Objectives: To describe a methodology used to keep practice guidelines up to date and to summarize data collected during the first year of implementing this plan with a cancer practice guidelines program.

Methods: The updating strategy includes regular searches of peer-reviewed literature and meeting proceedings, review and interpretation of new evidence, review and revision of clinical recommendations, and notification to practitioners and policy makers about new evidence and its impact on recommendations.

Results: Eighty pieces of new evidence were found relating to seventeen of the twenty guidelines included in this study. On average, four pieces of new evidence were found per guideline, but there was considerable variation across the guidelines. Of the eighty pieces, nineteen contributed to modifications of clinical recommendations in six practice guidelines, whereas the remaining evidence served to support the original recommendations. None of the modifications led to changes that advised against original recommendations. MEDLINE, the Cochrane Library, and meeting proceedings yielded many pieces of evidence, whereas CancerLit and HealthStar did not contribute significantly to the overall yield. Furthermore, key pieces of evidence that led to modifications to the recommendations were often identified by members of the disease site groups before appearing in electronic databases.

Conclusions: The updating process is resource intensive but yields important findings. In response to this evaluation, the updating protocol has been revised such that literature searches are conducted quarterly and the scope of sources searched routinely is restricted to MEDLINE, the Cochrane Library, and meeting proceedings.

Many would agree on the need to inform patients about the risks of medical conditions or treatments and to consider those risks in making medical decisions. The question is how to describe the risks and how to balance them with other factors in arriving at a decision. In this article, we present the thesis that part of the answer lies in defining an appropriate scale for risks that are often quite small. We propose that a convenient unit in which to measure most medical risks is the microprobability, a probability of 1 in 1 million. When the risk consequence is death, we can define a micromort as one microprobability of death. Medical risks can be placed in perspective by noting that we live in a society where people face about 270 micromorts per year from interactions with motor vehicles.

Continuing risks or hazards, such as are posed by following unhealthful practices or by the side-effects of drugs, can be described in the same micromort framework. If the consequence is not death, but some other serious consequence like blindness or amputation, the microrisk structure can be used to characterize the probability of disability.

Once the risks are described in the microrisk form, they can be evaluated in terms of the patient's willingness-to-pay to avoid them. The suggested procedure is illustrated in the case of a woman facing a cranial arteriogram of a suspected arterio-venous malformation. Generic curves allow such analyses to be performed approximately in terms of the patient's sex, age, and economic situation. More detailed analyses can be performed if desired.

Microrisk analysis is based on the proposition that precision in language permits the soundness of thought that produces clarity of action and peace of mind.

In Japan, screening programs for various cancers have been eagerly conducted as part of public health policy. However, these programs have not always produced the results that were originally expected. To improve the ill-planned and unscientific state of the current programs in Japan, two proposals are made.

The objective of this paper is to discuss why Bayesian statistics are not used more in healthcare decision making and what might be done to increase the use of Bayesian methods. First, a case is made for why Bayesian analysis should be used more widely. Serious weaknesses of commonly used frequentist methods are discussed and contrasted with advantages of Bayesian methods. Next, the question of why Bayesian methods are not used more widely is addressed, considering both philosophical differences and practical issues. Contrary to what some might think, the practical issues are more important in this regard. Finally, some steps to encourage increased use of Bayesian methods in healthcare decision making are presented and discussed. These ideas are straightforward but are by no means trivial to implement, largely because it is difficult to fight tradition and make major paradigm shifts quickly. The primary needs are improved Bayesian training at the basic level (which means textbooks and other materials as well as training of those who teach at the basic level), procedures to make Bayesian analysis easier to understand and use (better software and standard methods for displaying and communicating Bayesian outputs will help here), and the education of decision makers about the advantages of Bayesian methods in important healthcare decision-making problems.

Objectives: The objective of this study was to develop and implement a decision-making process for public funding of health services that links policy areas with health technology assessment and input from interested parties.

Methods: Health authorities, assessment organizations, and healthcare professionals were consulted as a follow-up to recommendations of an expert panel established by the Alberta government. The methods involved formulation of an eight-stage, collaborative process that incorporates identification through the health ministry of health technologies requiring review, assessment of the technologies using expert groups in Alberta, and consultation and formulation of advice within the ministry to inform ministerial funding decisions.

Results: All components of the decision process have been put in place and have collaborated to provide advice to inform policy on provincial health services. Of nineteen technologies selected for review, five have been completed and decisions made: laparoscopic adjustable gastric banding, fetal fibronectin assay for premature labor, newborn screening for cystic fibrosis, newborn screening for inborn errors of metabolism, and gastric electrical stimulation. A further six reviews are in progress, and reviews of the remaining technologies are planned for 2007.

Conclusions: Bridging the evidence-to-policy gap is more likely to succeed when the policy community is actively engaged and an explicit model is used to put health technology assessment into practice.

Objectives: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.

Methods: Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.

Results: The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective.

Conclusions and Policy Implications: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment.

Objectives: Coverage decisions are decisions by third party payers about whether and how much to pay for technologies or services, and under what conditions. Given their complexity, a systematic and transparent approach is needed. The DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) Project, a GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group initiative funded by the European Union, has developed GRADE Evidence to Decision (EtD) framework for different types of decisions, including coverage ones.

Methods: We used an iterative approach, including brainstorming to generate ideas, consultation with stakeholders, user testing, and pilot testing of the framework.

Results: The general structure of the EtD includes formulation of the question, an assessment using twelve criteria, and conclusions. Criteria that are relevant for coverage decisions are similar to those for clinical recommendations from a population perspective. Important differences between the two include the decision-making processes, accountability, and the nature of the judgments that need to be made for some criteria. Although cost-effectiveness is a key consideration when making coverage decisions, it may not be the determining factor. Strength of recommendation is not directly linked to the type of coverage decisions, but when there are important uncertainties, it may be possible to cover an intervention for a subgroup, in the context of research, with price negotiation, or with restrictions.

Conclusions: The EtD provides a systematic and transparent approach for making coverage decisions. It helps ensure consideration of key criteria that determine whether a technology or service should be covered and that judgments are informed by the best available evidence.

Objectives: To review and compare current Health Technology Assessment (HTA) activities for medical devices (MDs) across European HTA institutions.

Methods: A comprehensive approach was adopted to identify institutions involved in HTA in European countries. We systematically searched institutional Web sites and other online sources by using a structured tool to extract information on the role and link to decision making, structure, scope, process, methodological approach, and available HTA reports for each included institution.

Results: Information was obtained from eighty-four institutions, forty-seven of which were analyzed. Fifty-four methodological documents from twenty-three agencies in eighteen countries were identified. Only five agencies had separate documents for the assessment of MDs. A few agencies made separate provisions for the assessment of MDs in their general methods. The amount of publicly available HTA reports on MDs varied by device category and agency remit.

Conclusions: Despite growing consensus on their importance and international initiatives, such as the EUnetHTA Core Model®, specific tools for the assessment of MDs are rarely developed and implemented at the national level. Separate additional signposts incorporated in existing general methods guides may be sufficient for the evaluation of MDs.

Objectives: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.

Methods: A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.

Results: Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered €2,116 as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (€68) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to €5,300.

Conclusions: Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.

Background: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions.

Methods: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs.

Results: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate.

Conclusions: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction

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.

Objectives: The aim of this study was to assess the cost-effectiveness of a class-based exercise program supplementing a home-based program when compared with a home-based program alone. In addition, we estimated the probability that the supplementary class program is cost-effective over a range of values of a decision maker's willingness to pay for an additional quality-adjusted life-year (QALY).

Methods: The resource use and effectiveness data were collected as part of the clinical trial detailed elsewhere. Unit costs were estimated from published sources. The net benefit approach to cost-effectiveness analysis is used to estimate the probability of the intervention being cost-effective.

Results: The addition of a supplementary class-based group results in an increase in QALYs and lower costs. For all plausible values of a decision maker's willingness to pay for a QALY, the supplementary class group is likely to be cost-effective.

Conclusions: The addition of a class-based exercise program is likely to be cost-effective and, on current evidence, should be implemented.

Objectives: We assess the cost-effectiveness of smoking relapse prevention interventions designed to keep quitters from resuming the use of cigarettes. Because relapse prevention is complementary to smoking cessation efforts, the appropriate test of its cost-effectiveness is whether it reduces the incremental cost-effectiveness ratio (ICER) of smoking cessation. The major goal of the study is to carry out such a test.

Methods: Data from a randomized trial that ascertained the effectiveness of alternative modes of smoking relapse prevention are combined with ICER estimates of smoking cessation to assess whether relapse prevention is cost-effective.

Results: The trial produced convincing evidence that relapse prevention yields statistically significant reductions in the proportion of quitters who are smoking at 24 months postquit. The intervention effects are substantial enough to raise the denominator terms of the smoking cessation ICER and, thereby, offset the amount relapse prevention adds to cost numerator terms. In this sense, smoking relapse prevention tends to pay for itself.

Conclusions: Smoking relapse prevention is a highly cost-effective addition to current efforts to curb cigarette consumption. Complementary health interventions of this sort should be assessed by different methods than those commonly found in the cost-effectiveness literature.

Objectives: Assessment of the appropriateness of screening programs involves consideration of the harms as well as the benefits. These harms include the risk of false-negative results, the consequences of which have remained underinvestigated. This paper reports the results of a systematic literature review that aimed to assess the medical psychological, economic, and legal consequences of false-negative results in national screening programs.

Methods: The review included a comprehensive literature search and contact with experts to identify relevant literature. Most studies that were identified presented only anecdotal evidence. However, thirteen studies presented quantitative information on medical consequences of false negatives, eight studies presented information on psychological consequences, and two studies presented information on economic consequences.

Results: The strength of evidence from most of the primary studies was low. There is some evidence, however, that false-negative results may have a large legal impact. There is also a consensus in the literature that false negatives may have a negative impact on public confidence on screening; evidence is however limited.

Conclusions: False negatives are evident even in high-quality screening programs. They may have the potential to delay the detection of breast and cervical cancer, but there is little evidence to help in assessing their psychological consequences. They also may lead to legal action being taken by those affected and may reduce public confidence in screening. Their impact may be reduced by provision of full information to participants about the benefits and limitations of screening programs and by increasing public education on these issues.

Objectives: To assess the cost-effectiveness of brief physiotherapy intervention versus usual physiotherapy management in patients with neck pain of musculoskeletal origin in the community setting.

Methods: A cost-effectiveness analysis was conducted alongside a multicenter pragmatic randomized controlled clinical trial. Individuals 18 years of age and older with neck pain of more than 2 weeks were recruited from physiotherapy departments with referrals from general practitioners (GPs) in the East Yorkshire and North Lincolnshire regions in the United Kingdom. A total of 139 patients were allocated to the brief intervention, and 129 to the usual physiotherapy. Resource use data were prospectively collected on the number of physiotherapy sessions, hospital stay, specialist, and GP visits. Quality-adjusted life years (QALYs) were estimated using EQ-5D data collected at baseline, 3 and 12 months from the start of the treatment. The economic evaluation was conducted from the U.K. National Health System perspective.

Results: On average, brief intervention produced lower costs (£−68; 95 percent confidence interval [CI], £−103 to £−35) and marginally lower QALYs (−0.001; 95 percent CI, −0.030 to 0.028) compared with usual physiotherapy, resulting in an incremental cost per QALY of £68,000 for usual physiotherapy. These results are sensitive to patients' treatment preferences.

Conclusions: Usual physiotherapy may not be good value for money for the average individual in this trial but could be a cost-effective strategy for those who are indifferent toward which treatment they receive.

Objectives: The long-term cost-utility of a disease management program (DMP) for adults with asthma was assessed compared to usual care.

Methods: A DMP for patients with asthma has been developed and implemented in the region of Maastricht (The Netherlands). By integrating care, the program aims to continuously improve quality of care within existing budgets. A clinical trial was performed over a period of 15 months to collect data on costs and effects of the program and usual care. These data were used to inform a probabilistic decision-analytic model to estimate the 5-year impact of the program beyond follow-up. A societal perspective was adopted, with outcomes assessed in terms of costs per quality-adjusted life-year (QALY).

Results: The DMP is associated with a gain in QALYs compared to usual care (2.7±.2 versus 3.4±.8), at lower costs (€3,302±314 versus €2,973±304), thus leading to dominance. The probability that disease management is the more cost-effective strategy is 76 percent at a societal willingness to pay (WTP) for an additional QALY of €0, reaching 95 percent probability at a WTP of €1,000 per additional QALY.

Conclusions: Organizing health care according to the principles of disease management for adults with asthma has a high probability of being cost-effective and is associated with a gain in QALYs at lower costs.

Objectives: The aim of this study was to evaluate the long-term cost-utility of liraglutide versus glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted in Asian population.

Methods: The validated UKPDS Outcomes Model was used to project life expectancy, quality adjusted life-years (QALYs), incidence of diabetes-related complication and cost of complications in patients receiving those regimens. Baseline cohort characteristics and treatment effects were derived from an Asian study. China-specific complication costs and utility score were taken from local studies. Patients’ outcomes were modeled for 30 years and incremental cost-effectiveness ratios were calculated for liraglutide compared with glimepiride from the healthcare system perspective. Both future costs and clinical benefits were discounted at 3 percent. Sensitivity analyses were performed.

Results: Over a period of 30 years, compared with glimepiride, liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year) and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes-related complications leading to an incremental cost-effectiveness ratio per QALY gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY).

Conclusions: Long-term projections indicated that liraglutide was associated with increased life expectancy, QALYs, and reduced complication incidences comparing with glimepiride. When the UK cost of liraglutide was discounted by 38 percent, liraglutide would be a cost-effective option in China from the healthcare system perspective using the 3X GDP/capita per QALY as the WTP threshold.

Objectives: The E Sibling Project aims to address the needs of siblings of individuals affected by psychosis through provision of a comprehensive online intervention. The online intervention comprises four core elements, including: information on psychosis; various coping and promoting well-being strategies; siblings' blogs and discussion forum with peers; and an “Ask the Experts” function. After the intervention-prototype was developed, we tested its feasibility, usability and acceptability by siblings.

Methods: We evaluated the usability of the intervention-prototype using a non-randomised usability study with siblings of individuals diagnosed with psychosis. The usability study adapted Poulson et al's framework to collect subjective feedback from participants on ease of use, perceived usefulness and acceptability, together with objective usage data on the intervention.

Results: Twenty siblings were recruited to the usability test; 19 tried out the resource-prototype over a 4-week period and 17 completed the online evaluation after using the intervention. In total, 906 page-views were made by the participants and each spent about two hours using the resource. Participants evaluated the intervention as helpful, relevant and useful in terms of content, design and usability. Developments are needed to improve the navigation and intuitiveness of the resource.

Conclusions: Using an internet-based information-giving and peer support intervention to promote wellbeing and coping is feasible and acceptable to siblings of people with psychosis.