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. European Union (EU) guidelines are broader: they require all trials of medicinal products registered on their EU Clinical Trials Registry (EUCTR) since 2004 to report results within one year of completion. Our FDAAA TrialsTracker and EU TrialsTracker show all individual trials that breach these legal requirements. Each week we write about one unreported clinical trial: you can read more background here, and past entries are here.

This week’s trial
This week’s unreported trial is: “Effect of gabapentin as symptomatic therapy for cerebellar ataxia in degenerative and inflammatory CNS-disease” (2008-005167-33). This trial was also registered in the German Clinical Trials Register. The trial planned to enroll 72 participants with inflammatory (multiple sclerosis) or degenerative ataxia: it was randomised, placebo controlled, and double blinded. The intervention group received gabapentin 300 mg. The primary endpoint was the change in the SARA scale (an ataxia score) from enrollment to week seven. Secondary outcomes were: effect of treatment on oculomotor incoordination measured by video nystagmography at seven weeks; and quality of life measured by the United Huntingtons Disease Rating Scale.

Clinical discussion
It is estimated that 80% of MS patients suffer from ataxia. The prevalence of hereditary ataxia is highly variable and, as with late onset idiopathic cerebellar ataxia, is not well defined. Gabapentin is currently approved primarily for treatment of seizures and neuropathic pain; this study examines if gabapentin could also be of benefit in the treatment of ataxia. As ataxia has numerous causes and presentations, treatments for the disease are diverse and differ in what symptoms they aim to address.

Legislative discussion
Trials from the EU Clinical Trials Register will be regularly discussed in this series on unreported studies: it is therefore useful to set out how we ascertain whether trials are “unreported” and “overdue.” This issue is covered in detail in our recent BMJ paper, which showed that around half of all trials on the EU register have breached EU reporting guidelines: however, the above trial presents a simple example.

From December 2016 onward, any trial registered since 2004 is required to report results within 12 months of completion (and sooner for certain trials, such as those conducted in children). Establishing whether a trial is “complete,” and its completion date, is not entirely straightforward, because the register contains a record for each individual country in which each trial was conducted, and there can be different dates and trial statuses for each country. To be conservative, and avoid incorrectly identifying trials as breaching, we only regard a trial as “completed” if it is listed as “completed” in every country.

Next we need to check the date on which the trial completed. This is available via the “Date of the global end of the trial” field. This field is supposed to only be available when the trial has completed in every country, and should therefore match for every country: unfortunately, again, this isn’t always the case. Once again, we take a conservative approach: we use the latest date available, to assess whether a trial completed more than 12 months ago, and is therefore due to report results. If no date is provided, we cannot assess whether the trial is due to report, and so we put the trial into a third category of “trials with inconsistent data.”

Finally, we exclude phase 1 trials that do not involve a “paediatric investigation plan,” as these are excluded from the EU rules on reporting results.

By checking the relevant data fields in the entry for today’s unreported trial we can see that it was conducted in a single country (Germany), and is listed as “Completed” with a “Date of the global end of the trial” more than one year ago in that protocol (“2016-03-31”, as you can see in Section P of the registry entry). Lastly, we can see that this is a phase 4 trial (Section E.7.4, if you’re very interested!). Since this trial meets all the criteria of the EU rules, we can be confident that it is covered by the EU rules, and should already have reported its results directly onto the EU Clinical Trials Register. Sadly, the sponsor has not done so.

Conclusion
Sponsors are responsible under European rules for ensuring that their trial results are reported and compliant. They are also responsible for ensuring their registry data is accurate, and current. This unreported trial is sponsored by the Charité University Medicine Berlin. It completed on 31 March 2016. No PI is listed on the trial record. We hope our EU TrialsTracker will help organisations identify and fully report their trials onto EUCTR and that the sponsor will report the results of this 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.