Understanding Variation in Sets of N-of-1 Trials

Artur Araujo; Steven Julious; Stephen Senn

doi:10.1371/journal.pone.0167167

Understanding Variation in Sets of N-of-1 Trials

PLoS One. 2016 Dec 1;11(12):e0167167. doi: 10.1371/journal.pone.0167167. eCollection 2016.

Authors

Artur Araujo¹, Steven Julious², Stephen Senn¹

Affiliations

¹ Competence Center for Methodology and Statistics, Luxembourg Institute of Health, Strassen, Luxembourg.
² Medical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.

Abstract

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder's theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed.

MeSH terms

Algorithms
Biomedical Research / methods
Biomedical Research / statistics & numerical data
Clinical Trials as Topic*
Humans
Models, Statistical*
Research Design*

Grants and funding

SS and AA’s work was funded by the European Union’s FP7 programme grant number 602552 for the IDEAL project. AA has received additional funding from Boehringer-Ingelheim. The support of both funders is gratefully acknowledged The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.