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Systematic Review of N-of-1 Studies in Rare Genetic Neurodevelopmental Disorders: The Power of 1

Authors: Müller, Brands, van de Ven, Roes, Cornel, van Karnebeek, ... & van Eeghen, A. M. (2021)


Genetic neurodevelopmental disorders are often presented with various degrees of severity and complex syndromes, making it hard to formulate a treatment plan that fits all. Moreover, rare genetic diseases affect a small population. Therefore, it is necessary to use a personalized study methodology to develop evidence-based treatments. In this systematic review by Müller et al., twelve papers were selected and reviewed to identify areas for improvement in using N-of-1 studies for rare genetic neurodevelopmental diseases. This paper shows that N-of-1 studies were able to achieve patient-centered intervention and outcomes. Along with strengths, this review also identifies the limitation of N-of-1 studies and suggests ways to mitigate these limitations. As rare neurodevelopmental disorders are heterogeneous and affected by multiple environmental factors, there is a need to clarify inclusion and exclusion criteria, as well as other baseline characteristics, to improve generalizability. This systematic review also highlights the lack of statistical analysis in all 12 studies. There are methods and formulas available to be used to analyze inter-and intraindividual factors and how it affects treatment outcome. Other areas of improvement include compliance issues and inconsistencies with the terminology used in the N-of-1 trials, which could result in the exclusion of relevant studies. This systematic review shows how N-of-1 studies could potentially improve personalized treatment and be an alternative to Randomized Clinical Trials, specifically for rare genetic diseases. There are limitations to N-of-1 trials, but with improvements, the N-of-1 studies could provide evidence-based treatments for rare genetic disorders.


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Full Citation: Müller, A. R., Brands, M. M., van de Ven, P. M., Roes, K. C., Cornel, M. C., van Karnebeek, C. D., ... & van Eeghen, A. M. (2021). Systematic review of N-of-1 studies in rare genetic neurodevelopmental disorders: the power of 1. Neurology, 96(11), 529-540.



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