Belgium: What does the new clinical trial transparency law say?

lAn estimated 228 drug trials in Belgium are currently missing results.

Most major Belgium sponsors now appear to be working to fix the problem, with strong support from their national medicines agency. However, at least one major sponsor - CHU de Liège - has still made no progress whatsoever.

What can the Belgian medicines agency do in future when trial sponsors neglect to make their results public?

WHAT DOES EUROPEAN LAW SAY?

The EU Clinical Trial Regulation, which came into force in January 2022, clearly states that:

“Irrespective of the outcome of a clinical trial, within one year from the end of a clinical trial in all Member States concerned, the sponsor shall submit to the EU database a summary of the results of the clinical trial.” – Article 37(4)

WHAT DOES BELGIAN NATIONAL LAW SAY?

The EU Regulation was integrated into Belgian national law with the 2017 Loi relative aux essais cliniques de médicaments à usage humain.

The national medicines regulator FAMHP is responsible for applying the law. (Articles 5, 41 and 42)

[Note: FAMPH is also known as AFMPS or FAGG, depending on whether you prefer your acronyms in English, French or Flemish.]

Possible sanctions include a fine between 500 and 250,000 Euros, and a prison sentence between one month and two years.

The law explicitly states that these sanctions apply to violations of the results reporting requirement, alongside many other requirements set out by the EU regulation (Article 44).

For repeat offenders, the maximum penalties are a fine of 500,000 Euros and a three year prison sentence (Article 45, §1). In addition, a judge can ban repeat offenders from participating in clinical trials for three to ten years (Article 45, §7).

HOW WILL FINES BE IMPOSED?

The new law (Article 46) explicitly states that in the case of violations, the provisions set out in Article 17 of the 1964 Loi sur les medicaments apply.

Regulator FAMHP has the option of dealing with legal violations by offering the offender to settle the case under the 1964 law.

Essentially, FAMPH “proposes” that the offender pays a fine, the amount of which is set by FAMPH.

• If the offender pays the fine, FAMPH drops the issue. (However, the crown prosecutor may decide to take the case to court anyway.)

• If the offender refuses to pay, FAMPH hands over the case to the crown prosecutor.

The maximum fine that can be imposed is doubled if a similar offense has been committed by the trial sponsor during the three preceding years.

Under the 1964 law, the employer has to pay the fine (Article 17, §4). This means that pharma companies, universities and hospitals are financially liable. Individual researchers do not have to pay fines.

HOW WILL VIOLATIONS BE DETECTED?

According to information that FAMPH provided to a journalist:

“In practice, if an infringement is observed for clinical trials submitted under the Law of 7 May 2017, an observation will be made by a Good Clinical Practices inspector of the FAMHP, who can then draw up a PV of observations. This PV, together with the inspection report, is sent to the offender and the FAMHP official jurist (i.e. the head of the Legislation and Litigation Division).”

“The official jurist can then, in consultation with the inspection, propose an amicable settlement to the offender (for a minimum amount of 4,000 EUR, being the minimum amount of the fine multiplied by the applicable surcharges). If the offender does not accept the out-of-court settlement, the Public Prosecutor may initiate further proceedings.”

STRENGTHS AND WEAKNESSES

Belgium’s law contains strengths and weaknesses.

Strength: There is an efficient process for imposing fines.

Belgium’s regulator will have the ability to fine clinical trial sponsors that fail to make public the results of drug trials without having to go through the courts. This is important because regulators may be reluctant to enforce trial reporting laws if that involves a time-consuming legal process.

Weakness 1: The Belgian law only covers drug trials, not all clinical trials.

The law exclusively applies to Clinical Trials of Investigative Medicinal Products (CTIMPs) as defined by the European regulation (Article 2). From a patient perspective, it makes no sense to require transparency only for drug trials, but not for medical device trials.

Belgian lawmakers failed to seize the opportunity to introduce transparency requirements for all clinical trials. (There is nothing to stop any EU Member State from adopting transparency rules that go beyond the minimum required by European regulations.)

In contrast, the American disclosure law applies equally to (some) drug and device trials. The UK now plans to introduce a legal requirement to make the results of all interventional clinical trials public, regardless of whether they involve drugs, devices or other treatments such as surgery and physiotherapy.

In addition, the Belgian law only covers drug trials registered on the new European CTIS trial registry since January 2022. Therefore, it does not apply to already completed CTIMPs whose results are currently overdue.

Weakness 2: The process for identifying violations appears inefficient.

According to FAMPH, if an infringement is observed, an inspector can note this in an inspection report. This appears to be similar to the flawed system adopted by the American FDA, which only takes action if a violation is detected during a so-called BIMO inspection. FDA enforcement to date has been extremely slow. Even though over 3,000 clinical trial results are missing in the United States, the FDA is currently only sending out two notices per week.

FAMPH’s apparent reliance on inspections is strange. The new European CTIS trial registry will presumably allow the regulator to rapidly and efficiently identify all violations by Belgian sponsors and take immediate action to address these, rather than waiting for case-by-case inspection reports.

NEW SERIES: FROM EU REGULATION TO NATIONAL LAWS

This is the first post in a new TranspariMED series that will map out how the EU Clinical Trial Regulation has been integrated into national law by key European countries.

Since the end of January 2022, making public the results of drug trials has become a legal requirement across the European Union.

However, EU Member States individually integrated that requirement into their own national laws, at different times and using different processes. In addition, each Member State individually decided how it was going to enforce that rule, and set out the sanctions that can be applied if results are not made public.

TranspariMED’s series aims to clarify what these new rules are and how they will be enforced, and to identify ways in which national transparency systems can be strengthened.