Article Text

Efficacy of vitamin D3 supplementation on cancer mortality in the general population and the prognosis of patients with cancer: protocol of a systematic review and individual patient data meta-analysis of randomised controlled trials
  1. Ben Schöttker1,2,
  2. Sabine Kuznia1,3,
  3. Hermann Brenner1,2,4,5
  1. 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Baden-Württemberg, Germany
  2. 2Network Aging Research (NAR), University of Heidelberg, Heidelberg, Baden-Württemberg, Germany
  3. 3Medical Faculty Heidelberg - University of Heidelberg, Heidelberg, Germany
  4. 4Division of Preventive Oncology, German Cancer Research Centre (DKFZ) and National Centre for Tumor Diseases, Heidelberg, Baden-Württemberg, Germany
  5. 5German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany
  1. Correspondence to Dr Ben Schöttker; b.schoettker{at}


Introduction Vitamin D insufficiency is much more common among patients with cancer than the general population. Previous meta-analyses of controlled trials showed an approximately 15% reduction of cancer mortality by vitamin D supplementation compared with placebo or no treatment in the general population.

On top of updating the latest systematic review on vitamin D supplementation and cancer mortality in the general population, we aim to conduct the first meta-analyses of trials on vitamin D3 supplementation and cancer-specific and overall survival of patients with cancer. Besides, we will conduct for the first time subgroup analyses based on individual patient data collected from randomised controlled trials.

Methods and analysis A systematic review and individual patient data meta-analysis will be performed on randomised placebo-controlled trials with a vitamin D3 intervention. All databases are searched from inception without time restriction. The addressed outcomes are cancer mortality in the general population as well as cancer-specific and overall survival of patients with cancer. The quality appraisal of the studies will be evaluated by the Cochrane risk-of-bias tool for randomised trials. Trial results will be reanalysed using adjusted and unadjusted Cox proportional hazard regression models and meta-analyses are planned. Cochran’s Q-Test and the I2 index will be used to statistically assess the level of heterogeneity, while sensitivity and subgroup analyses serve to identify potential causes of heterogeneity. Subgroup analyses will be conducted for vitamin D3 dosing, follow-up time, age, sex, obesity, vitamin D deficiency/insufficiency, history of cancer and compliance. Publication bias will be assessed by funnel plots and Egger’s test.

Ethics and dissemination Ethical approval is not required since no human beings are involved in this systematic review. Results will be published in a peer-reviewed journal with open access. They will be presented at conferences and sent to patient advocacy groups and German oncological rehabilitation centres.

PROSPERO registration number CRD42020185566

  • nutritional support
  • oncology
  • nutrition & dietetics
  • public health
  • protocols & guidelines
  • epidemiology

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  • BS and SK are joint first authors.

  • BS and SK contributed equally.

  • Contributors All authors meet the ICMJE criteria for authorship as follows. BS and SK are the guarantors of the systematic review, therefore, are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors made substantial contributions to the conception of the work. BS and SK designed the search strategy and the risk of bias assessment strategy. BS developed the selection criteria, the data extraction criteria and the statistical methods. SK drafted the protocol publication, which BS and HB revised critically for important intellectual content. All authors approved the final version to be published.

  • Funding The authors did not receive any funding for the work on this systematic review protocol. The open access publication fee was paid from a research grant of the Wereld Kanker Onderzoek Fonds (WKOF), member of the World Cancer Research Fund network based in Amsterdam, the Netherlands (grant reference no.: 2018/1696).

  • Disclaimer The views of the authors do not necessarily reflect those of the German Cancer Research Centre.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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