What are European drug regulators doing to promote clinical trial reporting?

Four health groups have written to national drug regulators in ten key European Union countries to ask about their efforts to promote clinical trial reporting, and their legal powers to curb rampant medical research waste.

The letters explain to regulators that the groups seek information on:

“Regulatory strategies. Over 3,300 due CTIMP [drug trial] results are still missing on EudraCT [the European trial registry] because sponsors are not meeting their disclosure obligations. In this context, we seek to provide an overview of what NCAs [national drug regulators] are doing to remind sponsors of their obligations and to encourage and support compliance specifically regarding due CTIMPs missing results on EudraCT.”

“National legislation. In January 2022, the EU Clinical Trial Regulation fully came into force. National legislation should now require clinical trial sponsors in your country to make the results of some or all clinical trials public as per Article 37(4). National legislation should also specify the penalties for the infringement of the Regulation, as per Article 94. In this context, we seek to provide an overview of how the Regulation has been integrated into national legislation and NCA sanctioning processes. We also seek to provide an overview of national legal and regulatory reporting requirements for interventional clinical trials that are not CTIMPs.”

“Enforcement mechanisms. We seek to provide a detailed overview of how, in practice, NCAs plan to enforce reporting requirements for CTIMPs (and if applicable for non-CTIMP clinical trials).”

The letters were sent as part of a new joint initiative by Health Action International, the Transparency International Global Health Programme, Universities Allied for Essential Medicines (UAEM) Europe, and TranspariMED.

Regulators’ responses will eventually feed into a report providing a cross-country overview of the regulatory landscape for clinical trials and regulatory best practices in all ten countries, thereby contributing to improving the transparency and effectiveness of relevant regulation in Europe.

In the meantime, regulators’ responses will be posted in full on the TranspariMED website – so keep tuned to this blog.

Below the list of regulators contacted and the full set of questions.

List of regulators

The groups contacted the 11 national medicines regulators in the 10 European countries with the largest number of missing trial results as identified by DeVito et al 2021:

• Austria

• Belgium

• Denmark

• Finland

• France

• Germany (two regulators: BfArM and PEI)

• Italy

• Netherlands

• Spain

• Sweden

Eleven questions to national regulators

The letters asked regulators to provide detailed answers to the following 11 questions:

Regulatory strategies (questions apply to CTIMPs registered on EudraCT only)

Question 1: How many CTIMPs for which you are the NCA currently lacking results on EudraCT in violation of reporting obligations? Please break down the figure into (a) paediatric and (b) adult trials. If current data are not available, please provide the latest available data, and the date on which those data were collected.

Question 2: What steps have you taken to ensure that all completed clinical trials are accurately marked as completed and/or their correct completion dates added to the trial protocol on EudraCT?

Question 3: What steps have you taken to date to encourage and/or support sponsors’ compliance with their reporting obligation on EudraCT? For example, have you contacted investigators or sponsors over missing results, or provided guidance or training on results reporting?

Question 4: What steps are you planning to take during 2022 to encourage and/or support sponsors’ compliance with their reporting obligation on EudraCT?

National legislation

Question 5: What national laws and/or regulations incorporate the CTIMP reporting requirements set out in the EU Clinical Trial Regulation, Article 37(4)? Please provide the exact name and applicable article(s) of all relevant laws and regulations.

Question 6: What national laws and/or regulations define the penalties for infringements of the EU Clinical Trial Regulation, as set out in Article 94? Please provide the exact name and applicable article(s) of all relevant laws and regulations.

Question 7: Going forward, what penalties will you be able to impose for infringements of CTIMP reporting requirements? Please specify the penalties, for example the maximum fine(s) that you will be able to impose.

Question 8: Are there legal and/or regulatory requirements to make the results of interventional clinical trials that are not CTIMPs (including medical device trials and non-drug trials) public? If yes, please provide the exact name and applicable article(s) of all relevant laws and regulations.

Enforcement mechanisms

Question 9: Going forward, what are the mechanisms for detecting infringements of CTIMP reporting requirements? For example, will you detect infringements using CTIS data and/or GCP inspections? Please describe the detection process in detail, step by step.

Question 10: Going forward, what are the mechanisms for imposing penalties for infringements of CTIMP reporting requirements? For example, will you impose penalties immediately when an infringement has been detected, or will you first issue a warning notice? Will you be able to impose penalties directly, or will you have to go through the courts to impose penalties? Please describe the penalty imposition process in detail, step by step.

Question 11: If there are legal and/or regulatory requirements to make the results of interventional clinical trials that are not CTIMPs public [see Question 8], please outline in detail which (a) mechanisms for detecting infringements and (b) mechanisms for imposing penalties you are currently using and/or plan to put into place going forward.