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. 2021 Mar 16;96(11):529-540.
doi: 10.1212/WNL.0000000000011597. Epub 2021 Jan 27.

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

Annelieke R Müller  1 , Marion M M G Brands  1 , Peter M van de Ven  1 , Kit C B Roes  1 , Martina C Cornel  1 , Clara D M van Karnebeek  1 , Frits A Wijburg  1 , Joost G Daams  1 , Erik Boot  1 , Agnies M van Eeghen  2
Affiliations

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

Annelieke R Müller et al. Neurology. .

Abstract

Objective: To improve the use of N-of-1 studies in rare genetic neurodevelopmental disorders, we systematically reviewed the literature and formulated recommendations for future studies.

Methods: The systematic review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42020154720). EMBASE and MEDLINE were searched for relevant studies. Information was recorded on types of interventions, outcome measures, validity, strengths, and limitations using standard reporting guidelines and critical appraisal tools. Qualitative and descriptive analyses were performed.

Results: Twelve studies met the N-of-1 inclusion criteria, including both single trials and series. Interventions were mainly directed to neuropsychiatric manifestations. Main strengths were the use of personalized and clinically relevant outcomes in most studies. Generalizability was compromised due to limited use of validated and generalizable outcome measures.

Conclusion: N-of-1 studies are sporadically reported in rare genetic neurodevelopmental disorders. Properly executed N-of-1 studies may provide a powerful alternative to larger randomized controlled trials in rare disorders and a much needed bridge between practice and science. We provide recommendations for future N-of-1 studies in rare genetic neurodevelopmental disorders, ultimately optimizing evidence-based and personalized care.

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Figures

Figure 1
Figure 1. Schematic Presentation of Terminology Used for N-of-1 Trials
Figure 2
Figure 2. PRISMA Flowchart
PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analysis.
Figure 3
Figure 3. Schematic Representation of the Risk of Bias in N-of-1 Trials (RoBiNT) Scale
(A) Items of internal validity. (B) Items on external validity and interpretation. The y-axis indicates the included N-of-1 studies ordered per first authors. Circles indicate scores on the 3-point rating scale where 2 points were awarded for meeting the recommended stringent criteria (green), 1 point to otherwise defined criteria (yellow), and 0 points for not meeting the stringent criteria of the design standards (red).
Figure 4
Figure 4. Challenges and Recommendations for Conducting and Reporting N-of-1 Studies in Rare Genetic Neurodevelopmental Disorders
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References

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