Research & Innovation
Publications
Two-Arm Crossover Randomized Controlled Trial Versus Meta-Analysis of N-of-1 Studies
PMU Authors
Georg Zimmermann, Josef Niebauer
All Authors
Anna Eleonora Carrozzo, Georg Zimmermann, Arne C. Bathke, Daniel Neunhaeuserer, Josef Niebauer, Stefan T. Kulnik
Journal association
BIOMETRICAL JOURNAL. BIOMETRISCHE ZEITSCHRIFT
Abstract
N-of-1 trials are currently receiving broader attention in healthcare research when assessing the effectiveness of interventions. In contrast to the most commonly applied two-arm randomized controlled trial (RCT), in an N-of-1 design, the individual acts as their own control condition in the sense of a multiple crossover trial. N-of-1 trials can lead to a higher quality of patient by examining the effectiveness of an intervention at an individual level. Moreover, when a series of N-of-1 trials are properly aggregated, it becomes possible to detect an intervention effect at a population level. This work investigates whether a meta-analysis of summary data of a series of N-of-1 trials allows us to detect a statistically significant intervention effect with fewer participants than in a traditional, prospectively powered two-arm RCT and crossover design when evaluating a digital health intervention in cardiovascular care. After introducing these different analysis approaches, we compared the empirical properties in a simulation study both under the null hypothesis and with respect to power with different between-subject heterogeneity settings and in the presence of a carry-over effect. We further investigate the performance of a sequential aggregation procedure. In terms of simulated power, the threshold of 80% was achieved earlier for the aggregating procedure, requiring fewer participants.
Keywords
META-ANALYSIS, N-of-1 trials, Comparative effectiveness, crossover Design, Two-arm randomized controlled trial