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Methodological issues in randomized trials of pediatric acute diarrhea: evaluating probiotics and the need for standardized definitions and valid outcome measures Open Access


Other title
pediatric acute diarrhea
randomized trials
outcome measures
Type of item
Degree grantor
University of Alberta
Author or creator
Johnston, Bradley C.
Supervisor and department
Tsuyuki, Ross T. (Department of Medicine & School of Public Health)
Vohra, Sunita (Department of Pediatrics & School of Public Health)
Examining committee member and department
McFarland, Lynne V. (Department of Health Services Research and Development)
Huynh, Hien Q. (Department of Pediatrics)
Fedorak, Richard N. (Department of Medicine)
Rogers, W. Todd (Department of Educational Psychology)
Department of Medicine

Date accepted
Graduation date
Doctor of Philosopy
Degree level
BACKGROUND: In a 2006 WHO report, diarrheal diseases ranked second among conditions afflicting children. Pediatric acute diarrhea, although most often the result of a gastrointestinal infection, can also occur as a result of antibiotic exposure. This is often referred to as antibiotic-associated diarrhea (AAD). Previous research suggests that probiotics may be effective in the treatment or prevention of various types of PAD. METHODS: The first study involved a systematic review and meta-analysis of RCTs involving probiotics as an adjunct to antibiotics for preventing AAD in children. The second study was a systematic review of definitions and primary outcome measures employed in RCTs of PAD. The third study used a modified Delphi consensus procedure to develop a new instrument for evaluating the severity of PAD. The study involved steering committee discussions (phase 1) and two electronic surveys (phase 2 and 3) of leading experts in measurement and clinical gastroenterology. RESULTS: The per protocol meta-analysis of ten RCTs significantly favored probiotics to prevent the incidence of diarrhea (NNT = 10). However, this effect did not withstand ITT analysis and among included trials there was considerable inconsistency regarding definitions for the reviews primary outcome measure, the incidence of diarrhea. Study two identified 121 RCTs that reported 62 unique definitions of diarrhea, 64 unique definitions of diarrhea resolution and 62 unique primary outcome measures. Thirty-one trials used grading systems to support outcome evaluation. However, none of the trials (or their citations) reported evidence of their validation. In study three experts agreed on the inclusion of five attributes containing 13 items. Attributes proposed for the IPADDS include: Diarrhea Frequency and Duration, Vomiting Frequency and Duration, Fever, Restrictions in Normal Daily Activities and Dehydration. CONCLUSION: It is premature to draw a valid conclusion about the efficacy of probiotics for pediatric AAD. Definitions of diarrhea and primary outcome measures in RCTs of PAD are heterogeneous and lack evidence of validity. The third study represents content validity evidence for IPADDS. A numerical scoring system needs to be added and further empirical evidence of reliability and validity are required.
License granted by Bradley Johnston ( on 2009-09-11T22:06:43Z (GMT): 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 the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein 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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