Activity Score (DAS) as gold standard. Using Bayes’ theorem, prior probability and likelihood ratios were combined to estimate posterior probabilities of treatment response in individual patients.

Results: On the basis of the literature, the prior probability of response of RA patients to MTX was estimated 45 percent. At 3 months follow-up, this probability increased to 80 percent or decreased to 23 percent, depending on the changes that were observed in Health Assessment Questionnaire scores.

Conclusions: Bayesian reasoning can be applied to therapeutic issues in a way that is conceptually fully compatible with its use in diagnostics. As such, it can be used to bridge the gap between aggregate data and individual patient management.

Background: Most developing countries and resource-limited settings lack robust health technology assessment (HTA) systems. Because the development of locally relevant HTA is not immediately viable, and the extrapolation of external HTA is inappropriate, a new model for evaluating health technologies is required.

Objectives: The aim of this study was to describe the development and application of KNOW ESSENTIALS, a tool facilitating evidence-based decisions on health technologies by stakeholders in settings lacking formal HTA systems.

Methods: Current HTA methodology was examined through literature search. Additional issues relevant to resource-limited settings, but not adequately addressed in current methodology, were identified through further literature search, appraisal of contextually relevant issues, discussion with healthcare professionals familiar with the local context, and personal experience. A set of thirteen elements important for evidence-based decisions was identified, selected and combined into a tool with the mnemonic KNOW ESSENTIALS. Detailed definitions for each element, coding for the elements, and a system to evaluate a given health technology using the tool were developed.

Results and Conclusions: Developing countries and resource-limited settings face several challenges to informed decision making. Models that are relevant and applicable in high-income countries are unlikely in such settings. KNOW ESSENTIALS is an alternative that facilitates evidence-based decision making by stakeholders without formal expertise in HTA. The tool could be particularly useful, as an interim measure, in healthcare systems that are developing HTA capacity. It could also be useful anywhere when rapid evidence-based decisions on health technologies are required.

Objectives: The UK's National Institute for Health and Clinical Excellence (NICE) and the Jordan office of the Medicines Transparency Alliance embarked on a pilot project to design an evidence-based guideline for cost-effective pharmacological treatment of essential hypertension in Jordan. The project's objectives were to directly address a major health problem for Jordan by producing a guideline; and to delineate the strengths and weaknesses of Jordan's healthcare process to allow similar future efforts to be planned more efficiently.

Methods: The pilot spanned a period of approximately 8 months. Activities were overseen by local technical and guideline development teams, as well as experts from NICE. NICE's hypertension guidelines and economic model were used as a starting point. Parameters in the economic model were adjusted according to input and feedback from local experts with regards to Jordanian physician and patient practices, resource costs, and quality of life estimates. The results of the economic model were integrated with the updated available clinical trial literature.

Results: The outputs of the economic model were used to inform recommendations, in the form of a clinical algorithm. A report of the process and the strengths and weaknesses observed was developed, and recommendations for improvements were made.

Conclusions: The pilot represented the start of what is intended to be a healthcare process change for the country of Jordan. Issues emerged which can inform strategies to ensure a more cohesive and comprehensive approach to the cost-effective use of appropriate drugs in managing chronic disease in Jordan and countries operating in a similarly resource-constrained environment. Furthermore, our pilot highlights how richer countries with relevant experience in evidence-informed healthcare policy making can assist others in strengthening their decision-making methods and processes.

Background: For non-drug technologies, there is often residual uncertainty following systematic review, mainly due to inadequate evidence of efficacy. The unwillingness to make decisions in the presence of uncertainty may lead to passive diffusion and intuitive decision making with or without public pressure. This may affect health system sustainability. There is increasing interest in post-market evaluation through processes that include coverage with evidence development (CED) to address residual uncertainty regarding effectiveness and cost-effectiveness. Global experience of CED has been slow to develop despite their potential contribution to decision making.

Methods: Ontario's field evaluation program to better inform decision making represents a collaboration between physicians, policy decision makers and academic centers. We report results of the first ten CEDs from this program to assess whether they achieved their objective of influencing policy by addressing residual uncertainty following systematic review.

Results: Since 2003, nineteen field evaluation studies to resolve residual uncertainty following systematic review have been completed, ten of which met the criteria of CED and are the focus of this report. There was more than one patient subgroup or intervention in three of the CEDs. This provided the basis for evaluating thirteen outcomes. In each case, the CED addressed the uncertainty and led to a decision based on the systematic review and CED result. The CEDs led to adoption of the technology in six instances, modified adoption in three instances and withdrawal in four instances.

Conclusions: CED makes an important contribution to translating evidence to decision making. Methodologies are needed to increase the scope and reduce timelines for CEDs, such as the use of linked comprehensive and robust data sets and collaborative studies with other jurisdictions. CED before making long-term funding decisions, especially where there is uncertainty of effectiveness, safety or cost-effectiveness, should be increasingly funded by health systems.

Italy is one of the few countries that have matured substantial experience of risk-sharing agreements so far. The first performance-based arrangement was agreed in July 2006, and as of October 2010, eighteen contracts have been in force.

The complex management of discount schemes is entirely based on Web registries run by AIFA, the Italian drug agency. The system validates each prescription and automatically requests the hospital pharmacy by e-mail to release the drug. If a patient meets nonresponder criteria, the hospital pharmacist should apply for pay-back to the manufacturer.

There are still some important question marks to address. First of all, nonresponders have to be documented by health authorities, otherwise any undocumented nonresponder will be paid as a success. Another question concerns pre-set timing. Although the scientific rationale of the nonresponder criteria for each drug has not been made public, time frames appear too short to allow a reliable assessment. Another question is whether regions, which are financially accountable in Italy for pharmaceutical expenditure, are really able to claw back refunds from manufacturers. Unfortunately here again there are no official figures, and regions do not seem yet able to quantify the amount of pay-back matured in the 4 previous years. The delayed and incomplete availability of pay-back procedures may be one explanation.

The Problem: There is a shortage and maldistribution of medically trained health professionals to deliver cost-effective maternal and child health (MCH) services. Hence, cost-effective MCH services are not available to over half the population of Uganda and progress toward the Millennium Development Goals for MCH is slow. Optimizing the roles of less specialized health workers (“task shifting”) is one strategy to address the shortage and maldistribution of more specialized health professionals.

Policy Options: (i) Lay health workers (community health workers) may reduce morbidity and mortality in children under five and neonates; and training for traditional birth attendants may improve perinatal outcomes and appropriate referrals. (ii) Nursing assistants in facilities might increase the time available from nurses, midwives, and doctors to provide care that requires more training. (iii) Nurses and midwives to deliver cost-effective MCH interventions in areas where there is a shortage of doctors. (iv) Drug dispensers to promote and deliver cost-effective MCH interventions and improve the quality of the services they provide. The costs and cost-effectiveness of all four options are uncertain. Given the limitations of the currently available evidence, rigorous evaluation and monitoring of resource use and activities is warranted for all four options.

Implementation Strategies: A clear policy on optimizing health worker roles. Community mobilization and reduction of out-of-pocket costs to improve mothers’ knowledge and care-seeking behaviors, continuing education, and incentives to ensure health workers are competent and motivated, and community referral and transport schemes for MCH care are needed.

Objectives: The aim of this study was to establish a list of priority topics for methods research to support decision making at the National Institute for Health and Clinical Excellence (NICE).

Methods: Potential priorities for methods research topics were identified through a focused literature review, interviews, an email survey, a workshop and a Web-based feedback exercise. Participants were members of the NICE secretariat and its advisory bodies, representatives from academia, industry, and other organizations working closely with NICE. The Web exercise was open to anyone to complete but publicized among the above groups.

Results: A list of potential topics was collated. Priorities for further research differed according to the type of respondent and the extent to which they work directly with NICE. Priorities emerging from the group closest to NICE included: methodology for indirect and mixed treatment comparisons; synthesis of qualitative evidence; research relating to the use of quality-adjusted life-years (QALYs) in decision making; methods and empirical research for establishing the cost-effectiveness threshold; and determining how data on the uncertainty of effectiveness and cost-effectiveness data should be taken into account in the decision-making process. Priorities emerging from the broadest group of respondents (through the Web exercise) included: methods for extrapolating beyond evidence observed in trials, methods for capturing benefits not included in the QALY and methods to assess when technologies should be recommended in the context of further evidence gathering.

Conclusions: Consideration needs to be given to the needs of those who use the outputs of research for decision making when determining priorities for future methods research.

In their article, Niederstadt and Droste (1) suggest a clear representation of all search strategies for each database to be important. We agree but would like to suggest an even more robust representation of search strategies: a search strategy should be displayed as a string, rather than as a table. The advantage of this method of display is three-fold: it is clearer, it is less ambiguous, and it is easier to reproduce, adapt and apply in a database. Niederstadt and Droste also suggest to indicate the number of results per query. We deem this to be irrelevant. An indication of the number of results for each aspect would be more useful. Likewise, we consider the inclusion of a field code behind each term to be important as well. This will prevent ambiguity regarding the interpretation of the search by the search engine.

Many thanks to van der Hoorn and colleagues for their interest in our article and the interesting discussion points. Their comments are very important and deserve to be answered.