The UK’s medicines regulator MHRA is refusing to publicly identify clinical trials in which serious breaches of the protocol or Good Clinical Practice rules have been detected.
The MHRA is responsible for monitoring compliance with these rules in clinical trials of drugs in order to provide “assurance that the rights, safety and well-being of subjects are protected and that the results of [clinical trials] are credible.”
According to MHRA documents, a breach is classified as serious if it:
“is likely to effect to a significant degree:
a) the safety or physical or mental integrity of the subjects of the trial; or
b) the scientific value of the trial”
Examples of serious breaches include events that directly affected patient safety, underreporting of suspected unexpected serious adverse reactions, and concerns about data integrity.
(See here and here).
Companies, universities and NHS Trusts running trials are obliged to notify the MHRA within seven days of becoming aware of any such breach.
Following a warning earlier this year that clinical trial inspection reports were not being made public in the Unites States, TranspariMED filed a Freedom of Information request with the MHRA to check whether comparable documents are publicly accessible in the UK.
In its response, the MHRA explained that it had been notified of 87 serious breaches of Good Clinical Practice (GCP) during 2018, and that MHRA had performed 92 GCP inspections in the same year. (Only a small minority of breaches trigger an inspection; most inspections are routine and not linked to reports of breaches.)
The MHRA refused to identify which trials were affected by breaches, and refused to provide copies of its GCP inspection statements for those trials.
According to the MHRA, this information “is exempt from release” under section 44 because it would:
“[D]irectly breach our obligations of confidentiality… any information obtained for regulatory purposes… is a confidential matter between MHRA and the parties concerned… As section 44 is an ‘absolute’ exemption, there is no requirement to consider the balance of public interest.”
Experts have argued that access to information about serious breaches would have numerous benefits:
Journal editors could independently assess elements of trial quality in publication decisions
Systematic reviewers, meta-analysts and authors of clinical practice guidelines could take these reports into consideration
Funders and institutions could adopt preventative and corrective measures
Other regulators, including the European Medicines Agency, could use this information to inform their own decision-making
Sharing information on trial quality issues could support harmonization in assessments and actions across regulatory agencies
Till Bruckner, founder of TranspariMED, said:
"With hundreds of clinical trials of potential COVID-19 treatments now underway, regulatory transparency is more important than ever. Without access to this information, public health decision-makers, doctors, and patients will be unable to assess the reliability of evidence, potentially exposing patients to ineffective treatments that may do more harm than good."
Compared to medicines regulators in other countries, the MHRA generally has a strong reputation for transparency, especially when it comes to clinical trials.
For example, the MHRA has strongly supported efforts to improve drug trial reporting by UK universities, and was the first national regulator to systematically improve the quality of data on the European clinical trial registry EudraCT.
TranspariMED is considering requesting an internal review of the MHRA’s decision to withhold information on serious breaches and related documents.