# PROMIS-guided development and validation of a dimensional observer-report measure of positive and negative features of ASD

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $823,870

## Abstract

PROJECT SUMMARY
Marked heterogeneity among individuals with autism spectrum disorder (ASD) is a significant problem facing
the autism community. Heterogeneity makes it difficult to identify core biological disruptions. It also hampers
the development and validation of targeted and consistently effective therapeutics. In particular, the lack of
precise, psychometrically robust, change sensitive outcome measures for core symptomatology represents a
key barrier for clinical trials and for detecting mechanisms underlying manifest symptoms. This project
proposes to develop and validate an innovative new observer report measure for ASD that attempts to capture
heterogeneity in core symptoms along positive and negative dimensions, akin to those that have been
successful in quantifying heterogeneity and facilitating key biological and therapeutic discoveries in
schizophrenia. Using state-of-the-art procedures put forth by the NIH Patient-Reported Outcome Measurement
Information System (PROMIS®) initiative, this project will develop, calibrate, and validate a new tool - the
Positive and Negative Inventory for ASD (PNI) - for assessing core ASD symptoms with unprecedented
precision of symptom description and discrimination, along conceptually novel dimensions. First, our
preliminary item pool will be refined with key stakeholder input from caregivers and national experts. Next,
caregivers of 1,000 3-11 year old children with ASD and 400 typically developing and non-ASD clinical controls
will complete the PNI. A combination of classical item analysis and factor analysis will be used to identify the
best-performing items, which will then be calibrated using Item Response Theory (IRT) and co-calibrated with
legacy measures to demonstrate superiority of PNI item and scale function. Baseline inter-rater and 6-week
test-retest reliability, 24-week change sensitivity, and sensitivity in the context of an upcoming clinical trial all
will be assessed, both convergent and divergent validity will be tested, and a short form will be developed.
Preliminary data demonstrate both the utility of parsing individual behaviors, currently subsumed within larger
categories, into positive and negative dimensions and the success of PROMIS® methods and IRT for
developing sensitive tools for ASD. We anticipate that this innovative, scientifically rigorous study will result in a
calibrated and validated assessment tool for ASD with an empirically-supported factor structure and items that
are both precise in their descriptive capturing of symptoms and sensitive to variability in the latent dimensions,
within and across children. We also expect that the PNI will show excellent reliability and change sensitivity,
offering a promising outcome measure for use in ASD clinical trials. Long term, we expect this research to
have significant clinical benefits, including: 1) offering a new tool for assessing experimental therapeutics, 2)
providing a new framework within which to test brain me...

## Key facts

- **NIH application ID:** 9989914
- **Project number:** 5R01MH119172-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jennifer Foss-Feig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $823,870
- **Award type:** 5
- **Project period:** 2019-08-06 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989914

## Citation

> US National Institutes of Health, RePORTER application 9989914, PROMIS-guided development and validation of a dimensional observer-report measure of positive and negative features of ASD (5R01MH119172-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989914. Licensed CC0.

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