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.

Background: The cost-effectiveness of triptans in the treatment of migraine has not been assessed since generic sumatriptan entered the Finnish market in 2008.

Methods: Using systematic review and mixed treatment comparison, the effectiveness of triptans was estimated with regard to 2-hour response, 2-hour pain-free, recurrence, and any adverse event, using published clinical data. Direct and indirect costs (2010 EUR, societal perspective) and quality-adjusted life-years (QALYs) were evaluated over one acute migraine attack using a decision-tree model.

Results: The meta-analysis combined data from fifty-six publications. The highest probability of achieving the primary outcome, “sustained pain-free, no adverse event” (SNAE), was estimated for eletriptan 40 mg (20.9 percent). Sumatriptan 100 mg was the treatment with lowest estimated costs (€20.86), and the incremental cost-effectiveness ratio of eletriptan 40 mg compared with sumatriptan 100 mg was €43.65 per SNAE gained (€19,659 per QALY gained).

Conclusion: Depending on the decision-maker's willingness-to-pay threshold, either sumatriptan 100 mg or eletriptan 40 mg is likely to be cost-effective.

Objectives: The aim of this study was to promote approaches to health technology assessment (HTA) that are both evidence-based and values-based. We conducted a systematic review of published studies describing formal methods to consider equity in the context of cost-effectiveness analysis (CEA).

Methods: Candidate studies were identified through an unrestricted search of the Pub Med and EMBASE databases. The search closed on January 20, 2011. We identified additional studies by consulting experts and checking article bibliographies. Two authors independently reviewed each candidate study to determine inclusion and extracted data from studies retained for review. In addition to documenting methods, data extraction identified implicit and explicit notions of fairness. Data were synthesized in narrative form. Study quality was not assessed.

Results: Of the 695 candidate articles, 51 were retained for review. We identified three broad methods to facilitate quantitative consideration of equity concerns in economic evaluation: integration of distributional concerns through equity weights and social welfare functions, exploration of the opportunity costs of alternative policy options through mathematical programming, and multi-criteria decision analysis.

Conclusions: Several viable techniques to integrate equity concerns within CEA now exist, ranging from descriptive approaches to the quantitative methods studied in this review. Two obstacles at the normative level have impeded their use in decision making to date: the multiplicity of concepts and values discussed under the rubric of equity, and the lack of a widely accepted normative source on which to ground controversial value choices. Clarification of equity concepts and attention to procedural fairness may strengthen use of these techniques in HTA decision making.

Objectives: The aim of this study was to synthesize best practices for addressing clinical heterogeneity in systematic reviews and health technology assessments (HTAs).

Methods: We abstracted information from guidance documents and methods manuals made available by international organizations that develop systematic reviews and HTAs. We searched PubMed® to identify studies on clinical heterogeneity and subgroup analysis. Two authors independently abstracted and assessed relevant information.

Results: Methods manuals offer various definitions of clinical heterogeneity. In essence, clinical heterogeneity is considered variability in study population characteristics, interventions, and outcomes across studies. It can lead to effect-measure modification or statistical heterogeneity, which is defined as variability in estimated treatment effects beyond what would be expected by random error alone. Clinical and statistical heterogeneity are closely intertwined but they do not have a one-to-one relationship. The presence of statistical heterogeneity does not necessarily indicate that clinical heterogeneity is the causal factor. Methodological heterogeneity, biases, and random error can also cause statistical heterogeneity, alone or in combination with clinical heterogeneity.

Conclusions: Identifying potential modifiers of treatment effects (i.e., effect-measure modifiers) is important for researchers conducting systematic reviews and HTAs. Recognizing clinical heterogeneity and clarifying its implications helps decision makers to identify patients and patient populations who benefit the most, who benefit the least, and who are at greatest risk of experiencing adverse outcomes from a particular intervention.

Objectives: The aim of this study is to determine the relative value and contribution of searching different sources to identify adverse effects data.

Methods: The process of updating a systematic review and meta-analysis of thiazolidinedione-related fractures in patients with type 2 diabetes mellitus was used as a case study. For each source searched, a record was made for each relevant reference included in the review noting whether it was retrieved with the search strategy used and whether it was available but not retrieved. The sensitivity, precision, and number needed to read from searching each source and from different combinations of sources were also calculated.

Results: There were 58 relevant references which presented sufficient numerical data to be included in a meta-analysis of fractures and bone mineral density. The highest number of relevant references were retrieved from Science Citation Index (SCI) (35), followed by BIOSIS Previews (27) and EMBASE (24). The precision of the searches varied from 0.88% (Scirus) to 41.67% (CENTRAL). With the search strategies used, the minimum combination of sources required to retrieve all the relevant references was; the GlaxoSmithKline (GSK) website, Science Citation Index (SCI), EMBASE, BIOSIS Previews, British Library Direct, Medscape DrugInfo, handsearching and reference checking, AHFS First, and Thomson Reuters Integrity or Conference Papers Index (CPI).

Conclusions: In order to identify all the relevant references for this case study a number of different sources needed to be searched. The minimum combination of sources required to identify all the relevant references did not include MEDLINE

Objectives: Telemedicine applications could potentially solve many of the challenges faced by the healthcare sectors in Europe. However, a framework for assessment of these technologies is need by decision makers to assist them in choosing the most efficient and cost-effective technologies. Therefore in 2009 the European Commission initiated the development of a framework for assessing telemedicine applications, based on the users’ need for information for decision making. This article presents the Model for ASsessment of Telemedicine applications (MAST) developed in this study.

Methods: MAST was developed through workshops with users and stakeholders of telemedicine.

Results: Based on the workshops and using the EUnetHTA Core HTA Model as a starting point a three-element model was developed, including: (i) preceding considerations, (ii) multidisciplinary assessment, and (iii) transferability assessment. In the multidisciplinary assessment, the outcomes of telemedicine applications comprise seven domains, based on the domains in the EUnetHTA model.

Conclusions: MAST provides a structure for future assessment of telemedicine applications. MAST will be tested during 2010–13 in twenty studies of telemedicine applications in nine European countries in the EC project Renewing Health.

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.

Background: The benefits of pharmaceutical innovations are widely diffused; they accrue to the healthcare providers, patients, employers, and manufacturers. We estimate the societal monetary benefits of simvastatin in Canada and its distribution among different beneficiaries overtime.

Methods: Monetary benefits to developing and generic manufacturers were estimated by calculating public and private revenues minus the development costs of simvastatin and the contribution toward further research and development. We used a dynamic Markov model to estimate monetary benefits to healthcare and employment sectors in terms of cost avoidance associated with prevented cardiovascular events, including stroke and myocardial infarction, and lost productivity due to disability and premature death in working population.

Results: Cumulative monetary benefits of simvastatin from 1990 to 2009 were $4.8 billion (2010 CA$), of which developing and generic manufacturers, and healthcare and employment sectors accounted for 32 percent, 27 percent, 32 percent, and 9 percent, respectively. The yearly trend showed that after the patent expired in 2002 the generic manufacturers became dominant in the market. Benefits for the healthcare sector started to decrease from 2003 corresponding to the decreasing population taking simvastatin during the same time period. Sensitivity analysis showed the higher the compliance or the efficacy, the larger the benefits to healthcare and employment sectors, while monetary benefits for manufacturers were unchanged.

Conclusions: Societal monetary benefits of simvastatin are significant and the distributions of the benefits have changed overtime. Patent, compliance, and efficacy play a vital role in the estimation of the benefits. Analysis of all beneficiaries separately overtime is important when assessing the value of pharmaceutical innovation.

Objectives: The aim of this study is to review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes.

Methods: Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the Web sites of International Network of Agencies for Health Technology Assessment (INAHTA) members.

Results: A total of 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In seventy-one HTAs (48 percent) only diagnostic accuracy was reported, while in seventeen (11 percent) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in sixty-one HTAs (41 percent). Of these, forty-seven identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in approximately 60 percent of HTAs.

Conclusions: Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies.

Background: Peginterferon alfa and ribavirin combination therapy is an effective treatment for many patients with chronic hepatitis C virus (HCV). Reducing the length of treatment may be advantageous. We performed a systematic review and economic evaluation to assess shorter treatment duration of this regimen.

Methods: We searched fourteen bibliographic databases (including The Cochrane Library, Medline, and Embase) from 2000 to October 2009 and consulted experts and drug manufacturers. Eligible articles were randomized controlled trials (RCTs) selected according to predefined criteria. We undertook an economic evaluation to assess the cost-effectiveness of shortened treatment versus standard treatment in the UK.

Results: Six trials were included. In the sub-group of patients who had low viral load (LVL) and a rapid virological response (RVR), there were no statistically significant differences in sustained virological response (SVR) rates between patients who received standard treatment (range, 83 percent to 100 percent) and those who received shortened courses (range 84 percent to 96 percent) (24 weeks for genotype 1, 16 weeks for genotype 2/3). Shortened treatment resulted in cost savings, but in some scenarios also resulted in poorer outcome, compared with standard treatment. This requires a judgment to be made on the value of the quality-adjusted life-year loss resulting from adopting a shorter treatment regimen, if shorter treatment is associated with a lower SVR than standard treatment duration.

Conclusions: For chronic HCV patients who have LVL and achieve an RVR, shortened peginterferon and ribavirin combination therapy could be considered as a viable treatment option.

Objectives: The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions.

Study Design and Setting: We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes.

Results: None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials.

Conclusions: Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.

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: The aim of this study was to identify and characterize studies that have used quality-adjusted life-years (QALYs) based on measurements of patients’ health-related quality of life (HRQoL) as an indicator of effectiveness of screening programs.

Methods: Systematic search of the literature until March 2010, using several electronic databases. Initial screening of articles based on abstracts, and evaluation of full-text articles were done by at least two of the authors.

Results: The search identified 1,610 articles. Based on review of abstracts, 431 full-text articles were obtained for closer inspection and, of these, 81 reported QALYs based on patient-derived data using a valid HRQoL assessment. The most frequently used method to assess HRQoL was Time Trade-Off (55 percent) followed by EQ-5D (26 percent). The most frequently studied medical conditions were malignant diseases (23 percent) followed by cardiovascular diseases (19 percent). All studies employed some kind of modeling with the Markov model being the most prevalent type (65 percent). Majority of the articles (59 percent) concluded that the screening program studied was cost-effective.

Conclusions: The use of QALYs in the evaluation of screening programs has expanded during the last few years. However, only a minority of studies have used HRQoL data derived from patients, using direct or indirect valuation. Further investigation and harmonization of the methodology in evaluation of screening programs is needed to ensure better comparability across different screening programs.

Objectives: Reducing sexually transmitted infections (STI) and teenage pregnancy through effective health education is a high priority for health policy. Behavioral interventions which teach skills to practice safer sex may reduce the incidence of STIs. We evaluated the cost-effectiveness of school-based behavioral interventions in young people.

Methods: We developed an economic model to estimate the total number of STI cases averted, consequent gain in health related quality of life (HRQoL) and savings in medical costs, based on changes in sexual behavior. The parameters for the model were derived from a systematic literature search on the intervention effectiveness, epidemiology of STIs, sexual behavior and lifestyles, HRQoL and health service costs.

Results: The costs of providing teacher-led and peer-led behavioral interventions were €5.16 and €18 per pupil, respectively. For a cohort of 1000 boys and 1000 girls aged 15 years, the model estimated that the behavioral interventions would avert two STI cases and save 0.35 Quality Adjusted Life Years (QALYs). Compared to standard education, the incremental cost-effectiveness of the teacher-led and peer-led interventions was €24,268 and €96,938 per QALY gained, respectively.

Conclusions: School-based behavioral interventions which provide information and teach young people sexual health skills can bring about improvements in knowledge and increased self-efficacy, though these may be limited in terms of impact on sexual behavior. There was uncertainty around the results due to the limited effect of the intervention on behavioral outcomes and paucity of data for other input parameters.

Objectives: This study aims to compare two different search methods for determining the scope of a requested systematic review or health technology assessment. The first method (called the Direct Search Method) included performing direct searches in the Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessments (HTA). Using the comparison method (called the NHS Search Engine) we performed searches by means of the search engine of the British National Health Service, NHS Evidence.

Methods: We used an adapted cross-over design with a random allocation of fifty-five requests for systematic reviews. The main analyses were based on repeated measurements adjusted for the order in which the searches were conducted.

Results: The Direct Search Method generated on average fewer hits (48 percent [95 percent confidence interval {CI} 6 percent to 72 percent], had a higher precision (0.22 [95 percent CI, 0.13 to 0.30]) and more unique hits than when searching by means of the NHS Search Engine (50 percent [95 percent CI, 7 percent to 110 percent]). On the other hand, the Direct Search Method took longer (14.58 minutes [95 percent CI, 7.20 to 21.97]) and was perceived as somewhat less user-friendly than the NHS Search Engine (−0.60 [95 percent CI, −1.11 to −0.09]).

Conclusions: Although the Direct Search Method had some drawbacks such as being more time-consuming and less user-friendly, it generated more unique hits than the NHS Search Engine, retrieved on average fewer references and fewer irrelevant results.

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.

Objectives: This study reports on the Brazilian experience of developing a specialized bulletin, the Brazilian Health Technology Assessment Bulletin (BRATS), on health technology assessments (HTA).

Methods: The editorial process, format, and dissemination strategy of the publication are presented. A critical appraisal of the available issues was made using the checklist for HTA reports of the International Network of Agencies for Health Technology Assessment. The initial impact was estimated based on a retrospective observational measurement of the types of publications that cite the bulletin as a source of information. The publications citing BRATS were identified using Google Scholar.

Results: Since June 2008, fourteen issues of the bulletin have been produced. BRATS has not presented any significant limitation that would compromise generalizations of its results within the Brazilian context. The initial impact of the bulletin, however, has been small, which may be due to its exclusively electronic dissemination format and technical language. We found nine publications citing BRATS in Google Scholar.

Conclusions: It is hoped that the bulletin will promote the continuity of HTA actions among health-sector managers and professionals in Brazil.

Objectives: The European Code Against Cancer recommends individuals aged ≥50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening.

Methods: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered.

Results: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings.

Conclusion: Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.

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: In 2000, the first “Dutch Manual for Costing: Methods and Reference Prices for Economic Evaluations in Healthcare” was published, followed by an updated version in 2004. The purpose of the Manual is to facilitate the implementation and assessment of costing studies in economic evaluations. New developments necessitated the publication of a thoroughly updated version of the Manual in 2010. The present study aims to describe the main changes of the 2010 Manual compared with earlier editions of the Manual.

Methods: New and updated topics of the Manual were identified. The recommendations of the Manual were compared with the health economic guidelines of other countries, eliciting strengths and limitations of alternative methods.

Results: New topics in the Manual concern medical costs in life-years gained, the database of the Diagnosis Treatment Combination (DBC) casemix System, reference prices for the mental healthcare sector and the costs borne by informal care-givers. Updated topics relate to the friction cost method, discounting future effects and options for transferring cost results from international studies to the Dutch situation.

Conclusions: The Action Plan is quite similar to many health economic guidelines in healthcare. However, the recommendations on particular aspects may differ between national guidelines in some respects. Although the Manual may serve as an example to countries intending to develop a manual of this kind, it should always be kept in mind that preferred methods predominantly depend on a country's specific context.