CARDIOVASCULAR SCREENING OF YOUNG ATHLETES: A REVIEW OF ECONOMIC EVALUATIONS.

OBJECTIVES: Some experts have promoted preparticipative cardiovascular screening programs for young athletes and have claimed that such programs were cost-effective without performing a critical analysis of studies supporting this statement. In this systematic review, a critical assessment of economic evaluations on these programs is performed to determine if they really provide value for money. METHODS: A systematic review of economic evaluations was performed on December 24, 2014. Web sites of health technology assessment agencies, the Cochrane database of systematic review, the National Health Service Economic Evaluation Database of the Cochrane Library, EMBASE, Medline, Psychinfo, and EconLit were searched to retrieve (reviews of) economic evaluations. No language or time restrictions were imposed and predefined selection criteria were used. Selected studies were critically assessed applying a structured data extraction sheet. RESULTS: Five relevant economic evaluations were critically assessed. Results of these studies were mixed. However, those in favor of screening made (methodological) incorrect choices, of which the most important one was not taking into account a no-screening alternative as comparator. Compared with no screening, other strategies (history and physical examination or history and physical examination plus electrocardiogram) were not considered cost-effective. CONCLUSIONS: Results of primary economic evaluations should not be blindly copied without critical assessment. Economic evaluations in this field lack the support of robust evidence. Negative consequences of screening (false positive findings, overtreatment) should also be taken into account and may cause more harm than good. A mass screening of young athletes for cardiovascular diseases does not provide value for money and should be discouraged.

Effectiveness of catheter ablation of atrial fibrillation in Belgian practice: a cohort analysis on administrative data.

AIM: To assess the outcome and cost of catheter ablation of atrial fibrillation (AF) in Belgium. METHODS AND RESULTS: From a nationwide health insurers' database, we retrieved claims data of all patients that underwent a catheter ablation of AF from November 2007 through December 2008. Based on data on reimbursed procedures and drugs, we assessed AF recurrence using different models. Costs related to the index hospitalization were calculated. During the observation period, 830 patients underwent a first catheter ablation of AF. Two-year follow-up data were available for all patients, with an average follow-up of 30.2 months. Seventy-seven percent of patients were treated for paroxysmal AF. Recurrence of AF was defined as the occurrence of one of the following events: a repeat catheter ablation, an electric cardioversion or an antiarrhythmic drug (AAD) prescription, the latter two taking into account a blanking period of 3 months. Atrial fibrillation recurred in 59.8% of patients after 1 year and in 65.9% of them after 2 years. If AAD prescription was considered as an indicator for ablation failure only if it occurred after a 1 month AAD-free period, recurrence of AF occurred in 37.3% of patients after 1 year and in 49.9% after 2 years. Based on the prescription of rate and rhythm control drugs before the ablation, we conclude that up to 15.8% of patients underwent catheter ablation as first-line therapy. Catheter ablation of AF in Belgium on average costs about €9600 for the initial intervention. CONCLUSION: Since the effectiveness of catheter ablation of AF appears to be less favourable in real-world practice as compared with results reported in clinical trials, and given the high initial cost of the procedure, we suggest to strictly limiting the intervention to patients in whom it is currently believed to be most beneficial, i.e. those with severely symptomatic and drug-refractory paroxysmal AF with no or minimal structural heart disease.

The cost-utility of catheter ablation of atrial fibrillation: a systematic review and critical appraisal of economic evaluations.

BACKGROUND: A health technology assessment (HTA) of catheter ablation for atrial fibrillation (CA-AF) was commissioned by the Belgian government and performed by the Belgian Health Care Knowledge Centre (KCE). In this context, a systematic review of the economic literature was performed to assess the procedure's value for money. METHODS: A systematic search for economic literature about the cost-effectiveness of CA-AF was performed by consulting various databases: CRD (Centre for Reviews and Dissemination) HTA and CDSR (Cochrane Database of Systematic Reviews) Technology Assessment, websites of HTA institutes, NHS EED (NHS Economic Evaluation Database), Medline (OVID), EMBASE and EconLit. No time or language restrictions were imposed and pre-defined selection criteria were used. The two-step selection procedure was performed by two persons. References of the selected studies were checked for additional relevant citations. RESULTS: Out of 697 references, seven relevant studies were selected. Based on current evidence and economic considerations, the rationale to support catheter ablation as first-line treatment was lacking.The economic evaluations for second-line catheter ablation included several assumptions that make the results rather optimistic or subject to large uncertainty. First, overall AAD (antiarrhythmic drugs) use after ablation was higher in reality than assumed in the economic evaluations, which had its impact on costs and effects. Second, several models focused on the impact of ablation on preventing stroke. This was questionable because there was no direct hard evidence from RCTs to support this assumption. An indirect impact through stroke on mortality should also be regarded with caution. Furthermore, all models included an impact on quality of life (QoL)/utility and assumed a long-term impact. Unfortunately, none of the RCTs measured QoL with a generic utility instrument and information on the long-term impact on both mortality and QoL was lacking. CONCLUSIONS: Catheter ablation is associated with high initial costs and may lead to life-threatening complications. Its cost-effectiveness depends on the belief one places on the impact on utility and/or preventing stroke, and the duration of these effects. Having no hard evidence for these important variables is rather troublesome. Although the technique is widely spread, the scientific evidence is insufficient for drawing conclusions about the intervention's cost-effectiveness.

Legal and organizational aspects of remote cardiac monitoring: the example of implantable cardioverter defibrillators.

The remote monitoring of implantable cardioverter defibrillators (ICDs) recently emerged as an attractive technological innovation that proved to be reasonably safe in partially replacing the in-clinic follow-ups of ICD patients with no or only mild symptoms. Apart from the fact that strong evidence about any additional clinical benefits and/or cost-efficiency are still awaited, legal and organizational hurdles remain in place, hampering any possibility for adoption of remote cardiac monitoring. This paper identifies a number of legal and organizational constraints which urgently need to be addressed. An elaboration of the specific juridical guidance for the interpretation and application of the relevant legislation is called for.

Pre-market clinical evaluations of innovative high-risk medical devices in Europe.

OBJECTIVES: High-quality clinical evidence is most often lacking when novel high-risk devices enter the European market. At the same time, a randomized controlled trial (RCT) is often initiated as a requirement for obtaining market access in the US. Should coverage in Europe be postponed until RCT data are available? We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the US, and with medicines, where appropriate. METHODS: The literature and regulatory documents were checked. Representatives from industry, Competent Authorities, Notified Bodies, Ethics Committees, and HTA agencies were consulted. We also discuss patient safety and the transparency of information. RESULTS: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. Patients in Europe can thus have earlier access to a potentially lifesaving device, but at the risk of insufficiently documented efficacy and safety. Variations in the stringency of clinical reviews, both at the level of Notified Bodies and Competent Authorities, do not guarantee patient safety. We tried to document the design of premarket trials in Europe and number of patients exposed, but failed as this information is not made public. Furthermore, the Helsinki Declaration is not followed with respect to the registration and publication of premarket trials. CONCLUSIONS: For innovative high-risk devices, new EU legislation should require the premarket demonstration of clinical efficacy and safety, using an RCT if possible, and a transparent clinical review, preferably centralized.

Cost effectiveness of drug-eluting stents in Belgian practice: healthcare payer perspective.

BACKGROUND: There has been a steep increase in the number of percutaneous coronary intervention procedures performed for coronary heart disease since their introduction about 30 years ago. Recently, the use of drug-eluting stents (DES) compared with the original bare metal stents (BMS) has increased in many countries. OBJECTIVE: To assess the cost effectiveness of DES versus BMS in a real-world setting from the Belgian healthcare payer perspective. METHODS: We developed a decision analysis model to estimate incremental costs (year 2004 or 2007 values [depending on the underlying variable]) and effectiveness. Incremental effectiveness was calculated by combining relative benefits from published meta-analyses with real-world observations from a Belgian registry. Probabilistic modelling and sensitivity analyses were performed. The model had a 1-year time horizon. Sixteen sub groups were created based on the following characteristics: initial stent type, diabetic status, complex lesion and multi-vessel disease. Scenario analyses were performed for the influence on reinterventions and the duration of clopidogrel use. In each analysis, 1000 Monte Carlo simulations were performed. RESULTS: The incremental costs for switching from BMS to DES are substantial (approximately euro1000), while the benefits, expressed as QALYs, are extremely small (on average <0.001 QALYs gained). This led to very high incremental cost-effectiveness ratios: over euro860 000 per QALY gained in all subgroups and scenario analyses. CONCLUSION: Comparing DES with BMS, no life-years are gained and small quality-of-life improvements are achieved for short periods, resulting in a high likelihood that DES are not cost effective. When there is competition for scarce resources this should be considered when deciding on the reimbursement of this technology.

Safety of percutaneous aortic valve insertion. A systematic review.

BACKGROUND: The technique of percutaneous aortic valve implantation (PAVI) for the treatment of severe aortic stenosis (AS) has been introduced in 2002. Since then, many thousands such devices have worldwide been implanted in patients at high risk for conventional surgery. The procedure related mortality associated with PAVI as reported in published case series is substantial, although the intervention has never been formally compared with standard surgery. The objective of this study was to assess the safety of PAVI, and to compare it with published data reporting the risk associated with conventional aortic valve replacement in high-risk subjects. METHODS: Studies published in peer reviewed journals and presented at international meetings were searched in major medical databases. Further data were obtained from dedicated websites and through contacts with manufacturers. The following data were extracted: patient characteristics, success rate of valve insertion, operative risk status, early and late all-cause mortality. RESULTS: The first PAVI has been performed in 2002. Because of procedural complexity, the original transvenous approach from 2004 on has been replaced by the transarterial and transapical routes. Data originating from nearly 2700 non-transvenous PAVIs were identified. In order to reduce the impact of technical refinements and the procedural learning curve, procedure related safety data from series starting recruitment in April 2007 or later (n = 1975) were focused on. One-month mortality rates range from 6.4 to 7.4% in transfemoral (TF) and 11.6 to 18.6% in transapical (TA) series. Observational data from surgical series in patients with a comparable predicted operative risk, indicate mortality rates that are similar to those in TF PAVI but substantially lower than in TA PAVI. From all identified PAVI series, 6-month mortality rates, reflecting both procedural risk and mortality related to underlying co-morbidities, range from 10.0-25.0% in TF and 26.1-42.8% in TA series. It is not known what the survival of these patients would have been, had they been treated medically or by conventional surgery. CONCLUSION: Safety issues and short-term survival represent a major drawback for the implementation of PAVI, especially for the TA approach. Results from an ongoing randomised controlled trial (RCT) should be awaited before further using this technique in routine clinical practice. In the meantime, both for safety concerns and for ethical reasons, patients should only be subjected to PAVI within the boundaries of such an RCT.

Cost-effectiveness analyses of drug eluting stents versus bare metal stents: a systematic review of the literature.

OBJECTIVES: Drug eluting stents (DES) used to treat coronary lesions reduce rates of in-stent restenosis and therefore the need for repeat revascularization compared to bare metal stents (BMS). DES, however, are considerably more expensive than BMS. We evaluated whether DES are a cost-effective alternative for BMS. METHODS: Reports of Health Technology Assessment agencies were assessed and a systematic review of economic evaluations comparing DES with BMS was performed. RESULTS: Nineteen full economic evaluations were identified. Some studies indicate that DES may be cost-effective or even cost-saving in specific patients, when used for coronary lesions with a high propensity of restenosis such as long lesions, lesions in narrow vessels, or in patients with diabetes. Other studies mention DES is not cost effective at all with ICERs of more than 200,000 Canadian dollar per QALY gained. One of the main determining factors is the influence of protocol mandated angiographic follow-up in RCTs. The risk for a re-intervention using BMS ranges from 5% to 14% in registries and is much smaller than reported in RCTs (up to 30%). As a result, the absolute reduction in repeat revascularization by DES compared to BMS is smaller in real life. Moreover, using DES instead of BMS does not increase survival or decrease myocardial infarctions. The combination of (a) a higher cost (>euro700) for DES versus BMS; (b) no life-years gained; (c) a relatively small absolute reduction in repeat procedures; and (d) a small improvement in QoL for a short period (less than 0.15 during the first month after the re-intervention), results in unfavourable cost-effectiveness ratios. CONCLUSIONS: Although several studies conclude that DES may be cost effective in large subgroups of patients, under real-world conditions, the cost-effectiveness of DES is unfavourable in comparison with BMS.

Percutaneous pulmonary and aortic valve insertion in Belgium: going for conditional reimbursement or waiting for further evidence?

OBJECTIVES: The aim of this study was to assess current evidence supporting the use of percutaneous heart valves (PHV) in degenerative aortic valve and congenital pulmonary outflow tract disease, as compared to conservative medical therapy or traditional surgical valve replacement. METHODS: A systematic review of the literature on PHV was performed. RESULTS: No randomized controlled trials (RCT) on PHV have been published so far. Only observational data from series and data presented at cardiology meetings are available. Both percutaneous aortic valve (PAV) and percutaneous pulmonary valve (PPV) seem feasible in the hands of an experienced team. Safety, however, seems to be a problem in PAV, as shown by the high 30-day and 6-month mortality rates. CONCLUSIONS: Due to safety concerns, PAV reimbursement is not recommended and patients should only be subjected to PAV insertion within the boundaries of an RCT. In contrast, PPV implantation seems to be a safe and promising technology for which reimbursement under strict conditions may be recommended.

Testing the HTA core model: experiences from two pilot projects.

OBJECTIVES: The aim of this study was to analyze and describe process and outcomes of two pilot assessments based on the HTA Core Model, discuss the applicability of the model, and explore areas of development. METHODS: Data were gathered from HTA Core Model and pilot Core HTA documents, their validation feedback, questionnaires to investigators, meeting minutes, emails, and discussions in the coordinating team meetings in the Finnish Office for Health Technology Assessment (FINOHTA). RESULTS: The elementary structure of the HTA Core Model proved useful in preparing HTAs. Clear scoping and good coordination in timing and distribution of work would probably help improve applicability and avoid duplication of work. CONCLUSIONS: The HTA Core Model can be developed into a platform that enables and encourages true HTA collaboration in terms of distribution of work and maximum utilization of a common pool of structured HTA information for national HTA reports.

Cost-effectiveness of statins in the primary prevention of cardiovascular disease: a systematic review and economic analysis for Belgium.

OBJECTIVES: 8% of total drug spending by the Belgian government goes to statins. The aim of this study is to determine the cost-effectiveness of statins for the primary prevention of cardiovascular disease (CVD) in middle-aged Belgian populations. METHODS AND RESULTS: Economic evaluations were identified in a systematic literature search and were critically appraised. Furthermore, because prices decreased drastically, a previously published model was adapted applying recent cost data from the Belgian national health insurance. Eleven full economic evaluations were identified. Nine studies compared statins with no treatment and presented heterogeneous results. If alternative interventions, such as smoking cessation or low-dose aspirin treatment were included in the analysis, statin therapy became less cost-effective. Prescribing the cheapest statin on the Belgian market (< Euro 90 medication cost per year) resulted in an incremental cost of Euro 29,173 per life-year gained (LYG) in a male high-risk group aged 60 compared to low-dose aspirin. The incremental cost in a male moderate-risk group aged 50 was Euro 87,022/LYG. Low-dose aspirin was more cost-effective ranging from Euro 3,854/LYG to Euro 29,509/LYG compared to smoking cessation therapy. Smoking cessation therapy was the most cost-effective intervention, providing savings compared to no treatment. CONCLUSIONS: In Belgium, the cost-effectiveness of statins for the primary prevention of CVD is rather elevated in comparison with low-dose aspirin, even if the cheapest statin is prescribed. From an economic point of view, prevention with low-dose aspirin is more cost-effective and may present a first choice in primary prevention. Smoking cessation, which is a dominant strategy, should be encouraged at all times.

Cost effectiveness of implantable cardioverter-defibrillators for primary prevention in a Belgian context.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy was traditionally applied in patients who survived a cardiac arrest or who experienced a symptomatic ventricular tachyarrhythmia. Its use in primary prevention (i.e. in patients who have yet to experience a serious arrhythmic event, but who are considered at high risk for sudden cardiac death) has become more common, and policy makers question whether ICD therapy should be reimbursed in these instances. OBJECTIVE: To assess the cost effectiveness of primary prevention ICD therapy versus conventional therapy from the perspective of the Belgian health insurance system. METHOD: A lifetime 1-month cycle Markov model was constructed and populated with clinical and effectiveness data from the SCD-HeFT study and real-world Belgian cost data expressed in year 2005 values. Probabilistic modelling and sensitivity analyses were performed. RESULTS: ICD therapy results in 1.22 life-years gained (LYG) or 1.03 QALYs gained. The lifetime cost-effectiveness and cost-utility ratios were euro 59,989 (95% CI 35 873, 113 518) per LYG and euro 71 428 (95% CI 40 225, 134 623) per QALY gained, respectively. A cost-effectiveness ratio

Systematic Review of the Efficacy and Safety of High-intensity Focussed Ultrasound for Localised Prostate Cancer.

CONTEXT: High-intensity focussed ultrasound (HIFU) has been used for 10 yr to treat localised prostate cancer (PCa). OBJECTIVE: To evaluate systematically the evidence on the efficacy and side effects of HIFU in the primary treatment of localised PCa. EVIDENCE ACQUISITION: We performed a critical review and appraisal of Medline (Ovid), PreMedline, Embase, and Cochrane Database of Systematic Reviews publications on HIFU up to May 2013. One systematic review and 18 primary studies, all case series, were eligible. EVIDENCE SYNTHESIS: Outcomes were summarised and evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation methodology. Low-quality evidence suggests an overall survival rate after Ablatherm HIFU ranging from 80% to 89% for >5 yr. The PCa survival rate ranges from 97% to 99% for >5 yr. Effect of HIFU on quality of life remains undetermined. Erectile dysfunction was the most frequent adverse event reported from zero but up to 74% of patients. Adverse events affecting the urinary tract occurred in 0.7-31% of patients, bladder outlet obstruction in 4-51.5%, and they were more frequent in patients who had transurethral resection of the prostate the same day or within 2 d of HIFU. Outcomes vary for low- and high-risk categories. CONCLUSIONS: Good quality evidence on the efficacy of HIFU treatment for localised PCa is lacking. PATIENT SUMMARY: We reviewed all the data on treatment with high-intensity focussed ultrasound (HIFU) for localised prostate cancer (PCa). The quality of the evidence is very low because the information is based on a series of patients who received HIFU treatment with no comparison with active surveillance or radical treatment. Case series suggest an overall survival rate up to 89% and a PCa survival rate up to 99% after 5 yr, but these numbers vary according to the patient's risk category. Longer term and effects on quality of life are unknown.

Multidisciplinary outpatient rehabilitation following cardiac revascularization or valve surgery: patient-related factors for uptake.

BACKGROUND: There are concerns in Europe regarding the service provision and accessibility of multidisciplinary cardiac rehabilitation (MDCR) in general, and particularly in ambulatory settings. This paper analyses the utilization of outpatient MDCR and its determinants after cardiac revascularization or valve surgery in Belgium. METHODS: Claims rehabilitation data for all patients discharged in 2007 after a percutaneous cardiac intervention or cardiac surgery were available from the Belgian Common Sickness Funds Agency. Logistic regressions were performed to identify patients demographic and socioeconomic characteristics associated with the uptake of outpatient MDCR during the year following the hospital discharge. RESULTS: A total of 29,021 patients were included. During the hospitalization for the cardiac procedure, 44% were offered inpatient MDCR. After discharge, only 15.6% followed at least one session of outpatient MDCR. The chance of attending outpatient MDCR was lower for female, disabled, and older patients, as well as unemployed patients. The absence of an authorized MDCR centre in the neighbourhood of the patient's residence decreased the chance of attending outpatient MDCR, while living in a neighbourhood with a high education and income level increased this probability. CONCLUSION: These results confirm the low rates of MDCR attendance found in a previous study performed by the European Association of Cardiovascular Prevention and Rehabilitation. The study shows specific patient groups that should be targeted in priority, i.e. women, elderly, unemployed patients, disabled persons, and patients with a low socioeconomic status.