's Heeren Loo (A.R.M.), Amersfoort, the Netherlands, and Amsterdam UMC (A.R.M.), Pediatric Metabolic Diseases, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Pediatric Metabolic Diseases (M.M.G.B), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics (P.M.v.d.V.), Amsterdam UMC, Amsterdam, the Netherlands; Department of Health Evidence, Biostatistics (K.C.B.R.), Radboud University Medical Center, Radboud University, Nijmegen, the Netherlands; Department of Clinical Genetics (M.C.C.), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Pediatric Metabolic Diseases (C.D.M.v.K.), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands, and Department of Pediatrics (C.D.M.v.K.), Radboud University Medical Center, Radboud Centre for Mitochondrial Medicine, Nijmegen, the Netherlands; Pediatric Metabolic Diseases (F.A.W.), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Medical Library (J.G.D.), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 's Heeren Loo (E.B.), Amersfoort, the Netherlands, and Department of Psychiatry and Neuropsychology (E.B.), Maastricht University, Maastricht, the Netherlands, University Health Network (E.B.), The Dalglish Family 22q Clinic, Toronto, Ontario, Canada; and 's Heeren Loo (A.M.v.E.), Amersfoort, the Netherlands, Amsterdam UMC (A.M.v.E.), Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands, and Erasmus Medical Center (A.M.v.E.), ENCORE, Rotterdam, the Netherlands.
Neurology. 2021 Mar 16;96(11):529-540. doi: 10.1212/WNL.0000000000011597. Epub 2021 Jan 27.
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.
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.
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.
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.
为了提高在罕见遗传性神经发育障碍中使用 N-of-1 研究的水平，我们系统地回顾了文献并为未来的研究制定了建议。
系统评价方案已在 PROSPERO 国际前瞻性注册系统评价（CRD42020154720）中进行了注册。在 EMBASE 和 MEDLINE 中搜索了相关研究。使用标准报告指南和关键评估工具记录了干预措施类型、结局测量、有效性、优势和局限性等信息。进行了定性和描述性分析。
符合 N-of-1 纳入标准的研究有 12 项，包括单试验和系列研究。干预措施主要针对神经精神表现。由于很少使用经过验证和可推广的结局测量，因此大多数研究都使用了个性化和临床相关的结局，这是其主要优势。由于可推广性有限，因此普遍存在问题。
在罕见遗传性神经发育障碍中，N-of-1 研究的报道很少。适当执行的 N-of-1 研究可为罕见疾病中的更大规模随机对照试验提供有力替代方法，也为实践和科学之间架起了一座急需的桥梁。我们为罕见遗传性神经发育障碍中的未来 N-of-1 研究提供了建议，最终优化了基于证据的个体化治疗。
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