Many rare disease indications are studied predominantly, if not entirely, in pediatric populations. For many products, one or more of the key secondary endpoints will involve the use of developmental and cognitive assessments. These specific types of assessments are chosen to provide information on the subject’s development and growth over time. So, what are the most common assessments and how are they used?

Vineland Adaptive Behavior Scales

The Vineland Adaptive Behavior Scales, second edition (VABS-II) is a commonly used assessment for measuring adaptive behavior skills in children from birth through age 90. Adaptive behavior skills are those needed for daily living and everyday functioning. Although adaptive behavior is rarely used as a primary endpoint, it is often used as a secondary outcome and to determine which cognitive assessment will be best suited for a particular child’s developmental level. The assessment covers five domains— Communication, Daily Living Skills, Socialization, Motor skills, and Maladaptive Behavior (optional). The scales are divided into two methods of administration, namely a semi-structured interview format or a rating scale form completed by the parent/caregiver. The interview format is conducted with the individual’s parent or caregiver. Alternatively, the rating scale can be completed by the individual’s parent, caregiver or other respondent familiar with their behaviors. There is also a version for use with teachers for individual’s in school (or preschool). The assessment is one of the most popular measures of adaptive behavior in the US and other Western countries. It has also been used successfully in non-Western and rural populations, making it appropriate for use in global studies. Although it has been translated into some languages, for most international clinical trials, obtaining certified translations and culturally adapted assessments in languages no yet translated will be key. Due to the nature of this particular assessment, translating this scale may impact project timelines.

Bayley Scales of Infant and Toddler Development

The Bayley Scales of Infant and Toddler Development, third edition (BSID-III) is an internationally accepted assessment of development in children ages 1-42 months. It is one of the only developmental assessments appropriate for use in very young children and its less rigid format of administration and the inclusion of assessments in the motor domain make it ideal for the rare disease pediatric population. BSID-III looks at five key developmental domains—cognition, language, motor, social-emotional, and adaptive behavior. Some rare genetic disorders, like Mucopolysaccharidoses (MPS) types I-III or Spinal Muscular Atrophy (SMA), will require the assessment of very young children, and the BSID-III is often the best choice for doing so. The assessment can be challenging to learn since it requires a strong knowledge of the test items and how they are administered without the need to constantly reference a manual. Inaccuracies in the administration of this assessment can be an issue, so it is important to conduct thorough rater-training, use experienced raters, and have a data management plan designed to detect both administrative and technical errors, so that the final calculated endpoint(s) are accurate. For global clinical trials, it is important to know that the BSID-III is currently only available in English, an important consideration when considering timelines and licensing of materials.

Kaufman Assessment Battery for Children

The Kaufman Assessment Battery for Children, second edition (KABC-II) is used to assess cognitive development in children between the ages of 3 and 18. It is a relatively new intelligence test that combines a theoretical basis backed by cognitive and neuropsychological research. The battery consists of 18 core and supplemental tests across five areas—simultaneous processing, sequential processing, planning, learning, and knowledge. The actual number of subtests and which subtests are used is dependent on both the model chosen and the age of the subject. The KABC-II can be performed with subjects functioning below or above average, a useful feature considering most pediatric rare disease clinical trials require collection of developmental status information as an endpoint. Another important feature, depending on the nature of the patient population, is that it can be used to assess processing and cognitive abilities in non-verbal children. This Non-verbal Index battery of subtests is used most often in pediatric rare disease trials and allows for the assessment of children, regardless of their language impairment. In addition to the valuable features of the assessment, the KABC-II is generally considered to be a culturally fair assessment and is available in various languages, a significant consideration given that most rare disease clinical trials are global. Despite these benefits, the assessment does have a floor effect (below the 3-year level) and it is very structured which can be difficult to administer to young children with impairments in attention; therefore, it is important to consider the specific patient population being assessed and to determine whether this assessment is suitable for the clinical trial.

While each of these assessments have broad applicability to clinical research in pediatric populations, there are a wide array of assessments that can be used, some of which may be more appropriate for a given indication, patient population, or intended label claim. If you are interested in learning more about the assessments that may be appropriate for your study, contact us.

References & Supplemental Information

Kaufman, A. S., O’Neal, M. R., Avant, A. H., & Long, S. W. (1987). Review Article: Introduction to the Kaufman Assessment Battery for Children (K-ABC) for Pediatric Neuroclinicians. Journal of Child Neurology, 2(1), 3– 16

CHAPTER 7 – Screening and Assessment Tools, Editor(s): MARK L. WOLRAICH, DENNIS D. DROTAR, PAUL H. DWORKIN, ELLEN C. PERRIN, Developmental-Behavioral Pediatrics, Mosby,2008, Pages 123-201, ISBN 9780323040259,

Ballot, D. E., Ramdin, T., Rakotsoane, D., Agaba, F., Davies, V. A., Chirwa, T., & Cooper, P. A. (2017). Use of the Bayley Scales of Infant and Toddler Development, Third Edition, to Assess Developmental Outcome in Infants and Young Children in an Urban Setting in South Africa. International scholarly research notices, 2017, 1631760. doi:10.1155/2017/1631760

Costantini L, D’Ilario J, Moddemann D, Penner K, Schmidt B. Accuracy of Bayley Scores as Outcome Measures in Trials of Neonatal Therapies. JAMA Pediatr. 2015;169(2):188–189. doi:10.1001/jamapediatrics.2014.2965

Emily D’Antonio, Jin Y. Shin, Chapter Four – Families of Children with Intellectual Disabilities in Vietnam: Emerging Themes, Editor(s): Robert M. Hodapp, International Review of Research in Mental Retardation, Academic Press, Volume 38, 2009, Pages 93-123, ISSN 0074-7750, ISBN 9780123744678,