Statistical analysis
hypercalciuria
REGRESSION, ADVERSE EFFECTS, NEPHROCALCINOSIS, HYPERCALCEMIA
All statistical analyses were performed using R version 3.6.3 [The proportion of participants in the treatment and placebo arm achieving a 25(OH)D concentration > 75 nmol/L by hospital discharge was calculated, with the Wilson’s score used to generate 95% confidence intervals. Additionally, the difference in these proportions between groups was calculated, again with a 95% Wilson confidence interval, and Fisher’s exact test for comparing the proportions. As stated above, due to an instrumentation issue during analysis of the research samples, we instead used the clinical sample analyzed in real-time prior to hospital discharge to evaluate the primary outcome. As a clinical sample for the primary analysis was not available for all patients, an imputation procedure was performed when an accurate research measurement was available. First, using observed pairs of clinical and research measurements of 25(OH)D, a linear regression log-transformed model of clinical sample measurements on log-transformed research sample measurements was fitted. This model was then used to impute the clinical sample measurement when an accurate research sample measurement was available. The results were first reported using imputation of missing 25(OH)D values and second using solely the clinical sample 25(OH)D concentrations. An analysis of covariance (ANCOVA) was performed to compare 25(OH)D concentration from the clinical sample between treatment groups, adjusting for the baseline 25(OH)D concentration at the time of screening (prior to study drug administration).Secondary analyses included calculating proportions by treatment group of the following potential adverse effects of treatment: presence of nephrocalcinosis, persistent hypercalcemia, and persistent hypercalciuria. Wilson’s score was used to generate 95% confidence intervals for each above-mentioned proportion. As described in the trial protocol paper [Sub-analyses were performed whereby the proportion of participants in the treatment arm and in the placebo arm achieving 25(OH)D concentrations > 75 nmol/L was calculated with Wilson’s score’s test to generate 95% confidence intervals within six different subgroupings: (1) patients under and ≥ 40 kg or over; (2) patients with a 25(OH)D concentration at the time of screening above or ≤ 32 nmol/L; (3) newborns (< 30 days old) or ≥ 30 days of age; (4) by country of enrollment, Canada versus outside of Canada; (5) by race, and (6) by admitting diagnosis. To test for subgroup differences a logistic regression model was fit with a main effect of treatment arm, the subgroup variable (e.g. weight category), and an interaction between these two variables. The p-value for the estimated interaction was reported.