Assessment of a multisite standardized biospecimen collection protocol for immune phenotyping in neurodevelopmental disorders.

Multisite collection and preservation of peripheral blood mononuclear cells (PBMCs) for centralized analysis is an indispensable strategy for large cohort immune phenotyping studies. However, the absence of cross-site standardized protocols introduces unnecessary sample variance. Here we describe the protocol implemented by the Province of Ontario Neurodevelopmental Disorders (POND) Network's immune platform for the multisite collection, processing, and cryopreservation of PBMCs. We outline quality control standards and evaluate the performance of our PBMC processing and storage protocol. We also describe the Child Immune History Questionnaire results, an assessment tool evaluating pre-existing immune conditions in children with neurodevelopmental disorders (NDDs). Cell viability was assessed in samples from 178 participants based on strict quality control criteria. Overall, 83.1% of samples passed quality control standards. Samples collected and processed at the same site had higher quality control pass rates than samples that were collected and subsequently shipped to another site for processing. We investigated if freezer time impacted sample viability and found no difference in mean freezer time between samples that passed and failed quality control. The Child Immune History Questionnaire had a response rate of 87.1%. The described protocol produces viable samples that may be used in future immune phenotyping experiments.

Environmental scan of Canadian and UK policies for autism spectrum disorder diagnostic assessment.

OBJECTIVES: Many jurisdictions across Canada and internationally are grappling with providing diagnostic and intervention services for children with autism spectrum disorder (ASD). The objective was to compare Canadian and United Kingdom (UK) policies governing ASD diagnosis. METHODS: The policy scan extended from January 2000 to December 2017. Canadian federal, provincial/territorial, and UK government publications related to ASD diagnosis were retrieved from official websites by searching for ASD and related terms. Retrieved documents were filtered for relevance, with all relevant documents undergoing full text review. Data extracted included personnel and testing requirements for diagnosis, wait times, and eligibility for ASD services and funding. RESULTS: The included jurisdictions varied substantially in their approach to ASD diagnosis and eligibility for intervention. Nine of the 13 provinces/territories restrict which clinicians can diagnose ASD by requiring certain documentation for service eligibility. Three provinces require multi-disciplinary team assessment (British Columbia [BC], Quebec, and Nova Scotia [NS]). Three provinces (BC, NS, and Prince Edward Island [PEI]) require specific diagnostic tests for diagnosis. Only two provinces, BC and NS, have target wait times for assessment. Jurisdictions differed in whether they allowed children with a provisional diagnosis of ASD to access services. At a national level, the UK provides more clinical guidance for ASD diagnosis, which can be attributed to its centralized system of national healthcare delivery. CONCLUSIONS: ASD diagnostic assessment policies vary across Canada, and between Canada and the UK. Further evidence supporting ASD diagnostic practices is needed to streamline the journey from identification to intervention.

Development of a patient-centered conceptual model of the impact of living with autism spectrum disorder.

The aim of this study was to generate a patient-centered conceptual model of the impact of living with autism spectrum disorder, which can be used to support the selection of outcome measures for clinical trials. Following an initial literature review to identify preliminary concepts and inform an interview guide, in-depth face-to-face interviews were conducted with adolescents and adults with autism spectrum disorder (IQ ⩾ 70) (n = 10), as well as parents of children, adolescents, and adults with autism spectrum disorder (IQ ⩾ 70) (n = 26). Data were analyzed using established qualitative research methods. The resultant conceptual model contains three interrelated domains reflecting core symptoms of autism spectrum disorder (communication deficits, socialization deficits, and restrictive, repetitive patterns of behavior), three domains reflecting associated symptoms of autism spectrum disorder (physical, cognitive, and emotional/behavioral), and three domains representing the impacts of living with autism spectrum disorder (impacts on activities of daily living, school/work, and social life). Interview respondents also cited social communication deficits as priority targets for new treatments. The conceptual model provides a patient-centered perspective of relevant concepts of autism spectrum disorder from the perspectives of people with autism spectrum disorder and their parents and offers a valuable tool for identifying valid patient-centered outcome measures for future clinical trials.

Systematic review of clinical guidance documents for autism spectrum disorder diagnostic assessment in select regions.

Clinical guidance documents play an important role in ensuring access to high-quality autism spectrum disorder diagnostic assessment practices. The objective was to perform a systematic review of professional association and government clinical guidance documents for autism spectrum disorder diagnostic assessment, analyzing their quality and content. The government search was limited to English-speaking, single-payer, publicly funded health systems. A quality appraisal was conducted by two appraisers using the Appraisal of Guidelines Research and Evaluation, second edition tool. A content analysis was conducted for recommended clinical personnel and psychometric tools. The 11 documents demonstrated higher quality in Scope and Purpose (mean: 90.1, standard deviation: 7.4) and Clarity of Presentation (mean: 82.8, standard deviation: 9.4) and lower quality in Applicability (mean: 43.3, standard deviation: 23.8) and Rigor of Development (mean: 52, standard deviation: 21.9). All documents either recommended multidisciplinary team assessment or stated it was ideal. The documents varied substantially in their recommended tools and personnel for diagnostic assessment. There was little supporting evidence for team and personnel recommendations. Multiple guidance documents exist for autism spectrum disorder diagnostic assessments, with varying quality and recommendations. The substantial variation likely stems from insufficient evidence supporting assessment practices. Research is required to close the evidence gaps and inform high-quality clinical guidelines.