How will Brexit affect clinical trial registration and reporting in the UK?

With Brexit just over the horizon, the future framework for clinical trials of drugs and medical devices in the UK remains unclear.

NEW MEDICINES AND MEDICAL DEVICES BILL

The Medicines and Medical Devices Bill currently under discussion in Parliament would give the government sweeping powers to change the rules governing clinical trials without further legislation.

This flexibility could be used to maintain the UK’s alignment with the evolving European framework post Brexit, but the same powers could equally be used to take the UK off on a separate path – without requiring Parliamentary approval.

In a recent debate in the House of Lords, Baroness Barker reflected widespread worries over an executive power grab, warning that the Bill would confer excessive “emergency powers” on ministers to change rules by fiat.

Lord Bethell defended the Bill, arguing that:

“The Bill ensures that the legal frameworks around medical devices, human medicines, veterinary medicines and clinical trials can be updated to protect patient safety and reflect innovative practices. This is vital as negotiations on the UK’s future global relations continue… The powers will ensure that we have the flexibility to adapt our regulatory framework and that the UK retains a thriving clinical trials environment…”

Some Lords suggested a compromise solution in which the new powers would automatically expire after a set time period time, restoring control to parliament.

DRUG TRIALS VERSUS MEDICAL DEVICE TRIALS

As is common across Europe, there are separate regulations in the UK for trials of drugs (CTIMPs) and trials of medical devices.

• Companies and institutions running drug trials are already obliged to make their results public within 12 months.

• No comparable obligation to make results public exists for device trials, and other trials not involving drugs or devices, even though the outcomes of such trials can be equally or even more important to patients (example here).

NATIONAL TRANSPARENCY STRATEGY

The widely praised UK national transparency strategy released this summer seeks to strengthen transparency requirements for all interventional clinical trials to make their results public within 12 months of trial completion, irrespective of whether the trial involved a drug, a medical device, or some other kind of intervention. (The Health Research Authority, rather than the MHRA, is leading implementation of the strategy.)

However, the transparency strategy will only be fully implemented by 2022, and plans for sanctions have yet to be spelled out. Until then, the disclosure landscape for different types of trials will remain mixed.

TRANSPARENCY OF DRUG TRIALS

The UK will formally leave the European Union before the EU Clinical Trial Regulation governing drug trials comes into force. The British Medical Association has urged the government to ensure that the UK remains aligned with current and future European rules for conducting drug trials, so-called CTIMPs.

UK medicines regulator MHRA has announced that (presumably barring any last-minute agreement to the contrary with the European Union) from January 2021 onwards, drug trials will have to be registered on trial registries other than the European EudraCT:

“From 1 January 2021, you should continue to use existing and established international registers such as ISRCTN registry (UK), or ClinicalTrials.gov (USA)… Registration should occur before the first participant is recruited and no later than six weeks after recruitment of the first participant.”

The guidance makes clear that the UK will maintain existing EU trial reporting standards for drug trials immediately post Brexit. Trial sponsors will have to make trial results public on the registry (or registries) where the trial was originally registered within 12 months of trial completion.

Post Brexit, the MHRA might be able to impose sanctions on companies and universities that fail to make clinical trial results public.

According to the MHRA, the Medicines and Medical Devices Bill would:

“allow us to update UK legislation to make new transparency provisions as well as any appropriate sanctions for not complying with the new legislation. Any changes will, of course, be made following consultation.”

MHRA ACTIVELY PROMOTING TRANSPARENCY IN DRUG TRIALS

The MHRA will continue to actively follow up on trials whose results are overdue.

In a recent response to a Freedom of Information request filed by TranspariMED, the MHRA outlined its ongoing transparency efforts:

“To facilitate monitoring of publication of results, 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; however, no enforcement action is available as this is not an offence under the current legislation.”

The MHRA’s long-standing and largely successful efforts to promote trial reporting go far beyond those of some other national regulators in Europe, who appear to be doing little or nothing to promote compliance by trial sponsors.

For example, the MHRA has nearly completed its efforts to ensure that all UK entries on the European trial registry EudraCT are up to date. Regulators in many other European countries have yet to do this.

GAPS IN TRANSPARENCY OF MEDICAL DEVICE TRIALS

The MHRA is refusing to release a list of the clinical trials of new medical devices it has approved in recent years, despite government assurances that “plans are in place to make this information available to the public”.

In the wake of an independent review that flagged multiple weaknesses in medical device regulation in the UK, Minister of State Nadine Dorries informed parliament that:

"All trials of new medical devices being developed for the United Kingdom market are reviewed by the MHRA [Medicines and Healthcare products Regulatory Agency] before the devices are used on humans in these trials in the UK. The MHRA maintains a record of all such trials whether approved or refused. Plans are in place to make this information available to the public in future.”

“The MHRA only has oversight of medicines and medical devices trials and therefore do not have oversight of all non-drug trials… There is an expectation that all trials are registered and a lay summary made available on the HRA website.”

TranspariMED filed a Freedom of Information request to find out more.

In its response, the MHRA refused to provide a list of trials of new medical devices that it had approved, citing an exemption clause in the Freedom of Information Act. The MHRA declined to reveal when it plans to make this information public.

The MHRA also admitted that it does not keep track of whether the medical device trials it oversees make their results public:

“We can confirm that we do not hold the WHO primary registry numbers that you have requested. We do not detect which approved studies have made their outcomes public. We do request copies of the final reports for all approved clinical investigations.”

At the same time, the MHRA noted that the Medicines & Medical Devices Bill currently going through parliament would

“enable legislative changes to do what’s best for the UK, to support innovation and protect patients. These powers will also enable transparency to support patient safety work. Clinical investigations work will be part of these future considerations. MHRA do not have any definitive timescales at this stage.”

Approached for comment, the MHRA press office stated that:

“Currently we are required to adhere to Article 20 of the Medical Device Directive, which is restrictive on the publication of any commercial data, changing this approach to data sharing is a key priority for the Agency. Our devices division… is working hard to improve transparency, and clinical trial transparency will be a key aspect as we move forward as a standalone regulator.”

Till Bruckner, founder of TranspariMED, said:

“The government should make good on its promise to parliament and release basic identifying data on past and present medical device trials involving UK patients. Since 2013, sponsors have had to commit to register every clinical trial run in the UK on a public registry anyway, so providing basic information on these trials would not raise any concerns about commercial confidentiality.”