Clinical Outcome Assessments: Use of Normative Data in a Pediatric Rare Disease

Area of Science:

• Pediatric rare disease research
• Clinical trial methodology
• Outcome assessment development

Background:

• Pediatric rare diseases pose unique challenges for clinical trial design and outcome assessment selection.
• Lack of natural history data and wide age ranges in trials necessitate functional assessments with normative data.
• Distinguishing treatment effects from developmental changes in children is complex.

Purpose of the Study:

• To illustrate clinical outcome assessment (COA) selection in a pediatric rare disease setting, using hypophosphatasia (HPP) as an example.
• To highlight the importance of COAs with normative data for evaluating treatment efficacy in rare pediatric conditions.
• To emphasize the need for early integration of COAs in the drug development process for rare pediatric diseases.

Main Methods:

• Review of multiple clinical outcome assessments (COAs) used in hypophosphatasia (HPP) trials for asfotase alfa.
• Inclusion of assessments with normative data across various domains: motor skills, function, and mobility.
• Examples include Bayley Scales, Bruininks-Oseretsky Test, CHAQ, PODCI, dynamometry, 6-minute walk test, and mo-MIP-G.

Main Results:

• Multiple COAs were necessary to capture the multifaceted impact of asfotase alfa treatment in HPP.
• The selected COAs provided normative data, aiding in the interpretation of treatment effects versus developmental changes.
• The study demonstrates the utility of various instruments in assessing different functional domains.

Conclusions:

• Multiple, normatively-referenced COAs are essential for robust clinical trial design in pediatric rare diseases.
• Early selection and implementation of appropriate COAs are critical for successful drug development in this population.
• This approach helps differentiate treatment effects from natural developmental progression in children with rare diseases.