How compliance with results posting is tracked
How far sponsors meet the duty to post trial results is checked by studies that measure how many results go unreported, by public trackers that list each sponsor's missing results on the US and European registers, and by regulators who remind and contact the sponsors that fall short.
How far results go unreported
A 2016 study determined how many clinical trials that leading US academic medical centres had registered on ClinicalTrials.gov were published or had their results reported within two years of completion. Of 4,347 interventional trials identified across 51 centres between October 2007 and September 2010, results were disseminated for 2,892 (66%), and for 1,560 (35.9%) within 24 months of study completion. The study found poor performance and noticeable variation in the dissemination of results across the centres, and concluded that additional tools and mechanisms were needed to rectify the lack of timely reporting and publication, which impairs the research enterprise and threatens to undermine evidence-based clinical decision-making.
In a 2018 cohort study, compliance with the requirement to report results on the EU Clinical Trials Register was 50% over the year to 21 December 2016.
The head of a medical communications company held in 2018 that the pharmaceutical industry is better at disclosing the results of clinical trials than most other groups, academic, governmental and charitable research funders among them. Research he conducted with colleagues showed that nearly three quarters of industry-sponsored trials are disclosed, against less than half of non-industry trials. In his account, disclosure of the trials supporting drugs approved by the FDA and the European Medicines Agency is better still, typically 100%, and pharmaceutical companies consequently perform well in the recently launched FDAAA Trials Tracker from Ben Goldacre and the Oxford Centre for Evidence-Based Medicine, which measures compliance with the US FDAAA legislation. He explains the gap by industry being used to working in a highly regulated environment and meeting its legal and ethical commitments by deploying appropriate internal and external resources, professional medical writers and project managers in communications companies among them.
Public trackers
By June 2017 the TrialsTracker, built on ClinicalTrials.gov data, was running online on the EBM DataLab's site under the title "Who's not sharing their results?". Users could rank sponsors by the number of trials with missing results, the number of trials conducted and the proportion missing, and open a sponsor's record to see the number and proportion of its trials completed and reported in each year.
By December 2018 two trial trackers publicly monitored, as live informatics tools, whether the results of completed trials were entered on time: one for the trials relevant to FDAAA 801 and its Final Rule in the NIH database, the other for trials in the European register. The European tracker was then fully established, searchable by sponsor and showing the percentage of trials due to report that had reported.
The EU Trials Tracker, built by the Evidence-Based Medicine DataLab at the University of Oxford, lists by sponsor every interventional trial in the EU Clinical Trials Register. After it was published, the clinical trial disclosure group of one contract research organisation saw a surge of requests from clients, as the medical writer heading the group reported in 2019. The European Medicines Agency neither built nor monitors the tracker, but by then it was using it to contact sponsors directly, at the last contact details in the register, to tell them either that results were due, more than a year having passed since the global end of trial date, or that their data were inconsistent: sites listed as completed with no global end of trial date, a global end of trial date with some sites still listed as ongoing, or a blank trial status. Where the agency reached the right people, there was much surprise at how many sponsor studies were without results in the register. The Evidence-Based Medicine DataLab also built the FDAAA Trials Tracker, which lists by sponsor applicable trials, those beginning after 18 January 2017, and probable ones, beginning before and ending after that date. The FDA itself was not publicly tracking compliance. The head of the contract research organisation's disclosure group expected the effect of the trackers to be seen for some time to come, as more sponsors became aware of them and could see where they were non-compliant.
Reminders to sponsors
In mid-September 2018 the European Medicines Agency said it was compiling a report listing the sponsors on the European register that were not compliant with results posting requirements, planned for publication in September 2018, and would contact those sponsors individually.
Reporting clinical trial results in the European database is the direct responsibility of sponsors, and on 3 July 2019 the agency and the Heads of Medicines Agencies issued a joint letter reminding sponsors of their responsibilities. The letter particularly mentioned under-reporting by non-commercial sponsors and linked to resources that all stakeholders may find useful in meeting their reporting obligations.
In 2019 an editorial highlighted the shortfall in results reporting on trial registries by universities in Europe. It encouraged university triallists to take the lead in making the uploads and suggested that registries could send automated email reminders.