How will national regulators in Europe impose fines for missing clinical trial results?

In late 2021, national medicines regulators will get clear legal powers to impose fines and other sanctions on European companies and institutions that fail to make the results of their drug trials public. In this blog, TranspariMED's legal analyst Muhammad Dwistaraifa Rasendriya explains the legal context and how the process will work.

LEGAL BACKGROUND

The EU Clinical Trial Regulation obliges clinical trial sponsors to submit the result of their drug trials to the Clinical Trials Information System (CTIS), a new European trial registry due to be launched in late 2021.

As is already the case with the existing registry, sponsors will be obliged to make the results of drug trials public on the new registry within 12 months of trial completion (Article 37(4)). In the case of trials involving children, the timeline is 6 months.

The Regulation has already been in force since May 2014. However, the Regulation will only be fully applied once CTIS goes live in late 2021.

As soon as that happens, as with other European Union regulations, the Clinical Trial Regulation will immediately and automatically become directly applicable domestic law in all EU Member States (Article 288 TFEU).

(TranspariMED note: The new CTIS will not immediately replace the existing European EudraCT registry. Sponsors will continue to be obliged to upload the results of trials already registered on EudraCT onto EudraCT. From late onwards 2021, sponsors will have to register newly launched drug trials onto CTIS, and later report the results of those trials on CTIS. See this blog for more details.)

PROCESS FOR DETERMINING FINES

The Regulation explicitly requires all EU Member States to legislate on penalties for the infringement of the Regulation (Article 94).

Therefore, each country will decide how it will act when drug trial results are not uploaded on time, and what sanctions it will impose. There is no strict timeline for making these decisions, given that the Regulation is automatically binding regardless of what individual countries do.

The general trend is that Member States adopt legislation soon after a Regulation is passed (which in this case was in 2014), even before it comes into force (late 2021 in this case). For example, parliaments in the Netherlands and Belgium passed acts incorporating the General Data Protection Regulation (GDPR) into national law before it came into force at the European level. However, the approach could be very different in other EU Member States.

As a rule of thumb, when it comes to determining fines, European countries do so through a parliamentary act.

For example, a national parliament may draft a law that exactly mirrors the EU Regulation, and then add a few extra elements like the maximum fine for violations. Alternatively, a parliament may simply amend an existing law. As each Member State has its own legislative system, there is likely to some variation in the process. For example, in some countries, fines might be introduced via decree or regulatory decision; these would not require new legislation or parliamentary approval.

HOW HIGH WILL THE FINES BE?

While the Regulation explicitly requires Member States to adopt penalties for violations of the Regulation, Member States are free to decide which penalties to impose.

Presumably, most countries will opt to impose financial fines, but at least one country – Denmark – seems prepared to also impose prison sentences.

Because the Regulation is vague on the nature of penalties, Member States might only adopt a maximum penalty for any violation of the Regulation, rather than precisely defining penalties specifically for failing to make clinical trial results public.

(TranspariMED note: This appears to already have happened in Belgium, which has reportedly adopted a blanket 350,000 Euro maximum fine for any violation of the Regulation. Such non-specific penalties are suboptimal because they do not provide national medicines regulators with a clear legal and administrative pathway for imposing sanctions on sponsors that fail to upload trial results. To use an analogy, such laws give regulators a big stick, but no guidance about when and how to use it.)

WHEN WILL NATIONAL REGULATORS TAKE ACTION?

The power to oversee and enforce the Regulation lies with EU Member States, specifically with the national medicines regulators within each country. (The ‘National Competent Authority’ for each country is listed here).

These national regulators are empowered by the Clinical Trial Regulation to inspect the trial sponsors in their country (Article 78) and enact corrective measures (Article 77).

Thus, the enforcement of clinical trial reporting requirements in each country will depend not only on the exact legal framework, but also on how proactive national regulators are.

WHAT IF NATIONAL REGULATORS FAIL TO ENFORCE THE LAW?

The European Commission has the duty to ensure the application of European law in all Member States (Article 17 TEU) and supervises the enforcement of the Regulation by the national medicines agencies.

If Member States do not comply with the law, the Commission has the power to initiate an infringement procedure (Article 258 TFEU). In this procedure, the Commission first notifies the infringing Member State with a so-called ‘Reasoned Opinion’, giving the Member State the opportunity to reply and come into compliance. If the Commission is still unsatisfied, it can bring the infringing Member State before the Court of Justice of the European Union. If the court finds that the Member State has indeed infringed the law, it can impose a fine for every day that infringement continues (Article 263 TFEU).

TranspariMED comment

While there are some positive outliers – notably the UK’s MHRA before Brexit, and Denmark’s DKMA – many national regulators have so far neglected to promote transparency in clinical trials.

TranspariMED regularly encounters sponsors across Europe that are willing to do the right thing, but that do not even know that they should be making their trial results public on EudraCT because their national regulator never contacted them about this. (How hard can it be to write a few hundred letters?)

A 2012 European Commission guideline states that:

“Member States should verify that for clinical trials authorised by them the result-related information is posted to the Agency. Clinical trials for which no result-related information has been posted 9 months after the end of the trial for paediatric trials or 15 months for other trials will be flagged. This information will be publicly available.”

TranspariMED is not aware of any national medicines regulators that have made this information publicly available.

Going forward, TranspariMED and allied groups will step up their advocacy with national regulators across Europe and demand that they finally take action to safeguard patient interests and ensure that sponsors make all clinical trial results public as required by law.