Objectives: This study investigated the direct medical resource use and cost, informal care cost, and indirect cost associated with breast cancer in different states of the disease in normal clinical practice.

Methods: A retrospective database analysis was used to estimate direct medical resource use and cost, and a patient questionnaire was used to evaluate informal care and work capacity in different states of breast cancer.

Results: For patients younger than 65 years of age, the first year after a primary diagnosis total cost amounted to 280,000 SEK ($39,000) and the first year after a local or contralateral recurrence total cost was 351,000 SEK ($48,900). The second and following years after primary breast cancer or recurrence had substantially lower total cost, amounting to 94,000 SEK ($13,000). For patients with metastatic disease, the annual total cost was estimated to 334,000 SEK ($46,500). For patients older than 65 years of age, the total cost for the first year after a primary diagnosis amounted to 80,000 SEK ($11,200) and the total cost for the first year after a local or contralateral recurrence was 92,000 SEK ($12,900). The total cost for the second and following years after primary breast cancer or recurrence was estimated to 18,000 SEK ($2,600), and the total annual cost for patients with metastatic was 122,000 SEK ($17,000).

Conclusions: Both direct medical costs and indirect cost vary substantially between disease states. For patients under 65 year of age, indirect costs accounted for more than 50 percent of the total cost.

Objectives: Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the “gray+ literature.” However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.

Methods: We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+ literature.

Results: The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+ literature. Although in most cases the addition of gray+ data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.

Conclusions: We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+thinsp;literature and, where possible, obtain data from them.

The aim of this paper is to discuss the use of Bayesian methods in cost-effectiveness analysis (CEA) and the common ground between Bayesian and traditional frequentist approaches. A further aim is to explore the use of the net benefit statistic and its advantages over the incremental cost-effectiveness ratio (ICER) statistic. In particular, the use of cost-effectiveness acceptability curves is examined as a device for presenting the implications of uncertainty in a CEA to decision makers. Although it is argued that the interpretation of such curves as the probability that an intervention is cost-effective given the data requires a Bayesian approach, this should generate no misgivings for the frequentist. Furthermore, cost-effectiveness acceptability curves estimated using the net benefit statistic are exactly equivalent to those estimated from an appropriate analysis of ICERs on the cost-effectiveness plane. The principles examined in this paper are illustrated by application to the cost-effectiveness of blood pressure control in the U.K. Prospective Diabetes Study (UKPDS 40). Due to a lack of good-quality prior information on the cost and effectiveness of blood pressure control in diabetes, a Bayesian analysis assuming an uninformative prior is argued to be most appropriate. This generates exactly the same cost-effectiveness results as a standard frequentist analysis.

Objectives: While strategies for enhancing the dissemination and impact of Health Technology Assessment (HTA) are now being increasingly examined, the characteristics of HTA production have received less attention.

Methods: This study presents the results of a content analysis of the HTA documents (n=187) produced by six Canadian agencies from 1995 to 2001, supplemented by interviews with chief executive officers and researchers (n=40). The goal of this analysis was to characterize the agencies' portfolios and to analyze the challenges these agencies face in responding to the increased demand for HTA.

Results: On average, thirty HTA products were issued annually by the agencies. While the bulk of documents produced were full HTA reports (76 percent), two agencies showed significant diversification in their products. Three agencies in particular actively supported the publication of results in scientific journals. Three agencies showed evidence of adapting to different institutional environments by specializing in certain areas (drugs, health services). Overall, a significant portion of the agencies' HTAs contained data on costs (37 percent) and effectiveness (48 percent), whereas ethical and social issues were rarely addressed (17 percent). Most agencies addressed issues and outcomes that did not strictly fall under the typical definition of HTA but that increased the “contextualization” of their findings.

Conclusions: Our discussion highlights four paradoxes and reflects further on challenges raised by the coordination of HTA within large countries and among European states. This study concludes that HTA is being redefined in Canada as HTA agencies offer a more contextualized informational basis, an approach that may prove more compatible with the increased demand for HTA.

Previously, our group—the International Working Group for HTA Advancement—proposed a set of fifteen Key Principles that could be applied to health technology assessment (HTA) programs in different jurisdictions and across a range of organizations and perspectives. In this commentary, we investigate the extent to which these principles are supported and used by fourteen selected HTA organizations worldwide. We find that some principles are broadly supported: examples include being explicit about HTA goals and scope; considering a wide range of evidence and outcomes; and being unbiased and transparent. Other principles receive less widespread support: examples are addressing issues of generalizability and transferability; being transparent on the link between HTA findings and decision-making processes; considering a full societal perspective; and monitoring the implementation of HTA findings. The analysis also suggests a lack of consensus in the field about some principles—for example, considering a societal perspective. Our study highlights differences in the uptake of key principles for HTA and indicates considerable room for improvement for HTA organizations to adopt principles identified to reflect good HTA practices. Most HTA organizations espouse certain general concepts of good practice—for example, assessments should be unbiased and transparent. However, principles that require more intensive follow-up—for example, monitoring the implementation of HTA findings—have received little support and execution.

Objectives: The complexity of health technology assessment (HTA) has increased, in part because of its evolution through three distinct phases: the machine, the clinical outcomes, and the delivery models. However, the theoretical foundation for the field remains underdeveloped.

Methods: It is high time for HTA to bring together aspects of conceptual and theoretical works from other fields to strengthen the foundation of HTA.

Results: Many challenges await the further development of HTA. They can be captured around three research themes: adapting HTA to an evolving analysis object; translating HTA results into policy, management, and practice decisions; and evaluating organizational models of HTA.

Conclusions: Consolidating the scientific basis of HTA is essential if we are to succeed in increasing the relevance of HTA in some of the most challenging health-related decisions that we will make as individuals and societies.

Objectives: In the United States, medical devices represent an eighty-billion dollar a year market. The U.S. Food and Drug Administration rejects a significant number of applications of devices that reach the investigational stage. The prospects of improving patient condition, as well as firms' profits, are thus substantial, but fraught with uncertainties at the time when investments and design decisions are made. This study presents a quantitative model focused on the risk aspects of early technology assessment, designed to support the decisions of medical device firms in the investment and development stages.

Methods: The model is based on the engineering risk analysis method involving systems analysis and probability. It assumes use of all evidence available (both direct and indirect) and integrates the information through a linear formula of aggregation of probability distributions. The model is illustrated by a schematic version of the case of the AtrialShaper, a device for the reduction of stroke risk that is currently in the preprototype stage.

Results: The results of the modeling provide a more complete description of the evidence base available to support early-stage decisions, thus allowing comparison of alternative designs and management alternatives.

Conclusions: The model presented here provides early-stage decision-support to industry, but also benefits regulators and payers in their later assessment of new devices and associated procedures.

Objectives: The aim of this study is to explain factors influential to the diffusion of computed tomography (CTs) and magnetic resonance imaging (MRIs).

Methods: Variables were identified from a review of the literature on the diffusion of health technologies. A formal process was applied to build a conceptual model of the mechanism that drives technology diffusion. Variables for the analysis were classified as predisposing, enabling, or reinforcing factors, in keeping with a model commonly used to explain the diffusion of health behaviors. Multiple regression analysis was conducted using year 2000 OECD data.

Results: The results of this study showed that total health expenditure per capita (p < .01, both CTs and MRIs) and flexible payment methods to hospitals (p < .05, both CTs and MRIs) were significantly associated with the diffusion of CTs and MRIs (adjusted R2 = 0.477, 0.656, respectively).

Conclusions: This study presents a systematically developed model of the mechanism governing technology diffusion. Important findings from the study show that purchasing power, represented by total health expenditure per capita and economic incentives to hospitals in the form of flexible payment methods, were positively correlated with diffusion. Another important achievement of our model is that it accounts for all thirty OECD member countries without excluding any as outliers. This study shows that variation across countries in the diffusion of medical technology can be explained well by a logical model with multiple variables, the results of which hold profound implications for health policy regarding the adoption of innovations.

The scientific evidence for clinical effectiveness of transcutaneous electrical nerve stimulation (TENS) for treatment of acute, chronic, and labor and delivery pain is assessed in this paper, and it is concluded that there is little evidence for other than a limited use of TENS. The utilization of TENS in Canadian hospitals and payments for TENS services are addressed. Some practicalities regarding the use and assessment of health technologies are discussed.

Objectives: Multidisciplinary and multifactorial interventions seem to be effective in preventing falls. We aimed to assess the cost-effectiveness of a multidisciplinary fall prevention program compared with usual Dutch healthcare in community-dwelling people 65 years of age or older who experienced a fall.

Methods: Cost-effectiveness and cost-utility analysis were performed from a societal perspective. Falls and healthcare utilization were continuously measured for 12 months. Daily functioning and quality of life were measured at baseline, after 4 and 12 months. Bootstrap analyses were performed to estimate uncertainty of the findings and sensitivity analysis to assess the generalizability of assumptions made.

Results: One hundred sixty-six participants were randomly allocated to the experimental group and 167 to the control group. The overall response rate was 74 percent. Healthcare and patient and family costs of both groups were comparable. Our analyses showed no effect of the intervention program on falls, daily functioning, or quality of life measures.

Conclusions: The multidisciplinary intervention program to prevent falls was not cost-effective compared with usual care in the Netherlands. Notwithstanding our findings, however, falls still have an important impact on society and individuals in terms of costs and effects. Economic evaluations studying promising interventions to prevent falls, therefore, remain necessary.

Objectives: Infliximab is a costly therapy for active Crohn's disease resistant to corticosteroids and immunosuppressive medication. The purpose of this study was to examine whether a treatment including infliximab (episodic re-infusions for relapse or maintenance therapy every 8 weeks) was relevant compared with conventional management (surgery and medical treatment without infliximab) for nonfistulizing resistant Crohn's disease.

Methods: We performed a life-time cost-utility analysis with an analytic Markov decision model from the perspective of the third-party payer system. Utility measurement using Standard Gamble was used to adjust the survival time for each health state of the disease. Direct costs were estimated from standard management based on expert opinion. A sensitivity analysis was conducted to gauge the effects of uncertainty in the values assigned to variables.

Results: The incremental effectiveness with infliximab therapy is .761 Quality-Adjusted Life Years (QALYs) for an added cost ranging from 48,478.79 euros to 596,990.35 euros, depending on treatment procedure. The incremental cost utility ratio expressed in euros per QALYs saved varied from 63,700.82 euros (episodic re-infusions) to over 762,245.09 euros (maintenance therapy).

Conclusions: Infliximab therapy could be cost-effective in the case of relapse treatment only, whereas the marginal cost-utility ratio exceeds conventional benchmarks for maintenance therapy. This analysis will be supplemented by conducting further randomized controlled trials and prospective observational study, focused on the costs of illness (direct and indirect), patient preferences, the disease's clinical course, and infliximab safety.

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most prestigious health care technologies. Their popularity has grown rapidly, and an increasing proportion of health care resources is allocated to them. We studied patient- and hospital-related factors that cause variation in a major determinant of hospital costs, the length of hospital stay (LOS) for THA and TKA. We gathered data on 10,288 hip and 5,173 knee patients with primary or secondary arthrosis from the Finnish Arthroplasty Register, which we linked with the Finnish Hospital Discharge Register. Patientand hospital-related variations in LOS were explained using regression models. Of the patient-related factors, complications caused the greatest prolongation of hospital stay, but patient's age, gender, and charge category also influenced LOS. Hospital-related factors were major causes of LOS variation. In the hospitals the average case-mix-adjusted LOS ranged from less than a week to 3 weeks. The number of arthroplasties performed in hospital was inversely related to LOS. The within-hospital LOS figures for THA and TKA were strikingly similar and persistent.

Objectives: The aim of this study was to provide a comprehensive summary and interpretation of the current evidence on the use and validity of statistical methods to conduct indirect comparisons of treatment effects.

Methods: A narrative review was conducted.

Results: Well-conducted methodological studies provide good evidence that adjusted indirect comparisons can lead to results similar to those from direct comparisons. The internal validity of several statistical methods to conduct indirect comparisons, therefore, has been established. Meta-regression, logistic regression, or adjusted indirect comparisons should be the methods of first choice. Unadjusted indirect comparisons are always unacceptable. Deciding whether to combine direct and indirect evidence will be a matter of informed judgment based on the similarities and dissimilarities of populations and interventions. Unverifiable assumptions with respect to the similarity of compared studies and low power are serious limitations of indirect comparisons.

Conclusions: In the absence of sufficient head-to-head evidence, adjusted indirect comparisons can be viewed as additional analytical tools to determine the comparative efficacy and effectiveness of competing interventions. Researchers who use indirect comparisons need to keep the limitations in mind.

Eighty-one published papers on the performance of prostheses in total hip replacement were appraised. Sound methodology was demonstrated in 1 of 8 randomized controlled trials and 4 of 17 nonrandomized comparative studies. Of 56 case series without controls, 32 met the appraisal criteria, but these are intrinsically less useful. The published literature does not provide solid evidence for the superiority of cement-free or hybrid prostheses over modern cemented types.

In this study, we describe the current state of the Health Technology Assessment (HTA) system in England and Wales. This system rests on a distinction between assessment and appraisal and has three main strands: researcher-led HTA, the research and development program, and the HTA-NICE (National Institute for Clinical Excellence) process. We outline the pressures for HTA and how it has evolved in the British National Health Service. We discuss how HTA priorities are chosen, how HTA information is collected and assessed, how HTA evidence is used, and we make some observations about its impact. In our discussion, we consider some limitations of the HTA system, its possible divergence from evidence-based health care, its centralization, and some of the key challenges for managing HTA-driven policy. But we remain hopeful that HTA can contribute to better and more explicit decision-making within England and Wales.

Objectives: This study aims to review the development of health technology assessment (HTA), including the socioeconomic context, outputs, and policy utilization in the Thai setting.

Methods: This study was conducted through extensive document reviews including these published in both domestic and international literature.

Results: Evidence suggests that contextual elements of the health system, especially the country's economic status and health financing reforms, as well as their effects on government budgeting for medical and public health services, played an important role in the increasing needs and demands for HTA information among policy makers. In the midst of substantial economic growth during the years 1982 to 1996, several studies reported the rapid diffusion and poor distribution of health technologies, and inequitable access to high-cost technology in public and private hospitals. At the same time, economic analysis and its underpinning concept of efficiency were suggested by groups of scholars and health officials to guide national policy on the investment in health technology equipment. Related research and training programs were subsequently launched. However, none of these HTA units could be institutionalized into national bodies. From 1997 to 2005, an economic recession, followed by the introduction of a universal health coverage plan, triggered the demands for effective measures for cost containment and prioritization of health interventions. This made policy makers and researchers at the Ministry of Public Health (MOPH) pay increasing attention to economic appraisals, and several HTA programs were established in the Ministry. Despite the rising number of Thai health economic publications, a major problem at that period involved the poor quality of studies. Since 2006, economic recovery and demands from different interests to include expensive technologies in the public health benefit package have been crucial factors promoting the role of HTA in national policy decisions. Meanwhile, HTA capacity has been strengthened through the establishment of many health economic and HTA initiatives. An illustration of the work and contributions of the Health Intervention and Technology Assessment Program (HITAP) is provided. In this phase, HTA policy integration has been enhanced through different mechanisms and organizations.

Conclusion: Over the past two decades a notable progression has been made in relation to the capacity building of HTA research and its policy utility in Thailand. Such development has been shaped by multiple factors. It is anticipated that experience gained among academics, health officials, and civil society organizations will be helpful not only in sustaining the momentum but also in improving formal HTA systems in the future.

Objectives: Controversy exists regarding the optimal method of providing dialysis in critically ill patients with acute renal failure. We sought to determine the cost-effectiveness of treatment strategies.

Methods: Adult subjects requiring renal replacement therapy in a critical care setting who are candidates for intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) were considered within a Markov model. Alternative strategies including IHD, and standard or high dose CRRT were compared. The model considered relevant clinical and economic outcomes, and incorporated data on clinical effectiveness from a recent systematic review and high quality micro-costing data.

Results: In the base-case analysis, CRRT was associated with similar health outcomes but higher costs by ($3,679 more than IHD per patient). In scenarios considering alternate cost sources, and higher intensity of IHD (including daily and longer duration IHD), CRRT remained more costly. Sensitivity analysis indicated that even small differences in the risk of mortality or need for long-term chronic dialysis therapy among surviving patients benefits led to dramatic changes in the cost-effectiveness of the modalities considered.

Conclusions: Given the higher costs of providing CRRT and absence of demonstrated benefit, IHD is the preferred modality in critically ill patients who are candidates for either IHD or CRRT, although this conclusion should be revisited if future clinical trials establish differences in clinical effectiveness between modalities. Future interventions that are proven to improve renal recovery after acute renal failure are likely to be cost-effective, even if very resource intensive.

Two strategies for vaccine-delivery systems, both relying on concepts of controlled-release technology, are described in this review. The first strategy involves using biodegradable polymer microspheres for parenteral and oral delivery of antigens. The other strategy combines two technologies, the encapsulation of antigen within liposomes and liposome encapsulation in hydrogels, to protect them from a rapid degradation in vivo. Both strategies have shown promise in terms of increasing the immunogenicity of poorly immunogenic peptides and protein vaccines. The microencapsulation process, antigen stability, mechanism of antigen release, and optimal release kinetics for vaccine delivery are reviewed, and the strengths and weaknesses of each approach are discussed.