Half of clinical trials of medicines in Europe violate new transparency law

Half of all drug trials in Europe fail to report results as required by law, a new study has found.

Of 234 drug trials that had become due to report results, only 116 had reported results on time. A further 20 trials reported results late, and 98 trials completely failed to make substantive results public.

New law widely ignored

Under a law that came into force in 2022, pharma companies and universities running clinical trials of medicines in Europe are obliged to make their results public on the European CTIS registry within 12 months of trial completion.

The study provides an early snapshot of legal compliance and medical evidence gaps by looking at the fate of the first 234 clinical trials for which results should have been made available on CTIS, the new European trial registry.

(The CTIS registry currently contains more than 8,400 relevant clinical trials, but the vast majority are still ongoing or have only recently been completed.)

“The results came as a nasty surprise to me, and probably to people at the European Medicines Agency too,” said Till Bruckner, founder of TranspariMED and lead author of the study.

“The agency has put a lot of effort into helping companies and universities to understand and operate the new system. I expected to find a handful of trials that had fallen through the cracks. Instead, our team discovered that less than half of trial results had been made public as required.”

Patients and public health at risk

Failures to make clinical trial results public harm patients and undermine public health because they leave potentially dangerous gaps in the medical evidence base.

• In one notorious case, tens of thousands of patients died because the dangers of a new class of drugs were detected too late.

• In another case, billions of Euros in public money were (mis-)spent on a largely ineffective drug because the results of multiple ‘failed’ trials had remained hidden from regulators and health agencies.

  
  

A surprise finding of the study was that some sponsors had uploaded documents that did not actually contain results.

“We found 47 ostensible results documents on CTIS that did not report data for all primary outcomes, did not state how many people had participated in the trial, or both,” Till Bruckner said.

“Some of the documents were tragicomical. In some cases, we could not even tell whether any patients had been recruited. It appears that researchers were able to upload literally any junk in PDF format because regulators never checked what was inside those PDFs.”

 Image source: MedRxiv

(In future, the European Medicines Agency plans to require results to be uploaded in a structured numerical format, but the agency has not yet announced by what date the new system will be in place, or whether the data submitted will undergo quality checks.)

EMA pledges to take action

In an official statement responding to the study, the European Medicines Agency pledged to take action:

“When results are missing, it means this legal obligation has not been met... Transparency of clinical trial information is a priority and the European medicines regulatory network is:

• Adding the number of trials with a summary of the available results to the quarterly reports on the performance of the EU clinical trials environment...

• Supporting sponsors directly through improved guidance...

• Taking measures to improve the monitoring functionalities in CTIS and to support the timely submission and publication of clinical trial results in the system...

• Reminding sponsors via the National Contact Points to fulfil their legal obligations...”

Will national regulators impose fines?

“Based on past experience, I am optimistic that the European Medicines Agency will deliver on its promises,” Till Bruckner said. “But two big question marks remain. First, will regulators check to ensure that results documents do not contain junk? Second, when will the first national medicines agency fine a company for breaking the law?”

The EU Clinical Trials Regulation has been integrated into national legislation in all EU Member States, so national medicines regulators across Europe now have legal powers to sanction pharma companies and universities that fail to upload clinical trial results.

In a follow-on study, researchers will send each of the 30 national regulators a list of the unreported trials they are responsible for and ask them when and how they plan to enforce the law.

Stay tuned.

The study “Assessing Compliance with Reporting Requirements in European Phase II–IV Clinical Trials: A Cross-Sectional Observational Study” is available open access as a preprint. The study protocol contains an exhaustive discussion of CTIS rules and functionalities that other researchers may find useful. All data and code have been archived online.

Till Bruckner (ORCID) is currently doing a postdoc supervised by Gustav Nilsonne at Karolinska Institutet in Sweden. This research project was funded by the European Union (MSCA-PF 101152904).