Objectives: This study reviews the coverage and usefulness of a short-term register, established specifically for health technology assessment of a novel interventional procedure (minimally invasive repair of pectus excavatum, or the Nuss procedure).

Methods: Coverage of the register during 2004–07 was assessed by comparison with Hospital Episodes Statistics (HES) for England. Its usefulness was assessed by comparing safety and efficacy data with the published literature and by feedback from committee members who in 2009 were involved in reviewing NICE's original guidance from 2003.

Results: The register reported 260 cases from thirteen UK hospitals during nearly 9 years. During a coverage evaluation period of 3 years, there were 152 registered Nuss procedures. An additional 246 repairs of pectus excavatum were undertaken in twenty-six previously unidentified hospitals. Of the 246, 23 were Nuss procedures (from two hospitals), 140 were open procedures (from eleven hospitals), and 3 were coding errors. No details were available for eighty cases undertaken at ten hospitals. The quantity of published literature had increased substantially since publication of original guidance in 2003. It related mostly to technical and safety outcomes, whereas the register included patient reported outcomes. The literature and the register reported similar rates of major adverse events such as bar displacement (2–10 percent). Committee members considered that the Register made a useful contribution to guidance development.

Conclusions: This study shows that a register set up to support a health technology assessment process can produce useful data both about safety and about patient-reported outcomes. Coverage may be improved by active follow-up based on routine hospital statistics. Improvement in coding for new procedures is needed in the United Kingdom.

Objectives: Although endoscopic ultrasound (EUS) staging of esophageal cancer is established in clinical practice, high-quality evidence about its impact on patient outcomes is not available. This study aims to determine the impact of EUS for esophageal cancer staging on patient management and survival.

Methods: A systematic review was conducted using Medline, PreMedline, Embase, and The Cochrane Library. Included studies were (i) comparative studies reporting survival following EUS esophageal cancer staging, (ii) therapeutic impact studies reporting change in patient management following EUS. The quality of included studies was critically appraised.

Results: One systematic review, five studies reporting therapeutic impact, and two studies reporting patient survival were identified. The design and quality of the therapeutic impact studies varied widely. Management changed in 24–29 percent of patients following EUS staging of esophageal cancer (two studies). No studies provided data on the avoidance of surgery for this indication. One retrospective cohort study with historical control found EUS staging of esophageal cancer improved patient survival; a second study with similar design limitations did not find a survival benefit for EUS staging in patients undergoing resection. These studies had a high potential for bias, limiting the value of these findings.

Conclusions: Two studies provided evidence of a change in patient management following EUS for staging esophageal cancer, a higher level of evidence for a clinical benefit than can be obtained from accuracy studies alone. This evidence contributed to a recommendation for public funding of EUS in staging esophageal cancer in Australia.

Objectives: Many evaluations underestimate the utility associated with diagnostic interventions by failing to capture the nonclinical value of diagnostic information. This is a cause of bias in resource allocation decisions. A study was undertaken to investigate preferences for the assessment of cardiac risk, testing the suitability of conjoint analysis, a multiattribute preference elicitation method, in the field of clinical diagnosis.

Methods: Two conjoint analysis models focusing on selected characteristics of cardiac risk assessment in asymptomatic patients 40–50 years of age were applied to elicit preferences for cardiac risk assessment from samples of general practitioners and the general public in the United Kingdom and Italy. Both models were based on rankings of alternative scenarios, and the results were analyzed using multivariate analysis of variance and an ordered probit model.

Results: In both countries, members of the public attached at least three times more importance to prognostic value (relative to clinical value) than did general practitioners. Significantly different patterns were found in the two countries with regard to other characteristics of the assessment. Variation within samples was partly associated with personal characteristics.

Conclusions: Only a fraction of the value of cardiac risk assessment to individuals and physicians in this study was linked to health outcomes. The study confirmed the appropriateness and validity of conjoint analysis in the assessment of preferences for diagnostic interventions. A wider use of this technique might significantly strengthen the existing evidence-base for diagnostic interventions, leading to a more efficient use of health-care resources.

Background: Using multiples of India's per capita gross domestic product (GDP) as the threshold for economic value as suggested by the World Health Organization (WHO), decision analysis modeling was used to estimate a more affordable monthly cost in India for a hypothetical new cancer drug that provides a 3-month survival benefit to Indian patients with metastatic colorectal cancer (mCRC).

Methods: A decision model was developed to simulate progression-free and overall survival in mCRC patients receiving chemotherapy with and without the new drug. Costs for chemotherapy and side-effects management were obtained from both public and private hospitals in India. Utility estimates measured as quality-adjusted life-years (QALY) were determined by interviewing twenty-four oncology nurses using the Time Trade-Off technique. The monthly cost of the new drug was then estimated using a target threshold of US$9,300 per QALY gained, which is three times the Indian per capita GDP.

Results: The base-case analysis suggested that a price of US$98.00 per dose would be considered cost-effective from the Indian public healthcare perspective. If the drug were able to improve patient quality of life above the standard of care or survival from 3 to 6 months, the price per dose could increase to US$170 and US$253 and offer the same value.

Conclusions: The use of the WHO criteria for estimating the cost of a new drug based on economic value for a developing country like India is feasible and can be used to estimate a more affordable cost based on societal value thresholds.

Objective: To determine if a pre-assessment can be used to establish whether cost-effectiveness results would meet the actual information needs of Dutch healthcare decision makers.

Methods: Two recent studies in rehabilitation medicine served as study material. Based on Wholey, a limited pre-assessment was performed in which the potential impact of cost-effectiveness analysis (CEA) results on intended users' decision making was assessed. Desk research and semi-structured interviews with several intended users of CEA results were performed. These included general practitioners, representatives of health insurance companies, the Health Care Insurance Board (CvZ), and medical guidelines committees.

Results: In day-to-day decision making of the interviewed decision makers, a cost-effectiveness criterion seemed to be of limited importance. Instead, results from clinical effectiveness studies and budget impact studies appeared to be sufficient. CvZ, however, preferred relative cost-effectiveness to be a criterion for inclusion in future reimbursement guidelines. In both cases the limited pre-assessments changed the expectations of the investigators regarding decision-making impact of an economic evaluation.

Conclusion: This study revealed that the use of CEA results for Dutch micro- and meso-level healthcare decision making is not self-evident. The main purpose of CEA results is to support health policy making and planning at a macroeconomic level. Pre-assessment can be a valuable tool in designing a CEA to support the actual information needs of the decision makers.

Objectives: Traditionally, patients with chronic hepatitis C virus (HCV) infection have not received treatment until their infection reaches the moderate to severe stage. The aim of this systematic review was to assess the clinical effectiveness of pegylated (PEG) and non-pegylated interferon (IFN) alfa and ribavirin (RBV) for the treatment of adults with histologically mild HCV.

Methods: We performed a sensitive search of fourteen electronic bibliographic databases for literature that met criteria defined in a research protocol. Two reviewers independently selected studies, extracted data and assessed methodological quality.

Results: Ten randomized, controlled trials (RCTs) were included. Treatment with PEG + RBV combination therapy resulted in significantly higher sustained virological response (SVR) rates than treatment with IFN + RBV combination therapy. Treatment for 48 weeks with PEG + RBV was significantly more effective than the same treatment for 24 weeks. Significantly higher SVR rates were seen with IFN + RBV compared with either IFN monotherapy or no treatment. In the meta-analysis (four IFN trials), the relative risk of not experiencing an SVR was 0.59 (95 percent CI, 0.51 – 0.69) and was statistically significant (p < .00001). SVRs were higher for patients with genotype non-1 compared with genotype 1 for both PEG + RBV and IFN + RBV treatments.

Conclusions: Patients with histologically mild HCV can be successfully treated with both PEG and IFN combination therapy, and response rates are broadly comparable with those achieved in patients with advanced disease. Treating patients in the early milder stages of HCV is, therefore, a clinically effective option.

A clinical and economic evaluation of red blood cell (RBC) utilization in cancer patients during chemotherapy is described. Using a randomized sampling process, 100 patients who had received chemotherapy with or without cisplatin were selected (50 in each group). Multiple logistic regression was then used to identify risks factors for transfusion requirements. Twenty-five percent of patients in the cisplatin and 12% in the noncisplatin group received at least one blood transfusion during chemotherapy (p =.09). Depressed hemoglobin levels and cisplatin dosage were identified as risk factors for transfusion requirements. Combining all transfused patients revealed an overall cost of Can $599 (95% Cl: $513–$683) per transfusion. The results of the current study indicated that anemia is a common complication of cancer chemotherapy that can be costly to manage.

Health technology assessment as a formalized set of activities has a relatively short history. At its current stage of development, it is clear that it has global dimensions and impact. In this paper we review the history of health technology assessment, its development as a form of health services research, and its “institutionalization.” We then identify the reasons for its internationalization, review current international initiatives, and propose actions to be taken to improve cooperation among countries.

Objectives: Early warning systems are an integral part of many health technology assessment programs. Despite this finding, to date, there have been no quantitative evaluations of the accuracy of predictions made by these systems. We report a study evaluating the accuracy of predictions made by the main United Kingdom early warning system.

Methods: As prediction of impact is analogous to diagnosis, a method normally applied to determine the accuracy of diagnostic tests was used. The sensitivity, specificity, and predictive values of the National Horizon Scanning Centre's prediction methods were estimated with reference to an (imperfect) gold standard, that is, expert opinion of impact 3 to 5 years after prediction.

Results: The sensitivity of predictions was 71 percent (95 percent confidence interval [CI], 0.36–0.92), and the specificity was 73 percent (95 percent CI, 0.64–0.8). The negative predictive value was 98 percent (95 percent CI, 0.92–0.99), and the positive predictive value was 14 percent (95 percent CI, 0.06–0.3).

Conclusions: Forecasting is difficult, but the results suggest that this early warning system's predictions have an acceptable level of accuracy. However, there are caveats. The first is that early warning systems may themselves reduce the impact of a technology, as helping to control adoption and diffusion is their main purpose. The second is that the use of an imperfect gold standard may bias the results. As early warning systems are viewed as an increasingly important component of health technology assessment and decision making, their outcomes must be evaluated. The method used here should be investigated further and the accuracy of other early warning systems explored.

Early health technology assessment (HTA), which includes all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty, has seen many applications in recent years. However, it is still unclear how such early value assessments can be integrated into the technology innovation process. This commentary contributes to the discussion on the purposes early HTA can serve. Similarities and differences in the perspectives of five stakeholders (i.e., the hospital, the patient, the assessor, the medical device industry, and the policy maker) on the purpose, value, and potential challenges of early HTA are described. All five stakeholders agreed that integrating early HTA in the innovation process has the possibility to shape and refine an innovation, and inform research and development decisions. The early assessment, using a variety of methodologies, can provide insights that are relevant for all stakeholders but several challenges, for example, feasibility and responsibility, need to be addressed before early HTA can become standard practice. For early evaluations to be successful, all relevant stakeholders including patients need to be involved. Also, nimble, flexible assessment methods are needed that fit the dynamics of medical technology. Best practices should be shared to optimize both the innovation process and the methods to perform an early value assessment.

Objectives: Equity is one of the founding principles in most healthcare systems. Financial constraints entail an increased risk of exacerbating inequities and a greater need for evidence-based decisions. It is, therefore, both important and timely to enquire how equity can be addressed in health technology assessment (HTA) practice. We aimed to explore related practices from a broad range of HTA agencies, identify exemplary approaches and common concerns, and offer insights for future considerations.

Methods: HTA agencies for which both methodological guides and HTA reports were publicly available were selected from an initial comprehensive pool. Information was extracted on issues ranging from a general commitment to fairness to specific measures targeting both methodological and process-related elements.

Results: Methodological documents and ninety-eight reports from nineteen agencies were analyzed. Our findings indicate that equity was not a standard consideration in HTA report production. The nature of specific approaches and the amount of resources invested into including an equity perspective varied considerably. Specific measures (e.g., appropriate information sources, analytical tools, and schemes) were mentioned by almost half of the agencies analyzed. Albeit sporadic, both horizontal and vertical equity considerations were identified in included HTA reports.

Conclusions: While varying legal contexts and institutional principles can lead to different interpretations of equity at the decision point, a combination of methodological and process-related practices could contribute to more equity-sensitive evaluations, especially in conjunction with enhanced dissemination of existing methodological tools. Networking initiatives on behalf of existing collaborating platforms could play an important role in this direction.

Objective: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up.

Methods: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-α blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power.

Results: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models.

Conclusions: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.

Objectives: Stereotactic radiosurgery (SRS) is used to treat intracranial lesions and vascular malformations as an addition or replacement to whole brain radiotherapy and microsurgery. SRS can be delivered by hardware and software appended to standard linear accelerators (Linacs) or by dedicated systems such as Gamma Knife, which has been proposed as a more accurate and user friendly technology. Internationally, dedicated systems have been funded, despite limitations in evidence. However, some countries including Australia have not recommended additional reimbursement for dedicated systems. This study compares the costs of Linac radiosurgery with Gamma Knife radiosurgery.

Methods: Due to limited evidence on comparative effects, the economic analysis was restricted to a cost evaluation. The base-case analysis assumed a modified Linac was used only to treat SRS patients. However, because a modified Linac could be used to treat other radiotherapy patients, a second analysis assumed spare time was used to meet other radiotherapy needs, and Linac capital costs were apportioned according to SRS use.

Results: The incremental cost of Gamma Knife versus a modified Linac was estimated as AU$209 per patient. This result is sensitive to variations in assumptions. A second analysis proportioning capital costs according to SRS use showed that Gamma Knife may cost up to AU$1673 more per patient.

Conclusions: Gamma Knife may be cost competitive only if demand for SRS services is high enough to fully use equipment working time. However, given low patient demand and competing radiotherapy needs, Gamma Knife appears more costly and further evidence of survival or quality of life advantages may be required to justify reimbursement.

Objectives: Patient preferences should be a central consideration in healthcare decision making. However, stories of patients challenging regulatory and reimbursement decisions has led to questions on whether patient voices are being considered sufficiently during those decision making processes. This has led some to argue that it is necessary to quantify patient preferences before they can be adequately considered.

Methods: This study considers the lessons from the use of multi-criteria decision analysis (MCDA) for efforts to quantify patient preferences. It defines MCDA and summarizes the benefits it can provide to decision makers, identifies examples of MCDAs that have involved patients, and summarizes good practice guidelines as they relate to quantifying patient preferences.

Results: The guidance developed to support the use of MCDA in healthcare provide some useful considerations for the quantification of patient preferences, namely that researchers should give appropriate consideration to: the heterogeneity of patient preferences, and its relevance to decision makers; the cognitive challenges posed by different elicitation methods; and validity of the results they produce. Furthermore, it is important to consider how the relevance of these considerations varies with the decision being supported.

Conclusions: The MCDA literature holds important lessons for how patient preferences should be quantified to support healthcare decision making.

In the past decade the prevention and management of prematurity have begun to be addressed with more appropriate designs. A few strategies—very few—can now be recommended. A few, some widely implemented, can be abandoned. The risks and benefits of most interventions still require clarification.

Planning for a cost-effective mix of providers is an important aspect of health care reform. Currently, there are too many specialists and insufficient numbers of primary care providers. Nurses in advanced practice roles are an important resource for expanding the nation's supply of primary care providers.

Adaptive immunity requires both specific recognition of an antigen and its translation into appropriate lymphocyte responses. This paper reviews the striking differences in B- and T-lymphocyte antigen recognition, details the pathways for conversion of protein antigens into peptide–major histocompatibility complex molecule ligands for T-cell receptors, and summarizes the roles of costimulatory signals in lymphocyte activation. This information is used to suggest new approaches for the rational design of vaccines.

A comparison of two assessment methods, consensus among experts and research synthesis of the scientific literature, was performed using a surgical procedure, carotid endarterectomy (CE), as an example. These two methods have been widely advocated as being scientifically valid. While the comparison revealed a number of areas of general agreement, important differences between the two methods emerged. For example, 30-day mortality for asymptomatic patients was considered an effective outcome (ranked first) by the synthesis, but only “quivocal” (ranked third) of six major indicators reported by the consensus method. The synthesis results are also consistent with other literature reviews as well as with recent large-scale randomized trial results. A number of factors that could account for differences between the two methods were examined. Overall, use of consensus panels may be appropriate early in the development of an intervention where the evidence is sparse, while quantitative research synthesis is preferable when a number of high-quality studies have been performed.

Objectives: Case series constitute a weak form of evidence for effectiveness of health technologies. However, for a variety of reasons, such studies may be included in health technology assessments. There are no clear criteria for assessing the quality of case series. We carried out an empirical investigation of the association between outcome frequency and methodological characteristics in a sample of health technology assessments.

Methods: Systematic reviews of functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for chronic back pain, and percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic stable angina were identified as containing more than forty case series. Data were extracted by one reviewer and checked by a second on population characteristics, outcomes, and the following methodological features: sample size, prospective/retrospective approach, consecutive recruitment, multi- or single-center organization, length of follow-up, independence of outcome measurement, and date of publication. Association between methodological features and outcome were explored in univariate and multivariate analyses using parametric and nonparametric tests and robust regression or analysis of variance/analysis of covariance, as appropriate.

Results: Included reviews contained between forty-two and seventy-six case series studies, involving 5 to 172,283 participants. Reporting of methodological features was poor and limited the analyses. In general, we found little evidence of any association between methodological characteristics and outcome. Sample size is used as an inclusion criterion in many reviews of case series but was consistently shown to have no relationship to outcome in all analyses. A prospective approach was not associated with outcome. Insufficient data were available to explore consecutive recruitment. Mixed results were shown for length of follow-up, independence of outcome measurement, and publication date.

Conclusion: We found little evidence to support the use of many of the factors included in tools used for quality assessment of case series. Importantly, we found no relationship between study size and outcome across the four examples studied. Isolated examples of a potentially important relationship between other methodological factors and outcome were shown, for example, blinding of outcome measurement, but these examples were not shown consistently across the small number of examples studied. Further research into the determinants of quality in case series studies is required to support health technology assessment.