Synergy in Action

Autism Spectrum Disorder Working Group Activity / Deliverables

ISCTM/ECNP Joint Working Group
Chairs: Valentina Mantua, MD, PhD; Tiffany Farchione, MD; Celso Arango, MD, PhD

Most Recent Deliverables:
Publication: Drug development for Autism Spectrum Disorder (ASD): Progress, challenges, and future directions – European Neuropsychopharmacology, Volume 48, July 2021 (open access)
Publication: Opportunities and Challenges in Drug Development for ASD: Product of ISCTM/ECNP Joint Working Group – Special Edition Issue: European Neuropsychopharmacology, Volume 48

Most Recent Activity: Working Group session (closed session limited to those involved in developing the manuscript), 16th Annual Scientific Meeting – View Summary, 19 February 2020, Washington DC

ISCTM/ECNP Joint Session, Friday 6 September 2019, Copenhagen Denmark  
Working Group Session: 7 September, 2019 Autumn Conference – View Summary: This was a closed session limited to those involved in developing the manuscript.


There is a clear unmet need in the availability of medicinal products for the treatment of Autism. Despite the great amount of scientific investigation into the neurodevelopmental and biological causes of Autism, research has failed to deliver a therapy for the core features of Autism or a biomarker to stratify populations for potential treatments with different mechanism of action.

If a product were intended to be developed for the treatment of individuals with Autism Spectrum Disorder under the DSM5 definition, heterogeneity in phenotypes and clinical manifestations would be a major drawback for the planning of a clinical trial. In addition, the clinical presentational and the medical needs of the population vary largely with age; therefore, hardly any data could be extrapolated and age groups should be investigated independently. Despite the availability of tools for diagnosis and outcome assessment, the clinical meaningfulness of changes on these measures has yet to be defined.  It is not yet clear which outcome measure is most appropriate for use in clinical trials.  Strategies to address these challenges and others will be the focus of this working group. 

The ISCTM is a unique environment born out of the need to foster drug development in CNS disorder. ISCTM brings together multi-disciplinary expertise including industry, academia, regulators, patients, and family associations. For the purpose of optimizing a methodological framework for the conduct of clinical trials in Autism Spectrum Disorder wide participation of all stakeholders is needed, and therefore  ECNP has agreed to formally join ISCTM in supporting this effort.

Work plan:
The first phase of the Working Group will be to build a common knowledge, which would form the basis of a clinical trial methodology proposal. Issues to be addressed should include: population definition and stratification (IQ, biomarkers, age), endpoints and tools for outcome assessment, clinical trial duration, non-pharmacological therapies as background and comorbidities.

For the purpose of a literature review the Working Group identified 4 subgroups. Link to materials:  Working Group Project Page

— Biomarkers/Stratification (Dealing with Heterogeneity) EU-AIMS, ABC-CT
— Outcomes
— Top Molecular Targets and Pathways
— Trial Design

The results of the literature review were discussed during the Inaugural Working Group session – 2018 Autumn Conference – 15,16 October 2018, Marina del Rey. View Subgroup Presentations: 
Molecular Targets
Trial Design 

The two main biomarker consortia EU-AIMS and ABC-CT shared their methodology and preliminary results; digital phenotyping and the role of digital medicine was also discussed. The literature review allowed Working Group participants to optimize the focus the discussion on topics pertaining the specifically clinical trial methodology, rather than etiology of the disorder, drug discovery or potential molecular targets. Many questions remain unanswered and will form the basis for the discussion during the ISCTM/ECNP Joint session in Copenhagen (Deliverable 1). In particular, inclusion of individuals with intellectual disabilities in clinical trials, the different methodology requirements when individuals with co-morbidities are also included came as topics for discussion in the clinical trial subgroup. Trial duration, timing of intervention, and duration of treatment effect as opposed to disease modification were the topics receiving most of the attention from the subgroups, indeed the window of observation is directly connected with the adequacy of outcome measures.

The Working Group met in Washington DC during the ISCTM 15th Annual Meeting – 21 February 2019, Washington DC.  15th Annual Scientific Meeting – View Summary 

The Working Group has two main deliverables:

1) Develop a session which will be presented at the Joint ISCTM/ECNP meeting 6 September 2019, in Copenhagen 
2) Issue a publication in the form of a Special Issue of European Neuropsychopharmachology on Autism Spectrum Disorder Clinical Trial Methodology. Editors: Tiffany Farchione, Valentina Mantua, Celso Arango
The WG will meet in Copenhagen during the ISCTM/ECNP Joint Meeting, at that time it is foreseen that the session will be entirely devoted to the timeline and review of the publication (Delivery Group will also meet via regular telecons.)