Assessment of research waste part 2

wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation

Mark J. Bolland (Corresponding Author), Andrew Grey, Alison Avenell

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Abstract

BACKGROUND: Research waste can occur when trials are conducted in the wrong populations. Vitamin D deficient populations are most likely to benefit from vitamin D supplementation. We investigated waste attributable to randomised controlled trials (RCTs) of supplementation in populations that were not vitamin D deficient.

METHODS: In December 2015, we searched Pubmed, recent systematic reviews, and three trial registries for RCTs of vitamin D with clinical endpoints in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N ≥ 1000) RCTs. We investigated the proportion of RCTs that studied vitamin D deficient populations, temporal trends in baseline 25OHD, and whether investigators in large RCTs considered relevant 25OHD survey data or systematic reviews in their trial justifications.

RESULTS: Of 137 RCTs of vitamin D with clinical endpoints, 118 (86%) reported baseline mean/median 25OHD, which was < 25, 25-49, 50-74, and ≥ 75 nmol/L in 12 (10%), 62 (53%), 36 (31%), and 8 (7%) RCTs, respectively. In 70% of RCTs, baseline 25OHD was > 40 nmol/L. Baseline 25OHD increased over time. Before 2006, 38%, 62%, 0% and 0% of RCTs had baseline 25OHD < 25, 25-49, 50-74, and ≥ 75 nmol/L respectively; in 2011-15, the respective proportions were 9%, 49%, 37%, and 6%. Of 12 RCTs with baseline 25OHD < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing), 1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44% (8/18) of large completed RCTs cited relevant prior population 25OHD data, and only 3/10 (30%) relevant prior systematic reviews.

CONCLUSIONS: Up to 70% of RCTs of vitamin D with clinical endpoints, 71% of large completed RCTs, and 100% of ongoing large RCTs could be considered research waste because they studied cohorts that were not vitamin D deficient.

Original languageEnglish
Article number101
Number of pages14
JournalBMC Medical Research Methodology
Volume18
Issue number1
DOIs
Publication statusPublished - 3 Oct 2018

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Vitamin D
Randomized Controlled Trials
Research
Population
PubMed
Registries
Research Personnel

Keywords

  • vitamin D
  • deficiency
  • sufficiency
  • randomized controlled trials
  • research waste
  • fracture
  • cardiovascular disease
  • cancer
  • mortality

Cite this

Assessment of research waste part 2 : wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation. / Bolland, Mark J. (Corresponding Author); Grey, Andrew; Avenell, Alison.

In: BMC Medical Research Methodology, Vol. 18, No. 1, 101, 03.10.2018.

Research output: Contribution to journalArticle

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title = "Assessment of research waste part 2: wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation",
abstract = "BACKGROUND: Research waste can occur when trials are conducted in the wrong populations. Vitamin D deficient populations are most likely to benefit from vitamin D supplementation. We investigated waste attributable to randomised controlled trials (RCTs) of supplementation in populations that were not vitamin D deficient.METHODS: In December 2015, we searched Pubmed, recent systematic reviews, and three trial registries for RCTs of vitamin D with clinical endpoints in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N ≥ 1000) RCTs. We investigated the proportion of RCTs that studied vitamin D deficient populations, temporal trends in baseline 25OHD, and whether investigators in large RCTs considered relevant 25OHD survey data or systematic reviews in their trial justifications.RESULTS: Of 137 RCTs of vitamin D with clinical endpoints, 118 (86{\%}) reported baseline mean/median 25OHD, which was < 25, 25-49, 50-74, and ≥ 75 nmol/L in 12 (10{\%}), 62 (53{\%}), 36 (31{\%}), and 8 (7{\%}) RCTs, respectively. In 70{\%} of RCTs, baseline 25OHD was > 40 nmol/L. Baseline 25OHD increased over time. Before 2006, 38{\%}, 62{\%}, 0{\%} and 0{\%} of RCTs had baseline 25OHD < 25, 25-49, 50-74, and ≥ 75 nmol/L respectively; in 2011-15, the respective proportions were 9{\%}, 49{\%}, 37{\%}, and 6{\%}. Of 12 RCTs with baseline 25OHD < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing), 1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44{\%} (8/18) of large completed RCTs cited relevant prior population 25OHD data, and only 3/10 (30{\%}) relevant prior systematic reviews.CONCLUSIONS: Up to 70{\%} of RCTs of vitamin D with clinical endpoints, 71{\%} of large completed RCTs, and 100{\%} of ongoing large RCTs could be considered research waste because they studied cohorts that were not vitamin D deficient.",
keywords = "vitamin D, deficiency, sufficiency, randomized controlled trials, research waste, fracture, cardiovascular disease, cancer, mortality",
author = "Bolland, {Mark J.} and Andrew Grey and Alison Avenell",
note = "Acknowledgements: We thank the following for providing further information about their trial or survey: Paul Atyeo, Australian Bureau of Statistics, Australia; Anne Looker, Centers for Disease Control and Prevention, USA; Briony Romero and Rachel Neale, Queensland Institute of Medical Research, Berghofer Medical Research Institute, Australia. We also thank David Cooper, HSRU, University of Aberdeen, UK, for statistical advice; Shaun Treweek, HSRU, and Hilde Stromme, Norwegian Knowledge Centre for the Health Services, Oslo, for help locating a Norwegian publication. Funding: No specific funding was received for this study. MB receives salary support from the Health Research Council of New Zealand. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; and in the decision to submit the paper for publication.",
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T1 - Assessment of research waste part 2

T2 - wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation

AU - Bolland, Mark J.

AU - Grey, Andrew

AU - Avenell, Alison

N1 - Acknowledgements: We thank the following for providing further information about their trial or survey: Paul Atyeo, Australian Bureau of Statistics, Australia; Anne Looker, Centers for Disease Control and Prevention, USA; Briony Romero and Rachel Neale, Queensland Institute of Medical Research, Berghofer Medical Research Institute, Australia. We also thank David Cooper, HSRU, University of Aberdeen, UK, for statistical advice; Shaun Treweek, HSRU, and Hilde Stromme, Norwegian Knowledge Centre for the Health Services, Oslo, for help locating a Norwegian publication. Funding: No specific funding was received for this study. MB receives salary support from the Health Research Council of New Zealand. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; and in the decision to submit the paper for publication.

PY - 2018/10/3

Y1 - 2018/10/3

N2 - BACKGROUND: Research waste can occur when trials are conducted in the wrong populations. Vitamin D deficient populations are most likely to benefit from vitamin D supplementation. We investigated waste attributable to randomised controlled trials (RCTs) of supplementation in populations that were not vitamin D deficient.METHODS: In December 2015, we searched Pubmed, recent systematic reviews, and three trial registries for RCTs of vitamin D with clinical endpoints in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N ≥ 1000) RCTs. We investigated the proportion of RCTs that studied vitamin D deficient populations, temporal trends in baseline 25OHD, and whether investigators in large RCTs considered relevant 25OHD survey data or systematic reviews in their trial justifications.RESULTS: Of 137 RCTs of vitamin D with clinical endpoints, 118 (86%) reported baseline mean/median 25OHD, which was < 25, 25-49, 50-74, and ≥ 75 nmol/L in 12 (10%), 62 (53%), 36 (31%), and 8 (7%) RCTs, respectively. In 70% of RCTs, baseline 25OHD was > 40 nmol/L. Baseline 25OHD increased over time. Before 2006, 38%, 62%, 0% and 0% of RCTs had baseline 25OHD < 25, 25-49, 50-74, and ≥ 75 nmol/L respectively; in 2011-15, the respective proportions were 9%, 49%, 37%, and 6%. Of 12 RCTs with baseline 25OHD < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing), 1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44% (8/18) of large completed RCTs cited relevant prior population 25OHD data, and only 3/10 (30%) relevant prior systematic reviews.CONCLUSIONS: Up to 70% of RCTs of vitamin D with clinical endpoints, 71% of large completed RCTs, and 100% of ongoing large RCTs could be considered research waste because they studied cohorts that were not vitamin D deficient.

AB - BACKGROUND: Research waste can occur when trials are conducted in the wrong populations. Vitamin D deficient populations are most likely to benefit from vitamin D supplementation. We investigated waste attributable to randomised controlled trials (RCTs) of supplementation in populations that were not vitamin D deficient.METHODS: In December 2015, we searched Pubmed, recent systematic reviews, and three trial registries for RCTs of vitamin D with clinical endpoints in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N ≥ 1000) RCTs. We investigated the proportion of RCTs that studied vitamin D deficient populations, temporal trends in baseline 25OHD, and whether investigators in large RCTs considered relevant 25OHD survey data or systematic reviews in their trial justifications.RESULTS: Of 137 RCTs of vitamin D with clinical endpoints, 118 (86%) reported baseline mean/median 25OHD, which was < 25, 25-49, 50-74, and ≥ 75 nmol/L in 12 (10%), 62 (53%), 36 (31%), and 8 (7%) RCTs, respectively. In 70% of RCTs, baseline 25OHD was > 40 nmol/L. Baseline 25OHD increased over time. Before 2006, 38%, 62%, 0% and 0% of RCTs had baseline 25OHD < 25, 25-49, 50-74, and ≥ 75 nmol/L respectively; in 2011-15, the respective proportions were 9%, 49%, 37%, and 6%. Of 12 RCTs with baseline 25OHD < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing), 1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44% (8/18) of large completed RCTs cited relevant prior population 25OHD data, and only 3/10 (30%) relevant prior systematic reviews.CONCLUSIONS: Up to 70% of RCTs of vitamin D with clinical endpoints, 71% of large completed RCTs, and 100% of ongoing large RCTs could be considered research waste because they studied cohorts that were not vitamin D deficient.

KW - vitamin D

KW - deficiency

KW - sufficiency

KW - randomized controlled trials

KW - research waste

KW - fracture

KW - cardiovascular disease

KW - cancer

KW - mortality

U2 - 10.1186/s12874-018-0555-1

DO - 10.1186/s12874-018-0555-1

M3 - Article

VL - 18

JO - BMC Medical Research Methodology

JF - BMC Medical Research Methodology

SN - 1471-2288

IS - 1

M1 - 101

ER -