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

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

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

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

Background: A randomized controlled trial has shown that supervised, facility-based exercise training is effective in improving glycemic control in type 2 diabetes. However, these programs are associated with additional costs. This analysis assessed the cost-effectiveness of such programs.

Methods: Analysis used data from the Diabetes Aerobic and Resistance Exercise (DARE) clinical trial which compared three different exercise programs (resistance, aerobic or a combination of both) of 6 months duration with a control group (no exercise program). Clinical outcomes at 6 months were entered for individual patients into the UKPDS economic model for type 2 diabetes adapted for the Canadian context. From this, expected life-years, quality-adjusted life-years (QALYs) and costs were estimated for all patients within the trial.

Results: The combined exercise program was the most expensive ($40,050) followed by the aerobic program ($39,250), the resistance program ($38,300) and no program ($31,075). QALYs were highest for combined (8.94), followed by aerobic (8.77), resistance (8.73) and no program (8.70). The incremental cost per QALY gained for the combined exercise program was $4,792 compared with aerobic alone, $8,570 compared with resistance alone, and $37,872 compared with no program. The combined exercise program remained cost-effective for all scenarios considered within sensitivity analysis.

Conclusions: A program providing training in both resistance and aerobic exercise was the most cost-effective of the alternatives compared. Based on previous funding decisions, exercise training for individuals with diabetes can be considered an efficient use of resources.

Background: In recent years, there has been growing interest in evaluating the health and economic impact of medical devices. Payers increasingly rely on cost-effectiveness analyses in making their coverage decisions, and are adopting value-based purchasing initiatives. These analytic approaches, however, have been shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to the medical device context.

Methods: This study focuses on the development and evaluation of left ventricular assist devices (LVADs) to highlight the unique challenges involved in the design and conduct of device trials compared with pharmaceuticals.

Results: Devices are moving targets characterized by a much higher degree of post-introduction innovation and “learning by using” than pharmaceuticals. The cost effectiveness ratio of left ventricular assist devices for destination therapy, for example, decreased from around $600,000 per life year saved based on results from the pivotal trial to around $100,000 within a relatively short time period.

Conclusions: These dynamics pose fundamental challenges to the evaluation enterprise as well as the policy-making world, which this paper addresses.

Objectives: A treatment pathway model was developed to examine the costs and benefits of the current bowel cancer service in England and to evaluate potential alternatives in service provision. To use the pathway model, various parameters and probability distributions had to be specified. They could not all be determined from empirical evidence and, instead, expert opinion was elicited in the form of statistical quantities that gave the required information. The purpose of this study is to describe the procedures used to quantify expert opinion and note examples of good practice contained in the case study.

Methods: The required information was identified and preparatory discussion with four experts refined the questions they would be asked. In individual elicitation sessions they quantified their opinions, mainly in the form of point and interval estimates for specified variables. New methods have been developed for quantifying expert opinion and these were implemented in specialized software that uses interactive graphics. This software was used to elicit opinion about quantities related to measurable covariates.

Results: Assessments for thirty-four quantities were elicited and available checks supported their validity. Eight points of good practice in eliciting and using expert judgment were evident. Parameters and probability distributions needed for the pathway model were determined from the elicited assessments. Simulation results from the pathway model were used to inform policy on bowel cancer service provision.

Conclusions: The study illustrates that quantifying and using expert judgment can be acceptable in real problems of practical importance. For full benefit to be gained from expert knowledge, elicitation must be conducted carefully and should be reported in detail.

Objectives: The purpose of this study is to compare the approaches used for valuing family caregiver and care recipient time devoted to providing and receiving care.

Methods: Valuation approaches were operationalized within a cohort of cystic fibrosis care recipients (n = 110). Base-case analyses, grounded in human capital theory, applied earnings estimates to caregiving time to impute the market value of time lost from labor. Unpaid labor and leisure time was valued with a replacement cost (homemaker's wage rate). Total time costs were computed and sensitivity analyses were conducted to describe the effects of alternative valuation methods on total costs.

Results: The mean time cost per care recipient–caregiver dyad over 28 days was $2,026CAD. The majority (76 percent) of time costs were due to losses from unpaid labor and leisure time. Varying the valuation of paid labor time did not result in significantly different total time costs (p = .0877). However, varying the method of valuing unpaid labor and leisure time did significantly affect total costs (p < .0001).

Conclusions: Care recipients and caregivers primarily lost time from unpaid labor and leisure in the treatment of cystic fibrosis. Moreover, when the above losses were aggregated, the method of valuation greatly influenced overall results. The findings clearly indicate that omitting caregiver and unpaid labor and leisure costs may result in an inaccurate assessment of ambulatory and home-based healthcare programs.

Objectives: Model for ASsessment of Telemedicine Applications (MAST) is a health technology assessment (HTA) inspired framework for assessing the effectiveness and contribution to quality of telemedicine applications based on rigorous, scientific data. This study reports from a study of how it was used and perceived in twenty-one pilots of the European project RENEWING HEALTH (RH). The objectives of RH were to implement large-scale, real-life test beds for the validation and subsequent evaluation of innovative patient-centered telemedicine services. The study is a contribution to the appraisal of HTA methods.

Methods: A questionnaire was administered for project leaders of the pilots. It included questions about use and usefulness of MAST for (i) preceding considerations, (ii) evaluation of outcomes within seven domains, and (iii) considerations of transferability. Free text spaces allowed for proposals of improvement. The responses covered all pilots. A quantitative summary of use and a qualitative analysis of usefulness were performed.

Results: MAST was used and considered useful for pilot evaluations. Challenges included problems to scientifically determine alternative service options and outcome within the seven domains. Proposals for improvement included process studies and adding domains of technological usability, responsible innovation, health literacy, behavior change, caregiver perspectives and motivational issues of professionals.

Conclusions: MAST was used according to its structure. Its usefulness in patient centered pilots can be improved by adding new stakeholder groups. Interdependencies between scientific rigor, resources and timeliness should be addressed. Operational options for improvements include process studies, literature reviews and sequential mini-HTAs for identification of areas for more elaborate investigations.

Objectives: The Secondary Prevention of Heart disEase in geneRal practicE (SPHERE) trial has recently reported. This study examines the cost-effectiveness of the SPHERE intervention in both healthcare systems on the island of Ireland.

Methods: Incremental cost-effectiveness analysis. A probabilistic model was developed to combine within-trial and beyond-trial impacts of treatment to estimate the lifetime costs and benefits of two secondary prevention strategies: Intervention - tailored practice and patient care plans; and Control - standardized usual care.

Results: The intervention strategy resulted in mean cost savings per patient of €512.77 (95 percent confidence interval [CI], −1086.46–91.98) and an increase in mean quality-adjusted life-years (QALYs) per patient of 0.0051 (95 percent CI, −0.0101–0.0200), when compared with the control strategy. The probability of the intervention being cost-effective was 94 percent if decision makers are willing to pay €45,000 per additional QALY.

Conclusions: Decision makers in both settings must determine whether the level of evidence presented is sufficient to justify the adoption of the SPHERE intervention in clinical practice.

Objective: The objective of this study was to examine the economics of administering calcium and vitamin D3 to post-menopausal women in Sweden. We focus primarily on the cost-effectiveness of treating older women for whom clear evidence of efficacy is available. We supplement this information, however, with estimates of the cost-effectiveness of treating certain high-risk groups of younger women, while acknowledging the greater uncertainty involved.

Methods: We developed a Markov model for analyzing the occurrence and timing of hip fractures, based almost entirely on peer-reviewed data from Sweden. In a 3-year randomized clinical trial, the combination of calcium and vitamin D3 was shown to reduce the risk of hip fractures by 27%. Costs for treating hip fractures were based on 1,080 women who were hospitalized in Stockholm.

Results: Treatment of 70-year-old women was cost saving at efficacy as low as two-thirds that seen in the clinical trials, and upwards. Even at modest rates of efficacy, treatment of the high-risk 50- and 60-year-old cohorts was generally cost-effective and in some cases even cost saving. Particularly cost-effective was treatment of women with identified osteoporosis or a maternal family history of hip fracture.

Conclusion: Simulation results suggest a role for lifetime treatment of older women with calcium and vitamin D3 in Sweden. While there is more uncertainty underlying the treatment of younger women, our simulation results suggest that treatment may also be cost saving or at least cost-effective for many cohorts of high-risk 50- and particularly 60-year-old women, in particular those with osteoporosis or a maternal family history of hip fracture.

The Quebec Council on Health Care Technology Assessment was created in 1988. Its functions are to promote, support, and produce health care technology assessments and to advise the Minister of Health. An independent review of the council’s first four years of operation was commissioned. The evaluation team concluded that the council showed very good results in terms of the scope, quality, and impact of its production and succeeded in establishing its credibility. However, the evaluation team suggested that the council adopt a more active strategy toward the promotion and diffusion of its reports. Some critical determinants of success of the Quebec experience in technology assessment are discussed.

To increase access to care for cataract patients in Sweden, it was decided, starting in 1992, that all cataract patients listed for surgery and with priority should have their cataract extraction performed within three months. To evaluate the effect of this waiting time guarantee, a National Cataract Register (NCR) was initiated in late 1991. In 1992, 81% of all cataract extractions performed in Sweden were reported to the NCR; in 1993 this figure was 92%. Reasons for this high participation ratio are discussed. In 1993, 74.4% (range between different clinics, 40–99%) of the patients with priority had their operation performed within three months. Great variation in visual acuity and age was found in patients with priority among the different surgical units.

This paper explores the characteristics of health technology assessment (HTA) systems and practices in Asia. Representatives from nine countries were surveyed to understand each step of the HTA pathway. The analysis finds that although there are similarities in the processes of HTA and its application to inform decision making, there is variation in the number of topics assessed and the stakeholders involved in each step of the process. There is limited availability of resources and technical capacity and countries adopt different means to overcome these challenges by accepting industry submissions or adapting findings from other regions. Inclusion of stakeholders in the process of selecting topics, generating evidence, and making funding recommendations is critical to ensure relevance of HTA to country priorities. Lessons from this analysis may be instructive to other countries implementing HTA processes and inform future research on the feasibility of implementing a harmonized HTA system in the region.

Objectives: How to contain medical expenditures is a universal problem. The Japanese government has increased patient co-payments to control it. The purpose of this study is to clarify whether the increase in co-payments to 30 percent prevented patients with hypertension or diabetes mellitus from receiving necessary care in the Employee Health Insurance System.

Methods: The subjects were 211 patients with hypertension and 66 patients with diabetes mellitus who regularly visited physicians from October 2001 to March 2002 and were defined as a cohort that needed health care, and their medical indicators were examined between April and September 2002 (prestage) and between April and September 2003 (poststage).

Results: In the hypertensive patients with no complications, the compliance rate was 89.9 percent and 88.0 percent in the prestage, and poststage, respectively, showing no significant change. In the hypertensive patients with complications, the compliance rate was 90.5 percent and 92.1 percent in the prestage and poststage, respectively, showing no significant change. In the diabetic patients with complications, the compliance rate was 77.5 percent and 79.2 percent, in the prestage and poststage, respectively, with no significant change. In the diabetic patients with no complications, however, the compliance rate was 83.7 percent and 66.7 percent, in the prestage and poststage, respectively. A significant decrease was observed among diabetic patients without complications.

Conclusions: Increasing co-payments reduced necessary preventive care in diabetic patients without complications.

Objectives: This study examines the content and role of ethical analysis in health technology assessment (HTA) and horizon scanning publications. It proposes that ethical analysis in HTA is of at least two different types: an ethics of HTA and an ethics in HTA.

Methods: I examine the critical differences between these approaches through the examples of the analysis of genetic screening for breast cancer and home blood glucose testing in diabetes. I then argue that, although both approaches subscribe to similar views concerning HTA and ethics, they use different theoretical and methodological traditions to interpret and explain them.

Results and Conclusions: I conclude by suggesting that we need the interpretive insights of both these approaches, taken together, to explain why ethics has not been able yet to contribute fully to HTA and to demonstrate the scope and complexity of ethical work in this domain.

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.

The costs included in economic evaluations of health care vary from study to study. Based on the theory of cost-benefit analysis, the costs that should be included in an economic evaluation are those not already included in the measurement of willingness to pay (net willingness to pay above any treatment costs paid by the individual) in a cost-benefit analysis or in the easurement of effectiveness in a cost-effectiveness analysis. These costs can be defined as the onsumption externality of the treatment (the change in production minus consumption for those included in the treatment program). For a full economic evaluation, the consequences for those included in the treatment program and a caring externality (altruism) should also be added.

Objectives: The aim of this study was to illustrate the contribution of stakeholder engagement to the impact of health technology assessment (HTA) using an Irish HTA of a national public access defibrillation (PAD) program.

Background: In response to draft legislation that proposed a PAD program, the Minister for Health requested that Health Information and Quality Authority undertake an HTA to inform the design and implementation of a national PAD program and the necessary underpinning legislation. The draft legislation outlined a program requiring widespread installation and maintenance of automatic external defibrillators in specified premises.

Methods: Stakeholder engagement to optimize the impact of the HTA included one-to-one interviews with politicians, engagement with an Expert Advisory Group, public and targeted consultation, and positive media management.

Results: The HTA quantified the clinical benefits of the proposed PAD program as modest, identified that substantial costs would fall on small/medium businesses at a time of economic recession, and that none of the programs modeled were cost-effective. The Senator who proposed the Bill actively publicized the HTA process and its findings and encouraged participation in the public consultation. Participation of key stakeholders was important for the quality and acceptability of the HTA findings and advice. Media management promoted public engagement and understanding. The Bill did not progress.

Conclusions: The HTA informed the decision not to progress with legislation for a national PAD program. Engagement was tailored to ensure that key stakeholders including politicians and the public were informed of the HTA process, the findings, and the advice, thereby maximizing acceptance. Appropriate stakeholder engagement optimizes the impact of HTA.

Objectives: Fatigue is the most common symptom reported by cancer patients. The inclusion of health-related quality of life (HRQL) measures in routine clinical care of cancer patients may improve the management of fatigue. The primary objective of this study is to provide evidence on the magnitude of change in fatigue subscale scores using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) that is clinically important.

Methods: Consecutive patients with advanced primary lung cancer attending a Canadian tertiary care cancer and, prior to undergoing palliative chemotherapy, were enrolled in the study. Patients completed a battery of questionnaires [FACT-F, Qualitative Patients Self-report of Fatigue Level (QPSRF)] at baseline, follow-up and 2 weeks after their final cycle of chemotherapy. Clinicians assessed the patients using the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at baseline and each follow-up visit. FACT-F change scores were computed as the mean change in score (end of study score minus baseline score).

Results: A total of 43 patients with mean age of 59 years were enrolled in the study. Results revealed a mean change in FACT-F subscale score of 5.0 (SE 1.06) for those who rated themselves as more tired, 1.28 (SE 1.00) for those who rated themselves as the same (no change), and −1.52 (SE 0.84) for those patients who rated themselves as less tired.

Conclusions: We provide evidence on the magnitude of change in FACT-F score that is associated with the perception by patients of improvement in fatigue and magnitude of change in score that is associated with worsening in fatigue.

Objectives: The impact of learning effects on the variability of costs of new health technologies in a prospective payment system (PPS) through the case of intensity modulated radiation therapy (IMRT) was studied.

Methods: A series of consecutive patients treated in nine medical centers was enrolled in a prospective study. Direct costs were assessed from the perspective of the healthcare providers. We used a two-level model to explain the variability of costs: patients nested within centers. Learning effects at the center level were considered through a fixed effect (the learning curve slope) and a random effect (the initial cost level). Covariates were introduced to explain the patterns of variation in terms of patient characteristics.

Results: The mean direct cost of IMRT was €5,962 (range, €2,414–€24,733). Manpower accounted for 53 percent of this cost. Learning effects explained 42 percent of the variance between centers (which was 88 percent of the total variance) and were associated with a substantial decrease in treatment costs. The mean initial treatment direct cost was €6,332 in centers with a previous experience of IMRT, whereas it was €14,192 in centers implementing IMRT for the first time. Including logistics costs and overhead, the full cost of IMRT was €10,916. Average reimbursement was €6,987.

Conclusions: Learning effects are a strong confounding factor in the analysis of costs of innovative health technologies involving learning effects. In a PPS, innovative health technology involving learning effects necessitates specific reimbursement mechanisms.

Objectives: Leukemia, together with lymphoma and multiple myeloma, are hematological malignancies, malignancies of the blood-forming organs. There are four major types of leukemia: acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). There is a growing amount of literature of the health economic aspects of leukemia. However, no comprehensive review is yet performed on the health economic evidence for the disease. Hence, our aim was to review and analyze the existing literature on economic evaluations of the different types of leukemia.

Methods: A systematic literature search used electronic databases to identify published cost analyses and economic evaluations of leukemia treatments. After reviewing all identified studies, sixty studies were considered relevant for the purpose of the review.

Results: The identified studies were published after 1990, with a few exceptions. Many of the identified economic evaluations in leukemia, particularly for ALL and AML, may be defined as cost-minimization analyses, where only the costs of different treatment strategies are compared. In CML, a new treatment, imatinib, was introduced in 2001 and several cost-effectiveness analyses have since then been conducted comparing imatinib with previous first line treatments.

Conclusions: This review indicates that there is a shortage of cost-effectiveness information in leukemia. The introduction of new therapies will stress the need for new economic evaluations in this group of diseases. More information about the total costs, that is, including indirect costs, and quality of life effects would be valuable in future evaluations in leukemia.