Comparing ability and norm-referenced scores as clinical trial outcomes for neurodevelopmental disabilities: a simulation study

Journal of Neurodevelopmental Disorders

New Method

Jesse D. Troy¹  Aaron J. Kaat²  Audrey Thurm³  Cristan Farmer³ 

[1] Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA;Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD, USA;

关键词: Ability score;    Growth scale value;    Rasch analysis;    Item response theory;    Neurodevelopmental disability;    Rare genetic condition;    Floor effect;    Clinical trials;    Clinical outcome assessment;    Endpoints;   

DOI  :  10.1186/s11689-022-09474-6

 received in 2022-05-24, accepted in 2022-12-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundFor genetic conditions associated with neurodevelopmental disorder (GCAND), developmental domains such as motor ability, thinking and learning, social abilities, and communication are potential intervention targets. Performance on measures of developmental concepts can be expressed using several types of scores. Norm-referenced scores are intended for the diagnostic context, allowing for the identification of impairment relative to age-based expectations, and can exhibit dramatic floor effects when used in individuals with more significant limitations. Person ability scores, which are derived via Rasch analysis or item response theory, are available on many standardized tests and are intended to measure within-person change. However, they have not been used or evaluated as primary endpoints in GCAND clinical trials. In this study, we simulated a series of parallel-arm clinical trials under several chronological age and impairment conditions, to compare empirically the power and type I error rate of operationalizing test performance using ability scores rather than norm-referenced scores.ResultsUsing the Vineland Adaptive Behavior Scales as the example, we demonstrated an advantage in statistical power of ability scores over norm-referenced scores at extreme levels of impairment. This advantage was at least partially driven by floor effects in norm-referenced scores. For simulated conditions where impairment was less severe, ability scores outperformed norm-referenced scores, but they were more similar. The type I error rate closely approximated the nominal type I error rate of 5% for both scores.ConclusionThe results of this simulation demonstrate a substantial power and interpretative advantage of ability scores over norm-referenced scores for studies of GCAND that will enroll participants with high levels of impairment. These results are expected to generalize to studies of developmental concepts, regardless of the etiology or specific test. However, the relative advantage of ability scores is expected to be even greater for tests with a higher floor than the Vineland.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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