Nick DeVito and Ben Goldacre

Background

The US FDA Amendments Act (FDAAA 2007) requires certain clinical trials to report their results onto ClinicalTrials.gov within one year of completion. Our FDAAA TrialsTracker shows all individual trials that breach this legal requirement. Once a week, we write about one unreported clinical trial: you can read more background here.

Trial NCT01576783

This week’s unreported trial is titled “Omega Tots: A randomized, controlled trial of long-chain polyunsaturated fatty acid supplementation of toddler diets and developmental outcomes” (NCT01576783). This Phase 4 trial enrolled 307 preterm babies (gestational age <35 completed weeks) at a corrected age of 10-16 months. The study was randomized and blinded for all participants, care providers, investigators and outcomes assessors. The experimental intervention was omega fatty acid supplementation (DHA+AA); the control group was given a corn oil placebo. DHA is an omega 3 fatty acid and AA is an omega 6 fatty acid. The primary outcomes were: subject retention; adherence to treatment; and change in plasma and RBC fatty acid concentrations. The secondary outcome was change in the Bayley Scales of Infant and Toddler Development. Twelve “other outcomes” are also listed, focusing on various developmental measures including language development, body composition, behaviour, executive function, and sleep.

Clinical Discussion

As discussed in a previous unreported clinical trial of the week, an estimated 8.6% of births are preterm across the developed world. Preterm babies are at higher risk for neurodevelopmental issues related to the outcomes measured in this study.

A systematic review and meta-analysis published earlier this year examined trials of omega-3 supplementation in mothers and infants (with or without omega-6 supplementation). The authors found a positive effect for performance on the Bayley mental development index (MDI) in preterm babies given Omega-3 supplementation and concluded omega 3 supplementation of mothers or babies “improves childhood psychomotor and visual development, without significant effects on global IQ later in childhood, although the latter conclusion is based on fewer studies.”

Interestingly, the authors of that systematic review explicitly note that their analysis found evidence for publication bias related to Bayley MDI outcomes: this makes the publication of additional evidence, such as the large unreported trial under discussion today, particularly important. Of note, another study examining fatty acid supplementation by the same PI was published earlier this year, but results were not posted to ClinicalTrials.gov: however that trial was not covered by the FDAAA 2007 Final Rule requirements as its primary completion date was in 2015.

Legislative Discussion

We intend that this series should occasionally shed light on interesting issues around transparency rules, and how registry data is used. You can read some general background about the FDA Amendments Act 2007—and why a trial is considered “due”—here and here.

This unreported trial provides an interesting opportunity to review the different reporting requirements for different classes of trial outcome under the FDAAA 2007. The law requires that studies are due to report results within 12 months of the “Primary Completion Date”, which is defined as the last data collection point, for the last subject, for the primary outcome. According to the trial record, this unreported trial reached its primary completion date in April 2017. This means that all results on primary endpoints—as well as any completed secondary endpoints—should have been reported by April 2018. The trial is currently estimated to reach its study completion date for all endpoints in July 2018, meaning that all subsequent outcomes will need to be reported by July 2019.

Lastly, it is notable that the FDAAA 2007 requires day, month, and year for completion date, while this unreported trial gives only month and year. Complete dates are an important part of accurate compliance procedures and are required to be updated by law.

Conclusion

This unreported trial was sponsored by the study PI, Sara Keim, PhD of Nationwide Children’s Hospital in Columbus, Ohio. The Allen Foundation Inc., March of Dimes, Cures Within Reach And the Health Resources Services Administration are listed as collaborators. As of 2 July 2018, this trial is 63 days overdue to report. We hope the investigators will share the results of this unreported trial soon.

 

Ben Goldacre is a doctor, author, and director of the EBM DataLab at the University of Oxford. He co-founded the AllTrials campaign for trials transparency.

Competing interests: BG has received research funding from the Laura and John Arnold Foundation, the Wellcome Trust, the Oxford Biomedical Research Centre, the NHS National Institute for Health Research School of Primary Care Research, the Health Foundation, and the World Health Organization; he also receives personal income from speaking and writing for lay audiences on the misuse of science.

Nicholas J DeVito is a researcher at the EBM Datalab at the University of Oxford.

Competing interests: ND is employed on BG’s LJAF grant and is a Naji Foundation Scholar at the University of Oxford.