TY - JOUR
T1 - N-of-1 Trials in Neurology A Systematic Review
AU - Stunnenberg, Bas C.
AU - Berends, Joost
AU - Griggs, Robert C.
AU - Statland, Jeffrey
AU - Drost, Gea
AU - Nikles, Jane
AU - Groenewoud, Hans
AU - van Engelen, Baziel G. M.
AU - van der Wilt, Gert Jan
AU - Raaphorst, Joost
N1 - Funding Information: This study was financed by ZonMw, The Netherlands Organisation for Health Research and Development (project 152002029). Funding Information: R.C. Griggs reports grants (during the conduct of the study) from NIH, the Muscular Dystrophy Association, and the Parent Project for Muscular Dystrophy, as well as personal fees from Strongbridge Pharmaceuticals, Sarepta Pharmaceuticals, Marathon Pharmaceuticals, and Stealth Pharmaceuticals. J. Statland reports grants from National Institute of Neurological Disorders and Stroke, and FSH Society, as well as personal fees from Acceleron, Sarepta, Fulcrum, PTC, and Dyne Therapeutics. B.G.M. van Engelen reports grants from European Union's Horizon 2020 Research and Innovation Programme (Murab), European FP7 Programme (OPTIMISTIC), Association Francaise contre les Myopathies, Global FSH, The Netherlands Organisation for Health Research and Development (ZonMw), Prinses Beatrix Spierfonds, Stiching Spieren voor Spieren, Dutch FSHD Foundation, and Netherlands Organisation for Scientific Research (NWO), as well as personal fees from Fulcrum. J. Nikles has a commercial interest in N-of-1 Hub Pty Ltd consultancy company. The article was prepared in the absence of any financial relationships that could be construed as a conflict of interest. B.C. Stunnenberg, J. Berends, G. Drost, H. Groenewoud, G.J. van der Wilt, and J. Raaphorst report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures. Publisher Copyright: Copyright © 2021 American Academy of Neurology
PY - 2022/1/11
Y1 - 2022/1/11
N2 - Background and Objectives To perform a systematic review of published N-of-1 trials (e.g., single patient crossover trials) in neurologic disorders, including an assessment of methodologic quality and reporting. Methods We searched PubMed, MEDLINE, and Embase from inception date to the December 1, 2019, for reports on N-of-1 trials in neurologic disorders. Basic trial information on design, disease, intervention, analysis, and treatment success was extracted. Strengths and weaknesses of the N-of-1 trials were assessed with the Consolidated Standards of Reporting Trials extension for N-of-1 trials (CENT) 2015 criteria checklist and the Jadad score as measures of quality and reporting. Results We retrieved 40 reports of N-of-1 trials in neurologic disorders (19 individual N-of-1 trials, 21 series of N-of-1 trials). Most N-of-1 trials were performed in neuromuscular and neurodegenerative/movement disorders. Unlike the majority of trials that studied the main symptom(s) of a chronic stable condition, 9 N-of-1 trials studied a stable chronic symptom of a progressive or acute neurologic disorder. Besides pharmacologic interventions, electric stimulation protocols and nutritional products were studied. A mean total CENT score of 20.88 (SD 9.10, range 0–43) and mean total Jadad score of 2.90 (SD 2.15, range 0–5) were found as methodologic measures of quality and reporting across all N-of-1 trials. Discussion N-of-1 trials have been reported in numerous neurologic disorders, not only in chronic stable disorders, but also in progressive or acute disorders with a stable symptom. This indicates the emerging therapeutic area of N-of-1 trials in neurology. Methodologic quality and reporting of N-of-1 trials were found to be suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and following CENT guidelines. Because most N-of-1 trials remain unreported in medical literature, this systematic review probably represents only the tip of the iceberg of conducted N-of-1 trials in neurologic disorders. In addition to conventional trial designs, N-of-1 trials can help to bridge the gap between research and clinical care by providing an alternative, personalized level 1 evidence base for suitable treatments.
AB - Background and Objectives To perform a systematic review of published N-of-1 trials (e.g., single patient crossover trials) in neurologic disorders, including an assessment of methodologic quality and reporting. Methods We searched PubMed, MEDLINE, and Embase from inception date to the December 1, 2019, for reports on N-of-1 trials in neurologic disorders. Basic trial information on design, disease, intervention, analysis, and treatment success was extracted. Strengths and weaknesses of the N-of-1 trials were assessed with the Consolidated Standards of Reporting Trials extension for N-of-1 trials (CENT) 2015 criteria checklist and the Jadad score as measures of quality and reporting. Results We retrieved 40 reports of N-of-1 trials in neurologic disorders (19 individual N-of-1 trials, 21 series of N-of-1 trials). Most N-of-1 trials were performed in neuromuscular and neurodegenerative/movement disorders. Unlike the majority of trials that studied the main symptom(s) of a chronic stable condition, 9 N-of-1 trials studied a stable chronic symptom of a progressive or acute neurologic disorder. Besides pharmacologic interventions, electric stimulation protocols and nutritional products were studied. A mean total CENT score of 20.88 (SD 9.10, range 0–43) and mean total Jadad score of 2.90 (SD 2.15, range 0–5) were found as methodologic measures of quality and reporting across all N-of-1 trials. Discussion N-of-1 trials have been reported in numerous neurologic disorders, not only in chronic stable disorders, but also in progressive or acute disorders with a stable symptom. This indicates the emerging therapeutic area of N-of-1 trials in neurology. Methodologic quality and reporting of N-of-1 trials were found to be suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and following CENT guidelines. Because most N-of-1 trials remain unreported in medical literature, this systematic review probably represents only the tip of the iceberg of conducted N-of-1 trials in neurologic disorders. In addition to conventional trial designs, N-of-1 trials can help to bridge the gap between research and clinical care by providing an alternative, personalized level 1 evidence base for suitable treatments.
UR - http://www.scopus.com/inward/record.url?scp=85123345794&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000012998
DO - https://doi.org/10.1212/WNL.0000000000012998
M3 - Article
C2 - 34675101
SN - 0028-3878
VL - 98
SP - E174-E185
JO - Neurology
JF - Neurology
IS - 2
ER -