Objectives: The overall aim of this study is to discern whether and to what degree vaccination sites exhibit constant returns to scale.

Methods: Data Envelopment Analysis is used to compare all the facilities in the sample in terms of input costs used to produce multiple outputs. The application considers the Expanded Program on Immunization (EPI), which operated in Dhaka City, Bangladesh, during 1999.

Results: A preponderance of EPI sites were determined to be operating at increasing returns to scale.

Conclusions: Our findings question the applicability of cost-effectiveness analyses that assume constant returns to scale.

Objective: A United Kingdom Department of Health directive (EL[94]72) asked Health Authorities to manage the entry of new drugs into practice. There seem to be costs associated with the decision-making process of managed entry, but no clear evidence of benefit to patient populations. The objective of this study was to assess the potential costs and outcomes of different models of managed entry, using the example of donepezil in the North West Health Region of the U.K. National Health Service. This is a preliminary study designed to identify the key pieces of information required to evaluate the value of managed entry.

Methods: Decision analytic models of three Health Authorities' approaches to manage the entry of donepezil were used to estimate the expected costs and effectiveness of the process. Resource use data were obtained from published sources and the relevant Health Authority. Probabilistic sensitivity analysis was used to determine the robustness of the results.

Results: The process of managed entry of donepezil was associated with higher expected costs and higher expected outcome than no managed entry. The 95% confidence intervals for the net expected costs and net expected outcomes were relatively narrow and did not cross zero, which suggests a statistical difference between managed entry and no managed entry for donepezil. The incremental cost-effectiveness ratios for managed entry of donepezil indicate that, compared with no managed entry, there were substantial differences between the different models used in the three study sites. The expected cost per unit of cognitive function gained was between £18,000 in study site 001 to £28,000 in study site 010. The expected cost per person with a clinically significant improvement was between £140,000 and £230,000. The expected cost per QALY ranged from £470,000 to £19.3 million.

Conclusions: Managed entry does not appear to be a worthwhile mechanism to introduce drugs into practice. However, poor accessibility and availability of data means that the results are highly uncertain. The lack of data presents serious obstacles for both researchers and policy makers wishing to develop evidence-based policy and practice.

The use of probabilistic analysis as a means for analyzing uncertainty within economic analysis has grown in popularity in recent years as it has been recognized as the most complete method for propagating uncertainty with respect to input parameters in terms of uncertainty about outcomes of interest. The World Health Organization (WHO) in a series of recent reports and publications have recognized the role of probabilistic analysis in what they term generalized cost-effectiveness analysis. However, there are fundamental problems with the analysis and the interpretation of such analysis as proposed by WHO. This study highlights three specific points for concern and offers constructive criticism by recommending more appropriate approaches.

Objectives: Colorectal cancer is one of the most commonly occurring cancers in industrialized countries, yet appears to be amenable to screening. Amongst the many possible protocols is once-only screening by means of flexible sigmoidoscopy. This protocol is currently being investigated in a UK multicenter trial and the study provides estimates of the expected resource costs.

Methods: The direct health care costs of sigmoidoscopy and of all subsequent procedures were estimated from an audit of resource use of approximately 40,000 patients at thirteen centers. Patient-borne costs were estimated from the results of surveys conducted at twelve of these centers.

Results: The health service costs of a flexible sigmoidoscopy was estimated at £56. The total costs of screening (including private costs) averaged £82 per person screened, although costs varied by center. The total health service costs of screening and subsequent management averaged approximately £91 per person screened, again with variations between centers.

Conclusions: Even within a strict trial protocol, intercenter variation in costs can be detected, ascribable to variability in local management practices, local yield, and local patient-borne costs. Other recent estimates of flexible sigmoidoscopy costs vary widely. As these costs form the basis of technology assessment simulation models which, in turn, inform policy, obtaining realistic cost estimates within the appropriate health care setting is of paramount importance.

Objectives: To identify and assess the effects of general practitioner and patient characteristics on global adherence to pharmacotherapeutic guidelines.

Methods: In a cross-sectional study in the northern Netherlands, a two-level multilevel model was applied to patients (n=269,067) in 190 practices with a total of 251 general practitioners. The dependent variable was the global adherence to pharmacotherapeutic guidelines as a measure of good prescribing in a general practice setting.

Results: The mean global adherence was 82%. Two general practice variables, organization form and degree of urbanization influenced the global adherence, whereas all patient variables (age and gender) and the patient-related prescription characteristics (costs, volume, different ATC-codes) were significant predictors for the global adherence. The total explained variance was 28%.

Conclusions: Patient characteristics have a greater influence on prescribing behavior than general practitioner characteristics.We thank the health care insurance organization (Regionaal Ziekenfonds Groningen [RZG]) for supplying the data set. We also thank Eddie Bruin from the health care insurance organization for his assistance with data collection and Tom Snijders for data analysis and statistical advice.

Objectives: Recently, we developed a diagnostic rule for the diagnosis and treatment of children with meningeal signs. This rule may provide the physician with a rationale to decide on the use of diagnostic and treatment procedures in these children and to improve their care. In this study, we estimated cost savings of the rule compared with current practice.

Methods: Routine care data of 360 children visiting the emergency department of the Sophia Children's Hospital with meningeal signs between 1988 and 1998 were used. Costs of diagnostic tests and treatment were estimated by using financial accounts of an academic and a general pediatric hospital. The number of procedures actually performed and the resulting cost estimates (i.e. unit costs×volume) were compared with the estimated figures after application of the decision rule.

Results: The population of children with meningeal signs comprised 99 with bacterial meningitis (27%), 36 with another serious bacterial infection (10%), and 225 with a self-limiting disease (63%). Application of the rule would reduce lumbar punctures by 12% and hospitalizations for empirical treatment by 15% with the same diagnostic accuracy as current practice. Cost savings were estimated at €292 per patient (relative reduction 10%) and were mainly achieved in the treatment course (€259).

Conclusions: A diagnostic decision rule for children with meningeal signs has the potential to improve the appropriate use of medical resources, to be cost-effective, and to ascertain the absence of bacterial meningitis earlier.

Objectives: To develop and evaluate strategies for estimating hospitalization costs in multinational clinical trials.

Methods: Hospital cost estimates for eleven diagnoses were collected from twelve countries participating in a trial of therapies for congestive heart failure. Estimates were combined with U.S.-based diagnosis-related group weights to compute country-specific unit cost estimates for all reasons for hospitalization. Variations of hospital costing methods were developed. The unit cost method assigns a country-specific unit cost estimate to each hospitalization. The other methods adjust for length of stay using a daily cost (DC) estimate for each diagnosis, based on either the mean length of stay (DC-mean method) or the median length of stay (DC-median method) for each diagnosis in each country. Additional modifications were explored through adjustment of the distribution of daily costs incurred during a hospital stay.

Results: The mean cost for all hospitalizations was $10,242 (SD, 10,042) using the unit cost method, $10,242 (SD, 12,760) using the standard DC-mean method, and $13,967 (SD, 18,762) using the standard DC-median method. In comparisons of costs for all 5,486 hospitalizations incurred by a subset of 2,352 patients in the trial, the unit cost method provided 92% power to detect a $1,000 cost difference. The standard DC-mean method provided 76% power, and the standard DC-median method provided 44% power.

Conclusions: Hospital costing methods that adjust for differences in length of stay require a significantly larger sample to attain comparable statistical power as methods that assign unadjusted unit cost estimates to hospitalization events.

Objectives: Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the “gray+ literature.” However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.

Methods: We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+ literature.

Results: The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+ literature. Although in most cases the addition of gray+ data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.

Conclusions: We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+thinsp;literature and, where possible, obtain data from them.

Objectives: To improve processes of ambulatory care for patients with type 2 diabetes in a nationwide program.

Methods: Interrupted time-series analysis with audits of practice. To implement selected recommendations of national guidelines, educational outreach visits (office visits or phone discussions) were offered to all French physicians who diagnosed one case of type 2 diabetes during a six-month intervention period. Outcome measures were the number of HBA1c measurements recorded monthly in the medical insurance computer database and the proportion of diabetic patients for whom one test had been reimbursed during the previous six months (HBA1c, fasting blood glucose) or previous twelve months (serum cholesterol, serum creatinine, urine microalbumin, electrocardiogram, ophthalmologic examination).

Results: A total of 15,522 office visits and 9,062 telephone discussions were performed among 22,940 physicians. The increase in the monthly proportion of the number of HBA1c tests to the total number of laboratory tests was higher during the intervention period than during the preintervention (p value<.0001) and postintervention periods (p value<.001). Between the first audit (n=651,574) and the third audit (n=911,871), HBA1c measurements increased from 41.2% to 60.5% and blood glucose measurements performed alone decreased from 38.8% to 18.7%. Urine microalbumin measurements increased from 10.6% before to 15.3% after intervention. Only a slight increase was observed for other tests.

Conclusions: Physician to physician outreach visits can be an effective way to improve the processes of care for diabetes and to routinize nationwide use of practice guidelines.

Objectives: The need for consistency and standardization of methods for economic appraisals has been recognized for some time and has led to the development of several sets of guidelines for economic evaluations and for costs. Despite this, considerable diversity is still apparent in applied studies. Some of these diversities might be defensible, and some might not. The objectives of this study are to explore sources of variations in the methods used in applied studies and to discuss the nature of these variations and the possibility of reducing some of them.

Methods: We first use a systematic approach to identify the major sources of variation in costing methods used in applied economic evaluations. We then compare the methods used with the recommendations made in available guidelines.

Results: Four possible sources of variation are identified. The first is where guidelines do not agree in their recommendations; therefore, it is not surprising that applied studies use different methods. The second is where guidelines agree in principle but provide little detail on how to comply with their recommendations; and the third is where a particular methodological issue is not discussed in guidelines. The fourth reason is simply lack of compliance with accepted guidelines.

Conclusions: Variability in costing methods used in applied studies raises questions about the validity of their results and makes it difficult to compare the results of different studies. We discuss the implications for the transferability and generalizability of results and suggest ways to minimize the variability in the methods so that the results of costing studies and economic evaluations can be of more value to policy-makers.

Objectives: To develop and validate a paper-based instrument that is simple to administer and produces a reliable estimate of patient standard gamble (SG) utilities for current health status.

Methods: A 1-page paper questionnaire instrument, paper standard gamble (PSG), was designed to estimate SG utilities. We performed two studies to assess the validity of PSG. First we compared PSG and SG utilities for current health in patients with prostate cancer. They randomly received either PSG followed by SG or vice versa, always with an intervening SF-12. In the second validity study, we assessed the test-retest reliability of PSG by administering it to prostate cancer patients twice, at least 2 weeks apart.

Results: In the first study, utilities were assessed in 64 men (32 per SG/PSG order group). A paired-comparison t test suggested no difference between SG and PSG (mean difference = −0.007; 95% confidence interval (CI), $-$0.022 to 0.008). The concordance correlation coefficient was 0.92 (95% CI, 0.79 to 0.99). In the second study, test and retest PSGs were available for 184 patients. The concordance correlation coefficient was 0.88 (95% CI, 0.73 to 0.94).

Conclusions: These data suggest that PSG may serve as a reliable substitute for SG when current health utility is of interest. PSG may have particular advantages for acquisition of health-related quality-of-life data in longitudinal studies.

We are developing a decision support tool to help clinicians and policy makers estimate the impact of various coronary heart disease (CHD) treatments on disease outcomes for populations. We have created seven modules that correspond to states commonly encountered with CHD, that is, congestive heart failure, tachyarrhythmia, stable angina pectoris, acute coronary syndrome, bradycardia, postmyocardial infarction, and postcoronary artery bypass grafting, and a healthy individual module. Within each module, we created event-decision- intervention-outcome flow pathways to simulate risk of a clinical event and the expected outcome as the result of a particular intervention. We will combine disease state probability estimates based on the experience of the Olmsted County, Minnesota, population and estimates of intervention efficacy based on clinical trial data to estimate the impact of interventions on a population. We plan to make this tool available to the public through the internet.“This project was made possible through a Cooperative Agreement between the Center for Disease Control and Prevention (CDC) and the Association of Teachers of Preventive Medicine (ATPM), award # TS-0892; its contents are the responsibility of the authors and do not necessarily reflect the official views of the CDC or ATPM. Supported in part by an unrestricted research grant from McNeil Consumer Healthcare.”

Objectives: This study aims to assess the impact of articles with very high reprint orders (“high-reprint articles”) by measuring their citation in the subsequent literature as compared with a control group of articles.

Methods: The twenty-one articles (published in the Lancet in 1998) with reprint orders of over 10,000 were matched with a control set of twenty-one articles with smaller reprint orders. The Science Citation Index was used to obtain the number of citations for each of the forty-two articles.

Results: The twenty-one high-reprint articles were cited 2,548 times; the mean number of citations was 121 (range, 3 to 499 citations per article). Five of the twenty-one high-reprint articles had more than 200 citations, but seven (33%) were cited twenty-five times or fewer. The twenty-one control articles were cited 986 times; the mean number of citations was forty-seven (range, 1 to 165). Fifteen (71%) of the twenty-one control articles were cited twenty-five times or fewer. Thirteen of the high-reprint articles were reports of randomized trials with a mean of 163 citations. In the control articles, six were reports of randomized trials with a mean of eighty-eight citations.

Conclusions: Articles with a high-reprint order were cited more frequently than other articles. However, some high-reprint articles were cited infrequently. If the size of a reprint order is related to the importance of an article, those articles with very high reprint orders may, therefore, be perceived as more important. Further research is needed to explore other aspects of the relative importance and impact of high-reprint articles.

Objectives: To identify predictors of high-quality clinical practice guidelines.

Methods: A total of 86 guidelines from 11 countries were assessed by four independent appraisers per guideline using the AGREE instrument (23 items). Six aspects of guideline development were considered to explain the variation in quality scores: care level (primary/secondary care), scope (diagnosis/treatment), type of guideline (new/update), year of publication, type of agency (governmental/professional), and whether the guideline was produced within a structured and coordinated program.

Results: Guidelines produced within a guideline program and by governmental agencies had higher scores than their counterparts. Differences in the applicability of the guidelines could not be explained by the variables studied.

Conclusions: To ensure high quality, clinical guidelines should be produced within a structured and coordinated program. Professional organizations or specialist societies that aim to develop guidelines may adopt quality criteria from leading guideline agencies.

The issue of evidence for decision-making, including formal policy-making and public health policy, has increased rapidly in prominence during the past few years. The term “evidence-based” was first used in health care in 1992, when Sackett and others coined the term “evidence-based medicine” (42). More recently, many have asked if public health activities are based on evidence (2;8;13;19;30).

Objectives: To examine the cost-effectiveness of pediatric cochlear implantation over time.

Methods: A prospective study based on ninety-eight children implanted between 1989 and 1996 at Nottingham's Paediatric Cochlear Implantation Programme, UK. The influence of outcomes and other variables on total costs was examined using multivariate regression analysis.

Results: Having controlled for potential confounding variables, total cost was negatively related to year of implant and positively related to the number of hours of rehabilitation (p=.000).

Conclusions: Having controlled for outcomes (Categories of Auditory Performance and Speech Intelligibility Rating), the cost-effectiveness improved over time. This finding may be due to a learning curve and have policy implications.

Venous thrombosis (the formation, development, or existence of a blood clot in a vein) is common and carries a substantial risk for long-term suffering or death. Deep vein thromboses that break away from the vein, flow to the lungs, and block circulation (pulmonary emboli) cause over 1,000 deaths annually in Sweden and are the single most common cause of death during pregnancy and in surgical intervention where prophylaxis is not used. The risk for this disorder increases with age. At older ages it is more common in men; at younger ages it is more common in women. Annually, over 11,000 people are hospitalized for venous thrombosis or pulmonary embolism, and approximately 40,000 patients visit a physician in ambulatory care. In a longer perspective, many people are affected by leg swelling, varicose veins, and slowly healing leg ulcers (conditions not addressed in this report).

Objective: We have used multidisciplinary expert panels to assess the health benefits from two different emergency medical service programs in Norway. This gave the opportunity to study the reliability of the expert panel method.

Methods: Two panels assessed case reports for 18 children, and two other panels assessed case reports for 64 adult patients. The assessments of each case report were compared. These assessments were also compared with assessments of the same case reports, done by the same panels 1 and 9 years earlier.

Results: Two different panels agreed on the benefit/no benefit conclusion in at least 75% of the patients, both for children and adult patients (kappa 0.88–0.50). For groups of patients assessed to have some health benefit, the magnitude of the benefit estimates differed by 25% between the panels. When the same panels assessed the same patient groups twice, 1 and 9 years apart, their estimates of total benefit differed up to 30%. However, estimates for single patients, as well as estimates from single panel members, varied considerably more.

Conclusions: Use of multidisciplinary expert panels is a useful method for estimating health benefits on program level or for groups of patients. But assessments from single panelists, and for single patients may be seriously biased.

Objectives: A series of randomized controlled trials have demonstrated that screening for colorectal cancer (CRC) using the fecal occult blood (FOB) test can decrease mortality from this disease. These findings were used to develop an actuarial model to estimate the impact that a FOB screening program for colorectal cancer would have on the Canadian population.

Methods: The mortality experience of the year 2000 cohort of Canadians fifty to seventy-four years of age, with follow-up extending to 2010, was modelled according to three scenarios: no screening, annual screening, biennial screening. The primary screening tool was the FOB test using unrehydrated samples, with follow-up of positive test results using colonoscopy. The framework of the model was developed based on published findings from the relevant randomized controlled trials, available data, and a literature review that yielded parameter values for some model items.

Results: During the 10-year follow-up of the cohort, we estimated that 4,444 and 2,827 deaths would be averted with annual and biennial FOB screening, respectively. We estimated that for an annual FOB screening program, approximately 3,400 FOB tests would be required to prevent one death, whereas 2,700 tests would be required within a biennial program.

Conclusions: Our analysis documents the population health impact of using the FOB test to screen for CRC. Additional information on the natural history of the disease, and Canadian pilot data are needed to better model the effectiveness of population-based FOB screening programs.

The first (known) national consensus conference on matters of health care ever held in an east European country was conducted in Latvia in September of 2002. This conference marks one of the steps in the government's efforts to establish a sustainable mechanism for health technology assessment (HTA). The conference was organized by the agency now given the responsibility to develop HTA in Latvia.