Survival in stage IV ovarian cancer with increased use of debulking surgery and bevacizumab.

OBJECTIVES: Advanced ovarian cancer has a poor prognosis, with a 5 year survival probability of <30%. Attempts to improve survival have focused on debulking surgery and systemic therapy. We assessed the evolution of treatment patterns and survival of patients with advanced epithelial ovarian cancer with specific attention to changes in survival after introducing bevacizumab. METHODS: Population based data from the Belgian Cancer Registry were coupled with administrative reimbursement data from the compulsory health insurance organizations and the national database where date of death is registered, based on the patient's unique national number. Patients with epithelial ovarian cancer stage IV diagnosed in 2004-17 were included. The proportion of patients who underwent debulking surgery and received bevacizumab was calculated per incidence year. Survival was compared for the three incidence periods (2004-08, 2009-13, 2014-17) and before and after the introduction of bevacizumab. RESULTS: 2034 patients with stage IV epitheial ovarian cancer were included. From 2012 onwards, uptake of bevacizumab increased, with 50% of patients with stage IV ovarian cancer diagnosed in 2017 receiving bevacizumab. The proportion of stage IV patients who underwent debulking surgery also increased over time, from 21.1% in 2004-08 to 50.4% and 45.4% in 2009-13 and 2014-17, respectively. The 3 year observed survival probability fluctuated between 27% and 42% without a trend over time. The increase in debulking surgery was associated with improved survival (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79 to 0.98) but the introduction of bevacizumab was not (HR 0.94, 95% CI 0.85 to 1.03). For patients diagnosed in 2004, the mean cost per patient treated with oncological drugs was about €12 500, which doubled to about €25 000 for patients diagnosed in 2014 or later. CONCLUSIONS: Despite a rise in the use of debulking surgery and the introduction of bevacizumab into clinical practice, no improvement in 3 year survival probability was observed for patients with advanced ovarian cancer in Belgium.

Impact of shortened length of stay for delivery on the required bed capacity in maternity services: results from forecast analysis on administrative data.

BACKGROUND: We examine the implications of reducing the average length of stay (ALOS) for a delivery on the required capacity in terms of service volume and maternity beds in Belgium, using administrative data covering all inpatient stays in Belgian general hospitals over the period 2003-2014. METHODS: A projection model generates forecasts of all inpatient and day-care services with a time horizon of 2025. It adjusts the observed hospital use in 2014 to the combined effect of three evolutions: the change in population size and composition, the time trend evolution of ALOS, and the time trend evolution of the admission rates. In addition, we develop an alternative scenario to evaluate the impact of an accelerated reduction of ALOS. RESULTS: Between 2014 and 2025, we expect the number of deliveries to increase by 4.41%, and the number of stays in maternity services by 3.38%. At the same time, a reduction in ALOS is projected for all types of deliveries. The required capacity for maternity beds will decrease by 17%. In case of an accelerated reduction of the ALOS to reach international standards, this required capacity for maternity beds will decrease by more than 30%. CONCLUSIONS: Despite an expected increase in the number of deliveries, future hospital capacity in terms of maternity beds can be considerably reduced in Belgium, due to the continuing reduction of ALOS.

Survival of patients with unfavorable prognosis cutaneous melanoma with increased use of immunotherapy agents: a population-based study in Belgium.

BACKGROUND: Although metastatic cutaneous melanoma is associated with an unfavorable prognosis, innovative therapies including immunomodulating agents and targeted therapies have shown survival benefits in clinical trials. We assessed the impact of the introduction of innovative drugs into clinical practice on the survival of patients with metastatic cutaneous melanoma during the period 2004-2017, in Belgium. The evolution of associated expenses was also analyzed. METHODS: This is a retrospective population-based study using data from the national Belgian Cancer Registry, compulsory health insurance, and administrative survival data. The immunomodulating drugs were ipilimumab, nivolumab and pembrolizumab, while targeted therapies included vemurafenib, dabrafenib and trametinib. RESULTS: We did not identify a trend for improvement over time. Median survival (years) was 1.5 (95% CI: 1.1-1.8) in 2004-2008, 1.1 (95% CI: 0.8-1.5) in 2009-2013, and 1.6 (95% CI: 1.3-2.4) in 2014-2017, respectively. In contrast, survival improved in those with unknown primary tumor localization. In this group, median survival time was 2.0 (95% CI: 1.4-2.9) in the most recent period, while it was 1.1 (95% CI: 0.7-1.3) in 2009-2013, and 0.9 (95% CI: 0.6-1.2) in 2004-2008. The uptake of innovative drugs remained modest, with no drug being used by more than 30% of patients. Yearly expenditure was almost non-existent, and gradually increased, reaching several million euros in 2014-2017. CONCLUSION: Patients with metastatic cutaneous melanoma who were diagnosed between 2004 and 2017 showed no apparent improvement in survival. In contrast, increased survival was observed in the subgroup of patients with unknown primary tumor localization.

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.

Belgian observational survival data (incidence years 2004-2017) and expenditure for innovative oncology drugs in twelve cancer indications.

BACKGROUND: The Food and Drug Administration and European Medicines Agency typically approve market access for cancer drugs based on surrogate end-points, which do not always translate into substantiated improvements in outcomes that matter the most to patients, i.e. survival and quality of life. These drugs often, also, have a high price tag. We assessed whether there was an increase in cancer drug expenditure for a broad selection of indications, and whether this correlates with increased overall survival. METHODS: This cohort study used Belgian Cancer Registry data from 125,692 patients (12 cancer indications, incidence period 2004-2017), which was linked to reimbursement and survival data. This reliably represents the Belgian situation. One-to-five year observed survival probability, median survival time, oncology drug expenditure and mean oncology drug cost per patient were reviewed. FINDINGS: In almost all indications, total expenditure and average treatment cost for oncology drugs increased over the years (2004-2017). In contrast, mixed findings are observed for the evolution in overall survival probability and median survival time. While an absolute improvement in the 3-year survival probability of about 10% is noticed in non-small-cell lung cancer and chronic myeloid leukaemia, improvements in about half of the other indications are limited or even absent. INTERPRETATION: The Belgian observational data indicate that assuming 'innovative' oncology drugs always add value in terms of improved survival is often unjustified. The literature also highlights the problem of using surrogate end-points, and the lack of comparative evidence showing an added value of oncology drugs for both survival and quality of life at market approval or during the post-marketing phase. Comparative studies should be conducted in the pre-marketing phase that are suitable for registration purposes, aid reimbursement decisions and support physicians and patients when making treatment decisions.

What Does the Public Want? Structural Consideration of Citizen Preferences in Health Care Coverage Decisions.

Background. Multi-criteria decision analysis can improve the legitimacy of health care reimbursement decisions by taking societal preferences into account when weighting decision criteria. This study measures the relative importance of health care coverage criteria according to the Belgian general public and policy makers. Criteria are structured into three domains: therapeutic need, societal need, and new treatments' added value. Methods. A sample of 4,288 citizens and 161 policy makers performed a discrete choice experiment. Data were analyzed using multinomial logistic regression analysis. Level-independent criteria weights were determined using the log-likelihood method. Results. Both the general public and policy makers gave the highest weight to quality of life in the appraisal of therapeutic need (0.43 and 0.53, respectively). The general public judged life expectancy (0.14) as less important than inconvenience of current treatment (0.43), unlike decision makers (0.32 and 0.15). The general public gave more weight to "impact of a disease on public expenditures" (0.65) than to "prevalence of the disease" (0.56) when appraising societal need, whereas decision makers' weights were 0.44 and 0.56, respectively. When appraising added value, the general public gave similar weights to "impact on quality of life" and "impact on prevalence" (0.37 and 0.36), whereas decision makers judged "impact on quality of life" (0.39) more important than "impact on prevalence" (0.29). Both gave the lowest weight to impact on life expectancy (0.14 and 0.21). Limitations. Comparisons between the general public and policy makers should be treated with caution because the policy makers' sample size was small. Conclusion. Societal preferences can be measured and used as decision criteria weights in multi-criteria decision analysis. This cannot replace deliberation but can improve the transparency of health care coverage decision processes.