The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration—A cost-effectiveness analysis from a societal perspective

<div><p>Background</p><p>The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective.</p><p>Methods</p><p>We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice.</p><p>Results</p><p>Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab.</p><p>Conclusion</p><p>Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.</p></div

Acceptability curve of the three anti-VEGF treatments.

<p>The acceptability curve shows the probability of a treatment being cost-effective over a range of willingness-to-pay thresholds. The curve shows that bevacizumab is the most likely to be cost-effective until a willingness-to-pay threshold of €407,250 is reached, after which aflibercept is most likely to be cost-effective.</p

Results of meta-analysis.

<p>Results of meta-analysis.</p

Utility value per visual acuity category.

<p>Utility value per visual acuity category.</p

Differences in effectiveness and costs between treatments, per patient in the first year of treatment.

<p>The ICERs show that we pay €278,099 per QALY if we use aflibercept instead of bevacizumab and that ranibizumab is dominated by bevacizumab, meaning it is costlier, but does not yield health benefit.</p

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study

Background: Open radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. Objective: To assess the cost-effectiveness of RARC compared to ORC in bladder cancer. Design, setting, and participants: This economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. Outcome measurements and statistical analysis: Over 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. Results and limitations: The mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791–€18 720) for ORC and €21 266 (95% CI €19 163–€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431–€22 642) for ORC and €24 896 (95% CI €21 925–€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74–0.85) compared to 0.81 QALYs (95% CI 0.77–0.85) for ORC patients, resulting in a mean QALY difference of −0.02 (95% CI −0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. Conclusions: RARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. Patient summary: This study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive. This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214)

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.<br/

Effects of labor subcentres in urban property values. Case study of the metropolitan region of Barcelona

Power-pointThe research sought to develop a proposal for the classification of model identification based on the definition of sub and not on existing methodologies, establishing subcentres employment in the metropolitan area of Barcelona and implemented a validation method based on three axes, the explanation of the density of neighbors, mobility or ability to structure and travel flows, and ultimately its impact on the prices of housing situation.Peer ReviewedPostprint (published version