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

  • Author / Creator
    Punja, Salima
  • 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.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Medicine
  • Specialization
    • Experimental Medicine
  • Supervisor / co-supervisor and their department(s)
    • Vohra, Sunita (Pediatrics)
  • Examining committee members and their departments
    • Hartling, Lisa (Pediatrics)
    • Urichuk, Liana (Alberta Health Services)