Randomized controlled trials of Vitamin D and cancer incidence: A modeling study

Abstract

Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxy Vitamin D [25(OH)D] concentrations are inversely correlated with 15-20 types of cancer, few randomized controlled trials (RCTs) of Vitamin D support those findings. The poor design of some RCTs may account for that lack of support. Most Vitamin D RCTs to date have considered the Vitamin D dose, rather than initial, final, or changes in, serum 25(OH)D concentrations. Here a model is developed for use in designing and analyzing Vitamin D RCTs with application to cancer incidence. The input variables of the model are Vitamin D dose, baseline and achieved 25(OH)D concentrations, known rates of cancer for the population, and numbers of participants for the treatment and placebo arms is estimated - Vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance, using information from two Vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios. Further improvements to the conduct of Vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations, and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance, and to allow dosage adjustment for achievement of desired Vitamin D status.