Putting the Squeeze on Trial Reporting Failings in Europe

Growing evidence of deficiencies in clinical trial reporting in Europe has impelled the authorities to—somewhat dilatory—action, and discussions on how to improve the situation are now beginning among national regulators, the European Medicines Agency and the European Commission.

The move was prompted by a recent letter from transparency and health campaigners that documented widespread failures by trial sponsors to meet the requirements for reporting results. This alleged that more than 4,000 clinical trials of medicines—nearly a third of all trials undertaken in Europe—are missing results on the European trial registry, in violation of long-standing transparency rules. The University of Amsterdam has run 195 drug trials, but marked only 14 as completed—and posted results for none of them. Germany, France, Italy and Spain also stand accused of regulatory inaction, with data from EMA in late 2019 showing that results were missing for over 500 applications linked to drug trials involving children in those countries.

The letter, to the Heads of Medicines Agencies—the national regulators in the EU, urged the creation of a process to ensure that national competent authorities adopt and implement common minimum standards for promoting sponsors’ compliance with clinical trial results reporting requirements. "Despite significant improvements in sponsor compliance in recent years, thousands of due clinical trials are still missing results," it said. "The persistent failure of many sponsors to meet their obligations indicates that the European medicines regulatory system is currently neither effective nor efficient," it continued. It suggested that even minimal engagement by national authorities could rapidly improve sponsors’ compliance rates.

The Heads of Medicines Agencies have now confirmed that they discussed the letter, and there was wide recognition of "the importance of the sponsors fulfilling their obligation to make trial results public." However, the responsibility under European law lies with each national regulator, and “HMA is not in a position where the organization can impose standards on the national competent authorities.” So, it promised to "reach out to the European Commission and the European Medicines Agency with a view to initiate joint actions to improve clinical trial sponsors’ compliance."

TranspariMED, a civil society organization that has played a leading role in tracking non-reporting, welcomed the HMA engagement, while urging it to immediately provide a forum for national regulators where common standards could be developed for following up on unreported trials. Till Bruckner, founder of TranspariMED, said his organization "hopes that HMA will now actively work towards the creation of a regulatory system that no longer idly stands by when rules are broken, taxpayers’ money is wasted, and patients’ interests sidelined.”

He added that some national medicines regulators are already acting. He cited Denmark and Austria as recent examples where attention has led to significant improvements in trial reporting. But he raised questions over how energetic the authorities were being in Germany, France, Italy, Spain, the Netherlands, Belgium and Ireland. Bruckner says that the failings often result from ignorance among sponsors of the reporting requirements, and that national authorities could achieve some easy improvements simply by issuing alerts: many regulators are not even contacting those that break the rules, let alone enforcing compliance. “Running a single clinical trial can cost millions of Euros, but that money is wasted if the results are never made public. Is it really too much to ask regulators to send out a few hundred reminder letters to prevent valuable medical knowledge from being lost forever?” he asked.

The pressure for change is backed by Cochrane. It's Karla Soares-Weiser pointed out that without access to reliable information from all clinical trials, the evidence base on which to make judgements is incomplete—which "limits the scientific community’s ability to learn from research findings and can lead to patients being harmed.” Bettina Ryll, founder of Melanoma Patient Network Europe, another signatory to the initial letter to HMA, said that protection of future patients is being neglected, and "regulators must stop turning a blind eye."