N-of-1 Trials in Neurology: A Systematic Review.

Bas C Stunnenberg, Joost Berends, Robert C Griggs, Jeffrey Statland, Gea Drost, Jane Nikles, Hans Groenewoud, Baziel G M van Engelen, Gert Jan van der Wilt, Joost Raaphorst

Journal: Neurology 2022;98(2):e174-e185

PMID: 34675101

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Abstract

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.

Address: From the Department of Neurology (B.C.S., J.B., B.G.M.v.E.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, and Department of Health Evidence (H.G., G.J.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (R.C.G.), University of Rochester Medical Center, NY; Department of Neurology (J.S.), University of Kansas Medical Center, Kansas City; University of Groningen (G.D.), Department of Neurology and Neurosurgery, University Medical Center Groningen, Groningen, the Netherlands; University of Queensland Centre for Clinical Research (J.N.), University of Queensland, Herston, Brisbane, Australia; and Amsterdam UMC (J.R.), University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Netherlands. [email protected].; From the Department of Neurology (B.C.S., J.B., B.G.M.v.E.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, and Department of Health Evidence (H.G., G.J.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (R.C.G.), University of Rochester Medical Center, NY; Department of Neurology (J.S.), University of Kansas Medical Center, Kansas City; University of Groningen (G.D.), Department of Neurology and Neurosurgery, University Medical Center Groningen, Groningen, the Netherlands; University of Queensland Centre for Clinical Research (J.N.), University of Queensland, Herston, Brisbane, Australia; and Amsterdam UMC (J.R.), University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Netherlands.

DOI: 10.1212/WNL.0000000000012998

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MeSH Terms: Acute Disease, Checklist, Chronic Disease, Humans, Neurology