The effectiveness of a de-implementation strategy to reduce low-value blood management techniques in primary hip and knee arthroplasty: a pragmatic cluster-randomized controlled trial.

BACKGROUND: Perioperative autologous blood salvage and preoperative erythropoietin are not (cost) effective to reduce allogeneic transfusion in primary hip and knee arthroplasty, but are still used. This study aimed to evaluate the effectiveness of a theoretically informed multifaceted strategy to de-implement these low-value blood management techniques. METHODS: Twenty-one Dutch hospitals participated in this pragmatic cluster-randomized trial. At baseline, data were gathered for 924 patients from 10 intervention and 1040 patients from 11 control hospitals undergoing hip or knee arthroplasty. The intervention included a multifaceted de-implementation strategy which consisted of interactive education, feedback on blood management performance, and a comparison with benchmark hospitals, aimed at orthopedic surgeons and anesthesiologists. After the intervention, data were gathered for 997 patients from the intervention and 1096 patients from the control hospitals. The randomization outcome was revealed after the baseline measurement. Primary outcomes were use of blood salvage and erythropoietin. Secondary outcomes included postoperative hemoglobin, length of stay, allogeneic transfusions, and use of local infiltration analgesia (LIA) and tranexamic acid (TXA). RESULTS: The use of blood salvage (OR 0.08, 95% CI 0.02 to 0.30) and erythropoietin (OR 0.30, 95% CI 0.09 to 0.97) reduced significantly over time, but did not differ between intervention and control hospitals (blood salvage OR 1.74 95% CI 0.27 to 11.39, erythropoietin OR 1.33, 95% CI 0.26 to 6.84). Postoperative hemoglobin levels were significantly higher (ß 0.21, 95% CI 0.08 to 0.34) and length of stay shorter (ß -0.36, 95% CI -0.64 to -0.09) in hospitals receiving the multifaceted strategy, compared with control hospitals and after adjustment for baseline. Transfusions did not differ between the intervention and control hospitals (OR 1.06, 95% CI 0.63 to 1.78). Both LIA (OR 0.0, 95% CI 0.0 to 0.0) and TXA (OR 0.3, 95% CI 0.2 to 0.5) were significantly associated with the reduction in blood salvage over time. CONCLUSIONS: Blood salvage and erythropoietin use reduced over time, but not differently between intervention and control hospitals. The reduction in blood salvage was associated with increased use of local infiltration analgesia and tranexamic acid, suggesting that de-implementation is assisted by the substitution of techniques. The reduction in blood salvage and erythropoietin did not lead to a deterioration in patient-related secondary outcomes. TRIAL REGISTRATION: www.trialregister.nl, NTR4044.

Effectiveness and cost-effectiveness of a proactive, goal-oriented, integrated care model in general practice for older people. A cluster randomised controlled trial: Integrated Systematic Care for older People--the ISCOPE study.

BACKGROUND: older people often experience complex problems. Because of multiple problems, care for older people in general practice needs to shift from a 'problem-based, disease-oriented' care aiming at improvement of outcomes per disease to a 'goal-oriented care', aiming at improvement of functioning and personal quality of life, integrating all healthcare providers. Feasibility and cost-effectiveness of this proactive and integrated way of working are not yet established. DESIGN: cluster randomised trial. PARTICIPANTS: all persons aged ≥75 in 59 general practices (30 intervention, 29 control), with a combination of problems, as identified with a structured postal questionnaire with 21 questions on four health domains. INTERVENTION: for participants with problems on ≥3 domains, general practitioners (GPs) made an integrated care plan using a functional geriatric approach. Control practices: care as usual. OUTCOME MEASURES: (i) quality of life (QoL), (ii) activities of daily living, (iii) satisfaction with delivered health care and (iv) cost-effectiveness of the intervention at 1-year follow-up. TRIAL REGISTRATION: Netherlands trial register, NTR1946. RESULTS: of the 11,476 registered eligible older persons, 7,285 (63%) participated in the screening. One thousand nine hundred and twenty-one (26%) had problems on ≥3 health domains. For 225 randomly chosen persons, a care plan was made. No beneficial effects were found on QoL, patients' functioning or healthcare use/costs. GPs experienced better overview of the care and stability, e.g. less unexpected demands, in the care. CONCLUSIONS: GPs prefer proactive integrated care. 'Horizontal' care using care plans for older people with complex problems can be a valuable tool in general practice. However, no direct beneficial effect was found for older persons.

Cost-Effectiveness of Short-Term Inpatient Psychotherapy Based on Transactional Analysis in Patients With Personality Disorder.

Short-term inpatient psychotherapy based on transactional analysis (STIP-TA) in patients with personality disorders (PD) has shown to be more effective than comparable other specialized psychotherapies (OP). The aim of this study was to assess whether the higher effectiveness of STIP-TA also results in a better cost-effectiveness. Patients treated with STIP-TA were matched with patients treated with OP by the propensity score. Healthcare costs and lost productivity costs were measured over 3 years and from the societal perspective. Cost-effectiveness was represented by costs per quality adjusted life years (QALYs). Uncertainty was assessed using bootstrapping. Mean 3-year costs were €59,834 for STIP-TA and €69,337 for OP, a difference of -€9,503, 95% CI [-32,561, 15,726]. QALYs were 2.29 for STIP-TA and 2.05 for OP, a difference of .24, 95% CI [.05, .44]. STIP-TA is a dominant treatment compared to OP: less costly and more effective. We conclude that STIP-TA is a cost-effective treatment in PD patients.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Variability in vulnerability assessment of older people by individual general practitioners: a cross-sectional study.

BACKGROUND: In clinical practice, GPs appeared to have an internalized concept of "vulnerability." This study investigates the variability between general practitioners (GPs) in their vulnerability-assessment of older persons. METHODS: Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non-vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and practice characteristics were collected. From a sample of 2828 patients the following domains were recorded: sociodemographic, functional [instrumental activities in daily living (IADL), basic activities in daily living (BADL)], somatic (number of diseases, polypharmacy), psychological (Mini-Mental State Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong-Gierveld Loneliness Scale; DJG). Variability in GPs' assessment of vulnerability was tested with mixed effects logistic regression. P-values for variability (pvar) were calculated by the log-likelihood ratio test. RESULTS: Participating GPs assessed the vulnerability of 10,361 patients. The median percentage of vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and psychological domains, GPs uniformly took into account the patient characteristics 'total number of diseases' (OR 1.7, 90% range  = 0, p var = 1), 'polypharmacy' (OR 2.3, 90% range  = 0, p var = 1) and 'GDS-15' (OR 1.6, 90% range  = 0, p var = 1). GPs vary in the way they assessed their patients' vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p var < 0.001, BADL: median OR 2.4, 90% range 2.9, p var < 0.001) and the social domain (DJG: median OR 1.2, 90% range  = 1.2, p var < 0.001). CONCLUSIONS: GPs seem to share a medical concept of vulnerability, since they take somatic and psychological characteristics uniformly into account in the vulnerability-assessment of older persons. In the functional and social domains, however, variability was found. Vulnerability assessment by GPs might be a promising instrument to select older people for geriatric care if more uniformity could be achieved. TRIAL REGISTRATION: Netherlands Trial Register NTR1946.

Assessment of intraventricular time differences in healthy children using two-dimensional speckle-tracking echocardiography.

BACKGROUND: Parameters describing intraventricular time differences are increasingly assessed in both adults and children. However, to appreciate the implications of these parameters in children, knowledge of the applicability of adult techniques in children is essential. Hence, the aim of this study was to assess the applicability of speckle-tracking strain-derived parameters in children, paying special attention to age and heart rate dependency. METHODS: One hundred eighty-three healthy subjects (aged 0-19 years) were included. Left ventricular global peak strain, time to global peak strain, and parameters describing intraventricular time differences were assessed using speckle-tracking strain imaging in the apical two-chamber, three-chamber, and four-chamber views (longitudinal strain) and the parasternal short-axis view (radial and circumferential strain). Parameters describing intraventricular time differences included the standard deviation of time to peak strain and differences in time to peak strain between two specified segments. Age and heart rate dependency were evaluated using regression analysis, and intraobserver and interobserver variability were tested. RESULTS: Acquisition and analysis of longitudinal six-segment time-strain curves was successful in 94.8% of subjects and radial and circumferential time-strain curves in 89.5%. No clinically significant linear relation was observed between age or heart rate and parameters describing intraventricular time differences. The coefficient of variation of time to global peak strain parameters was <10, while it was >10 for parameters describing intraventricular time differences. CONCLUSIONS: The feasibility of speckle-tracking strain analysis in children is relatively good. Furthermore, no linear relation was observed between age or heart rate and parameters describing intraventricular time differences. However, the limited reproducibility of some parameters describing intraventricular time differences will confine their applicability in clinical practice.

Effects of a stepped-care intervention programme among older subjects who screened positive for depressive symptoms in general practice: the PROMODE randomised controlled trial.

OBJECTIVES: to determine (cost)-effectiveness of a stepped-care intervention programme among subjects ≥ 75 years who screened positive for depressive symptoms in general practice. DESIGN: the pragmatic cluster-randomised controlled trial with 12-month follow-up. SETTING: sixty-seven Dutch general practices. SUBJECTS: two hundred and thirty-nine subjects ≥ 75 years screened positive for untreated depressive symptoms (15-item Geriatric Depression Scale ≥ 5). METHODS: usual care (34 practices, 118 subjects) was compared with the stepped-care intervention (33 practices, 121 subjects) consisting of three steps: individual counselling; Coping with Depression course; and-if indicated-referral back to general practitioner to discuss further treatment. Measurements included severity of depressive symptoms [Montgomery-Åsberg Depression Rating Scale (MADRS)], quality of life, mortality and costs. RESULTS: at baseline subjects mostly were mildly/moderately depressed. At 6 months MADRS scores had improved more in the usual care than the intervention group (-2.9 versus -1.1 points, P=0.032), but not at 12 months (-3.1 versus -4.6, P=0.084). No significant differences were found within two separate age groups (75-79 years and ≥ 80 years). In intervention practices, 83% accepted referral to the stepped-care programme, and 19% accepted course participation. The control group appeared to have received more psychological care. CONCLUSIONS: among older subjects who screened positive for depressive symptoms, an offered stepped-care intervention programme was not (cost)-effective compared with usual care, possibly due to a low uptake of the course offer. TRIAL REGISTRATION: www.controlled-trials.com/ISRCTN 71142851v.

The combined analysis of uncertainty and patient heterogeneity in medical decision models.

The analysis of both patient heterogeneity and parameter uncertainty in decision models is increasingly recommended. In addition, the complexity of current medical decision models commonly requires simulating individual subjects, which introduces stochastic uncertainty. The combined analysis of uncertainty and heterogeneity often involves complex nested Monte Carlo simulations to obtain the model outcomes of interest. In this article, the authors distinguish eight model types, each dealing with a different combination of patient heterogeneity, parameter uncertainty, and stochastic uncertainty. The analyses that are required to obtain the model outcomes are expressed in equations, explained in stepwise algorithms, and demonstrated in examples. Patient heterogeneity is represented by frequency distributions and analyzed with Monte Carlo simulation. Parameter uncertainty is represented by probability distributions and analyzed with 2nd-order Monte Carlo simulation (aka probabilistic sensitivity analysis). Stochastic uncertainty is analyzed with 1st-order Monte Carlo simulation (i.e., trials or random walks). This article can be used as a reference for analyzing complex models with more than one type of uncertainty and patient heterogeneity.

Uncertainty and patient heterogeneity in medical decision models.

Parameter uncertainty, patient heterogeneity, and stochastic uncertainty of outcomes are increasingly important concepts in medical decision models. The purpose of this study is to demonstrate the various methods to analyze uncertainty and patient heterogeneity in a decision model. The authors distinguish various purposes of medical decision modeling, serving various stakeholders. Differences and analogies between the analyses are pointed out, as well as practical issues. The analyses are demonstrated with an example comparing imaging tests for patients with chest pain. For complicated analyses step-by-step algorithms are provided. The focus is on Monte Carlo simulation and value of information analysis. Increasing model complexity is a major challenge for probabilistic sensitivity analysis and value of information analysis. The authors discuss nested analyses that are required in patient-level models, and in nonlinear models for analyses of partial value of information analysis.

Value of information analyses of economic randomized controlled trials: the treatment of intermittent claudication.

OBJECTIVE: The aim of this study is to design the optimal study comparing endovascular revascularization and supervised exercise training for patients with intermittent claudication and to demonstrate value of information (VOI) analysis of patient-level data from an economic randomized controlled trial to guide future research. METHODS: We applied a net benefit framework to patient-level data on costs and quality-of-life of a previous randomized controlled trial. VOI analyses were performed using Monte Carlo simulation. We estimated the total expected value of perfect information (total EVPI), the total expected value of sample information (total EVSI), the partial expected value of perfect information (partial EVPI), and the partial expected value of sample information (partial EVSI). These VOI analyses identified the key parameters and the optimal sample size of future study designs. Sensitivity analyses were performed to explore the robustness of our assumptions about the population to benefit, the willingness-to-pay threshold, and the study costs. The VOI analyses are demonstrated in statistical software (R) and a spreadsheet (Excel) allowing other investigators to apply VOI analysis to their patient-level data. RESULTS: The optimal study design for the treatment of intermittent claudication involves a randomized controlled trial collecting data on the quality-adjusted life expectancy and additional admission costs for 525 patients per treatment arm. The optimal sample size remained between 400 and 600 patients for a willingness-to-pay threshold between euro30,000 and euro100,000/quality-adjusted life-years, for even extreme assumptions about the study costs, and for a range of 3 to 7 years that future patients will benefit from the results of the proposed study. CONCLUSIONS: 1) The optimal study for patients with intermittent claudication collects data on two key parameters for 525 patients per trial arm; and 2) we have shown that value of information analysis provides an explicit framework to determine the optimal sample size and identify key parameters for the design of future clinical trials.

The use of propensity score methods in psychotherapy research. A practical application.

BACKGROUND: Randomized controlled trials are considered the best scientific proof of effectiveness. There is increasing concern, though, about their feasibility in psychotherapy research. We discuss a quasi-experimental study design for situations in which a randomized controlled trial is not feasible. Here, as an alternative strategy, the propensity score (PS) method is used to correct for selection bias. METHODS: We used data from a Dutch research project, SCEPTRE (Study on Cost-Effectiveness of Personality Disorder Treatment). The sample consisted of 749 psychotherapy patients with personality pathology. We tested whether the PS method was useful and applicable. We examined differences between 2 treatment groups (short vs. long treatment duration) in pretreatment characteristics before and after PS correction. This revealed the impact of the PS on outcome differences. RESULTS: The PS offered statistical control over observed pretreatment differences between patients in a non-randomized study. CONCLUSIONS: When a randomized controlled trial is not possible, this quasi-experimental design using the PS could be a feasible alternative. Its advantages and limitations are discussed. Implemented carefully, this method is promising for future effectiveness research.

Multicenter randomized controlled trial of the costs and effects of noninvasive diagnostic imaging in patients with peripheral arterial disease: the DIPAD trial.

OBJECTIVE: The purpose of our study was to compare the costs and effects of three noninvasive imaging tests as the initial imaging test in the diagnostic workup of patients with peripheral arterial disease. MATERIALS AND METHODS: Of 984 patients assessed for eligibility, 514 patients with peripheral arterial disease were randomized to MR angiography (MRA) or duplex sonography in three hospitals and to MRA or CT angiography (CTA) in one hospital. The outcome measures included the clinical utility, functional patient outcomes, quality of life, and actual diagnostic and therapeutic costs related to the initial imaging test during 6 months of follow-up. RESULTS: With adjustment for potentially predictive baseline variables, the learning curve, and hospital setting, a significantly higher confidence and less additional imaging were found for MRA and CTA compared with duplex sonography. No statistically significant differences were found in improvement in functional patient outcomes and quality of life among the groups. The total costs were significantly higher for MRA and duplex sonography than for CTA. CONCLUSION: The results suggest that both CTA and MRA are clinically more useful than duplex sonography and that CTA leads to cost savings compared with both MRA and duplex sonography in the initial imaging evaluation of peripheral arterial disease.

Value of information analysis used to determine the necessity of additional research: MR imaging in acute knee trauma as an example.

PURPOSE: To help guide future outcomes research regarding the use of magnetic resonance (MR) imaging in patients with acute knee trauma in an emergency department setting, with use of prospective data from a randomized clinical trial and value of information analysis. MATERIALS AND METHODS: A total of 189 patients (123 male, 66 female; mean age, 33.4 years) were randomly assigned to undergo radiography alone (n = 93) or radiography and MR imaging (n = 96). Institutional review board approval and informed consent (parental consent for minors) were obtained. During 6 months of follow-up, data on quality of life and 39 cost parameters were collected. Value-of-information analysis was used to estimate the expected benefit of future research to eliminate the decision uncertainty that remained after trial completion. In addition, the parameters that were responsible for most of the decision uncertainty were identified, the expected benefits of various study designs were evaluated, and the optimal sample size was estimated. RESULTS: Only three parameters were responsible for most of the decision uncertainty: number of quality-adjusted life-years, cost of an overnight hospital stay, and friction costs. A study in which data on these three parameters are gathered would have an optimal sample size of 3500 patients per arm and would be expected to result in a societal benefit of euro 5.6 million or 70 quality-adjusted life-years. CONCLUSION: The optimal study design for use of MR imaging to evaluate acute knee trauma involves a trial in which there are 3500 patients per trial arm, and data on the number of quality-adjusted life-years, cost of an overnight hospital stay, and friction costs are collected.

Limitations of acceptability curves for presenting uncertainty in cost-effectiveness analysis.

Clinical journals increasingly illustrate uncertainty about the cost and effect of health care interventions using cost-effectiveness acceptability curves (CEACs). CEACs present the probability that each competing alternative is optimal for a range of values of the cost-effectiveness threshold. The objective of this article is to demonstrate the limitations of CEACs for presenting uncertainty in cost-effectiveness analyses. These limitations arise because the CEAC is unable to distinguish dramatically different joint distributions of incremental cost and effect. A CEAC is not sensitive to any change of the incremental joint distribution in the upper left and lower right quadrants of the cost-effectiveness plane; neither is it sensitive to radial shift of the incremental joint distribution in the upper right and lower left quadrants. As a result, CEACs are ambiguous to risk-averse policy makers, inhibit integration with risk attitude, hamper synthesis with other evidence or opinions, and are unhelpful to assess the need for more research. Moreover, CEACs may mislead policy makers and can incorrectly suggest medical importance. Both for guiding immediate decisions and for prioritizing future research, these considerable drawbacks of CEACs should make us rethink their use in communicating uncertainty. As opposed to CEACs, confidence and credible intervals do not conflate magnitude and precision of the net benefit of health care interventions. Therefore, they allow (in)formal synthesis of study results with risk attitude and other evidence or opinions. Presenting the value of information in addition to these intervals allows policy makers to evaluate the need for more empirical research.

Vessel wall calcifications at multi-detector row CT angiography in patients with peripheral arterial disease: effect on clinical utility and clinical predictors.

PURPOSE: To evaluate retrospectively the effect of vessel wall calcifications on the clinical utility of multi-detector row computed tomographic (CT) angiography performed in patients with peripheral arterial disease and to identify clinical predictors for the presence of vessel wall calcifications. MATERIALS AND METHODS: The study was approved by the hospital institutional review board, and informed consent was obtained from all patients. For this study the authors included patients from two randomized controlled trials that measured the costs and effects of diagnostic imaging in patients with peripheral arterial disease. All patients underwent CT angiography and were followed up for 6 months. Clinical utility was measured on the basis of therapeutic confidence (rated on a 10-point scale) in the results of initial CT angiography and the need for additional vascular imaging. Univariable and multivariable logistic and linear regression analysis and the area under the receiver operating characteristic curve were used to evaluate the effect of vessel wall calcifications on the clinical utility of CT angiography and the use of patient characteristics to predict the number of calcified segments at CT angiography. RESULTS: A total of 145 patients were included (mean age, 64 years; 70% men). The authors found that the number of calcified segments was a significant predictor of the need for additional imaging (P = .001) and of the confidence scores (P < .001). The number of calcified segments discriminated between patients who required additional imaging after CT angiography and those who did not (area under the receiver operating characteristic curve, 0.66; 95% confidence interval: 0.54, 0.77). Age, diabetes mellitus, and cardiac disease were significant predictors of the number of calcified segments in both the univariable and multivariable analyses (P < .05). CONCLUSION: Vessel wall calcifications decrease the clinical utility of CT angiography in patients with peripheral arterial disease. Diabetes mellitus, cardiac disease, and elderly age (older than 84 years) are independently predictive for the presence of vessel wall calcifications.

Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs.

OBJECTIVE: To assess use and channeling of cyclooxygenase 2 selective inhibitors (coxibs) over time and to estimate the percentage of coxib users with cardiovascular contraindications. METHODS: The study population comprised all coxib and nonselective nonsteroidal antiinflammatory drug (NSAID) users in the Integrated Primary Care Information project between January 2000 and December 2004. The prevalence of risk factors for NSAID-related upper gastrointestinal ulcer complications, cardiovascular disease, and cerebrovascular disease at the start of treatment was compared between users of coxibs and users of nonselective NSAIDs. RESULTS: The study population included 72,841 nonselective NSAID users and 10,739 coxib users. The prevalence of risk factors for NSAID-related gastrointestinal complications was higher in coxib users than nonselective NSAID users (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.10-1.26). Similarly, the prevalence of prior cardiovascular disease was higher in coxib users than in nonselective NSAID users (OR 1.35, 95% CI 1.28-1.43). Channeling of coxibs to patients with NSAID-related gastrointestinal risk factors declined after 2001 but increased again in 2004, whereas the channeling of coxibs to patients with cardiovascular disease remained constant. Less than 15% of all coxib users had history of ischemic coronary or cerebrovascular disease. Among coxib users with increased risk for NSAID-related gastrointestinal disorders, 27% had history of ischemic coronary or cerebrovascular disease. CONCLUSION: This study demonstrates that coxibs were preferentially prescribed to patients with risk factors for NSAID-related gastrointestinal disorders and/or cardiovascular diseases. Only one-quarter of coxib users with increased risk for NSAID-related gastrointestinal complications had cardiovascular conditions compatible with recent European safety contraindications for coxibs.

Apparent and internal validity of a Monte Carlo-Markov model for cardiovascular disease in a cohort follow-up study.

OBJECTIVE: To determine the apparent and internal validity of the Rotterdam Ischemic heart disease & Stroke Computer (RISC) model, a Monte Carlo-Markov model, designed to evaluate the impact of cardiovascular disease (CVD) risk factors and their modification on life expectancy (LE) and cardiovascular disease-free LE (DFLE) in a general population (hereinafter, these will be referred to together as (DF)LE). METHODS: The model is based on data from the Rotterdam Study, a cohort follow-up study of 6871 subjects aged 55 years and older who visited the research center for risk factor assessment at baseline (1990-1993) and completed a follow-up visit 7 years later (original cohort). The transition probabilities and risk factor trends used in the RISC model were based on data from 3501 subjects (the study cohort). To validate the RISC model, the number of simulated CVD events during 7 years' follow-up were compared with the observed number of events in the study cohort and the original cohort, respectively, and simulated (DF)LEs were compared with the (DF)LEs calculated from multistate life tables. RESULTS: Both in the study cohort and in the original cohort, the simulated distribution of CVD events was consistent with the observed number of events (CVD deaths: 7.1% v. 6.6% and 7.4% v. 7.6%, respectively; non-CVD deaths: 11.2% v. 11.5% and 12.9% v. 13.0%, respectively). The distribution of (DF)LEs estimated with the RISC model consistently encompassed the (DF)LEs calculated with multistate life tables. CONCLUSIONS: The simulated events and (DF)LE estimates from the RISC model are consistent with observed data from a cohort follow-up study.

Identifying key parameters in cost-effectiveness analysis using value of information: a comparison of methods.

Decisions in health care must be made, despite uncertainty about benefits, risks, and costs. Value of information analysis is a theoretically sound method to estimate the expected value of future quantitative research pertaining to an uncertain decision. If the expected value of future research does not exceed the cost of research, additional research is not justified, and decisions should be based on current evidence, despite the uncertainty. To assess the importance of individual parameters relevant to a decision, different value of information methods have been suggested. The generally recommended method assumes that the expected value of perfect knowledge concerning a parameter is estimated as the reduction in expected opportunity loss. This method, however, results in biased expected values and incorrect importance ranking of parameters. The objective of this paper is to set out the correct methods to estimate the partial expected value of perfect information and to demonstrate why the generally recommended method is incorrect conceptually and mathematically.

DSA versus multi-detector row CT angiography in peripheral arterial disease: randomized controlled trial.

PURPOSE: To prospectively compare therapeutic confidence in, patient outcomes (in terms of quality of life) after, and the costs of digital subtraction angiography (DSA) with those of multi-detector row computed tomographic (CT) angiography as the initial diagnostic imaging test in patients with peripheral arterial disease (PAD). MATERIALS AND METHODS: Institutional medical ethics committee approval and patient informed consent were obtained. Between April 2000 and August 2001, patients with PAD were randomly assigned to undergo either DSA or multi-detector row CT angiography as the initial diagnostic imaging test. Outcomes were the therapeutic confidence assessed by physicians (on a scale from 0 to 10), the need for additional imaging, the health-related quality of life at 6-month follow-up, diagnostic and therapeutic costs, and the costs for a hospital stay. Costs were computed from a hospital perspective according to Dutch guidelines for cost calculations in health care. Mean outcomes were compared between groups with unpaired t testing and were adjusted for predictive baseline characteristics with multivariable regression analysis. RESULTS: Among the 145 patients, 72 were randomly allocated to the DSA group and 73 to the CT angiography group. One patient in the DSA group had to be excluded. Mean age was 63 years in the DSA group and 64 years in the CT angiography group. There were 47 men in the DSA group and 58 men in the CT angiography group. Physician confidence in making a correct therapeutic choice was significantly higher at DSA (mean confidence score, 8.2) than at CT angiography (mean score, 7.2; P < .001). During 6-month follow-up, 14% less additional imaging was performed in the DSA group than in the CT angiography group (P = .3). No significant quality-of-life differences were found between groups. The diagnostic cost associated with DSA (564 +/- 210 euro [standard deviation]) was significantly higher than that associated with CT angiography (363 +/- 273 euro), a difference of -201 euro (95% confidence interval: -281 euro, -120 euro; P < .001). Therapeutic and hospitalization costs were similar for both strategies. CONCLUSION: These results suggest that use of noninvasive multi-detector row CT angiography instead of DSA as the initial diagnostic imaging test for PAD provides sufficient information for therapeutic decision making and reduces imaging costs.

Imaging peripheral arterial disease: a randomized controlled trial comparing contrast-enhanced MR angiography and multi-detector row CT angiography.

PURPOSE: To prospectively evaluate clinical utility, patient outcomes, and costs of contrast material-enhanced magnetic resonance (MR) angiography compared with multi-detector row computed tomographic (CT) angiography for initial imaging in the diagnostic work-up of patients with peripheral arterial disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Patients referred for diagnostic imaging work-up to evaluate the feasibility of a revascularization procedure were randomly assigned to undergo either MR angiography or CT angiography. Clinical utility was assessed with therapeutic confidence (scale of 0-10) at initial imaging and with the need for additional imaging. Patient outcomes included ankle-brachial index, maximum walking distance, change in clinical status, and health-related quality of life. Actual diagnostic and therapeutic costs were calculated from the hospital perspective. Differences between group means were calculated with unpaired t tests and 95% confidence intervals. RESULTS: A total of 157 consecutive patients with peripheral arterial disease were prospectively randomized to undergo MR angiography (51 men, 27 women; mean age, 63 years) or CT angiography (50 men, 29 women; mean age, 64 years). For one of the 78 patients in the MR group, no data were available. Mean confidence for MR angiography (7.7) was slightly lower than that for CT angiography (8.0, P = .8). During 6 months of follow-up, 13 patients in the MR group compared with 10 patients in the CT group underwent additional vascular imaging (P = .5). Although not statistically significant, there was a consistent trend of less improvement in the MR group across all patient outcomes. The average cost for diagnostic imaging was 359 ($438) higher in the MR group than in the CT group (95% confidence interval: 209, 511 [$255, $623]; P < .001). Therapeutic costs were higher in the MR group, but the difference was not significant. CONCLUSION: The results suggest that CT angiography has some advantages over MR angiography in the initial evaluation of peripheral arterial disease.