Research Integrity Update - Feb 2024

Our Research Integrity Team at the Bennett Institute has recently published two new papers related to our ongoing TrialsTracker work. We wanted to share a brief overview of both papers, their main takeaways, and where you can find the full-text to read more!

What is the utility of the EUCTR?

The first paper, published in BMJ Medicine, builds on our prior work examining the EU Clinical Trials Register (EUCTR). The EUCTR has grown substantially as a repository for results of clinical trials since we first started our EU TrialsTracker in 2018. This work sparked hearings in the UK and an international advocacy effort to improve compliance with EU trial reporting guidelines which has paid dividends. As of this month the EU TrialsTracker shows just under 85% of all trials we can assess as “due” as having results.

We therefore thought it would be useful to quantify the utility of the EUCTR as a results repository. After all, even with the arrival of the new CTIS registry, the EUCTR archive will contain registrations for nearly 44,000 trials of which 23,000 currently have a result attached to them. It would be useful for anyone with an interest in efficiently searching, and collecting, the results of clinical trials, such as researchers conducting evidence synthesis, to know if the EUCTR is worth checking. Prior work on ClinicalTrials.gov had shown that for many trials registered there, the results submitted to the registry are the only public version of results that exist.

To do this we identified completed trials, and trials that look like they should have completed but had incomplete data on the EUCTR. This left us with around 25,000 trials. We then sampled 500 trials and began searching for results. We checked the EUCTR, ClinicalTrials.gov, the ISRCTN, and the literature for results using a comprehensive search strategy. If we found evidence a trial never happened, we replaced it in the sample.

We found that 383 trials (77%) had results somewhere we looked. Results appeared on the EUCTR (53.2%) at about the same rate as they appear in the literature (58.6%). Among those 383 trials with any result, 55 (14%) were only available on the EUCTR, while 28.2% were only available in a journal publication. For those trials also registered on ClinicalTrials.gov, only 3 only had results available on that registry. Results also generally appeared on the EUCTR as quickly as the literature.

Overall, the EUCTR seemed to reliably contain the timely results of European-based clinical trials at rates commensurate, or better than, other common dissemination routes. So what does this mean? We believe this is good evidence that the EUCTR should be specifically recommended in guidance to systematic reviewers, such as the Cochrane Handbook. The database will not only contain some results not available elsewhere, but also may increase the efficiency of searches for results compared to standard literature searches. However, given the amount of trials with no results (n=117) or with results elsewhere but not on the EUCTR (n=117), there is a clear indication that things could be even better. The European Medicines Agency, and EU/EEA member states, should take care to ensure the new CTIS registry improves on the standard set by the EUCTR and take full advantage of the powers granted to them in the new EU trial regulations to penalise noncompliance.

Trials transparency at UK public research institutions.

As we mentioned earlier, our EU TrialsTracker tool had quite an impact in the UK when it first launched. The House of Commons Science and Technology committee, headed by MP Norman Lamb, sent letters to all UK Universities and NHS Trusts, at the time still beholden to EU rules, urging them to improve their compliance. This sparked a wave of activity in the UK trials space. Institutions began addressing their backlog of unreported trials and the Government committed to support increased transparency efforts including the launch of the HRA’s Make It Public Campaign.

Given this attention to the trial reporting space, and the upcoming changes due to Brexit, we conducted a qualitative interview study with research governance and management personnel from throughout the UK. The results were published in the journal Health Policy.

We spoke to 14 research governance and managerial staff across 11 institutions in England, Scotland and Wales about how transparency of clinical trials was managed, tracked, and perceived at UK public universities and NHS trusts. This provided interesting insights into these processes and highlights both best practices, and barriers, to ensuring clinical trials are registered and reported.

Some of our key findings from this work were:

• Despite widespread agreement on the value of transparency, the issue became most salient following the attention from the SciTech Committee. This raised the profile of the issue within institutions and made it a priority to address. However, some were sceptical as to whether this would lead to sustainable change.
• Improving communication with researchers, setting up better, documented policies and processes for oversight and record-keeping, and centralising oversight of transparency issues were common actions taken by research support offices.
• Research offices are tasked with a multitude of responsibilities, and therefore managing transparency responsibilities is most focused on those trials that are covered by legislative or regulatory mandates. While there was a desire to be more holistic, often time resource constraints, due to a lack of funding for core governance activities, forced administrators to prioritise and triage.
• Interviewees identified a number of networks and resources they are useful to them in sharing knowledge, keeping up-to-date on changes in the space, and asking questions. These networks were cited as particularly useful in dealing with technical frustrations, for instance around the use of the EUCTR/EudraCT portal.

Using EU reporting compliance as a barometer, the UK was far and away the European leaders in trial reporting. We believe it is valuable to understand and document the processes that these institutions undertook to reach that status, their motivations for doing so, and what issues they faced. Many of the steps described in this work may be transferable to other institutions and research governance personnel can examine the feasibility of these changes to their own contexts to improve transparency practice.

As always, if you have any comments or questions about our work, feel free to email us at bennett@phc.ox.ac.uk.