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The Analysis of Continuous Data from N-of-1 Trials Using Paired Cycles: a Simple Tutorial

Overview
Journal Trials
Publisher Biomed Central
Date 2024 Feb 16
PMID 38365817
Authors
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Abstract

N-of-1 trials are defined and the popular paired cycle design is introduced, together with an explanation as to how suitable sequences may be constructed.Various approaches to analysing such trials are explained and illustrated using a simulated data set. It is explained how choosing an appropriate analysis depends on the question one wishes to answer. It is also shown that for a given question, various equivalent approaches to analysis can be found, a fact which may be exploited to expand the possible software routines that may be used.Sets of N-of-1 trials are analogous to sets of parallel group trials. This means that software for carrying out meta-analysis can be used to combine results from N-of-1 trials. In doing so, it is necessary to make one important change, however. Because degrees of freedom for estimating variances for individual subjects will be scarce, it is advisable to estimate local standard errors using pooled variances. How this may be done is explained and fixed and random effect approaches to combining results are illustrated.

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References
1.
DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

2.
Van Den Noortgate W, Onghena P . Estimating the mean effect size in meta-analysis: bias, precision, and mean squared error of different weighting methods. Behav Res Methods Instrum Comput. 2004; 35(4):504-11. DOI: 10.3758/bf03195529. View

3.
Senn S . Sample size considerations for n-of-1 trials. Stat Methods Med Res. 2017; 28(2):372-383. DOI: 10.1177/0962280217726801. View

4.
Senn S . Controversies concerning randomization and additivity in clinical trials. Stat Med. 2004; 23(24):3729-53. DOI: 10.1002/sim.2074. View

5.
Rosenberger W, Uschner D, Wang Y . Randomization: The forgotten component of the randomized clinical trial. Stat Med. 2018; 38(1):1-12. DOI: 10.1002/sim.7901. View