Leukoreduction, filtering white blood cells from transfusion blood, effectively avoids leukocyte-related complications of blood transfusion. The technology has proven its relative cost-effectiveness for specific patient populations. With the advent of variant Creutzfeldt–Jakob disease, a transmittable spongiform encephalopathy caused by mad cow disease (bovine spongiform encephalopathy), the hard hit United Kingdom introduced universal leukoreduction for all patients as a precaution for transmission of prions in 1999. This costly policy was followed by many other countries, in the absence of much evidence of an actual health problem or of a more than presumed effectiveness of leukoreduction in preventing prion transmission. The core problem proved to be legal. The blood banks are legally accountable for blood safety. This accountability is absolute, based on avoidance of all possible risks, regardless of costs. This strategy leads to inefficiencies in health care: (i) blood safety management is guided by available rather than cost-effective technology, and (ii) private insurance premiums for civil liability are sharply increasing, while they are in no way related to the expected returns and the high and increasing blood safety. A rational safety policy is to be optimal, taking into account costs and effects of the safety procedures. This issue will need an open discussion with the general public of the real risks and a clear and unambiguous definition of proportionality in the precautionary principle, based on the European law.

Objectives: The aim of this study was to conduct a systematic review of the evidence for treatments for retinoblastoma in children.

Methods: Seventeen electronic databases were searched. Two reviewers independently selected studies. Studies of participants diagnosed with childhood retinoblastoma, any interventions, and all clinical outcomes were eligible. Randomized and nonrandomized controlled trials and cohort studies with clear comparisons between treatment groups were included. Methodological quality was assessed.

Results: Thirty-one observational comparative studies were included, of which twenty-seven were retrospective. The methodological quality was generally poor, with a high risk of selection bias in all studies. Although there were high levels of treatment success in many of the studies, due to the limitations of the evidence identified, it was not possible to make meaningful and robust conclusions about the relative effectiveness of different treatment approaches for retinoblastoma in children.

Conclusions: Good quality randomized controlled trials are required. Where controlled trials are not feasible, only high quality prospective, nonrandomized studies should be given consideration, due to the generally higher risk of bias in retrospective studies.

Objectives: The objective of this study was to examine and explain the differential international diffusion of six health innovations.

Methods: A retrospective diffusion study was undertaken of sildenafil, cyclooxygenase-II (COX II) inhibitors, beta interferon, verteporfin, deep brain stimulators, and drug-eluting coronary stents in ten countries—Australia, Canada, Denmark, France, The Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. We plotted diffusion curves of daily defined doses per quarter, vials or implants per million population, and examined the association between diffusion and five key variables.

Results: Canada, Switzerland, and Sweden are generally high users of new technologies; Spain, Denmark, and particularly the United Kingdom are low users. Almost all countries experienced rapid adoption of sildenafil with diffusion to a similar level; there was variable adoption and diffusion of COX II inhibitors, verteporfin, and interferon beta; drug-eluting stents penetrated the market in a similar way in all but one country; and two countries had very different adoption patterns for deep brain stimulators. Above average health spending and the presence of health technology assessment (HTA) or other guidance reports are consistently associated with increased diffusion. Early warning activity and a national coverage decision being taken are more likely to be associated with a reduced diffusion.

Conclusions: The significant differences in diffusion between different countries are not consistent with a neat evidence-based world. The tools available to policy makers to control diffusion (early warning systems, HTA, and a fourth hurdle) play some part in influencing diffusion but need close scrutiny of how successfully they operate.

Objectives: The aim of this study was to develop a guide to identifying and managing risks for health technology assessment (HTA) programs and to obtain opinions on this topic from HTA agencies.

Methods: The risks and approaches to their management were compiled, drawing on experiences from HTA programs and the risk assessment literature. Opinion on this classification was obtained from members of the International Network of Agencies for Health Technology Assessment (INAHTA).

Results: Twenty-one risks for HTA programs were identified under the categories Formulation of HTA Questions, Preparation of the HTA Product, Dissemination, and Contracting. For each risk area, potential consequences and suggested management approaches were outlined. Responses from ten HTA programs indicated substantial agreement regarding the risks that had been identified and on the importance of risk management for their own operations.

Conclusions: Prudent management of HTA programs should take into account the risks related to external factors.

Objectives: It is generally accepted that home peak flow monitoring increases patients' self-management and could lead to cost savings. The aim of this review was to analyze costs and the cost-effectiveness of self-management based on peak flow monitoring interventions in asthma.

Methods: Twenty-one studies were included in this review. Data were extracted, and methodological and economic quality were assessed. These studies presented economic information regarding self-management interventions based on peak flow monitoring in asthmatics. The mean methodological quality was 4.6 (maximum 8), and the mean economic quality was 12.0 (maximum 15).

Results: In eighteen studies, the interventions led to net savings compared with usual care or less intensive intervention. Only three studies found the total costs to be higher in the intervention group. In thirteen of the seventeen studies that analyzed health outcomes, at least one of the reported health outcomes improved statistically significantly after the intervention. However, the methods of economic evaluation differed among the studies and were not always in line with the standard methodology.

Conclusions: The interventions, costs, and outcomes were very diverse. The results emphasize the need for guidelines to increase the comparability of cost-effectiveness evaluations relating to asthma. Only then will it be possible to conclude whether interventions for asthmatics, such as self-management based on peak flow monitoring interventions, are cost-effective.

Objectives: This study reports the cost-effectiveness of a preventive intervention, consisting of counseling and specific support for the mother–infant relationship, targeted at women at high risk of developing postnatal depression.

Methods: A prospective economic evaluation was conducted alongside a pragmatic randomized controlled trial in which women considered at high risk of developing postnatal depression were allocated randomly to the preventive intervention (n = 74) or to routine primary care (n = 77). The primary outcome measure was the duration of postnatal depression experienced during the first 18 months postpartum. Data on health and social care use by women and their infants up to 18 months postpartum were collected, using a combination of prospective diaries and face-to-face interviews, and then were combined with unit costs (£, year 2000 prices) to obtain a net cost per mother–infant dyad. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics at alternative willingness to pay thresholds held by decision makers for preventing 1 month of postnatal depression.

Results: Women in the preventive intervention group were depressed for an average of 2.21 months (9.57 weeks) during the study period, whereas women in the routine primary care group were depressed for an average of 2.70 months (11.71 weeks). The mean health and social care costs were estimated at £2,396.9 per mother–infant dyad in the preventive intervention group and £2,277.5 per mother–infant dyad in the routine primary care group, providing a mean cost difference of £119.5 (bootstrap 95 percent confidence interval [CI], −535.4, 784.9). At a willingness to pay threshold of £1,000 per month of postnatal depression avoided, the probability that the preventive intervention is cost-effective is .71 and the mean net benefit is £383.4 (bootstrap 95 percent CI, −£863.3–£1,581.5).

Conclusions: The preventive intervention is likely to be cost-effective even at relatively low willingness to pay thresholds for preventing 1 month of postnatal depression during the first 18 months postpartum. Given the negative impact of postnatal depression on later child development, further research is required that investigates the longer-term cost-effectiveness of the preventive intervention in high risk women.

Objectives: Acute otitis media (AOM) is one of the most common diseases of childhood, representing a major disease burden on the society. New evidence-based guidelines for AOM, focusing on children under 7 years of age, were introduced in Finland in 1999. The aim of this study was to evaluate the cost-effectiveness of implementing those guidelines in Finland.

Methods: A 5-year prospective trial was conducted in thirty community primary healthcare centers in Finland. All AOM patients between 0 and 6 years of age visiting the study health centers for the first time, for this episode of illness, during 1 week in November 1998 (n = 579) and November 2002 (n = 369) were included in this study. The outcome measure was the percentage of symptom-free patients.

Results: The mean direct cost of an AOM episode per patient stayed almost the same after implementing the guidelines, €152 in 1998 and €150 in 2002. After implementing the guidelines, the percentage of symptom-free patients was 10 percentage points higher than before the guidelines. The treatment after the implementation of the guidelines, thus, was a dominant strategy.

Conclusions: Implementing the guidelines to the treatment of AOM in children was associated with extra health benefits at slightly lower direct costs and, thus, is a dominant strategy. The focus of this study was on the short-term effects of the treatment; including long-term effects in the analysis might affect the results.

Objectives: The objective of this study was to develop a method to allocate treatment effects when patients switch medication frequently in longitudinal observational studies and apply the approach to assess the cost-effectiveness of treatments in the Schizophrenia Outpatient Health Outcomes (SOHO) study.

Methods: Data were collected on patients at entry to the SOHO study at 3, 6, and 12 months. The 12-month follow-up period was considered as three epochs: 0–3 months, 3–6 months, and 6–12 months. Patients who switched treatment at 3 months had their new treatment considered as a new baseline observation, as these two 3-month observations provide two sets of information on the cost-effectiveness of a drug in the first 3 months after initiation. Multivariate regression analysis was used to adjust for baseline covariates. The model allowed for flexible functional forms, and the cost data were modeled using an exponential mean function. Bootstrapping assessed the uncertainty of the estimated parameters and incremental cost-effectiveness analysis decision rule.

Results and Conclusions: We show the feasibility of the epoch analysis approach using data from the SOHO study comparing two antipsychotics. Estimates for the incremental cost and effectiveness per epoch over the full 12-month period are presented. Using the estimates of 200 bootstrap samples, we demonstrate how one drug is cost-effective compared with another.

Objectives: The objective of this study was to develop a model to assess the cost-effectiveness of a new treatment for patients with depression.

Methods: A Markov simulation model was constructed to evaluate standard care for depression as performed in clinical practice compared with a new treatment for depression. Costs and effects were estimated for time horizons of 6 months to 5 years. A naturalistic longitudinal observational study provided data on costs, quality of life, and transition probabilities. Data on long-term consequences of depression and mortality risks were collected from the literature. Cost-effectiveness was quantified as quality-adjusted life-years (QALYs) gained from the new treatment compared with standard care, and the societal perspective was taken. Probabilistic analyses were conducted to present the uncertainty in the results, and sensitivity analyses were conducted on key parameters used in the model.

Results: Compared with standard care, the new hypothetical therapy was predicted to substantially decrease costs and was also associated with gains in QALYs. With an improved treatment effect of 50 percent on achieving full remission, the net cost savings were 20,000 Swedish kronor over a 5-year follow-up time, given equal costs of treatments. Patients gained .073 QALYs over 5 years. The results are sensitive to changes in assigned treatment effects.

Conclusions: The present study provides a new model for assessing the cost-effectiveness of treatments for depression by incorporating full remission as the treatment goal and QALYs as the primary outcome measure. Moreover, we show the usefulness of naturalistic real-life data on costs and quality of life and transition probabilities when modeling the disease over time.

Objectives: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed.

Methods: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed for the situation at hand. Due to challenging circumstances, the cost assessment turned out to be ex-post and top-down.

Results: Cost per treatment sequence is estimated to be approximately €976, whereas the incremental cost (compared with usual care) is approximately €682. The cost estimate is uncertain and may be as high as €1.877.

Conclusions: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective.

Objectives: The objective of this study was to collect all systematic reviews on invasive strategies for acute coronary syndromes (ACS) and reanalyze the data in these reviews to reach combined estimates, as well as to make predictions on the effectiveness and risk of harm so as to facilitate relevant decision making in health care.

Methods: The data sources used were the following electronic databases, searched from 1994 to September 2004: Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; DARE, HTA, EED (NHS CRD); MEDLINE(R) In-Process, Other Non-Indexed Citations, MEDLINE(R), and PubMed (2000 to 2004). References to the identified systematic reviews were checked. An ancillary search to identify recent randomized controlled trials (RCTs) covering the period from January 2003 to January 2006 was done in MEDLINE(R). We included systematic reviews of RCTs on patients with ACS. In unstable angina and non–ST-elevation myocardial infarction (UA/NSTEMI), eligible reviews had to compare early routine invasive strategy with early selective invasive strategy. In ST-elevation myocardial infarction (STEMI), a comparison between primary percutaneous coronary intervention (PCI) and thrombolytic therapy was required. The methodological quality of the reviews was assessed, and a standardized data extraction form was used. Results for the main outcomes of the RCTs in the reviews were reanalyzed. An additional search of those RCTs not included in the meta-analyses was performed for UA/NSTEMI and short-term morality data on STEMI. Bayesian models were constructed to estimate the uncertainty about a possible treatment effect and to make predictions and probability statements. Main results are based on these analyses. Mortality was considered as the primary outcome measure.

Results: One systematic review on invasive strategies was identified for UA/NSTEMI and nine on invasive strategies for STEMI. Five reviews of the latter that were published after the year 2000 were included for the final analysis. The median quality score was 10.5 (range, 7–13; n = 6) on a scale from 0 to 18 points. An updated literature search identified one further RCT on UA/NSTEMI. Regarding NSTEMI and mortality, the average risk difference favoring an early invasive treatment strategy compared with early conservative strategy was .6 percent (95 percent credible interval [CrI], −2.1 to 1.0). Predicted risk (relative risk/risk difference scales) of doing harm was 26.7/26.6 percent. Regarding STEMI and mortality, the absolute risk reduction in favor of primary PCI over thrombolysis was 4.1 percent (95 percent CrI, −7.1 to −1.1) when PCI was compared with streptokinase and 1.2 percent (95 percent CrI, −2.7 to .2) when compared with fibrin-specific thrombolytics. Predicted risk of harm was 8.9/5.3 percent and 8.0/13.3 percent, respectively.

Conclusions: There seems to be at present no solid evidence for survival benefit on early invasive strategy for UA/NSTEMI as a broad diagnostic group, and the risk of doing harm should be considered. Also, the evidence for PCI to decrease early mortality after STEMI is scanty. Estimations of predicted harm may further aid decisions on whether to implement the new treatment over the old one. It may also give an additional dimension for interpreting the results of any meta-analysis.

Objectives: The aim of this study was to obtain information from members of the International Network of Agencies for Health Technology Assessment (INAHTA) on their involvement of consumers (patients, carers, and related organizations) in their programs.

Methods: A questionnaire for a survey was developed and sent to member agencies in October 2005.

Results: Of the thirty-seven agencies that provided responses, 57 percent involve consumers in some aspects of their HTA programs and 83 percent intend to involve consumers in the future. Summaries of HTA reports that are intended to be easily understood by consumers are prepared by 49 percent of the agencies, and 36 percent involve consumers in dissemination of HTA material.

Conclusions: Most INAHTA members involve consumers in some aspects of their programs, although not always routinely. Involvement seems likely to increase in the future.

Objectives: The aims of the present study were to investigate the awareness among dentists and dental hygienists of evidence-based reports and guidelines on tobacco cessation activities and the impact these publications had on clinical practice.

Methods: A questionnaire was mailed to dental hygienists and dentists in Stockholm County, Sweden, and the results were compared with a previous investigation.

Results: Among the respondents, awareness of a popular science version of a systematic review on smoking and its effect on oral health was reported by 90 percent of the hygienists and 66 percent of the dentists. The information was used in clinical work by 34 percent of the dentists and 54 percent of the hygienists. Reported changes in patterns of practice were more frequent recommendations to use nicotine replacement therapy and a more widespread use of setting quit dates. Approximately one quarter of the dental professionals reported that they had increased tobacco cessation consultation because of the results from the reports.

Conclusions: Changes in patterns of practice were observed after dissemination of evidence-based information on tobacco cessation. Methods that were proven to be effective in the evidence-based report such as discussing quit dates and recommending nicotine replacement therapy were more commonly used after the publication of the report. Short, popular versions of extensive systematic reviews seem to be useful for implementing evidence-based knowledge and changing clinical practice.

The Health Evidence Network (HEN) was established approximately 3 years ago as a service to the health policy makers in the fifty-two member states of World Health Organization (WHO) Europe. The objective of the HEN is to (i) make it easier for policy makers to access evidence-based studies in the field of health, and to (ii) provide synthesis of available evidence around specific policy issues in health.

Objectives: The aim of this study was to demonstrate the best way of identifying all relevant published health economic evaluation studies, which have increased in number rapidly in the past few decades. Nevertheless, health technology assessment projects are often faced with a scarcity of relevant studies.

Methods: Six bibliographic databases were searched using various individually adapted strategies. The particular example involves the cost-effectiveness of diagnosing gastroesophageal reflux disease. Inclusion and exclusion criteria were formulated.

Results: After irrelevant studies and duplicates had been excluded, sixty-eight abstracts were reviewed. We chose forty-one of them as relevant for full-text review, which identified fourteen papers as having met the inclusion criteria. Most of the relevant studies were identified by searching the National Health Service Economic Evaluation Database (NHS EED) and PubMed databases.

Conclusions: A search in NHS EED, by means of the Cochrane Library or the Center for Reviews and Dissimination, along with a supplementary search in PubMed, is generally an appropriate, cost-effective strategy. However, because “cost-effectiveness” is not consistently indexed with Medical Subject Heading terms in PubMed, all economic search terms need to be used to fully identify the relevant references.

Objectives: In the next decades, the number of stroke patients is expected to increase. Furthermore, organizational changes, such as stroke services, are expected to be implemented on a large scale. The purpose of this study is to estimate the future healthcare costs by taking into account the expected increase of stroke patients and a nationwide implementation of stroke services.

Methods: By means of a dynamic multistate life table, the total number of stroke patients can be projected. The model calculates the annual number of patients by age and gender. The total healthcare costs are calculated by multiplying the average healthcare costs specified by age, gender, and healthcare sector with the total number of stroke patients specified by age and gender.

Results: In the year 2000, the healthcare costs for stroke amounted to €1.62 billion. This amount is approximately 4.4 percent of the total national healthcare budget. Projections of the total costs of stroke based on current practice result in an increase of 28 percent (€2.08 billion) in the year 2020. A nationwide implementation of stroke services in 2020 would result in a substantial reduction of the costs of stroke (€1.81 billion: 13 percent cost reduction) compared with the regular care scenario.

Conclusions: A nationwide implementation of stroke services is a strong policy tool for cost containment of health care in an aging population like that in the Netherlands. Policy makers should optimize the organization of stroke care.

Objectives: In France, new guidelines for clinical practices concerning cystic fibrosis came out in 2002, underscoring the need for early and intensive management of this disease. Because no recent health economic studies on cystic fibrosis in France were available, we conducted a cost-analysis study before the new guidelines were put into practice, with a view to a later study on the medical and economic impact of these guidelines.

Methods: A cost-analysis study was performed of the inpatient and outpatient costs of patients with cystic fibrosis for the 2000–2001 period. The various direct costs were estimated on a sample of sixty-five adult and pediatric patients managed for cystic fibrosis in two reference medical centers. Data were obtained from medical records, and questionnaires were filled out by the patients. Analysis was made from the perspective of the French healthcare system.

Results: We studied sixty-five patients, 54 percent male patients and 72 percent children under 18 years of age. The total cost of cystic fibrosis care totaled 16,189 euros per year and per patient. Outpatient costs accounted for 88 percent of the total cost versus 12 percent for inpatient costs; medication costs were the highest with 21 percent of the total cost for home intravenous antibiotic treatments and 49 percent of the total cost for chronic medications.

Conclusions: The results show that outpatient costs were higher than inpatient costs, which could be related to the importance granted to home health care in France, notably for intravenous antibiotic treatments given for pulmonary complications.

Objectives: The aim of this study was to evaluate utilization trends of the diagnostic imaging examinations during the past decade in a university hospital in Turkey.

Methods: Patient registries of a university hospital were used for the years 1995 and 2003. The data set consisted of patients' admissions, social security status, and diagnostic imaging tests.

Results: When compared with 1995 data, the total number of diagnostic imaging examinations and patient admissions increased 65.9 percent and 81.6 percent, respectively, in the year 2003. Although the total number of diagnostic imaging tests decreased 9.0 percent, there was a 145.4 percent increase in magnetic resonance imaging (MRI) examinations. Nevertheless, radiological diagnostic procedures consisted of 12.8 percent of the total hospital revenues in 1995 and 9.4 percent in 2003.

Conclusions: This study shows that approximately one third of inpatients underwent MRI and computed tomography examinations in 2003. The utilization rates of diagnostic imaging procedures, especially new technologies, need to be considered carefully with respect to appropriateness of procedures and planning of services.

Objectives: The objectives of this study were to analyze the current structure of the Turkish pharmaceuticals market to explain the latest developments and to offer some insight into the likely policy issues that this sector will face.

Methods: Systematic searches of the relevant Turkish and English research literature were made, using electronic databases in addition to written reports.

Results: The pharmaceutical industry in Turkey currently has eighty-seven manufacturing firms, eleven raw material manufacturers and thirty-eight importing firms. These add up to a total of 136 firms, 35 of which are driven by foreign capital, with 8 of these foreign-run firms having their own plants in Turkey. The industry employs approximately 19,000 personnel. In terms of growth, the value of pharmaceutical products in Turkey recently has exceeded that in Europe. In addition, per capita drug consumption levels are quite low compared with the Organisation for Economic Co-operation and Development and European Union countries. Major international players in the medical equipment and pharmaceutical products sector have also been opening offices in Turkey to reap the benefits of this rapidly evolving market.

Conclusions: The pharmaceutical industry in Turkey is quite advanced and diverse, with high quality, generic pharmaceutical products being manufactured as well as poor quality copies that have not been appropriately tested in terms of bioequivalence and bioavailability. The country faces a low level of drug consumption due to economic and cultural constraints compared with Western countries. Governmental control and regulations are key issues because the majority of drug purchases (70–80 percent) throughout the country are currently reimbursable through public sector agencies such as the Pension Fund and the Social Insurance Organization.