Mattias Neyt

A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population

Background Patients with severe aortic stenosis and coexisting non-cardiac conditions may be at high risk for surgical replacement of the aortic valve or even be no candidates for surgery. In these patients, transcatheter aortic valve implantation (TAVI) is suggested as an alternative. Results of the PARTNER (Placement of AoRTic TraNscathetER Valve) trial comparing the clinical effectiveness of TAVI with surgical valve replacement and standard therapy were published. The authors assessed the cost-effectiveness of TAVI in Belgium. Methods A Markov model of incremental costs, effects (survival and quality of life) and incremental cost-effectiveness of TAVI was developed. The impact on survival, number of events and quality of life was based on the PARTNER trial. Costs per event were context specific. Results In high-risk operable patients, even if the minor differences in 30-day and 1-year mortality are taken into account, the incremental cost-effectiveness ratio (ICER) remains on average above €750 000 per quality-adjusted life-year (QALY) gained (incremental cost: €20 400; incremental effect: 0.03 QALYs). In inoperable patients, an ICER of €44 900 per QALY (incremental cost: €33 200; incremental effect: 0.74 QALYs) is calculated, including a life-long extrapolation of the mortality benefit. This result was sensitive to the assumed time horizon. The subgroup of anatomically inoperable patients had better outcomes than medically inoperable patients, with ICERs decreasing more than €10 000/QALY. Conclusions It is inappropriate to consider reimbursement of TAVI for high-risk operable patients. Reimbursing TAVI in inoperable patients in essence is a political decision. From an economic perspective, it would be prudent to first target patients that are inoperable because of anatomical prohibitive conditions. In the search for evidence, the authors identified non-published negative results from a randomised controlled TAVI trial. The study sponsor should be more willing to share this information to allow balanced evaluations and policy recommendations. Payers should require these data before taking reimbursement decisions.

Transcatheter aortic valve implantation (TAVI): risky and costly

Many of the 40 000 transcatheter procedures so far carried out cannot be justified on medical or cost effectiveness grounds. Hans Van Brabandt, Mattias Neyt, and Frank Hulstaert examine why practice has gone beyond the evidence

Trastuzumab in Early Stage Breast Cancer: A Cost-Effectiveness Analysis for Belgium

OBJECTIVES Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payers perspective. METHODS We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. RESULTS In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. CONCLUSIONS The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

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.

Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis

Background The first- and second-trimester screening for trisomy 21 (T21) are reimbursed for all pregnant women in Belgium. Using a cut-off risk of 1:300 for T21, about 5% of all pregnant women are referred for definitive prenatal diagnosis using an invasive test, at a sensitivity of (only) 72.5%. The sensitivity and specificity of the non-invasive prenatal test (NIPT) are over 99% but come at a cost of €460 (£373) per test. The objective is to estimate the consequences of introducing NIPT for the detection of T21. Methods A cost-consequences analysis was performed presenting the impact on benefits, harms and costs. Context-specific real-world information was available to set up a model reflecting the current screening situation in Belgium. This model was used to construct the second and first line NIPT screening scenarios applying information from the literature on NIPTs test accuracy. Results Introducing NIPT in the first or second line reduces harm by decreasing the number of procedure-related miscarriages after invasive testing. In contrast with NIPT in the second line, offering NIPT in the first line additionally will miss fewer cases of T21 due to less false-negative test results. The introduction of NIPT in the second line results in cost savings, which is not true for NIPT at the current price in the first line. If NIPT is offered to all pregnant women, the price should be lowered to about €150 to keep the screening cost per T21 diagnosis constant. Conclusions In Belgium, the introduction and reimbursement of NIPT as a second line triage test significantly reduces procedure-related miscarriages without increasing the short-term screening costs. Offering and reimbursing NIPT in the first line to all pregnant women is preferred in the long term, as it would, in addition, miss fewer cases of T21. However, taking into account the governments limited resources for universal reimbursement, the price of NIPT should first be lowered substantially before this can be realised.

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.

The long-term evolution of quality, of life for disease-free breast cancer survivors : a comparative study in Belgium

Abstract Aim: Little is known about the longterm evolution of Quality of Life (QoL) for breast cancer treated patients. The study aims to describe this evolution of QoL in a group of Belgian breast cancer survivors. Methods: We gathered information on treatment, general health, activity problems, disease symptoms, pain, emotions, work, social activities, self-care, housekeeping, sexuality, and meaning of life. One hundred seventy-four disease-free survivors in Flanders (Belgium) participated in this study, which were grouped as being disease free less than one year (39), between one and five years (70), and more than five years (65). The data allowed us to analyse QoL for different dimensions over the three survivor groups. Results: The longer the survival time, the more QoL of breast cancer treated patients ameliorated and the less breast cancer had a major impact on QoL. Scores for doing intense activities, being tired, emotional health, social activities, and meaning of life were statistically significantly better in the long-term survivor group. The influence of breast cancer was more persistent for sexual QoL items. Conclusion: It is important for patients to know what they may expect after treatment. This kind of patient-reported information on the evolution of QoL is of great value to healthcare workers. Results may be used to encourage patients who are newly diagnosed with breast cancer or for patients who do not believe in further progress for some QoL aspects. When informing breast cancer patients, a fundamental difference has to be made between the several QoL aspects and time over which improvements may be expected.

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

BackgroundImplantable 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.ObjectiveTo assess the cost effectiveness of primary prevention ICD therapy versus conventional therapy from the perspective of the Belgian health insurance system.MethodA 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.ResultsICD therapy results in 1.22 life-years gained (LYG) or 1.03 QALYs gained. The lifetime cost-effectiveness and cost-utility ratios were €59 989 (95% CI 35 873, 113 518) per LYG and €71 428 (95% CI 40 225, 134 623) per QALY gained, respectively. A cost-effectiveness ratio <€50 000 per QALY gained was obtained in 15.5% of 1000 simulations. Increasing the service life of the device from 5 to 7 years would improve the cost effectiveness to €57 229 (95% CI 32 568, 106 410) per QALY gained.ConclusionsICD therapy may not be judged cost effective for the primary prevention of death in patients with a SCD-HeFT profile in the Belgian context using current technology and patient selection. A combination of price reductions and increased service life of the device may alter this conclusion.

Harms and benefits of screening young people to prevent sudden cardiac death

Sudden cardiac death of young athletes needs to be avoided but does screening really help? Hans Van Brabandt and colleagues look at the evidence

Safety of percutaneous aortic valve insertion. A systematic review

BackgroundThe 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.MethodsStudies 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.ResultsThe 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.ConclusionSafety 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.