Objectives: Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint.

Methods: A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption.

Results: Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses.

Conclusions: This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.

Objectives: Due to the aging baby boom population, utilization rates of diagnostic imaging (i.e., X-ray, CT, and MRI scanning) have risen rapidly relative to other health services. The aim of this study is to investigate the utilization patterns of outpatient diagnostic imaging services (X-ray, CT, and MRI) across the late life course (65 years and older).

Methods: A population-based retrospective cohort study was conducted for the period April 1, 2005, to March 31, 2006. All Ontario residents aged 65+ and eligible for government health insurance were included in the analysis.

Results: Utilization of diagnostic imaging followed an inverted U-pattern: increasing with advancing age, peaking in the 80–84 age group for CT scans and in the 70–74 age group for MRI and X-rays, and then declining in the later years. Overall, females received significantly more X-rays than males (p < .01), but males received significantly more CT and MRI scans (p < .01). A small proportion of high-users of radiology services accounted for a large proportion of overall utilization. Finally, our analysis revealed that a disproportionately large proportion of high-users of MRI services were in the highest SES quintile. No SES differences were observed for X-ray or CT scans.

Conclusions: Population aging will lead to increased demand for healthcare services. Utilization of outpatient diagnostic imaging services is associated with age, gender, and SES. Given the increasing demand and the limited resources available, there may be a need for programs to target underserved populations to reduce remediable inequities. Whereas patient-level decisions regarding the use of diagnostic imaging are rightfully determined on the basis of clinical factors, allocation decisions should also be informed by the ethical principles of equity and fairness.

Objectives: In 2003, the National Institute for Health and Clinical Excellence (NICE) advised that liquid based cytology (LBC) should be adopted for cervical screening in England. The aim of this study was to explore the cost implications of implementing the NICE guidance in cytology laboratories. The ThinPrep® technology was used as the case study.

Methods: An optimization model was developed to analyze options for leasing alternative LBC processing machines with different capacities. Variables entered in the model included: the cost of the contract with the supplier, the laboratory labor cost, and inter-laboratory transport costs. All costs referred to the 2005–06 financial year. A simulation program calculated mileages within laboratory networks. Alternative strategies for contracting by laboratories acting independently and by Quality Assessment Regional Centres (QARC) were analyzed.

Results: Centralizing the processing of specimens in “hub and spoke” laboratory networks was the least costly strategy. Total annual costs for England using existing transport links were £14,807,000 for 5-year contracts. If all laboratories installed processors, the annual cost for 5-year contracts placed by QARCs was £14,941,000 compared with £16,359,000 if the laboratories placed their own contracts. Three-year contracts averaged an additional £1 million: £15,912,000 for networks and £17,304,000 for independent laboratory contracts.

Conclusions: Deciding on the mode of implementation of a NICE guidance can be challenging for decision makers. These cost minimization appraisal techniques are equally applicable to national screening programs in general and to other health technologies for which there are significant cost implications associated with innovative policy directives.

Objectives: The aim of this study was to elucidate, whether shift from first generation antipsychotics (FGA) to olanzapine can affect health-related quality of life (HRQoL) of residually symptomatic schizophrenic outpatients.

Methods: Patients were randomized to either olanzapine or to continuation on their FGA. The 15D-measured HRQoL at baseline and end-point (after 12 weeks) was compared.

Results: Patients (n = 21) randomized to olanzapine achieved better HRQoL than those (n = 21) who continued on their FGA. This difference on the 15D (0.048 on a 0–1 scale; p = .037) was clinically important and comparable to that resulting from common surgical interventions, for example, hip or knee replacement.

Conclusions: HRQoL of stable outpatients with residual symptoms or adverse effects may improve substantially after shift from FGAs to olanzapine.

Objectives: The aim of this study was to examine location of systematic reviews of test accuracy in five specialist review databases: York CRD's DARE and HTA databases, Medion (University of Maastricht), C-EBLM (International Federation of Clinical Chemistry), and the ARIF in-house database (University of Birmingham).

Methods: Searches were limited to the period 1996–2006. Test accuracy reviews were located using in-house diagnostic search filters and with help from database producers where databases were not confined to test accuracy reviews. References were coded according to disease area, review purpose, and test application. Ease of use, volume, overlap, and content of databases was noted.

Results: A large degree of overlap existed between databases. Medion contained the largest number (n = 672) and the largest number of unique (n = 328) test accuracy references. A combination of three databases identified only 76% of test reviews. All databases were rated as easy to search but varied with respect to timeliness and compatibility with reference management software. Most reviews evaluated test accuracy (85%) but the HTA database had a larger proportion of cost-effectiveness and screening reviews and C-EBLM more reviews addressing early test development. Most reviews were conducted in secondary care settings.

Conclusions: Specialist review databases offer an essential addition to general bibliographic databases where application of diagnostic method filters can compromise search sensitivity. Important differences exist between databases in terms of ease of use and content. Our findings raise the question whether the current balance of research setting, in particular the predominance of research on tests used in secondary care, matches the needs of decision makers.

Objectives and Methods: Many authors have argued that ethical, legal, and social issues (“ELSIs”) should be explicitly integrated into health technology assessment (HTA), yet doing so poses challenges. This discussion may be particularly salient for technologies viewed as ethically complex, such as genetic screening. Here we provide a brief overview of contemporary discussions of the issues from the HTA literature. We then describe key existing policy evaluation frameworks in the fields of disease screening and public health genomics. Finally, we map the insights from the HTA literature to the policy evaluation frameworks, with discussion of the implications for HTA in genetic screening.

Results and Conclusions: A critical discussion in the HTA literature considers the definition of ELSIs in HTA, highlighting the importance of thinking beyond ELSIs as impacts of technology. Existing HTA guidance on integrating ELSIs relates to three broad approaches: literature synthesis, involvement of experts, and consideration of stakeholder values. The thirteen key policy evaluation frameworks relating to disease screening and public health genomics identified a range of ELSIs relevant to genetic screening. Beyond straightforward impacts of screening, these ELSIs require consideration of factors such as the social and political context surrounding policy decisions. The three broad approaches to addressing ELSIs described above are apparent in the screening/genomics literatures. In integrating these findings we suggest that the method chosen for addressing ELSIs in HTA for genetic screening may determine which ELSIs are prioritized; and that an important challenge is the lack of guidance for evaluating such methods.

From the heydays of HTA in the 1970s, it has been argued that ethics should be a part of HTA. Despite more than 30 years with repeated intentions, only few HTA reports include ethical analysis, and there is little agreement on methods for integrating ethics. This poses the question of why it is so important to integrate ethics in HTA? The article analyzes ten arguments for making ethics part of HTA. The validity of the arguments depend on what we mean by “integrating,” “ethics,” and “HTA.” Some of the counterarguments explain why it has taken so long to integrate ethics in HTA and why there are so many ethical approaches. Nevertheless, some of the arguments for making ethics part of HTA appear to be compelling. Health care is a moral endeavor, and the vast potential of technology poses complex moral challenges. A thorough assessment of technology would include reflection on these moral aspects. Ethics provides such a moral reflection. Health technology is a way to improve the life of human individuals. This involves questions of what “the good life” is, and hence ethical issues. Trying to ignore such questions may inflict with the moral foundation of health care: to help people. Additionally, HTA is an evaluation, and as such also a reflection on values. Hence, there is a profound affinity between HTA and ethics. Accordingly, ethics cannot be “integrated” in HTA as ethics is already a constitutive part of HTA. However, ethics can be acknowledged and emphasized.

Objectives: The aim of this study was to assess the evidence that reuse of medical devices marketed for single use only (SUDs) is safe, effective and cost-effective, and to consider the use and health services impact of this practice in Canada.

Methods: A systematic review was performed of studies that reported clinical or economic outcomes following reuse of SUDs in humans. Direct costs of adverse health events associated with SUD reuse and indications of budget impact were obtained using data for devices for laparoscopic cholecystectomy and coronary angioplasty. Legal and ethical issues were reviewed, drawing on material relevant to Canada. Data on current reuse of SUDs were obtained through a survey of Canadian acute care hospitals.

Results: Studies of variable quality suggested that SUD reuse could be safe and effective, and would give cost savings, if there were no adverse events. Eliminating reuse of SUDs for laparoscopic cholecystectomy and coronary angioplasty would add less than 0.1 percent to costs of the procedures over 1 year. Adverse health events associated with device reuse create liability risks; patients should be informed of any known or foreseeable risks of reuse. Most of the 28 percent (111/398) of acute hospitals that reprocess SUDs do so in-house. Some do not have a written policy or an incident reporting mechanism.

Conclusions: There is insufficient evidence to establish the safety, efficacy and cost-effectiveness of reusing SUDs. Legal and ethical issues require attention to minimize liability and maintain patient safety and trust. Some hospitals that reprocess SUDs do not have adequate documentation. These findings do not support the reuse of SUDs in Canadian hospitals.

Objectives: To examine the production of Health Technology Assessments (HTAs) with economic evaluations (EEs) conducted by Canadian HTA agencies.

Methods: This research used a three-step approach: (i) the Web sites of five Canadian organizations promoting HTA were searched to identify HTA reports with EEs; (ii) HTA agencies were surveyed to verify that our information was complete with respect to HTA activities and to describe the factors that influence the HTA process in Canada (i.e., selection of HTA topics, execution, dissemination of results and future trends); (iii) HTAs with EEs were appraised in terms of study design, retrieval of clinical and economic evidence, resource utilization and costing, effectiveness measures, treatment of uncertainty as well as presence of a budget impact analysis (BIA), and policy recommendations.

Results: Two hundred forty-nine HTA reports were identified of which 19 percent included EEs (n = 48). Decision analytic techniques were used in approximately 75 percent of the forty-eight EEs and probabilistic sensitivity analyses were commonly used by all agencies to deal with parameter uncertainty. BIAs or policy recommendations were given in 50 percent of the evaluations. Differences between agencies were observed in terms of selection of topics, focus of assessment and production of HTA (e.g., in-house activities). Major barriers to the conduct of HTAs with EEs were capacity, a lack of interest by decision makers and a lack of robust clinical information.

Conclusions: The results of this research point to the need for increased HTA training, collaboration, evidence synthesis, and use of pragmatic “real world” evaluations.

Objectives: Information technology is a rapidly expanding branch of science which has affected other sciences. One example of using information technology in medicine is the Electronic Medical Records system. One medical university in Iran decided to introduce such system in its hospital. This study was designed to identify the factors which influence the quality of medical documentation when paper-based records are replaced with electronic records.

Methods: A set of 300 electronic medical records was randomly selected and evaluated against eleven checklists in terms of documentation of medical information, availability, accuracy and ease of use. To get the opinion of the care-providers on the electronic medical records system, ten physicians and ten nurses were interviewed by using of semi-structured guidelines. The results were also compared with a prior study with 300 paper-based medical records.

Results: The quality of documentation of the medical records was improved in areas where nurses were involved, but those parts which needed physicians' involvement were actually worse. High workloads, shortage of bedside hardware and lack of software features were prominent influential factors in the quality of documentation. The results also indicate that the retrieval of information from the electronic medical records is easier and faster, especially in emergency situations.

Conclusions: The electronic medical records system can be a good substitute for the paper-based medical records system. However, according to this study, some factors such as low physician acceptance of the electronic medical record system, lack of administrative mechanisms (for instance supervision, neglecting physicians and/or nurses in the development and implementation phases and also continuous training), availability of hardware as well as lack of specific software features can negatively affect transition from a paper-based system to an electronic system.

Objectives: Analysis of and understanding the utilization patterns of diagnostic imaging technologies is important for planning health systems especially in middle- and low-income countries. Almost all published studies have been focused on utilization trends or utilization rates of magnetic resonance imaging (MRI) over time and little has been published about utilization patterns of MRI. This study aims to identify and describe the utilization pattern of MRI in Iran.

Methods: Data was collected from referrals and MRI reports of the population covered by one of the largest insurance organizations (Social Security Organization [SSO]) with more than 27 million beneficiaries in the Country. We focused on patients who had undergone an MRI examination during 1 month (October 13 to November 12), 2005. The data collected consisted of 1,656 referrals for MR imaging and 1,547 MRI reports.

Results: No clear association was found between the number of referrals per 100,000 population and the number of MRI machines per 100,000 population (r = 0.30; p = .13). Neurosurgeons, orthopedists, and neurologists contributed to more than 88 percent of MRI utilization. The Spinal column (55 percent), brain (25.5 percent), and knee (11.0 percent) were the most common parts of the body scanned by MRI.

Conclusions: Having identified some of the most frequent users of MRI technology, any plan for modifying or improving MRI use should focus mainly on these specialties. International evidence on using the technology for examining brain and spine indicate that MRI is mainly used in diagnosing the central nervous system (CNS) diseases.

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.

Background: Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges.

Objectives: The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments.

Methods: We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development.

Results: Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications.

Conclusions: Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

Objectives: Although increasing effort is being devoted to developing strategies to increase knowledge transfer and the uptake of health technology assessment (HTA) by various stakeholders, very little is known about the utilization and dissemination of HTA findings by patient and consumer organizations. The goal of this study is to understand how and why patient and consumer organizations use HTA findings within their organizations, and what factors influence how and when they communicate their findings to members or other organizations.

Methods: We examined the use and dissemination of four controversial HTA reports by sixteen patient and consumer organizations in Ontario and Quebec. We gathered data from semistructured interviews conducted between December 2006 and April 2007.

Results: Although HTA findings are often used by the patient and consumer organizations, key differences were observed in exactly how the four HTA reports were used. Three types of use (instrumental, conceptual, and symbolic) are reported and illustrated. We highlight the importance of the organization's mission and knowledge base in explaining the types of use observed.

Conclusions: We contend that the use and dissemination of HTA reports by specific groups could help in widening the debate around controversial health technologies. The implications and opportunities for HTA agencies relate to the following: (i) identification of “lay” organizations that could help in disseminating results; (ii) acknowledgement of a “lay” audience for HTA findings; (iii) strategic inclusion of advocacy groups during the assessment process for highly controversial technologies; and (iv) contribution of these organizations to the push efforts of knowledge transfer.

Objectives: To compare four contingent valuation elicitation methods as a means to estimate the value of a pneumococcal vaccine in Bangladesh and to test if the elicitation methods are subject to bias and if they produce valid responses.

Methods: Three hundred sixty-one households with at least one child under 5 years of age were recruited in Dhaka, Bangladesh. Subjects were cluster-randomized to various elicitation methods: open-ended, dichotomous choice (at one of two asking prices), payment card (one of two cards with differing ranges). The dichotomous choice method was then followed up with a bidding game methodology, with the dichotomous choice price acting as the starting price for the bidding game. Analysis focused on summary statistics, demand curve estimation and multivariate regression analysis to test for validity and bias.

Results: Thirty-one households refused to participate, leaving a total of 330 participating households (a 91.4 percent response rate). Willingness to pay estimates varied significantly across the methods (p < .001), with average estimates varying between $2.34 and $18 (US). The open-ended elicitation method was found to produce highly inflated values that were insensitive to construct validity tests. The dichotomous choice method produced quantity (demand) estimates rather than value estimates, and there was some evidence of yea saying. The payment card elicitation method was found to be affected by range bias. The bidding game elicitation method was found to be less sensitive to starting point bias and yea-saying.

Conclusions: Different elicitation format do give rise to different demand curves; however, this may be partially due to the fact that they do not measure the same outcome. For example, the dichotomous choice format produces a demand curve, while the payment card, open-ended and bidding game produce inverse demand curves. All formats are prone to multiple biases. When choosing an elicitation format, it is important to first consider the purpose and use of the data. Each elicitation method has strengths and weaknesses and can be used for different purposes in technology assessment.

Objectives: The purpose of this study was to empirically explore whether individuals take their expected income into consideration when directly valuing predefined health states. This was intended to help determine how to handle productivity costs due to morbidity in a cost-effectiveness analysis.

Methods: Two hundred students each valued four hypothetical health states by using time trade-off (TTO) and a visual analogue scale (VAS). The students were randomly assigned to two groups. One group was simply asked, without mentioning income, to value the different health states (the non-income group). The other group was explicitly asked to consider their expected income in relation to the health states in their valuations (the income group).

Results: For health states that are usually assumed to have a large effect on income, the valuations made by the income group seemed to be lower than the valuations made by the non-income group. Among the students in the non-income group, 96 percent stated that they had not thought about their expected income when they valued the health states. In the income group, 40 percent believed that their expected income had affected their valuations of the health states.

Conclusion: The results show that, as long as income is not mentioned, most individuals do not seem to consider their expected income when they value health states. This indicates that productivity costs due to morbidity are not captured within individuals' health state valuations. These findings, therefore, suggest that productivity costs due to morbidity should be included as a cost in cost-effectiveness analyses.

Objectives: In the Netherlands, allocation decisions have not yet been explicitly based on the Value of Statistical Life. However, when policy makers decide whether or not to implement life saving interventions this trade-off is made implicitly. This study aimed to gain insights into this trade-off, hereafter referred to as Implicit Value of Statistical Life (IVSL), by means of a retrospective investment analysis of life saving interventions implemented in the Netherlands.

Methods: A literature search was conducted to find life saving intervention cases meeting the requirements for IVSL calculation. A final sample of ten cases was included in the study concerning interventions implemented in different societal sectors. For each case, an IVSL estimate was calculated according to a uniform method.

Results: IVSL estimates derived from the intervention cases differed considerably and ranged from €1 to almost €11 million. Differences were most extreme when comparing IVSL estimates concerning interventions implemented in different societal sectors. However, IVSL estimates also varied greatly between interventions in the same sector and even within the same interventions when critical assumptions were altered.

Conclusion: Our findings suggest that there are great imbalances between societal investments for preventing a statistical death. This highlights the need for further deliberation about how to improve transparency of policy decisions. An approach ex ante determining the Value of Statistical Life by means of empirical methods and based on societal preferences might circumvent the problems associated with the IVSL and needs further exploration.

Objectives: The aim of this study was to benchmark the proposal forms used by a sample of Italian hospitals to inform the budget process for the adoption of new technology to understand the relationship with the guidelines provided by the Health Technology Assessment (HTA) literature.

Methods: A literature review was first undertaken to identify the frameworks developed to support decision making regarding new technology at a hospital level. A checklist of criteria drawn up according to five main perspectives (technology, patient, organization, economics, and level of evidence) has been formalized to review and compare the collected proposal forms.

Results: The “technology” perspective appears to have been broadly covered. The “patient” perspective has focused to clinical issues and partially neglects other dimensions such as patient satisfaction and potential adverse events. The “organization” dimension has paid little attention to change management. The “economics” dimension has been broadly covered, even though a sensitivity analysis has not been considered. The “level of evidence” that is required for submitting the proposal form is little.

Conclusions: The proposal forms used to inform the budget process regarding the adoption of new technology are accountable for a limited set of dimensions from among those proposed in literature. Further research is required to understand how to render technology assessment multidimensional, multidisciplinary, evidence-based, and accountable at a hospital level.

As more countries use HTA to inform decisions on the reimbursement of health technologies, harmonization of evidence requirements between jurisdictions has been proposed, mainly on the grounds of improved efficiency. Harmonization has the potential to avoid duplication of effort for both manufacturers and HTA bodies involved in preparing and reviewing HTA submissions for innovative technologies. However, it also carries risks of loss of local control over decisions, the application of general data standards which are not universally accepted and slowing the rate of development of innovation in the analytical disciplines supporting HTA. This study reviews the issues associated with harmonization taking into account the perspectives of the multiple stakeholders. This study draws on experiences from recent initiatives intended to promote the harmonization of HTA and experience from related fields, particularly regulatory approval of new medical technologies.

Objectives: To report on a workshop, and subsequent discussions, that reviewed the achievements and progress of the EuroScan collaboration since its establishment in 1999 to share information on the methods and results of early identification and assessment of new and emerging health technologies; considered challenges to the collaboration; and discussed its possible future direction.

Methods: A workshop was held in Stockholm in September 2006, with thirty-two participants from ten countries and representatives from EuroScan member agencies, policy makers involved in policy or decision making relating to new technologies, and invited external commentators from international HTA networks. The workshop used a mix of presentations, panel and audience discussions, and small group work to consider the achievements and challenges put forward.

Results: EuroScan has developed as a sustainable network, and has made progress on all tasks in its initial action plan, with the EuroScan information sharing database on new and emerging technologies being one of the collaboration's key achievements. Identified immediate concerns for the network included consideration of the impact of its current name and membership model; acknowledgement and publication of the full range of benefits of membership; contribution to and development of the database to encourage increased information sharing; and EuroScan's ongoing interaction with the wider HTA world.

Conclusions: The workshop was a useful mechanism for reviewing the work of EuroScan and for creating a platform to take the collaboration forward. The workshop affirmed the benefits of the network to individual members; posed some significant challenges to the network to consider; and acted as a stimulus for an interim name change to better represent the global membership, and a major review of the EuroScan database of identified and assessed emerging health technologies.