The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

Ian H. de Boer; David K. Prince; Kayleen Williams; Norrina B. Allen; Gregory L. Burke; Andrew N. Hoofnagle; Simon Hsu; Xiaohui Li; Kiang J. Liu; Robyn L. McClelland; Erin D. Michos; Bruce M. Psaty; Steven J. Shea; Kenneth M. Rice; Jerome I. Rotter; David S. Siscovick; Russell P. Tracy; Karol E. Watson; Bryan R. Kestenbaum

doi:10.1016/j.cct.2021.106318

The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

Ian H. de Boer^*, David K. Prince, Kayleen Williams, Norrina B. Allen, Gregory L. Burke, Andrew N. Hoofnagle, Simon Hsu, Xiaohui Li, Kiang J. Liu, Robyn L. McClelland, Erin D. Michos, Bruce M. Psaty, Steven J. Shea, Kenneth M. Rice, Jerome I. Rotter, David S. Siscovick, Russell P. Tracy, Karol E. Watson, Bryan R. Kestenbaum

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The INdividual response to VITamin D (INVITe) trial was a randomized, placebo-controlled, parallel group trial of vitamin D₃ supplementation (2000 IU daily) designed to determine clinical and genetic characteristics that modify the response to vitamin D supplementation. To enhance internal and external validity and reduce cost, the INVITe trial was nested within the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective observational cohort study. The INVITe trial enrolled a community-based population of 666 racially and ethnically diverse participants from January 2017 to April 2019. This represents 30% of 2210 MESA participants approached for screening, and 96% of those found to be eligible. Barriers to enrollment included delayed initiation of the trial relative to scheduled MESA study visits, a lower number of available MESA participants than expected, and a high prevalence (18%) of high-dose vitamin D supplementation (>1000 IU daily, an exclusion criterion). The final study visit was attended by 611 participants (92%), and median adherence was 98%. Our experience suggests that integration of a randomized trial into an existing observational cohort study may leverage strengths of the source population and enhance enrollment, retention, and adherence, although with limited enrollment capacity. The INVITe trial will use rigorously-collected data to advance understanding of individual determinants of vitamin D response.

Original language	English (US)
Article number	106318
Journal	Contemporary Clinical Trials
Volume	103
DOIs	https://doi.org/10.1016/j.cct.2021.106318
State	Published - Apr 2021

Funding

The MESA INVITe trial was funded by R01HL096875 from the National Heart, Lung, and Blood Institute (NHLBI). Additional support for MESA came from contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the NHLBI, grants UL1-TR-000040 and UL1-TR-001420 from NCATS, and UL1-RR-025005 from NCRR. Funding for MESA Family is provided by grants R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, and R01-HL-071259 from the NHLBI, UL1-TR-001079 and UL1-TR-001881 from NCATS, and grant UL1-RR-033176 from NCRR. Additional support came from grants R01DK088762, R01DK099199 and 2T32DK007467-36 from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors thank the MESA investigators, staff, and participants as well as the INVITe trial Data Safety Monitoring Board (Kelley Branch, MD [chair], Edward Lipkin, MD, and Adam Szpiro, PhD) for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. The MESA INVITe trial was funded by R01HL096875 from the National Heart, Lung, and Blood Institute (NHLBI). Additional support for MESA came from contracts 75N92020D00001 , HHSN268201500003I , N01-HC-95159 , 75N92020D00005 , N01-HC-95160 , 75N92020D00002 , N01-HC-95161 , 75N92020D00003 , N01-HC-95162 , 75N92020D00006 , N01-HC-95163 , 75N92020D00004 , N01-HC-95164 , 75N92020D00007 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 and N01-HC-95169 from the NHLBI , grants UL1-TR-000040 and UL1-TR-001420 from NCATS , and UL1-RR-025005 from NCRR . Funding for MESA Family is provided by grants R01-HL-071051 , R01-HL-071205 , R01-HL-071250 , R01-HL-071251 , R01-HL-071252 , R01-HL-071258 , and R01-HL-071259 from the NHLBI, UL1-TR-001079 and UL1-TR-001881 from NCATS , and grant UL1-RR-033176 from NCRR . Additional support came from grants R01DK088762 , R01DK099199 and 2T32DK007467-36 from the National Institute of Diabetes and Digestive and Kidney Diseases . The authors thank the MESA investigators, staff, and participants as well as the INVITe trial Data Safety Monitoring Board (Kelley Branch, MD [chair], Edward Lipkin, MD, and Adam Szpiro, PhD) for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org . The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Keywords

Clinical trial
Observational cohort study
Pharmacogenomics
Vitamin D

ASJC Scopus subject areas

Pharmacology (medical)

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10.1016/j.cct.2021.106318

Cite this

de Boer, I. H., Prince, D. K., Williams, K., Allen, N. B., Burke, G. L., Hoofnagle, A. N., Hsu, S., Li, X., Liu, K. J., McClelland, R. L., Michos, E. D., Psaty, B. M., Shea, S. J., Rice, K. M., Rotter, J. I., Siscovick, D. S., Tracy, R. P., Watson, K. E., & Kestenbaum, B. R. (2021). The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study. Contemporary Clinical Trials, 103, Article 106318. https://doi.org/10.1016/j.cct.2021.106318

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title = "The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study",

abstract = "The INdividual response to VITamin D (INVITe) trial was a randomized, placebo-controlled, parallel group trial of vitamin D3 supplementation (2000 IU daily) designed to determine clinical and genetic characteristics that modify the response to vitamin D supplementation. To enhance internal and external validity and reduce cost, the INVITe trial was nested within the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective observational cohort study. The INVITe trial enrolled a community-based population of 666 racially and ethnically diverse participants from January 2017 to April 2019. This represents 30% of 2210 MESA participants approached for screening, and 96% of those found to be eligible. Barriers to enrollment included delayed initiation of the trial relative to scheduled MESA study visits, a lower number of available MESA participants than expected, and a high prevalence (18%) of high-dose vitamin D supplementation (>1000 IU daily, an exclusion criterion). The final study visit was attended by 611 participants (92%), and median adherence was 98%. Our experience suggests that integration of a randomized trial into an existing observational cohort study may leverage strengths of the source population and enhance enrollment, retention, and adherence, although with limited enrollment capacity. The INVITe trial will use rigorously-collected data to advance understanding of individual determinants of vitamin D response.",

keywords = "Clinical trial, Observational cohort study, Pharmacogenomics, Vitamin D",

author = "{de Boer}, {Ian H.} and Prince, {David K.} and Kayleen Williams and Allen, {Norrina B.} and Burke, {Gregory L.} and Hoofnagle, {Andrew N.} and Simon Hsu and Xiaohui Li and Liu, {Kiang J.} and McClelland, {Robyn L.} and Michos, {Erin D.} and Psaty, {Bruce M.} and Shea, {Steven J.} and Rice, {Kenneth M.} and Rotter, {Jerome I.} and Siscovick, {David S.} and Tracy, {Russell P.} and Watson, {Karol E.} and Kestenbaum, {Bryan R.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = apr,

doi = "10.1016/j.cct.2021.106318",

language = "English (US)",

volume = "103",

journal = "Contemporary Clinical Trials",

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de Boer, IH, Prince, DK, Williams, K, Allen, NB, Burke, GL, Hoofnagle, AN, Hsu, S, Li, X, Liu, KJ, McClelland, RL, Michos, ED, Psaty, BM, Shea, SJ, Rice, KM, Rotter, JI, Siscovick, DS, Tracy, RP, Watson, KE & Kestenbaum, BR 2021, 'The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study', Contemporary Clinical Trials, vol. 103, 106318. https://doi.org/10.1016/j.cct.2021.106318

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T1 - The multi-ethnic study of atherosclerosis individual response to vitamin D trial

T2 - Building a randomized clinical trial into an observational cohort study

AU - de Boer, Ian H.

AU - Prince, David K.

AU - Williams, Kayleen

AU - Allen, Norrina B.

AU - Burke, Gregory L.

AU - Hoofnagle, Andrew N.

AU - Hsu, Simon

AU - Li, Xiaohui

AU - Liu, Kiang J.

AU - McClelland, Robyn L.

AU - Michos, Erin D.

AU - Psaty, Bruce M.

AU - Shea, Steven J.

AU - Rice, Kenneth M.

AU - Rotter, Jerome I.

AU - Siscovick, David S.

AU - Tracy, Russell P.

AU - Watson, Karol E.

AU - Kestenbaum, Bryan R.

PY - 2021/4

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KW - Clinical trial

KW - Observational cohort study

KW - Pharmacogenomics

KW - Vitamin D

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The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

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