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Permanent link (DOI): https://doi.org/10.7939/R3W08WP4M

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N-of-1 Methods and their Contribution to Systematic Reviews and Meta-analyses Open Access

Descriptions

Other title
Subject/Keyword
ADHD
systematic review
amphetamine
N-of-1 trial
meta-analysis
methylphenidate
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Punja, Salima
Supervisor and department
Vohra, Sunita (Pediatrics)
Examining committee member and department
Urichuk, Liana (Alberta Health Services)
Hartling, Lisa (Pediatrics)
Department
Department of Medicine
Specialization
Experimental Medicine
Date accepted
2014-09-11T15:40:16Z
Graduation date
2014-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Background: N-of-1 trials are prospectively planned, multiple crossover evaluations, conducted in individual patients. Evidence shows that a range of designs and statistical methods have been applied to N-of-1 trials. This thesis helps to provide a comprehensive understanding about the methodology and reporting of N-of-1 trials by synthesizing all published evidence. Furthermore, while the primary objective of N-of-1 trials is to assess treatment response in individual patients, this thesis explores whether any secondary benefits can be derived from N-of-1 trials and the data they generate. Given the number of N-of-1 trials conducted in the area of attention deficit/hyperactivity disorder, this condition was chosen as the clinical model explored in the thesis. Objectives: i) To provide a systematic overview of published N-of-1 trials; ii) To assess how N-of-1 trials that have been conducted to assess the same interventions for the same conditions, using identical outcome measures can be aggregated in order to yield group estimates of treatment effect; and iii) To assess how N-of-1 trials can be combined with RCT data into a single meta-analysis. Methods: A series of systematic reviews were conducted in which each review consisted of a thorough search strategy, an assessment of inclusion of primary studies, a risk of bias assessment and either a qualitative or quantitative synthesis of data. A second reviewer was involved in all reviews. Results: This thesis found that N-of-1 trials have been conducted in over 50 conditions, and that the majority of published N-of-1 trials are published as a series. Our findings also indicate that N-of-1 trials can be meta-analyzed across participants in order to yield population treatment effect estimates. Furthermore, we found that combining N-of-1 trials with RCT data into a single meta-analysis, impacts both the magnitude and precision of overall treatment effect estimates. Conclusions: This thesis examined the potential for N-of-1 trials beyond their primary purpose of providing estimates of individual treatment effectiveness and demonstrates a method of aggregating N-of-1 trials across participants as well as with RCT evidence. Clinical and research recommendations on how to move this field forward have been provided.
Language
English
DOI
doi:10.7939/R3W08WP4M
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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