Economic analysis of early intervention for autistic children: findings from four case studies in England, Ireland, Italy and Spain

Background: Many autistic children experience difficulties in their communication and language skills development, with consequences for ’social development into adulthood, often resulting in challenges over the life-course and high economic impacts for individuals, families and society. The PACT (Preschool-Autism-Communication-Trial) intervention is effective in terms of improved social communication and some secondary outcomes. A previously published within-trial economic analysis found that results at 13 months did not support its cost-effectiveness. We modelled cost-effectiveness over 6 years and across four European countries. Methods: Using simulation modelling, we built on economic analyses in the original trial, exploring longer-term cost-effectiveness at 6 years (in England). We adapted our model to undertake an economic analysis of PACT in Ireland, Italy and Spain. Data on resource use were taken from the original trial and a more recent Irish observational study. Results: PACT is cost-saving over time from a societal perspective, even though we confirmed that, at 13 months post-delivery, PACT is more expensive than usual treatment (across all countries) when given to preschool autistic children. After 6 years, we found that PACT has lower costs than usual treatment in terms of unpaid care provided by parents (in all countries). Also, if we consider only out-of-pocket expenses from an Irish study, PACT costs less than usual treatment. Discussion: PACT may be recommended as a cost-saving early intervention for families with an autistic child

Autism with co-occurring epilepsy care pathway in Europe

Background: Autism and epilepsy often occur together. Epilepsy and other associated conditions have a substantial impact on the well-being of autistic people and their families, reduce quality of life and increase premature mortality. Despite this, there is a lack of studies investigating the care pathway of autistic children with co-occurring epilepsy in Europe. Methods: We analyzed the care pathway for autistic children with associated epilepsy in Italy, Spain and the UK from the perspective of caregivers (using a survey aimed at caregivers of autistic children 0-18 years old), the autistic community and professionals, in order to identify major barriers preventing caregivers and autistic children from receiving timely screening and treatment of possible co-occurring epilepsy. Results: Across all three countries, analysis of the current care pathway showed a lack of systematic screening of epilepsy in all autistic children, delayed treatment of epilepsy in autistic children after diagnosis, lack of treatment of co-occurring epilepsy and incorrect use of antiepileptic drugs. A major challenge is the lack of evidence-based harmonized guidelines for autism with co-occurring epilepsy in these countries. Conclusions: Our findings show both heterogeneity and major gaps in the care pathway for autism with associated epilepsy and the great efforts that caregivers must make for timely screening, diagnosis and adequate management of epilepsy in autistic children. We call for policy harmonization in Europe in order to improve the experiences and quality of life of autistic people and their families

Autism care pathway in Europe

BACKGROUND: Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life. Despite its personal, familial, and societal impact, Europe-wide harmonised guidelines are still lacking for early detection, diagnosis, and intervention, leading to an overall unsatisfactory autistic person and carer journey. METHODS: The care pathway for autistic children and adolescents was analysed in Italy, Spain and the UK from the perspective of carers (using a survey aimed at caregivers of autistic children 0-18 years old), the autistic community, and professionals in order to identify major barriers (treatment gaps) preventing carers from receiving information, support, and timely screening/diagnosis and intervention. RESULTS: Across all three countries, analysis of the current care pathway showed: long waits from the time carers raised their first concerns about a child's development and/or behaviour until screening and confirmed diagnosis; delayed or no access to intervention once a diagnosis was confirmed; limited information about autism and how to access early detection services; and deficient support for families throughout the journey. CONCLUSIONS: These findings call for policy harmonisation in Europe to shorten long wait times for diagnosis and intervention and therefore, improve autistic people and their families' journey experience and quality of life

Economic evaluation of anti-epileptic medicines for autistic children with epilepsy

We examine the cost-effectiveness of treating epilepsy with anti-epileptic medicines in autistic children, looking at impacts on healthcare providers (in England, Ireland, Italy and Spain) and children’s families (in Ireland). We find carbamazepine to be the most cost-effective drug to try first in children with newly diagnosed focal seizures. For England and Spain, oxcarbazepine is the most cost-effective treatment when taken as additional treatment for those children whose response to monotherapy is suboptimal. In Ireland and Italy, gabapentin is the most cost-effective option. Our additional scenario analysis presents the aggregate cost to families with autistic children who are being treated for epilepsy: this cost is considerably higher than healthcare provider expenditure

Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders

From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems

The metabotropic glutamate receptor 5 (mGluR5) is a key regulator of excitatory (E) glutamate and inhibitory (I) γ-amino butyric acid (GABA) signalling in the brain. Despite the close functional ties between mGluR5 and E/I signalling, no-one has directly examined the relationship between mGluR5 and glutamate or GABA in vivo in the human brain of autistic individuals. We measured [18F] FPEB (18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile) binding in 15 adults (6 with Autism Spectrum Disorder) using two regions of interest, the left dorsomedial prefrontal cortex and a region primarily composed of left striatum and thalamus. These two regions were mapped out using MEGA-PRESS voxels and then superimposed on reconstructed PET images. This allowed for direct comparison between mGluR5, GABA + and Glx. To better understand the molecular underpinnings of our results we used an autoradiography study of mGluR5 in three mouse models associated with ASD: Cntnap2 knockout, Shank3 knockout, and 16p11.2 deletion. Autistic individuals had significantly higher [18F] FPEB binding (t (13) = −2.86, p = 0.047) in the left striatum/thalamus region of interest as compared to controls. Within this region, there was a strong negative correlation between GABA + and mGluR5 density across the entire cohort (Pearson’s correlation: r (14) = −0.763, p = 0.002). Cntnap2 KO mice had significantly higher mGlu5 receptor binding in the striatum (caudate-putamen) as compared to wild-type (WT) mice (n = 15, p = 0.03). There were no differences in mGluR5 binding for mice with the Shank3 knockout or 16p11.2 deletion. Given that Cntnap2 is associated with a specific striatal deficit of parvalbumin positive GABA interneurons and ‘autistic’ features, our findings suggest that an increase in mGluR5 in ASD may relate to GABAergic interneuron abnormalities