A randomized placebo-controlled trial of vitamin D supplementation for reduction of mortality and cancer: Statistical analysis plan for the D-Health Trial

Mary Waterhouse¹, Dallas R English², Bruce K Armstrong³, Catherine Baxter¹, Briony Duarte Romero¹, Peter R Ebeling⁴, Gunter Hartel¹, Michael G Kimlin⁵, Donald S A McLeod¹, Rachel L O'Connell⁶, Jolieke C van der Pols⁷, Alison J Venn⁸, Penelope M Webb¹, David C Whiteman¹, Rachel E Neale^{1

9}

Affiliations

¹ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
² Melbourne School of Population Health, University of Melbourne, Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia.
³ School of Public Health, University of Sydney, Sydney, Australia.
⁴ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
⁵ Health Research Institute, University of Sunshine Coast, Sippy Downs, Australia.
⁶ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
⁷ School of Exercise and Nutrition Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁹ School of Public Health, The University of Queensland, Brisbane, Australia.

PMID: 30886934
PMCID: PMC6402378
DOI: 10.1016/j.conctc.2019.100333

A randomized placebo-controlled trial of vitamin D supplementation for reduction of mortality and cancer: Statistical analysis plan for the D-Health Trial

Mary Waterhouse et al. Contemp Clin Trials Commun. 2019.

. 2019 Feb 20:14:100333.

doi: 10.1016/j.conctc.2019.100333. eCollection 2019 Jun.

Authors

Affiliations

¹ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
² Melbourne School of Population Health, University of Melbourne, Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia.
³ School of Public Health, University of Sydney, Sydney, Australia.
⁴ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
⁵ Health Research Institute, University of Sunshine Coast, Sippy Downs, Australia.
⁶ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
⁷ School of Exercise and Nutrition Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁹ School of Public Health, The University of Queensland, Brisbane, Australia.

PMID: 30886934
PMCID: PMC6402378
DOI: 10.1016/j.conctc.2019.100333

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 D₃) 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.

Keywords: Cancer; Mortality; Randomized controlled trial; Statistical analysis plan; Vitamin D.

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A randomized placebo-controlled trial of vitamin D supplementation for reduction of mortality and cancer: Statistical analysis plan for the D-Health Trial

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A randomized placebo-controlled trial of vitamin D supplementation for reduction of mortality and cancer: Statistical analysis plan for the D-Health Trial

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