Objectives: The use of economic evaluation studies (EE) in the decision-making process within the health-care system of nine Latin American (LA) and three European countries was investigated. The aim was to identify the opportunities, obstacles, and changes needed to facilitate the introduction of EE as a formal tool in health-care decision-making processes in LA.

Methods: A comparative study was conducted based on existing literature and information provided through a questionnaire applied to decision makers in Argentina, Brazil, Colombia, Cuba, Mexico, Nicaragua, Peru, Portugal Spain, United Kingdom, Uruguay, and Venezuela. Systematic electronic searches of HEED, NHS EED, and LILACS were conducted to identify published economic evaluation studies in LA from 1982 onward.

Results: There is relatively little evidence of the conduct and use of EE within the health care systems in LA. Electronic searches retrieved 554 records; however, only 93 were EE. In the nine LA participating countries, broad allocation of health-care resources is primarily based on political criteria, historical records, geographical areas, and specific groups of patients and diseases. Public-health provision and inclusion of services in health-insurance package are responsibilities of the Ministry of Health. Decisions regarding the purchase of medicines are primarily made through public tenders, and mainly based on differences in clinical efficacy and the price of health technologies of interest.

Conclusions: To expedite the process of incorporating EE as a formal tool to inform decision-making processes within the health-care systems in LA countries, two main conditions need to be fulfilled. First, adequate resources and skills need to be available to conduct EE of good quality. Second, decision-making procedures need to be modified to accommodate “evidence-based” approaches such as EE.

The extensive benefits of the total hip (THA) and knee (TKA) replacements are well documented, but surprisingly little is known about their economics. We assessed costs, cost-effectiveness (C/E), and patient-related C/E variances in THA and TKA from data on 276 THA and 176 TKA patients. Patients with primary arthrosis, primary operation, and total joint replacement were recruited from seven hospitals between March 1991 and June 1992. Their use of health and other welfare services together with health-related quality of life (HRQoL) were measured before the surgery and at 6, 12, and 24 months postoperatively. HRQoL was assessed by the 15D, a 15-dimensional HRQoL instrument, and the Nottingham Health Profile. Costs were assessed from questionnaire responses, the Finnish Hospital Discharge Register, and Finnish Arthroplasty Register. Total hospital costs per patient were 45,000 FIM (US $10,500) for THA and 49,600 FIM (US $11,500) for TKA. Prosthesis costs comprised 21 % of these costs in THA and 24% in TKA. On average, hip patients gained more in terms of HRQoL, and the operations were more cost-effective. The C/E ratio for younger (« 60 years) knee patients did not differ from those in all age groups of hip patients, whereas TKAs in those over 60 years had a worse C/E ratio compared with all other patient subgroups. It was concluded that allocation efficiency can be improved by considering not only the intervention but also patient characteristics such as age. Indeed, the C/E ratio varied more across age groups of knee patients than between average THA and TKA patients.

This article describes a collection of meta-analysis techniques based on Bayesian statistics for interpreting, adjusting, and combining evidence to estimate parameters and outcomes important to the assessment of health technologies. The result of an analysis by the Confidence Profile Method is a joint posterior probability distribution for the parameters of interest, from which marginal distributions for any particular parameter can be calculated. The method can be used to analyze problems involving a variety of types of outcomes, a variety of measures of effect, and a variety of experimental designs. This article presents the elements necessary for analysis, including prior distributions, likelihood functions, and specific models for experimental designs that include adjustment for biases.

This report is about setting priorities for health technology assessment (HTA). HTA examines systematically the consequences of the application of health technologies (broadly defined to include any health care intervention) to support decision making in policy and practice. Only a fraction of existing health technologies have been formally evaluated, and many more appear each year. Resources for HTA are, however, limited so that priorities have to be set, whether explicitly or implicitly. The aim of setting priorities for HTA should be to identify those assessments that offer the greatest benefits in relation to their cost, and thus to maximize the benefit derived from investments in HTA.

Objectives: The aim of this study is to review briefly different methods for determining the optimal retrieval of studies for inclusion in a health technology assessment (HTA) report.

Methods: This study reviews the methodology literature related to specific methods for evaluating yield from literature searching strategies and for deciding whether to continue or desist in the searching process.

Results: Eight different methods were identified. These include using the Capture–recapture technique; obtaining Feedback from the commissioner of the HTA report; seeking the Disconfirming case; undertaking comparison against a known Gold standard; evaluating retrieval of Known items; recognizing the Law of diminishing returns, specifying a priori Stopping rules, and identifying a point of Theoretical saturation.

Conclusions: While this study identified a variety of possible methods, there has been very little formal evaluation of the specific strengths and weaknesses of the different techniques. The author proposes an evaluation agenda drawing on an examination of existing data together with exploration of the specific impact of missing relevant studies.

Objectives: The Finnish Diabetes Prevention Study (DPS) was a randomized intervention program that evaluated the effect of intensive lifestyle modification on the development of diabetes mellitus type 2 in patients with impaired glucose tolerance. As such, a program is demanding in terms of resources; it is necessary to assess whether it would be money well spent. This determination was the purpose of this study.

Methods: We developed a simulation model to assess the economic consequences of an intervention like the one studied in DPS in a Swedish setting. The model used data from the trial itself to assess the effect of intervention on the risk of diabetes and on risk factors for cardiovascular disease. Results from the United Kingdom Prospective Diabetes Study were used to estimate the risk of cardiovascular disease and stroke. Cost data were derived from Swedish studies. The intervention was assumed to be applied to eligible patients from a population-based screening program of 60-year-olds in the County of Stockholm from which the baseline characteristics of the patients was used.

Results: The model predicted that implementing the program would be cost-saving from the healthcare payers' perspective. Furthermore, it was associated with an increase in estimated survival of .18 years. Taking into consideration the increased consumption by patients due to their longer survival, the predicted cost-effectiveness ratio was 2,363€ per quality-adjusted life-year gained.

Conclusions: Lifestyle intervention directed toward high-risk subjects would be cost-saving for the healthcare payer and highly cost-effective for society as a whole.

Objectives: The need for consistency and standardization of methods for economic appraisals has been recognized for some time and has led to the development of several sets of guidelines for economic evaluations and for costs. Despite this, considerable diversity is still apparent in applied studies. Some of these diversities might be defensible, and some might not. The objectives of this study are to explore sources of variations in the methods used in applied studies and to discuss the nature of these variations and the possibility of reducing some of them.

Methods: We first use a systematic approach to identify the major sources of variation in costing methods used in applied economic evaluations. We then compare the methods used with the recommendations made in available guidelines.

Results: Four possible sources of variation are identified. The first is where guidelines do not agree in their recommendations; therefore, it is not surprising that applied studies use different methods. The second is where guidelines agree in principle but provide little detail on how to comply with their recommendations; and the third is where a particular methodological issue is not discussed in guidelines. The fourth reason is simply lack of compliance with accepted guidelines.

Conclusions: Variability in costing methods used in applied studies raises questions about the validity of their results and makes it difficult to compare the results of different studies. We discuss the implications for the transferability and generalizability of results and suggest ways to minimize the variability in the methods so that the results of costing studies and economic evaluations can be of more value to policy-makers.

Objectives: Medical device companies are under growing pressure to provide health-economic evaluations of their products. Cost-effectiveness analyses are commonly undertaken as a one-off exercise at the late stage of development of new technologies; however, the benefits of an iterative use of economic evaluation during the development process of new products have been acknowledged in the literature. Furthermore, the use of Bayesian methods within health technology assessment has been shown to be of particular value in the dynamic framework of technology appraisal when new information becomes available in the life cycle of technologies.

Methods: In this study, we set out a methodology to adapt these methods for their application to directly support investment decisions in a commercial setting from early stages of the development of new medical devices.

Results and Conclusions: Starting with relatively simple analysis from the very early development phase and proceeding to greater depth of analysis at later stages, a Bayesian approach facilitates the incorporation of all available evidence and would help companies to make better informed choices at each decision point.

Objectives: Many existing healthcare interventions diffused before modern evidence-based standards of clinical- and cost-effectiveness. Disinvestment from ineffective or inappropriately applied practices is growing as a priority for international health policy, both for improved quality of care and sustainability of resource allocation. Australian policy stakeholders were canvassed to assess their perspectives on the challenges and the nature of disinvestment.

Methods: Senior health policy stakeholders from Australia were criterion and snow-ball sampled (to identify opinion leaders). Participants were primed with a potential disinvestment case study and took part in individual semistructured interviews that focused on mechanisms and challenges within health policy to support disinvestment. Interviews were taped and transcribed for thematic analysis. Participant comments were de-identified.

Results: Ten stakeholders were interviewed before saturation was reached. Three primary themes were identified. (i) The current focus on assessment of new and emerging health technologies/practices and lack of attention toward existing practices is due to resource limitations and methodological complexity. Participants considered a parallel model to that of Australia's current assessment process for new medical technologies is best-positioned to facilitate disinvestment. (ii) To advance the disinvestment agenda requires an explicit focus on the potential for cost-savings coupled with improved quality of care. (iii) Support (financial and collaborative) is needed for research advancement in the methodological underpinnings associated with health technology assessment and for disinvestment specifically.

Conclusions: In this exploratory study, stakeholders support the notion that systematic policy approaches to disinvestment will improve equity, efficiency, quality, and safety of health care, as well as sustainability of resource allocation.

Objectives: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers.

Methods: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3).

Results: A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type.

Conclusions: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.

The Cochrane Database of Systematic Reviews (CDSR) evolved in response to Archie Cochrane's challenge to the medical profession to assemble “a critical summary, adapted periodically, of all . . . relevant randomized controlled trials”. CDSR has been an electronic publication from its inception and this has meant that Cochrane reviews (i) need not be constrained by lack of space; (ii) can be updated as new information becomes available and when mistakes or other ways of improving them are identified; and (iii) can be cross-linked to other, related sources of relevant information. Although CDSR has become widely cited, it must continue to evolve in the light of technological and methodological developments, and in response to the needs of people making decisions about health care.

Objectives: To identify major differences and similarities in the development of clinical guidelines in different European countries.

Methods: A collaboration of researchers is funded by the European Commission to compare the approaches to guideline development in collaborators' countries. The program encompasses a series of tasks, the first being to identify and document current guideline procedures in the collaborating countries. A survey gathered information on guideline production, dissemination, and implementation in the 10 European countries involved in the project consortium: Denmark, England and Wales, Finland, France, Germany, Italy, the Netherlands, Scotland, Spain (both the Basque Country and Catalonia), and Switzerland.

Results: Seven countries have a national policy on guideline production, dissemination, and implementation, and three countries are discussing their policies. A majority of guidelines are currently produced at the national level in six of the countries and at the regional or local level in the other four. Central or national funding supports guideline production in six countries. Additional sources of funding include medical societies, pharmaceutical companies, and health insurance companies. Several of the countries have published or are preparing evaluations of their dissemination strategies.

Conclusions: The survey highlighted wide variation in the methods and policies of guideline development in Europe. The Appraisal of Guidelines, Research, and Evaluation in Europe (AGREE) Collaboration research program will identify the characteristics of the “better” guideline programs and will provide the basis for more research-generated policy initiatives in the future, helping to ensure that guidelines play a major role in improving patient care in the millennium.

Objectives: A vaccine to prevent diseases due to human papillomavirus (HPV) types 6, 11, 16, and 18 is now available in France. The objective of this study was to assess the health and economic impact in France of implementing a quadrivalent HPV vaccine alongside existing screening practices versus screening alone.

Methods: A Markov model of the natural history of HPV infection incorporating screening and vaccination, was adapted to the French context. A vaccine that would prevent 100 percent of HPV 6, 11, 16, and 18-associated diseases, with lifetime duration and 80 percent coverage, given to girls at age 14 in conjunction with current screening was compared with screening alone. Results were analyzed from both a direct healthcare cost perspective (DCP) and a third-party payer perspective (TPP). Indirect costs such as productivity loss were not taken into account in this analysis.

Results: The incremental cost per life-year gained from vaccination was €12,429 (TPP) and €20,455 (DCP). The incremental cost per quality-adjusted life-year (QALY) for the introduction of HPV vaccination alongside the French cervical cancer screening program was €8,408 (TPP) and €13,809 (DCP). Sensitivity analyses demonstrated that cost-effectiveness was stable, but was most sensitive to the discount rate used for costs and benefits.

Conclusions: Considering the commonly accepted threshold of €50,000 per QALY, these analyses support the fact that adding a quadrivalent HPV vaccine to the current screening program in France is a cost-effective strategy for reducing the burden of cervical cancer, precancerous lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Objective: To adjust patients' time trade-off (TTO) scores using information on their utility functions for survival time to derive a measure of health state utility equivalent to the standard gamble (SG).

Methods: A sample of 199 cardiovascular patients were asked three TTO and SG questions (to assess their own health state), and three certainty equivalent questions (to assess their utility function for survival time) in an interview.

Results: Patients' utility functions for time were increasingly concave, but being unable to model this successfully, a constant function with an averaged level of concavity was used. The raw TTO scores were significantly higher than SG scores, while the adjusted TTO scores were equivalent to the SG.

Conclusions: Raw time trade-off scores will give biased estimates of health state utility when patients' utility functions for time are not linear, but these can be adjusted to yield true utilities. The constant proportional risk-posture assumption of the conventional QALY model, on which previous attempts to adjust time trade-offs have been based, was not supported by the data.

Objectives: Synthesizing qualitative research is an important means of ensuring the needs, preferences, and experiences of patients are taken into account by service providers and policy makers, but the range of methods available can appear confusing. This study presents the methods for synthesizing qualitative research most used in health research to-date and, specifically those with a potential role in health technology assessment.

Methods: To identify reviews conducted using the eight main methods for synthesizing qualitative studies, nine electronic databases were searched using key terms including meta-ethnography and synthesis. A summary table groups the identified reviews by their use of the eight methods, highlighting the methods used most generally and specifically in relation to health technology assessment topics.

Results: Although there is debate about how best to identify and quality appraise qualitative research for synthesis, 107 reviews were identified using one of the eight main methods. Four methods (meta-ethnography, meta-study, meta-summary, and thematic synthesis) have been most widely used and have a role within health technology assessment. Meta-ethnography is the leading method for synthesizing qualitative health research. Thematic synthesis is also useful for integrating qualitative and quantitative findings. Four other methods (critical interpretive synthesis, grounded theory synthesis, meta-interpretation, and cross-case analysis) have been under-used in health research and their potential in health technology assessments is currently under-developed.

Conclusions: Synthesizing individual qualitative studies has becoming increasingly common in recent years. Although this is still an emerging research discipline such an approach is one means of promoting the patient-centeredness of health technology assessments.

Objectives: The increasing use of full economic evaluations has led to the development of various instruments to assess their quality. The purpose of this study was to compare the frequently used British Medical Journal (BMJ) check-list and two new instruments: the Consensus Health Economic Criteria (CHEC) list and the Quality of Health Economic Studies (QHES) instrument. The analysis was based on a practical exercise on economic evaluations of the surgical treatment of obesity.

Methods: The quality of nine selected studies was assessed independently by two health economists. To compare instruments, the Spearman rank correlation coefficient was calculated for each assessor. Moreover, the test–retest reliability for each instrument was assessed with the intraclass correlation coefficient (ICC) (3,1). Finally, the inter-rater agreement for each instrument was estimated at two levels: comparison of the total score of each article by the ICC(2,1) and comparison of results per item by kappa values.

Results: The Spearman's rank correlation coefficient between instruments was usually high (rho > 0.70). Furthermore, test–retest reliability was good for every instruments, that is, 0.98 (95 percent CI, 0.86–0.99) for the BMJ check-list, 0.97 (95 percent CI, 0.73–0.98) for the CHEC list, and 0.95 (95 percent CI, 0.75–0.99) for the QHES instrument. However, inter-rater agreement was poor (kappa < 0.40 for most items and ICC(2,1) ≤ 0.5).

Conclusions: The study shows that the results of the quality assessment of economic evaluations are not so much influenced by the instrument used but more by the assessor. Therefore, quality assessments should be performed by at least two independent experts and final scoring based on consensus.

Methodology for evaluation of impact of health technology assessments (HTAs) is outlined and its use illustrated by applying it to 21 HTAs produced by CETS. Impact on policies and technology diffusion was identified in documents, through interviews, questionnaires, and use of data banks. There was evidence that all but three reports influenced policy and that cost-minimization studies caused savings of between $16 million and $27 million annually. Precise estimates of impact will seldom be possible, but systematic documentation of effects is feasible.

Objectives: This study aims to estimate the annual U.S. societal costs associated with treatment of metastatic breast cancer (MBC) patients using an incidence-based cost-of-illness (COI) framework.

Methods: An incidence-based COI model was constructed in which MBC patients were simulated from diagnosis through active treatment, palliative care, and death over 5 years. Key model parameters included: annual incidence of breast cancer in the metastatic stage, utilization of cancer therapies and other medical care resources, treatment-related adverse events, unit costs, work days missed by patient and caregiver, and wage rates. Overall survival was based on SEER data and costs were assigned to living patients monthly, according to their disease management phase. The outcomes measures were total discounted societal costs, cost/year, and cost/patient-year.

Results: The annual incidence of MBC in the United States in 2007 was estimated to be 49,674 patients (de novo and progressed from earlier stages). The total discounted cost to society attributable to MBC was $12.2 billion for the incident cohort, or $98,571 per patient-year. The 5-year direct medical cost of this incident cohort was $9.3 billion, or $75,415 per patient-year. Treatment-related costs (active treatment, toxicity management, and medical follow-up) contributed 44 percent of MBC expenditure, followed by palliative/best supportive care costs (31 percent). Lost productivity accounted for approximately 21 percent of the total cost ($2.6 billion over 5 years or $21,153 per patient-year).

Conclusions: The societal burden of MBC in the United States is substantial. Earlier detection and effective treatment could lead to a significant decrease in costs while improving overall disease prognosis.

Cross-design synthesis is a new (and still evolving) strategy for providing quantitative results that capture the strengths and minimize the weaknesses of different kinds of research. The strategy, which is being developed to answer questions about the effects of treatment in medical practice, includes (a) identifying complementary research designs and studies conducted according to those designs; (b) completing an in-depth assessment of each study with respect to the chief potential bias(es) that are associated with its design; (c) making “secondary adjustments” of study results to correct known biases; and (d) developing synthesis frameworks and models that will minimize the impact of hidden biases.