Understanding Critical Clinical Outcome Assessments (COAs) Used in Clinical Trials

Quick Overview

Dr. Anjali Sadhwani discussed the use of clinical outcome assessments (COAs) in clinical trials. COAs are used to measure the effectiveness of treatments and interventions. There are different types of COAs, including performance-based, patient-reported, observer-reported, and clinician-reported measures. These measures assess various domains of development, such as cognitive skills, adaptive functioning, language, and motor skills. The Bailey Scales of Infant Development and the Vineland Behavior Scale are commonly used COAs in clinical trials for assessing development in children. Dr. Sadhwani highlighted the challenges and improvements in using these measures, including the need for standardization and the assessment of meaningful change. The goal is to provide a comprehensive assessment of a child’s development and capture meaningful changes over time.

Introduction

Dr. Anjali Sadhwani, an expert in Angelman Syndrome, discusses the importance of understanding critical clinical outcome assessments (COAs) used in clinical trials. She highlights the different types of outcome measures used and their significance in evaluating the effectiveness of treatments. Dr. Sadhwani also emphasizes the need for standardized administration of these measures to ensure consistency and accuracy in capturing changes over time.

Types of Outcome Measures

Dr. Sadhwani explains the four types of outcome measures used in clinical trials:

1. Performance-based outcome measures: These measures involve instructing participants to perform specific tasks, such as putting pegs in a pegboard or walking up and down stairs.

2. Patient-reported outcome measures: These measures involve asking individuals about their feelings and experiences, which may not be applicable to nonverbal children with Angelman Syndrome.

3. Observer-reported outcome measures: These measures involve gathering information from parents or caregivers about the child’s behavior and abilities, such as eating, toilet training, and gross motor skills.

4. Clinician-reported outcome measures: These measures involve clinicians assessing the child’s gait, gross motor skills, and other physical abilities. It is important for these measures to be approved by the FDA for use in clinical trials.

Characteristics of Outcome Measures

Dr. Sadhwani acknowledges that outcome measures do not represent the entirety of a child’s abilities and potential. She explains that while these measures provide estimates of predicted functioning, they can be influenced by various factors such as sleep patterns, seizures, and behavior. However, outcome measures must possess certain characteristics, including validity, reliability, psychometric soundness, and sensitivity to change.

Domains Assessed in Clinical Trials

Dr. Sadhwani focuses on the domains of development assessed in clinical trials, including cognitive skills, learning, problem-solving, adaptive functioning, receptive language, expressive communication, fine motor development, and gross motor development. She highlights the importance of these domains and their relevance to parents as demonstrated by the disease concept study.

Challenges in Assessing Cognitive Development

Dr. Sadhwani discusses the challenges in assessing cognitive development, particularly in individuals with Angelman Syndrome. Traditional IQ tests often require basic skills that may not be present in all individuals with the syndrome. She explains the difficulties in interpreting test scores and the limitations of standard scores and age equivalent scores. Dr. Sadhwani suggests that the Bailey Scales of Infant Development is currently the best option for assessing development in this population.

The Bailey Scales of Infant Development

Dr. Sadhwani provides an overview of the Bailey Scales of Infant Development, a well-validated measure of developmental progression. She explains that the Bailey assesses development in five domains: cognition, receptive communication, expressive communication, fine motor skills, and gross motor skills. Dr. Sadhwani acknowledges the limitations of the Bailey but emphasizes its usefulness in assessing development and capturing change over time.

Assessing Change with the Bailey

Dr. Sadhwani presents data from the natural history study, demonstrating that individuals with Angelman Syndrome continue to make progress in development over time. She explains that the growth scale value (GSV) is the best measure for assessing change in developmental progression. The GSV is derived from raw scores and has good statistical qualities for detecting improvement over time.

Improving the Use of the Bailey in Angelman Syndrome

Dr. Sadhwani discusses the ongoing efforts to improve the use of the Bailey in Angelman Syndrome. These efforts include item review, video review of administration, discussions with stakeholders, interviews with evaluators and parents, development of better accommodations and recommendations for item administration, guidelines for training new administrators, and the development of a measure of fidelity and validity. The goal is to standardize the administration of the Bailey across different studies and clinical settings.

The Vineland Behavior Scale

Dr. Sadhwani introduces the Vineland Behavior Scale as a parent-completed measure for assessing adaptive functioning. She explains that the Vineland assesses development in 10 domains, including communication, motor skills, socialization, and daily living skills. Dr. Sadhwani highlights the overlap between the Vineland and the Bailey in certain domains and presents data showing that the Vineland can also capture change over time.

Correlation Between the Bailey and Vineland

Dr. Sadhwani addresses the correlation between the Bailey and Vineland. She explains that the two measures are highly correlated, indicating their consistency in assessing development.

Assessing Clinically Meaningful Change

Dr. Sadhwani discusses the assessment of clinically meaningful change using the Vineland Behavior Scale. She explains the process of gathering input from parents and clinicians through Delphi panels to determine the smallest level of change that is noticeable and impactful in a child’s daily functioning. The goal is to establish thresholds for clinically meaningful change in both the Vineland and the Bailey.

Conclusion

Dr. Sadhwani concludes by emphasizing the appropriateness and validity of the Bailey and Vineland as measures for assessing development in clinical trials. She highlights the importance of standardized administration to ensure consistency and accuracy. Dr. Sadhwani expresses gratitude to her colleagues and the families who have contributed to the research and efforts to improve these measures.