A Methodological Review of Randomised n-of-1 Trials.

Abstract

Abstract Background n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of a decade, including how the n-of-1 design has been employed to study both rare and non-rare conditions. Methods Databases and clinical trials registries were searched for articles including “n-of-1” in the title between 1st January 2011 and 5th May 2021. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables. Results We identified 52 studies meeting our eligibility criteria, eight of which (15.4%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neuropsychiatric conditions (n = 16, 30.8). The median (interquartile range, IQR) number of participants randomised was 10 (1–20) and 11 trials (21.2%) involved a single patient only. 35 (67.3%) trials evaluated drug interventions and 38 (73.1%) trials were placebo controlled. Trials had a median (IQR) of six (5–8) periods and compared a median (IQR) of two (2–2) health technologies. 41 (78.8%) trials incorporated blinding and 23 (44.3%) had a washout period. 37 trials (71.2%) used patient reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 32 (61.5%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions. Conclusions Our review has summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations and the implementation of these studies. Registration: Not applicable.