PurposeTo assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM).MethodsMEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument.ResultsThe search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease.ConclusionThe results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery.Electronic supplementary materialThe online version of this article (10.1007/s00270-018-1959-3) contains supplementary material, which is available to authorized users.

BackgroundPatients 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.MethodsA 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.ResultsIn 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.ConclusionsIt 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.

BackgroundThe 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.MethodsA 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 NIPT's test accuracy.ResultsIntroducing 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.ConclusionsIn 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 government's limited resources for universal reimbursement, the price of NIPT should first be lowered substantially before this can be realised.

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

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Trastuzumab is a promising but very expensive antibody. With the current pressure on health-care budgets, cost implications of using trastuzumab in adjuvant setting must be calculated before use of the product becomes wide-spread. This provides essential information for price-setting policies and for policy makers considering reimbursement.

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

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.