Trial reportAnnals of clinical and translational neurology2019
Reproducibility of cognitive endpoints in clinical trials: lessons from neurofibromatosis type 1.
Trial report in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 3 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Visuospatial and Visuomotor Abilities of Individuals with Neurofibromatosis Type 1: A Systematic Review and Meta-analysis.Neuropsychology review · 2026Pooled it
- Brain volumes in genetic syndromes associated with mTOR dysregulation: a systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Is cognitive profiling in NF1 still optional? A systematic review of current assessment practices.Frontiers in neurologyPooled it
- Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial.Scientific reports · 2022Trial
- Executive Functioning, Attention Problems, and Social Impairments in Youth with Neurofibromatosis Type 1 and Autism Spectrum Disorder.Journal of pediatric neuropsychology · 2026Article
- Age-varying associations between parent-reported executive function and internalizing/externalizing problems in children with neurofibromatosis type 1: an integrative analysis of data from nine institutions.Journal of the International Neuropsychological Society : JINS · 2026Article
- Academic Achievement of Children and Adolescents with Neurofibromatosis Type 1: A Systematic Review and Meta-Analysis.Neuropsychology review · 2025Review
- Cognition and behavior in neurofibromatosis type 1: report and perspective from the Cognition and Behavior in NF1 (CABIN) Task Force.Genes & development · 2025Article
- The significance of calcium ions in cerebral ischemia-reperfusion injury: mechanisms and intervention strategies.Frontiers in molecular biosciences · 2025Review
- Gender-Specific Fine Motor Skill Learning Is Impaired by Myelin-Targeted Neurofibromatosis Type 1 Gene Mutation.Cancers · 2024Article
- Article
- Review
- From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.International journal of molecular sciences · 2023Review
- Statins in Children with Neurofibromatosis Type 1: A Systematic Review of Randomized Controlled Trials.Children (Basel, Switzerland) · 2023Review
- Article
- GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy.Molecular therapy. Methods & clinical development · 2022Review
- Review of neuropsychological outcomes in isolated methylmalonic acidemia: recommendations for assessing impact of treatments.Metabolic brain disease · 2022Review
- Cognitive and Electrophysiological Correlates of Working Memory Impairments in Neurofibromatosis Type 1.Journal of autism and developmental disorders · 2022Article
- Functional network alterations in young brain tumor patients with radiotherapy-induced memory impairments and vascular injury.Frontiers in neurology · 2022Article
- Auditory Dysfunction Among Individuals With Neurofibromatosis Type 1.JAMA network open · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 13 institutions in 2 countries.
Funding
Abstract
objectiveRapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism-based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test-retest reliability of the measures and the application of data reduction techniques to improve reproducibility.
methodsData were analyzed from the STARS clinical trial (n = 146), a multi-center double-blind placebo-controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra-class correlation coefficients were generated between pre- and post-performances (16-week interval) on neuropsychological endpoints in the placebo group to determine test-retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error.
resultsTest-retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test-retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data.
interpretationThese data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test-retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.