A Randomized Placebo-controlled Trial of Vitamin D Supplementation for Reduction of Mortality and Cancer: Statistical Analysis Plan for the D-Health Trial

Overview

Journal Contemp Clin Trials Commun

Date 2019 Mar 20

PMID 30886934

Citations 7

Authors

Mary Waterhouse

Dallas R English

Bruce K Armstrong

Catherine Baxter

Briony Duarte Romero

Peter R Ebeling

Gunter Hartel

Michael G Kimlin

Donald S A McLeod

Rachel L OConnell

Jolieke C van der Pols

Alison J Venn

Penelope M Webb

David C Whiteman

Rachel E Neale

Affiliations

Soon will be listed here.

Abstract

Background: Many observational studies have reported an association between vitamin D and non-skeletal health outcomes. The D-Health Trial was launched to determine if supplementing the older population with high monthly doses of Vitamin D can prevent cancer and premature mortality. The intervention is ongoing but here we provide a detailed statistical analysis plan for the primary and secondary outcomes of the D-Health Trial.

Methods/design: The D-Health Trial is a double-blind, randomized, placebo-controlled trial. Between February 2014 and May 2015, 21,315 people were randomized in a 1:1 ratio to receive monthly doses of either 60,000 IU of cholecalciferol (vitamin D) or placebo for five years. The primary outcome is all-cause mortality and the secondary outcomes are total cancer incidence and colorectal cancer incidence. These will be ascertained via linkage to death and cancer registries. The primary analysis for each outcome will follow an intention-to-treat approach; we will use flexible parametric survival models to investigate the association between supplementation and time to an event. We describe in detail sophisticated secondary analyses that consider non-compliance and contamination due to off-study supplementation.

Conclusions: Publication of this statistical analysis plan in advance of the intervention's completion, and adherence to it, will avoid data-driven analyses of the primary and secondary outcomes and ensure robust reporting of outcomes.

Clinical Trial Registration Number: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. Registered on 4 July 2013.

Citing Articles

Association of serum vitamin D with diagnosis and growth of abdominal aortic aneurysm.

Thanigaimani S, Neale R, Waterhouse M, Moxon J, Yeap B, Norman P JVS Vasc Sci. 2024; 5:100208.

PMID: 39219591 PMC: 11362639. DOI: 10.1016/j.jvssci.2024.100208.

Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.

Thompson B, Waterhouse M, English D, McLeod D, Armstrong B, Baxter C BMJ. 2023; 381:e075230.

PMID: 37380191 PMC: 10302209. DOI: 10.1136/bmj-2023-075230.

The effect of vitamin D supplementation on the gut microbiome in older Australians - Results from analyses of the D-Health Trial.

Pham H, Waterhouse M, Rahman S, Baxter C, Duarte Romero B, McLeod D Gut Microbes. 2023; 15(1):2221429.

PMID: 37287399 PMC: 10251798. DOI: 10.1080/19490976.2023.2221429.

Effect of vitamin D supplementation on depression in older Australian adults.

Rahman S, Waterhouse M, Duarte Romero B, Baxter C, English D, Almeida O Int J Geriatr Psychiatry. 2022; 38(1):e5847.

PMID: 36462182 PMC: 10108111. DOI: 10.1002/gps.5847.

Critical Appraisal of Large Vitamin D Randomized Controlled Trials.

Pilz S, Trummer C, Theiler-Schwetz V, Grubler M, Verheyen N, Odler B Nutrients. 2022; 14(2).

PMID: 35057483 PMC: 8778517. DOI: 10.3390/nu14020303.

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