title: An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial.
abstract: BACKGROUND
  The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study.
  
  
  METHODS
  The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention.
  
  
  CONCLUSIONS
  The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).
authors.affiliation: Division of Pediatric Medicine, Department of Pediatrics, Pediatrics Outcomes Research Team, The Hospital for Sick Children, Room 109708, 10th Floor, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. kawsari.abdullah@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. kawsari.abdullah@sickkids.ca.
authors.forename: Kawsari
authors.initials: K
authors.lastname: Abdullah
authors.affiliation: The Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, M5B 1W8, Toronto, ON, Canada. kevin.thorpe@utoronto.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. kevin.thorpe@utoronto.ca.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Thorpe
authors.affiliation: Department of Psychology, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. eva.mamak@sickkids.ca.
authors.forename: Eva
authors.initials: E
authors.lastname: Mamak
authors.affiliation: Division of Pediatric Medicine, Department of Pediatrics, Pediatrics Outcomes Research Team, The Hospital for Sick Children, Room 109708, 10th Floor, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. jonathon.maguire@utoronto.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. jonathon.maguire@utoronto.ca.|The Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, M5B 1W8, Toronto, ON, Canada. jonathon.maguire@utoronto.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. jonathon.maguire@utoronto.ca.|Department of Pediatrics, St. Michael's Hospital, University of Toronto, 30 Bond Street, M5B 1W8, Toronto, Canada. jonathon.maguire@utoronto.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. jonathon.maguire@utoronto.ca.
authors.forename: Jonathon L
authors.initials: JL
authors.lastname: Maguire
authors.affiliation: Division of Pediatric Medicine, Department of Pediatrics, Pediatrics Outcomes Research Team, The Hospital for Sick Children, Room 109708, 10th Floor, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. catherine.birken@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. catherine.birken@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. catherine.birken@sickkids.ca.|Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, floor 10, room#109832, M5G 0A4, Toronto, ON, Canada. catherine.birken@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. catherine.birken@sickkids.ca.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Birken
authors.affiliation: Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. dfehlings@hollandbloorview.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. dfehlings@hollandbloorview.ca.|Division of Developmental Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, and Bloorview Research Institute, 150 Kilgour Road, M4G 1R8, Toronto, ON, Canada. dfehlings@hollandbloorview.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. dfehlings@hollandbloorview.ca.
authors.forename: Darcy
authors.initials: D
authors.lastname: Fehlings
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. anthony.hanley@utoronto.ca.|Department of Nutritional Sciences, University of Toronto, FitzGerald Building, 150 College Street, Room 316, M5S 3E2, Toronto, ON, Canada. anthony.hanley@utoronto.ca.|Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. anthony.hanley@utoronto.ca.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hanley
authors.affiliation: Division of Pediatric Medicine, Department of Pediatrics, Pediatrics Outcomes Research Team, The Hospital for Sick Children, Room 109708, 10th Floor, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. colin.macarthur@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. colin.macarthur@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. colin.macarthur@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. colin.macarthur@sickkids.ca.|Research Institute, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, M5G 0A4, Toronto, ON, Canada. colin.macarthur@sickkids.ca.
authors.forename: Colin
authors.initials: C
authors.lastname: Macarthur
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, floor 10, room#109832, M5G 0A4, Toronto, ON, Canada. Stanley.zlotkin@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Department of Nutritional Sciences, University of Toronto, FitzGerald Building, 150 College Street, Room 316, M5S 3E2, Toronto, ON, Canada. Stanley.zlotkin@sickkids.ca.|Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Centre for Global Child Health, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. Stanley.zlotkin@sickkids.ca.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Zlotkin
authors.affiliation: Division of Pediatric Medicine, Department of Pediatrics, Pediatrics Outcomes Research Team, The Hospital for Sick Children, Room 109708, 10th Floor, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. patricia.parkin@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3M6, Toronto, Canada. patricia.parkin@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3M7, Toronto, Canada. patricia.parkin@sickkids.ca.|Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, floor 10, room#109832, M5G 0A4, Toronto, ON, Canada. patricia.parkin@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. patricia.parkin@sickkids.ca.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Parkin
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D003677:Deficiency Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007501:Iron / Q000008:administration & dosage* / Q000097:blood; D000090463:Iron Deficiencies; D008297:Male; D055118:Medication Adherence; D009048:Motor Skills; D009483:Neuropsychological Tests; D009864:Ontario; D010865:Pilot Projects; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007501:Iron