When assessing the communication ability of individuals with neurodevelopmental disorders (NDDs) in the context of clinical trials, existing clinical outcome assessments (COAs) have significant limitations, including the inability to differentiate among individuals and lack of input from parent advocates.
With a grant from the U.S. Food and Drug Administration (FDA), Center for Health Measurement (CHM) investigators will work with COMBINEDBrain, a patient advocacy consortium, to expand the ORCA measure to a range of NDD populations.
Expanded ORCA
The project, Expanding the Observer-Reported Communication Ability (ORCA) Measure: Measuring the communication ability of individuals with rare, neurodevelopmental disorders, will use rigorous qualitative and quantitative methods to support the ORCA measure’s use with 12 other NDDs. The study team includes experts in:
- COA development
- Communication
- Clinical trials
- Neuropsychology
The team also includes a Stakeholder Engagement Group consisting of 16 leaders in the field including parents, patient advocates, and clinicians who will provide access to 12 distinct NDD populations. An External Technical Advisory Committee (ETAC) will provide additional guidance and will consist of:
- Clinicians
- Methodologists
- Speech-language pathologists
- Industry experts
- Patient advocates
Project Updates
- Evaluation of the communication concepts and related behaviors in the ORCA measure:
- Concept elicitation interviews were conducted with 115 caregivers representing 12 neurodevelopmental disorders (see list further below). Caregivers discussed how their children typically communicate and reviewed the original version of the ORCA measure to evaluate how well it captured their children’s communication abilities. A manuscript describing our findings was published in The Journal of Child Psychology and Psychiatry. (hyperlink to: https://doi.org/10.1111/jcpp.70063 )
- Updates to the ORCA measure:
- Based on findings from the concept elicitation interviews, the ORCA measure was modified to include questions on additional communication concepts, including humor, feelings and emotions, and alerting the caregiver when the child was not feeling well or hurt.
- Evaluation of the clarity and relevance of the modified ORCA measure for individuals with a neurodevelopmental disorder:
- Two rounds of cognitive interviews were conducted with 25 caregivers representing 12 neurodevelopmental disorders (see list further below). Caregivers provided feedback on how well the ORCA measure captured communication abilities and behaviors they have observed in their children, how well the questions were worded, and how easy it was to answer them. The ORCA measure was refined to clarify the instructions and questions.
- Evaluation of the clarity and relevance of the modified ORCA measure for neurotypically developing children:
- Cognitive interviews were conducted with 16 caregivers of neurotypical children aged 6 to 35 months. Caregivers' feedback confirmed the appropriateness of the ORCA measure in this population. This supports inclusion of this population in the subsequent quantitative study to derive reference scores on the ORCA measure.
- Evaluation of the psychometric properties of the ORCA measure and collecting data on the validity of the measure for individuals with neurodevelopmental disorders:
- In the fall of 2026, a longitudinal quantitative study will be launched to collect data from caregivers across 12 different neurodevelopmental disorders (see list further below).
- Estimating reference scores for the ORCA measure for neurotypically developing children:
- In the winter of 2026, quantitative data will be collected from caregivers of neurotypically developing children in different age groups (6-8 months, 9-11 months, 12-17 months, 18-23 months, 24-35 months).
Neurodevelopmental Disorders Included in this Project:
- Bosch-Boonstra-Schaaf optic atrophy syndrome
- GRIN2B-related neurodevelopmental disorder
- Hao-Fountain syndrome
- HNRNPH2-related disorders
- Hunter syndrome
- Malan syndrome
- Phelan McDermid syndrome
- Schinzel-Giedion syndrome
- SCN2A-related disorders
- SETBP1 neurodevelopmental disorder (SETBP1-haploinsufficiency disorder/SETBP1-related disorder)
- STXBP1-related disorders
- SYNGAP1-related intellectual disability
ORCA Measure
Read more about the original ORCA measure
Funding Disclosure
This program is part of the CDER Pilot Grant Program, which is under the FDA’s Patient-Focused Drug Development (PFDD) efforts to support the use of meaningful and valid outcomes in regulatory trials.
Disclosure Language:
Bryce Reeve, Nicole Lucas, Molly McFatrich, Li Lin, Christina Zigler, Kelly Gordon, and Harrison Jones have developed the technology that is being used in the study. If the technology (the ORCA measure, V1.0 and V2.0) is commercially successful in the future, the developers and Duke University may benefit financially.