title: Statistical design considerations applicable to clinical trials of iodine supplementation in pregnant women who may be mildly iodine deficient.
abstract: No large, randomized, placebo-controlled trial of iodine supplementation in pregnant women in a region of mild or moderate iodine deficiency has been completed in which a primary outcome measure was an assessment of the neurobehavioral development of the offspring at age ≥2 y. In this article, I discuss considerations for the design of such a trial in a region of mild iodine deficiency, with a focus on statistical methods and approaches. Exposure and design issues include the ethics of using a placebo, the potential for overexposure to iodine, and the possibility of community randomization. The main scientific goal of the trial is important in determining the follow-up period. If the goal is to determine whether iodine supplementation during pregnancy improves neurobehavioral development in the offspring, then follow-up should continue until a reasonably reliable assessment can be conducted, which might be at age ≥2 y. Once the timing of assessment is decided, the impact of potential loss to follow-up should be considered so that appropriate statistical methods can be incorporated into the design. The minimum sample size can be calculated by using a sample size formula that incorporates noncompliance and assumes that a certain proportion of study participants do not have any outcome observed. To have sufficient power to detect a reasonably modest difference in neurobehavioral development scores using an assessment tool with an SD of 15, a large number of participants (>500/group) is required. The minimum adequate number of participants may be even larger (>1300/group) depending on the magnitude of the difference in outcome between the supplementation and placebo groups, the estimated proportion of the iodine-supplementation group that fails to take the supplement, and the estimated proportion of pregnancies that do not produce outcome measurements.
authors.affiliation: Office of Biostatistics Research, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD jt3t@nih.gov.
authors.forename: James F
authors.initials: JF
authors.lastname: Troendle
mesh_terms: D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007455:Iodine / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use; D009752:Nutritional Status; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011295:Prenatal Care; D039401:Prenatal Nutritional Physiological Phenomena; D012107:Research Design / Q000706:statistics & numerical data; D014131:Trace Elements / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014131:Trace Elements; D007455:Iodine
keywords: clinical trials; iodine supplementation; outcomes measurement; pregnancy; statistical methods