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

Objective

To perform a systematic review of published N-of-1 trials (e.g. single patient cross-over trials) in neurological disorders, including an assessment of methodological quality and reporting.

Methods

We searched PubMed, MEDLINE and Embase, from inception date - the first of December 2019, for reports on N-of-1 trials in neurological 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 using the CONSORT 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 neurological 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, nine N-of-1 trials studied a stable chronic symptom of a progressive or acute neurological disorder. Besides pharmacological interventions, electrical 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 methodological measures of quality and reporting across all N-of-1 trials

Conclusions

N-of-1 trials have been reported in numerous neurological 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.Methodological quality and reporting of N-of-1 trials were found suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and follow CENT guidelines. As most N-of-1 trials remain unreported in medical literature, this systematic review probably only represent the tip of the iceberg of conducted N-of-1 trials in neurological 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.