Background: Comprehensive health technology assessments (HTAs) include thorough reflections on ethical issues associated with health technologies, their use, and value-based decisions in the assessment process. As methods of information retrieval for effectiveness assessments are not applicable to information retrieval on ethical issues, a specific methodological approach is necessary.

Objectives: In the absence of existing adapted methods, our objective was to develop a methodological approach for the systematic retrieval of information on ethical issues related to health technologies.

Method and Results: A literature search was conducted to verify the non-existence of published comprehensive methodological approaches for the information retrieval on ethical issues for HTAs, and resulted in no hits. We, therefore, developed a step-by-step workflow following the workflow of information retrieval for effectiveness assessments: Step 1: Translation of the search question using the PICO scheme and additional components. Step 2: Concept building by modeling and linking search components. Step 3: Identification of synonyms in all relevant languages. Step 4: Selection of relevant information sources. Step 5: Design of search strategies for bibliographic databases. Step 6: Execution of search strategies and information seeking, including hand-searching. Step 7: Saving of retrieval results and standardized reporting of the process and results. Step 8: Final quality check and calculation of precision and recall.

Conclusions: Systematic searching for information on ethical issues related to health technologies can be performed following the common retrieval workflow for effectiveness assessments, but should be performed separately applying adapted procedures and search terms on ethical issues relevant to the research question.

A desirable element of cost-effectiveness analysis (CEA) modeling is a systematic way to relate uncertainty about input parameters to uncertainty in the computational results of the CEA model. Use of Bayesian statistical estimation and Monte Carlo simulation provides a natural way to compute a posterior probability distribution for each CEA result. We demonstrate this approach by reanalyzing a previously published CEA evaluating the incremental cost-effectiveness of tissue plasminogen activator compared to streptokinase for thrombolysis in acute myocardial infarction patients using data from the GUSTO trial and other auxiliary data sources. We illustrate Bayesian estimation for proportions, mean costs, and mean quality-of-life weights. The computations are performed using the Bayesian analysis software WinBUGS, distributed by the MRC Biostatistics Unit, Cambridge, England.

Objectives: The evaluation of telemedicine from the patient's point of view has focused on the patient pathway and patient satisfaction. However, research in this field does not provide us with the means to assess a patient's perception of the procedure if their reasoning ability is impaired. In this study, we use direct observation of a patient's behavior and mood to assess their perception of an oral teleconsultation procedure.

Methods: This study has been conducted in the context of a pilot project using an asynchronous teleconsultation to improve access to dental care for the dependent elderly, disabled people, and prisoners, some of whom may be cognitively impaired. We use a direct observation form consisting of five behavioral variables and eight affect variables to reflect the patient's experience of the oral teleconsultation procedure.

Results: A total of 135 patients were evaluated; 10 refused the procedure. Psychotic patients (n = 33) had a somewhat negative experience during the oral teleconsultation procedure. Patients who were not psychotic had a positive experience; this decreased as we moved from the autonomous to the semi-autonomous and then to the dependent sub-group. Some gender differences were also noted.

Conclusions: Improving evidence on evaluating the acceptance of the cognitively impaired is required to improve the technology development process so that it can be translated into an improved patient experience and adherence. Although the study was specifically focused on teledentistry, the approach described in this study could be adapted to other forms of teleconsultation.

Background: Home hemodialysis offers potential advantages over hospital hemodialysis, including the opportunity for more frequent and/or longer dialysis sessions. Expanding home hemodialysis services may help cope with the increasing numbers of people requiring hemodialysis.

Methods: We sought comparative studies or systematic reviews of home versus hospital/satellite unit hemodialysis for people with end-stage renal failure (ESRF). Outcomes included quality of life and survival. We searched MEDLINE, EMBASE, HealthSTAR, CINAHL, PREMEDLINE, and BIOSIS. Two reviewers independently extracted data and assessed the quality of the studies included.

Results: Twenty-seven studies of variable quality were included. People on home hemodialysis generally experienced a better quality of life and lived longer than those on hospital hemodialysis. Their partners, however, found home hemodialysis more stressful. Four studies using a Cox proportional hazards model to compare home with hospital hemodialysis reported a lower mortality risk for home hemodialysis. Of two studies using a Cox model to compare home with satellite unit hemodialysis, one reported a similar mortality risk, whereas the other reported a lower mortality risk for home hemodialysis.

Conclusions: Home hemodialysis was generally associated with better outcomes than hospital hemodialysis and (more modestly so) satellite unit hemodialysis, in terms of quality of life, survival, and other measures of effectiveness. People on home hemodialysis, however, are a highly selected group. Home hemodialysis also provides the opportunity for more frequent and/or longer dialysis sessions than would otherwise be possible. It is difficult to disentangle the true effects of home hemodialysis from such influencing factors.

Objectives: To describe the number of trials and participants in a typical systematic review from The Cochrane Database of Systematic Reviews.

Methods: The number of trials in 1,000 Cochrane systematic reviews in issue 1, 2001 of The Cochrane Database of Systematic Reviews was counted for three categories of trial: included trials, ongoing trials, and trials awaiting assessment for inclusion. (The term trial is used in this paper, although a small number of Cochrane reviews include studies that are not trials.) The total number of participants in included trials was extracted from a sample of reviews.

Results: A total of 9,778 trials were included in the Cochrane reviews. There were a further 356 ongoing trials and 1,138 trials awaiting assessment for inclusion. A typical review contained six included trials. Forty percent of the reviews listed ongoing trials and/or trials awaiting assessment for inclusion. Based on a sample of 258 reviews, the median number of participants per review was 945 (interquartile range, 313 to 2,511) per review and 118 (interquartile range, 60 to 241) per trial.

Conclusion: This report is a descriptive study of the number of trials and participants in a typical Cochrane review from The Cochrane Library, issue 1, 2001.

Objectives: The Human Genome Project has led to a multitude of new potential screening targets on the level of human DNA. The aim of this systematic review is to critically summarize the evidence from health economic evaluations of genetic screening in the literature.

Methods: Based on an extensive explorative search, an appropriate algorithm for a systematic database search was developed. Twenty-one health economic evaluations were identified and appraised using published quality criteria.

Results: Genetic screening for eight conditions has been found to be investigated by health economic evaluation: hereditary breast and ovarian cancer, familial adenomatous polyposis (FAP) colorectal cancer, hereditary nonpolyposis colorectal carcinoma (HNPCC), retinoblastoma, familial hypercholesterolemia, hereditary hemochromatosis, insulin-dependent diabetes mellitus, and cystic fibrosis. Results range from dominated to cost-saving. Population-wide genetic screening may be considered cost-effective with limited quality of evidence only for three conditions. The methodology of the studies was of varying quality. Cost-effectiveness was primarily influenced by mutation prevalence, genetic test costs, mortality risk, effectiveness of treatment, age at screening, and discount rate.

Conclusions: Health economic evidence on genetic screening is limited: Only few conditions have properly been evaluated. Based on the existing evidence, healthcare decision makers should consider the introduction of selective genetic screening for FAP and HNPCC. As genetic test costs are declining, the existing evaluations may warrant updating. Especially in the case of hereditary hemochromatosis, genetic population screening may be about to turn from a dominated to a cost-effective or even cost-saving intervention.

Despite their potential utility, clinicians are skeptical about claims data as a substrate for clinical research. Clinicians' concerns are centered on two issues—the quality of the data and the fairness of comparisons that are made. To increase the impact of claims data research on clinical practice, several strategies should be pursued.

Objectives: To examine differences in the ethical judgments made by Research Ethics Committees (RECs) or Institutional Review Boards (IRBs).

Methods: We did a review of the literature and included any study that attempted to compare the ethical judgments made by different RECs or IRBs when reviewing one or more protocol.

Results: There were twenty-six articles reporting such discrepancies across Europe, within the United Kingdom, Spain, and United States. Of these studies, there were only five reports of some RECs approving while others rejecting the same protocol. All studies, however, reported differences in the clarifications and revisions asked of researchers regarding consent, recruitment, risks and benefits, compensation arrangements, and scientific issues.

Conclusions: The studies were generally anecdotal reports of researchers trying to do research. New rules requiring a single ethical opinion for multi-site research at least in European Member States may simply conceal problematic issues in REC decision making. In the last analysis, we should expect a certain degree of variation and differences if we are to keep a committee system of review, although there is a pressing need to investigate the way in which RECs make these judgments. In particular, we need to identify the source of any aberrations, distortions, or confusions that could arbitrarily affect these judgments. Furthermore, local conditions remain important ethical considerations and should not be sidelined in pursuit of greater “consistency.”

Objectives: Many hospitals in New Zealand have been using clinical priority assessment criteria (CPAC) to select and prioritize patients for access to publicly funded elective surgery. CPAC usually consist of clinical, patient-experienced, and social measures. The objective of this study was to determine how robust patient rankings were and the extent to which the patients selected were those who benefited the most from surgery.

Methods: Patients prioritized for cataract (n = 101), prostate (n = 103), and hip or knee joint replacement (n = 137) surgery according to CPAC were assessed using the EQ-5D, SF-12, and condition-related patient-experienced health status measures before and after treatment. Correlations between the rankings of patients on the CPACs and the alternative instruments were explored.

Results: For each surgery group, the CPAC ranking of patients was not strongly correlated with rankings obtained using their before-treatment EQ-5D (valued) profiles or the SF-12, although there was some correlation with rankings according to the condition-related measures. Improvements in the health status of patients who were operated on, as measured by the change in their EQ-5D values, were poorly correlated with equivalent changes on the SF-12 and condition-related measures. Patients' baseline health status according to the CPAC, the EQ-5D, and the SF-12 patient-experienced measures was only slightly related to the magnitude of benefit following surgery. The strongest predictors of improvement in health status were the baseline condition-related measures.

Conclusions: The current method of prioritizing patients in New Zealand requires reconsideration, although a gold standard method for prioritization is not immediately apparent from these results.

To examine the validity of the additive quality-adjusted lite year model used to evaluate a multiphase health state, data from a pilot study of mammography were used to determine whether the values assigned to a multiphase postmastectomy health state could be estimated from a combination of the independently rated constituent health state values. The results suggest that they cannot.

Objectives: The aim of this study was to evaluate the cost-effectiveness of four risk-lowering interventions (smoking cessation, antihypertensives, aspirin, and statins) in primary prevention of cardiovascular disease.

Methods: Using data from the Framingham Heart Study and the Framingham Offspring study, we built life tables to model the benefits of the selected interventions. Participants were classified by age and level of risk of coronary heart disease. The effects of risk reduction are obtained as numbers of death averted and life-years saved within a 10-year period. Estimates of risk reduction by the interventions were obtained from meta-analyses and costs from Dutch sources.

Results: The most cost-effective is smoking cessation therapy, representing savings in all situations. Aspirin is the second most cost-effective (€2,263 to €16,949 per year of life saved) followed by antihypertensives. Statins are the least cost-effective (€73,971 to €190,276 per year of life saved).

Conclusions: A cost-effective strategy should offer smoking cessation for smokers and aspirin for moderate and high levels of risk among men 45 years of age and older. Statin therapy is the most expensive option in primary prevention at levels of 10-year coronary heart disease risk below 30 percent and should not constitute the first choice of treatment in these populations.

There are marked geographical variations in rates of medical and surgical intervention at every level of aggregation and in every aspect of medical practice. These data raise a range of important theoretical, methodological, and policy issues. Much the same pattern of variation characterizes the prescription and consumption of therapeutic drugs. Data from a survey of general practice in New Zealand confirm the existence of extensive variability in prescribing. Multilevel techniques are deployed to isolate the specific interpractitioner element in this variability. Controlling for patient, diagnostic, and practitioner variables improves the predictive power of the model but does not reduce the extent of interpractitioner variability in prescribing rates. The existence of such variability raises questions about the role of clinical uncertainty and professional autonomy in the promotion of rational therapeutics in medical practice.

Objectives: Individual patient data (IPD) meta-analyses have been proposed as a major improvement in meta-analytic methods to study subgroup effects. Subgroup effects of conventional and IPD meta-analyses using identical data have not been compared. Our objective is to compare such subgroup effects using the data of six trials (n = 1,643) on the effectiveness of antibiotics in children with acute otitis media (AOM).

Methods: Effects (relative risks, risk differences [RD], and their confidence intervals [CI]) of antibiotics in subgroups of children with AOM resulting from (i) conventional meta-analysis using summary statistics derived from published data (CMA), (ii) two-stage approach to IPD meta-analysis using summary statistics derived from IPD (IPDMA-2), and (iii) one-stage approach to IPD meta-analysis where IPD is pooled into a single data set (IPDMA-1) were compared.

Results: In the conventional meta-analysis, only two of the six studies were included, because only these reported on relevant subgroup effects. The conventional meta-analysis showed larger (age < 2 years) or smaller (age ≥ 2 years) subgroup effects and wider CIs than both IPD meta-analyses (age < 2 years: RDCMA -21 percent, RDIPDMA-1 -16 percent, RDIPDMA-2 -15 percent; age ≥2 years: RDCMA -5 percent, RDIPDMA-1 -11 percent, RDIPDMA-2 -11 percent). The most important reason for these discrepant results is that the two studies included in the conventional meta-analysis reported outcomes that were different both from each other and from the IPD meta-analyses.

Conclusions: This empirical example shows that conventional meta-analyses do not allow proper subgroup analyses, whereas IPD meta-analyses produce more accurate subgroup effects. We also found no differences between the one- and two-stage meta-analytic approaches.

Objectives: The aim of this study was to estimate the cost-effectiveness of rituximab in patients not responding adequately to the first tumor necrosis factor (TNF) inhibitor using a model constructed to predict resource consumption and health outcomes in a population-based registry of biological treatments in Southern Sweden (SSATG).

Methods: The model was developed as a discrete event simulation model, using SSATG data for the years 1999–2007. The data set included 1,903 patients with complete data on treatments (up to three treatment lines), functional capacity (HAQ), disease activity (DAS28), and utility (EQ-5D). Resource consumption was based on a regular population-based survey of patients in Southern Sweden. Rituximab was incorporated as second line treatment, using effectiveness data for the active group (N = 311) in a clinical trial comparing rituximab to placebo (REFLEX). It is thus compared to the mix of second line biologics used in SSATG. The analysis starts after failure of the first TNF inhibitor. Results are reported as costs (€2008) per quality-adjusted life-year (QALY; both discounted 3 percent), for the societal perspective in Sweden.

Results: Total costs in the rituximab strategy are estimated at €401,100 compared with €403,000 in the TNF-inhibitor arm. Total QALYs are 5.98 and 5.78, respectively. The findings were found to be robust in extensive sensitivity analysis.

Conclusions: In our model, a strategy where rituximab is used as second line treatment after failure of the first TNF inhibitor provides a small saving (essentially due to the lower price of rituximab) and a QALY gain (due to better effect than the mix of second line TNF inhibitors).

Objectives: Given the resource-intensive nature of stroke rehabilitation, it is important that services be delivered in an evidence-based and cost-efficient manner. The objective of this review was to assess the evidence on the relative cost or cost-effectiveness of three rehabilitation services after stroke: stroke unit care versus care on another hospital ward, early supported discharge (ESD) services versus “usual care,” and community or home-based rehabilitation versus “usual care.”

Methods: A systematic literature review of cost analyses or economic evaluations was performed. Study characteristics and results (including mean total cost per patient) were summarized. The level of evidence concerning relative cost or cost-effectiveness for each service type was determined qualitatively.

Results: Fifteen studies met the inclusion criteria: three on stroke unit care, eight on ESD services, and four on community-based rehabilitation. All were classified as cost-consequences analysis or cost analysis. The time horizon was generally short (1 year or less). The comparators and the scope of costs varied between studies.

Conclusions: There was “some” evidence that the mean total cost per patient of rehabilitation in a stroke unit is comparable to care provided in another hospital ward. There is “moderate” evidence that ESD services provide care at modestly lower total costs than usual care for stroke patients with mild or moderate disability. There was “insufficient” evidence concerning the cost of community-based rehabilitation compared with usual care. Several methodological problems were encountered when analyzing the economic evidence.

We challenge assumptions that have guided much research and policy aimed at understanding and reducing medical practice variation. Paramount is the focus on doctors as the cause of variation to the neglect of other possible influences. Some research literature suggests that patients, families, and the community context of practice may also influence treatment decisions. Failure to question present assumptions, despite weak evidence in support of them, may account for inability to explain persistent practice variation, develop appropriate implementable guidelines, or anticipate the effect on treatment decisions of greater patient involvement. In this paper, we discuss the weak response to the NIH Consensus Conference on early stage breast cancer because it may have reflected these problems. We urge a more complex and more empirical approach in explaining treatment choice and guidelines sensitive to the potential for value differences.

Objectives: This study explores several variables of the EQ-5D child version, a multi-attribute utility instrument, in children with chronic conditions.

Methods: A convenience sample was selected from hospital outpatient records and school records. The sample included children aged 7–18 years with the following chronic conditions: asthma, rheumatic disorders, diabetes, and speech/language and/or hearing disorders. The practicality, convergent validity, and discriminant power were compared with a generic quality of life questionnaire for children (TACQOL) and the 2-week test–retest reliability was assessed.

Results: A total of 182 children or their parents completed the first questionnaire and 161 children/parents completed both questionnaires. The practicality of the EQ-5D was good. Low to moderate correlations were found between the utilities and VAS scores and the TACQOL scales. The discriminant power of the EQ-5D items was low overall and was greater for children with a rheumatic disorder than for children with the other conditions. In the subset of children who experienced no health change between the test and the retest, the reliability of the EQ-5D was moderate to high.

Conclusions: The EQ-5D seems suitable for children, although the use of an additional disease-specific questionnaire is still recommended. The EQ-5D seems the most suitable for children with a chronic physical condition and appears to be reliable for children with a stable health status.