Nick DeVito and Ben Goldacre
Today we describe a trial that reported late, in breach of the FDA Amendments Act 2007. This late reporting is especially notable, because the FDA themselves are a collaborator on the trial in question. The FDA can impose a fine of $10,000 a day for every overdue or unreported trial, and today’s trial was left unreported for 82 days. The FDA issuing (or not issuing) fines on a trial for which they are a collaborator raises interesting issues around conflict of interest.
During the writing of this piece, the sponsor submitted results to ClinicalTrials.gov on 11 December 2018. Under the FDAAA requirements to report within 1 year of the primary completion date, it was 82 days late to report. Although we usually focus on unreported trials, we felt this trial still warranted discussion given the collaborator and topics involved. While results have been submitted (very late) the quality control process for this submission means it will likely be a month or more before actual results are available on ClinicalTrials.gov.
We have previously explained how the law views journal publications, rather than registry reporting. A journal article detailing this trial was published in 2017. This publication does not meet the FDAAA 2007 reporting requirements. The law requires sponsors to post results directly onto the register, and for good reason: while journals have repeatedly been shown to breach reporting guidelines such as CONSORT, registry reports require you to give data on all prespecified outcomes. The published evidence to date shows that registry reports are more complete than journal publications.
ClinicalTrials.gov shows an actual enrollment of 16 participants; the journal article states 26 were enrolled and treated.
The ClinicalTrials.gov entry lists the trial status as “Completed” while the article states that “the study was halted after a planned interim analysis.” This means it should be listed as “Terminated” with the rationale for termination provided on ClinicalTrials.gov.
The primary outcome, measuring exacerbations between the two arms, match. The secondary outcomes, however, do not match. The paper reports “the effect of each immunosuppressive therapy on ADAMTS13 biomarkers in the context of clinical response criteria” while the registry lists the “number of exchange procedures to achieve clinical remission and the relapse rate after tapering the adjuvant immune-based therapy.” This was a long-term outcome, so it may have been impossible to measure, given the termination of the study: but this is not addressed in the manuscript (CONSORT requires all outcome switches to be flagged and explained). Meanwhile ADAMTS13 biomarker measures are reported in the paper, but never mentioned in the registry entry (again, CONSORT permits additional non-prespecified outcomes, but only if they are flagged as such, and explained).
These discrepancies above show the importance of a properly maintained registry entry along with full reporting of results, on the register, in accordance with the law. It is concerning that the FDA, the organisation in charge of ensuring compliance with the whole of the FDAAA 2007, is the funder of research that has failed to meet registration and reporting requirements.
This late reporting trial was sponsored by Ohio State University in collaboration with FDA. The PI is Dr. Spero R Cataland. As of 11 December 2018, this trial submitted results 82 days late and will likely not be available for public viewing until well over 100 days after it was due to report results, and more than 465 days after it completed.
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.