Many European regulators still fail to take action on missing clinical trial results

Hidden medical evidence harms patients, but many European regulators still claim that they have no power to improve trial reporting - which is simply not true.

In fact, several national medicines regulators in Europe are already successful at improving compliance with reporting requirements and preventing reseach waste.

This blog presents examples of regulatory failures and regulatory successes from across Europe, and a look into the future of trial regulation.

EXAMPLES OF REGULATORY FAILURES

The European Medicines Agency and the Heads of Medicines Agencies have clearly and publicly stated that clinical trial sponsors are obliged to make the results of their drug trials public.

However, regulators in some countries appear to have failed to inform trial sponsors of their obligations.

• Italy. A large Italian university recently (incorrectly) told TranspariMED that uploading trial results was the responsibility of the Italian regulator AIFA, rather than the university's own responsibility. This misperception suggests that AIFA has done little to explain the rules to the Italian institutions it is responsible for regulating. Not surprisingly, Italian universities' transparency record is terrible.

• Scandinavia. This summer, a coalition of health and integrity groups led by TranspariMED wrote to 56 universities and hospitals around Europe flagging their weak reporting performance and encouraging them to fix the problem. Two Scandinavian universities replied that they will now start fixing the problem. Apparently, their national regulators had never informed them that they were breaking the rules. Reporting rates in both of those countries remain low.

• Germany. Also this summer, TranspariMED contacted two small pharmaceutical companies in Germany and Luxembourg on Twitter, noting that they had failed to report their trial results. In both cases, the companies immediately promised to resolve the issue; one company has already uploaded several results. To date, the two German regulators have not directly contacted trial sponsors in violation of transparency rules. Leaving advocacy groups to chase down non-compliant pharma companies on social media seems an unwise regulatory strategy when patient safety is at stake.

EXAMPLES OF REGULATORY SUCCESSES

National regulators in the UK, Austria and Denmark actively engage with trial sponsors. Trial sponsors in these three countries have far better compliance rates than the European average.

Directly contacting sponsors (MHRA, Britain)

"MHRA systems upgrades over the past year means that individual cases raise a flag where no record of results posting has been received in the expected timeframe following notification of the end of trial. These cases will be followed-up and our Good Clinical Practice (GCP) inspectorate colleagues informed where a response is not forthcoming.”

“Our GCP inspectors will review compliance on inspection, as they do currently. If issues are found on inspection, a finding is given, and corrective and preventative action is required by the sponsor to address the shortcoming."

Round tables with major sponsors (BASG, Austria)

Austria's BASG hosts bi-monthly round tables with major trial sponsors and other stakeholders to support their compliance with regulations, and to help them to prepare for the day the EU Clinical Trial Regulation fully comes into force.

According to one participant, these round tables have helped to foster trust between the regulator and sponsors. All parties now work closely together to jointly overcome challenges and improve compliance..

Carrots and sticks for trial sponsors (DKMA, Denmark)

Denmark's DKMA developed a manual and other guidance for researchers on how to upload results onto the European trial registry. In addition, DKMA systematically follows up with trial sponsors that fail to make results public.

In addition to assisting trial sponsors, DKMA also holds them to account. The regulator recently announced that it will direct the public prosecutor to prosecute trial sponsors that continue to violate transparency rules. Sponsors that fail to report results risk fines, and may even get sent to prison for up to four months.

Cleaning up registry data (MHRA, Britain)

Thousands of completed trials are incorrectly marked as 'ongoing' on the European trial registry. The MHRA launched a systematic clean-up operation to fix the problem. Today, nearly all drug trials conducted in the UK are listed on the registry with their correct status and accurate completion dates.

Listening to non-commercial sponsors (EMA, Brussels)

Many national regulators seem to never have sat down in a room with universities to discover why they find uploading results so difficult. Last year, the European Medicines Agency (EMA) set a positive example by meeting a group of non-commercial trial sponsors in Berlin and listening to their concerns. Over the following months, EMA removed a lot of the technical obstacles that trial sponsors had complained about, facilitating compliance across Europe.

PREPARING TO ENFORCE THE LAW

When the EU Clinical Trial Regulation fully comes into force in late 2021, it will become legally binding in all EU Member States.

At that point, national regulators in all European countries will finally have a firm legal basis for issuing fines and other sanctions against companies and institutions that fail to make clinical trial results public.

Regulators will only be able to use their new powers effectively if they prepare the ground now:

1. Develop a mechanism for detecting violations

2. Develop a process for following up on violations (sending warning letters etc)

3. Draw up a detailed sanctions catalogue

4. Develop a mechanism for routinely and efficiently issuing fines for violations

5. Create a plan for dealing with persistent or repeat offenders

REQUIRING ALL TRIALS TO MAKE THEIR RESULTS PUBLIC

There is nothing to stop individual EU Member States from adopting clinical trial transparency requirements that exceed European standards.

The EU Clinical Trial Regulation only covers some drug trials (so-called CTIMPs). Trials of medical devices are - and will continue to be - subject to far weaker transparency requirements, and other non-drug trials are not subject to any transparency rules at all on the European level.

For example, the results of a small trial of a new drug that never makes it to the market have to be made public, but it is legal to hide from the public the results of a large trial of a pacemaker that has already been implanted into tens of thousands of patients.

Regulators should encourage policy makers in their countries to study the UK's national transparency strategy.

The UK strategy will require the results of all interventional clinical trials - drug trials, device trials, and any other trials - to be made public within 12 months, overseen by a government agency that will routinely monitor compliance.

Regulators do not have the power to write laws, but they should help those who write the laws to ensure that every clinical trial is registered and fully reported - without exceptions.