Navigating the outcome maze: a scoping review of outcomes and instruments in clinical trials in genetic neurodevelopmental disorders and intellectual disability

Annelieke R Müller, Nadia Y van Silfhout, Bibiche den Hollander, Dick H C Kampman, Lianne Bakkum, Marion M M G Brands, Lotte Haverman, Caroline B Terwee, Carlo Schuengel, Joost Daams, David Hessl, Frits A Wijburg, Erik Boot, Agnies M van Eeghen

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging.

OBJECTIVES: The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID.

ELIGIBILITY CRITERIA: Clinical trials in individuals with GNDs and ID for any intervention over the past 10 years were included in the review.

SOURCES OF EVIDENCE: MEDLINE, PsycINFO, and Cochrane CENTRAL were searched. Titles and abstracts were independently screened for eligibility with a subsample of 10% double-screening for interrater reliability. Data from full texts were independently reviewed. Discrepancies were discussed until consensus was reached.

CHARTING METHODS: Information was recorded on patient populations, interventions, designs, outcomes, measurement instruments, and type of reporter when applicable. Qualitative and descriptive analyses were performed.

RESULTS: We included 312 studies reporting 91 different outcomes, with cognitive function most frequently measured (28%). Various outcome measurement instruments ( n  = 457) were used, with 288 in only a single clinical trial. There were 18 genetic condition-specific instruments and 16 measures were designed ad-hoc for one particular trial. Types of report included proxy-report (39%), self-report (22%), clinician-report (16%), observer-report (6%), self-assisted report (1%), or unknown (16%).

CONCLUSION: This scoping review of current practice reveals a myriad of outcomes and outcome measurement instruments for clinical trials in GNDs and ID. This complicates generalization, evidence synthesis, and evaluation. It underlines the need for consensus on suitability, validity, and relevancy of instruments, ultimately resulting in a core outcome set. A series of steps is proposed to move from the myriad of measures to a more unified approach.

Original languageEnglish
Pages (from-to)26330040241245721
JournalTherapeutic Advances in Rare Disease
Publication statusPublished - 1 Jan 2024


  • intellectual disability
  • measures
  • outcomes
  • psychiatry
  • quality of life
  • rare genetic disorders

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