Assessment of research waste part 2: wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation

Alison Avenell,Andrew Grey,Mark J Bolland

doi:10.1186/s12874-018-0555-1

Abstract

BackgroundResearch 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.MethodsIn 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.ResultsOf 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.ConclusionsUp 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.

Highlights

Research waste can occur when trials are conducted in the wrong populations
We set out to determine what proportion of Randomised controlled trial (RCT) of vitamin D supplementation with clinical endpoints has been conducted in vitamin D deficient populations, and whether baseline 25-hydroxyvitamin D (25OHD) in such RCTs have changed over time
Baseline 25OHD in randomised controlled trials From 4682 unique Pubmed records and 38 systematic reviews, we identified 779 publications from 547 RCTs of vitamin D, of which 137 (111,976 participants) reported a clinical endpoint in the Abstract (Additional file 1: Tables S1, S2, S3 and Figure S1)

Summary

Introduction

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. In the first report [2], we focused on redundant research characterized by the undertaking and publication of uninformative observational studies and randomised controlled trials (RCTs) with surrogate endpoints long after the need for large RCTs with ‘hard’ clinical endpoints was established. In this second report, we address waste characterised by conducting RCTs in poorly targeted population groups. We determined whether investigators reported relevant systematic reviews in their trial justification, as recommended [1, 12]

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Discussion

Conclusion