Buskens, E.

A method for the early health technology assessment of novel biomarker measurement in primary prevention programs (Article)

2012-10-15T00:00:00Z

Many promising biomarkers for stratifying individuals at risk of developing a chronic disease or subsequent complications have been identified. Research into the potential cost-effectiveness of applying these biomarkers in actual clinical settings has however been lacking. Investors and analysts may improve their venture decision making should they have indicative estimates of the potential costs and effects associated with a new biomarker technology already at the early stages of its development. To assist in obtaining such estimates, this paper presents a general method for the early health technology assessment of a novel biomarker technology. The setting considered is that of primary prevention programs where initial screening to select high-risk individuals eligible for a subsequent intervention occurs, for example, prevention of type 2 diabetes. The method is based on quantifying the health outcomes and downstream healthcare consumption of all individuals who get reclassified as a result of moving from a screening variant based on traditional risk factors to a screening variant based on traditional risk factors plus a novel biomarker. As these individuals form well-defined subpopulations, a combination of disease progression modeling and sensitivity analysis can be used to perform an initial assessment of the maximum increase in screening cost for which the use of the new biomarker technology is still likely to be cost effective.

Impact of secondary cardiovascular events on health status (Article)

2012-01-01T00:00:00Z

Objectives: Estimates regarding the impact of secondary cardiovascular events on health status in patients treated for cardiovascular disease are scarce and of limited accuracy. Methods: We obtained individual patient data on health status (EuroQol five-dimensional questionnaire) and secondary cardiovascular events (death, myocardial infarction, cerebrovascular accidents, amputation, extracranial bleeding, and reinterventions) observed during 12 to 36 months of follow-up. Data originated from five completed clinical trials on revascularization in coronary heart disease (n = 2593) or peripheral arterial disease (PAD; n = 1379). We used linear mixed-effects modeling to estimate the acute impact of the initial secondary event and the health status before and after the event. Results: A total of 1595 patients had at least one secondary event. Loss of health status just before the event ranged from 0.36 utility score for amputation in women with PAD to zero for cerebrovascular accident in men with PAD. In patients with coronary heart disease, pre-event health status loss ranged from 0.34 for extracranial bleeding in women to 0.10 for myocardial infarction in women. The acute impact of secondary events ranged from minor deterioration for cerebrovascular accident (-0.03) to improvement after all other events, ranging from +0.01 for occlusion to +0.22 for amputation. Women had significantly lower pre-event scores than did men: -0.04 to -0.10 in coronary heart disease and -0.04 to -0.27 in PAD. Older patients had mostly large but insignificantly lower pre-event scores than did younger patients (range +0.04 to -0.67). Conclusions: Secondary events after revascularization in patients with cardiovascular disease are associated with health status loss before the event, while acute impact of the events was mostly small.

Erratum to: Differences in quality of life of hemodialysis patients between dialysis centers (Article)

2011-07-25T00:00:00Z

Differences in quality of life of hemodialysis patients between dialysis centers (Article)

2011-06-02T00:00:00Z

Purpose: Hemodialysis patients undergo frequent and long visits to the clinic to receive adequate dialysis treatment, medical guidance, and support. This may affect health-related quality of life (HRQOL). Although HRQOL is a very important management aspect in hemodialysis patients, there is a paucity of information on the differences in HRQOL between centers. We set out to assess the differences in HRQOL of hemodialysis patients between dialysis centers and explore which modifiable center characteristics could explain possible differences. Methods: This cross-sectional study evaluated 570 hemodialysis patients from 24 Dutch dialysis centers. HRQOL was measured with the Kidney Disease Quality Of Life-Short Form (KDQOL-SF). Results: After adjustment for differences in case-mix, three HRQOL domains differed between dialysis centers: the physical composite score (PCS, P = 0.01), quality of social interaction (P = 0.04), and dialysis staff encouragement (P = 0.001). These center differences had a range of 11-21 points on a scale of 0-100, depending on the domain. Two center characteristics showed a clinical relevant relation with patients' HRQOL: dieticians' fulltime-equivalent and the type of dialysis center. Conclusion: This study showed that clinical relevant differences exist between dialysis centers in multiple HRQOL domains. This is especially remarkable as hemodialysis is a highly standardized therapy.

Changes in quality of life over time-Dutch haemodialysis patients and general population compared (Article)

2011-06-01T00:00:00Z

Background. Improving the health-related quality of life (HRQOL) for haemodialysis patients is a considerable challenge. The aim of the present study was to compare changes in HRQOL in haemodialysis patients with those observed in the general population over a 10-year period and explore factors that might explain possible differences.Methods. We compared 126 haemodialysis patients assessed in 1995 in the Netherlands Cooperative Study on the Adequacy of Dialysis-1 (NECOSAD-I) with 515 patients enrolled in 2006 in the ongoing Convective Transport Study (CONTRAST). Changes in HRQOL in these cohorts were compared with two representative samples from the general Dutch population, assessed in 1992 (n = 1,063) and 2001 (n = 10,600). HRQOL was measured with the SF-36 questionnaire. Differences in HRQOL were analysed with ANCOVA to adjust for demographic variables. To assess possible differences, we used multivariable regression analysis.Results. HRQOL in haemodialysis patients in 2006 [CONTRAST, mean age 63 ± 14 years (SD), 62% male] was significantly better than in 1995 (NECOSAD-I, 59 ± 16 years, 53% male) in four domains of the SF-36: bodily pain (+ 5 points, P = 0.009), vitality (+ 7, P < 0.001), role-emotional (+ 14, P < 0.001) and mental health (+ 8, P < 0.001), after adjusting for demographic variables. This increment could partly be explained by improved haemoglobin and phosphate levels. Compared to the general population, HRQOL improvement was most outspoken in two domains: bodily pain (+ 6, P = 0.01) and role-emotional (+ 8, P = 0.007).Conclusions. This study showed an improvement of HRQOL in haemodialysis patients over an 11-year period of time, independent of global changes in the general population.

A stochastic multicriteria model for evidence-based decision making in drug benefit-risk analysis (Article)

2011-05-30T00:00:00Z

Drug benefit-risk (BR) analysis is based on firm clinical evidence regarding various safety and efficacy outcomes. In this paper, we propose a new and more formal approach for constructing a supporting multi-criteria model that fully takes into account the evidence on efficacy and adverse drug reactions. Our approach is based on the stochastic multi-criteria acceptability analysis methodology, which allows us to compute the typical value judgments that support a decision, to quantify decision uncertainty, and to compute a comprehensive BR profile. We construct a multi-criteria model for the therapeutic group of second-generation antidepressants. We assess fluoxetine and venlafaxine together with placebo according to incidence of treatment response and three common adverse drug reactions by using data from a published study. Our model shows that there are clear trade-offs among the treatment alternatives.

Disrupting the rhythm of depression: Design and protocol of a randomized controlled trial on preventing relapse using brief cognitive therapy with or without antidepressants (Article)

2011-01-12T00:00:00Z

Background: Maintenance treatment with antidepressants is the leading strategy to prevent relapse and recurrence in patients with recurrent major depressive disorder (MDD) who have responded to acute treatment with antidepressants (AD). However, in clinical practice most patients (up to 70-80%) are not willing to take this medication after remission or take too low dosages. Moreover, as patients need to take medication for several years, it may not be the most cost-effective strategy. The best established effective and available alternative is brief cognitive therapy (CT). However, it is unclear whether brief CT while tapering antidepressants (AD) is an effective alternative for long term use of AD in recurrent depression. In addition, it is unclear whether the combination of AD to brief CT is beneficial.Methods/design: Therefore, we will compare the effectiveness and cost-effectiveness of brief CT while tapering AD to maintenance AD and the combination of CT with maintenance AD. In addition, we examine whether the prophylactic effect of CT was due to CT tackling illness related risk factors for recurrence such as residual symptoms or to its efficacy to modify presumed vulnerability factors of recurrence (e.g. rigid explicit and/or implicit dysfunctional attitudes). This is a multicenter RCT comparing the above treatment scenarios. Remitted patients on AD with at least two previous depressive episodes in the past five years (n = 276) will be recruited. The primary outcome is time related proportion of depression relapse/recurrence during minimal 15 months using DSM-IV-R criteria as assessed by the Structural Clinical Interview for Depression. Secondary outcome: economic evaluation (using a societal perspective) and number, duration and severity of relapses/recurrences.Discussion: This will be the first trial to investigate whether CT is effective in preventing relapse to depression in recurrent depression while tapering antidepressant treatment compared to antidepressant treatment alone and the combination of both. In addition, we explore explicit and implicit mediators of CT.Trial registration: Netherlands Trial Register (NTR): NTR1907.

Suspected carotid artery stenosis: Cost-effectiveness of CT angiography in work-up of patients with recent TIA or minor ischemic stroke (Article)

2010-08-01T00:00:00Z

Purpose: To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack (TIA) or minor stroke who are suspected of having carotid artery stenosis (CAS). Materials and Methods: All prospectively evaluated patients provided informed consent, and the local ethics committee approved this study. Diagnostic performance, treatment, long-term events, quality of life, and costs resulting from strategies employing duplex ultrasonography (US), computed tomographic (CT) angiography, contrast material-enhanced magnetic resonance (MR) angiography, and combinations of these modalities were modeled in a decision tree and Markov model. Data sources included a prospective diagnostic cohort study, a meta-analysis, and a review of the literature. Outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net health benefits (QALY-equivalents), with a willingness-to-pay threshold of €50 000 per QALY and a societal perspective. The strategy with the highest net health benefit was considered the most cost effective. Extensive one-way, two-way, and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed. The reference case analysis assumed that patients underwent surgery 2-4 weeks after the first symptoms, and the effect of earlier intervention was explored. Results: The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99% stenoses was the most cost-effective strategy, with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women, respectively. In men, the CT angiography strategy with a 70%-99% cutoff yielded slightly more QALYs, at an incremental cost of €71 419 per QALY, compared with duplex US combined with CT angiography. In patients with a high-risk profile, in patients with a high prior probability of disease, and when patients could be treated within 2 weeks after the first symptoms, the CT angiography strategy with surgery for 50%-99% stenoses was the most cost-effective strategy. Conclusion: In diagnosing CAS, duplex US should be the initial test, and, if its results are positive, CT angiography should be performed; patients with 70%-99% stenoses should then undergo carotid endarterectomy. In patients with a high-risk profile, a high probability of CAS, or who can undergo surgery without delay, immediate CT angiography and surgery for 50%-99% stenoses is indicated.

A step-up approach or open necrosectomy for necrotizing pancreatitis (Article)

2010-04-22T00:00:00Z

Background: Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. Methods: In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. Results: The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P = 0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P = 0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P = 0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P = 0.03) and new-onset diabetes (16% vs. 38%, P = 0.02). Conclusions: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.). Copyright

Surgeon equipoise as an inclusion criterion for the evaluation of nonoperative versus operative treatment of thoracolumbar spinal injuries (Article)

2008-11-01T00:00:00Z

BACKGROUND CONTEXT: Prospective studies have failed to demonstrate the superiority of either operative or nonoperative treatment of thoracolumbar fractures. Similar to other surgical fields, research has been limited by the variability in surgical interventions, difficult recruitment, infrequent pathology, and the urgency of interventions. PURPOSE: To outline factors precluding randomized controlled trials in spinal fractures research, and describe a novel methodology that seeks to improve on the design of observational studies. STUDY DESIGN/SETTING: A preliminary report describing an observational study design with clinical equipoise as an inclusion criterion. The proposed methodology is a cohort study with head-to-head comparison of operative and nonoperative treatment regimens in an expertise-based trial fashion. Patients are selected retrospectively by an expert panel and clinical outcomes are assessed to compare competing treatment regimens. Surgeon equipoise served as an inclusion criterion. PATIENT SAMPLE: Patients with closed or open thoracolumbar spinal fracture with or without neurological impairment, presenting to one of two different trauma centers between 1991 and 2005 (N = 760). OUTCOME MEASURES: Homogeneity of baseline clinical and demographic data and distribution of prognostic risk factors between the operative and the nonoperative cohort. METHODS: Patients treated for spine fractures at two University hospitals practicing opposing methods of fracture intervention were identified by medical diagnosis code searches (n = 760). A panel of spine treatment experts, blinded to the treatment received clinically has assessed each case retrospectively. Patients were included in the study when there was disagreement on the preferred treatment, that is, operative or nonoperative treatment of the injury. Baseline and initial data of a study evaluating nonoperative versus operative spinal fracture treatment are presented. RESULTS: One hundred and ninety patients were included in the study accounting for a panel discordance rate of 29%. The distribution of baseline characteristics and demographics of the study populations were equal across the parallel cohorts enrolled in the study, that is, no differences in prognostic factors were observed. CONCLUSIONS: The use of clinical equipoise as an inclusion criterion in comparative studies may be used to avoid selection bias. Using multivariate analysis of retrospectively assembled parallel cohorts, a valid comparison of operative and nonoperative spine fracture treatment strategies and their outcomes is possible.

Traumatic thoracic and lumbar spinal fractures: operative or nonoperative treatment: comparison of two treatment strategies by means of surgeon equipoise (Article)

2008-04-01T00:00:00Z

STUDY DESIGN: A center parallel cohort study with blinded inclusion based on clinical equipoise. OBJECTIVE: To compare outcomes of nonoperative and operative treatment strategies in terms of quality of life and neurologic and functional status. SUMMARY OF BACKGROUND DATA: Despite a considerable body of literature, sound evidence regarding the optimal treatment for traumatic thoracic and lumbar spine fractures is lacking. METHODS: Medical records of patients hospitalized for traumatic spinal fractures between 1991 and 2002 were identified in 2 trauma centers in the same country with established and different treatment strategies. Eligibility was retrospectively assessed for each case by a panel of orthopaedic surgeons who were representative of the 2 medical centers, and who were blinded to the treatment actually administered. Patients were included in the study when there was disagreement on the suggested treatment method. Thus, 2 comparable groups were identified undergoing nonoperative or operative treatment. Outcome assessment and comparison across groups focused on quality of life, residual pain, neurologic recovery, and employment in the middle-long-term follow-up. RESULTS: Discordance in regards to choice of treatment was identified in 190 (95 treated nonoperative, 95 operative) of 636 potentially eligible patients. Patients were comparable regarding baseline characteristics, except for a somewhat higher proportion of males and neurologic impairment in the operative group. Seventeen percent of the nonoperative and 21% of the operative group developed complications and 3 patients displayed neurologic deterioration for which a treatment change was considered necessary. Follow-up was complete in 79%; mean follow-up time was 6.2 years with a minimum of 2 years. Pain scores, disability indexes, and general health outcome were comparable at follow-up. Compared with matched population norms, outcomes were poorer regardless of treatment method. Neurologic recovery was better in the operative group, but this difference did not reach statistical significance. Multivariate regression analyses revealed that female gender and neurologic impairment were independent predictors of poor functional outcome. Eighty-eight and 83% of the nonoperatively and operatively treated patients were employed at some point after a rehabilitation period. CONCLUSION: Overall outcome of nonoperative and operative treatment in middle-long-term follow up is comparable, although there seems to be a difference in neurologic recovery patterns. Studies on the cost-effectiveness of treatment options and the patterns of recovery within 2 years after injury would assist in guideline development and stimulate interest for future research.

Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial (Article)

2008-02-15T00:00:00Z

Background: Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis. Methods: In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score ≥8, Imrie score ≥3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications-ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites-during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949. Findings: One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1·06, 95% CI 0·75-1·51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2·53, 95% CI 1·22-5·25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0·004). Interpretation: In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

Cost-effectiveness of conventional and endovascular repair of abdominal aortic aneurysms: Results of a randomized trial (Article)

2007-11-01T00:00:00Z

Background: Two randomized trials have shown similar mid-term outcomes for survival and quality of life after endovascular and conventional open repair of abdominal aortic aneurysms (AAA). With reduced hospital and intensive care stay, endovascular repair has been hypothesized to be more efficient than open repair. The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial was undertaken to assess the balance of costs and effects of endovascular vs open aneurysm repair. Methods: We conducted a multicenter, randomized trial comparing endovascular repair with open repair in 351 patients with an AAA and studied costs, cost-effectiveness, and clinical outcome 1 year after surgery. In addition to clinical outcome, costs and quality of life were recorded up to 1 year in 170 patients in the endovascular repair group and in 170 in the open repair group. Incremental cost-effectiveness ratios were estimated for cost per life-year, event-free life-year, and quality adjusted life-year (QALY) gained. Uncertainty regarding these outcomes was assessed using bootstrapping. Results: Patients in the endovascular repair group experienced 0.72 QALY vs 0.73 in the open repair group (absolute difference, 0.01; 95% confidence interval [CI], -0.038 to 0.058). Endovascular repair was associated with additional €4293 direct costs (€18,179 vs €13.886; 95% CI, €2,770 to €5,830). Most of the bootstrap estimates indicated that endovascular repair resulted in slightly longer overall and event-free survival associated with respective incremental cost-effectiveness ratios of €76,100 and €171,500 per year gained. Open repair appeared the dominant strategy in costs per QALY. Conclusion: Presently, routine use of endovascular repair in patients also eligible for open repair does not result in a QALY gain at 1 year postoperatively, provides only a marginal overall survival benefit, and is associated with a substantial, if not prohibitive, increase in costs.

Diagnostic performance of duplex ultrasound in patients suspected of carotid artery disease: the ipsilateral versus contralateral artery. (Article)

2005-10-01T00:00:00Z

BACKGROUND AND PURPOSE: To evaluate duplex ultrasonographic thresholds for the determination of 70% to 99% stenosis of the ipsilateral and contralateral internal carotid artery in patients with symptoms of amaurosis fugax, transient ischemic attack (TIA), or minor stroke based on 2 criteria: maximizing accuracy and optimizing cost-effectiveness and to compare these with current recommendations. METHODS: From January 1997 to January 2000, a prospective multicenter study was conducted including 350 consecutive patients with symptoms of amaurosis fugax, TIA, or minor stroke who underwent bilateral duplex ultrasonography and digital subtraction angiography. A linear regression analysis was performed to estimate the degree of angiographic stenosis as a function of the peak systolic velocity (PSV). PSV thresholds were calculated for the ipsilateral and contralateral carotid arteries based on maximizing accuracy and optimizing cost-effectiveness. RESULTS: The PSV measurements significantly overestimated the angiographic stenosis in the contralateral artery (9.5%; 95% CI, 6.3% to 12.7%) compared with the ipsilateral carotid artery. The recommended PSV threshold for the diagnosis of 70% to 99% stenosis is 230 cm/s. Maximizing accuracy, the optimal PSV threshold for the ipsilateral artery was 280 cm/s, and for the contralateral artery, 370 cm/s for diagnosing a 70% to 99% stenosis. Optimizing cost-effectiveness, the optimal PSV threshold was 220 cm/s for ipsilateral and 290 cm/s for contralateral carotid arteries. CONCLUSIONS: PSV measurements overestimate the degree of angiographic stenosis in the contralateral carotid artery in patients with symptoms of amaurosis fugax, TIA, or minor stroke. Separate PSV thresholds should be used for the ipsilateral and contralateral carotid artery. PSV thresholds that optimize cost-effectiveness differ from the recommended thresholds and from thresholds that maximize accuracy.

Routine prenatal screening for congenital heart disease: what can be expected? A decision-analytic approach (Article)

1997-01-01T00:00:00Z

OBJECTIVES: This study assessed the potential impact of fetal ultrasound screening on the number of newborns affected by cardiac anomalies. METHODS: A decision model was developed that included the prevalence and history of congenital heart disease, characteristics of ultrasound, risk of abortion, and attitude toward pregnancy termination. Probabilities were obtained with a literature survey; sensitivity analysis showed their influence on expected outcomes. RESULTS: Presently, screening programs may prevent the birth of approximately 1300 severely affected newborns per million second-trimester pregnancies. However, over 2000 terminations of pregnancy would be required, 750 of which would have ended in intrauterine death or spontaneous abortion. Further, 9900 false-positive screening results would occur, requiring referral. Only the sensitivity of routine screening and attitude toward termination of pregnancy appeared to influence the yield substantially. CONCLUSIONS: The impact of routine screening for congenital heart disease appeared relatively small. Further data may be required to fully assess the utility of prenatal screening.

Prenatal ultrasound screening for congenital heart disease : an epidemiologic perspective (Doctoral Thesis)

1994-12-21T00:00:00Z