How to Manage Clinical Trials During the Coronavirus Pandemic

The scale of the challenge posed by the coronavirus pandemic to the Sponsors and Investigators of clinical trials only continues to increase with the implementation of a UK-wide lockdown.

Fortunately, the MHRA aims to be "as pragmatic and flexible as possible with regards to regulatory requirements for clinical trials" during this period, although the safety of trial participants remains the MHRA's first priority.

Details of what the MHRA expects of those engaged in clinical trials during the pandemic are set out in new guidance issued last week. Here are our five key takeaways from the guidance:

• In some circumstances it will be acceptable to deliver the Investigational Medicinal Product ("IMP") to a trial participant's home.
  
  This decision should be made following a risk assessment that is recorded internally. As long as this decision does not impact on participant safety and participant consent has been obtained, no substantial notification amendment to the MHRA will be required. The following are some of the questions which the MHRA asks be taken into account when coming to the decision:

- Storage Requirements - Does the medicine have any particular storage requirements? How will these be addressed during posting? Should a temperature monitoring device be used during transport?

- Delays in Posting - Would delays have the potential to affect continuity of supply?

- Medicine Accountability - What mechanism will be used to confirm trial participants have received the IMP? Should the IMP be sent "signed for" or by courier?

- IMP Administration - Do any of the trial participants require training in order to administer the IMP safely and correctly?

• The MHRA will support the remote monitoring of clinical trials where appropriate.
  
  If remote monitoring is being considered, the guidance asks Investigators and Sponsors to think about a number of matters, including:

- Issues around confidentiality if there will be access to patients' Electronic Health Records away from the current trial site.

- The need to obtain consent from each trial participant before any associated identifier leaves the trial site and to ensure that trial participants are assured that their confidentiality will be protected.

- Avoiding the need for clinical staff to take on the extra burden of scanning and uploading of documents during this period of extreme pressure for the NHS.

- The use of alternative means of oversight such as teleconferences and videoconferences.

• Phone calls may be used instead of in-person visits.
  
  Where possible, it is acceptable to use calls instead of protocol-directed in-person study visits. The MHRA confirms that this will not be a serious breach of the protocol and no substantial amendment to update the protocol will be required. However, any such protocol deviation should always be well documented internally.
  
  

• The MHRA anticipates an increase in protocol deviations that do not constitute serious breaches.
  
  Protocol deviations are to be expected as a result of: 

- patients being asked to avoid medical facilities due to the risk of infection; patients' reluctance to travel to areas with high population densities; and 

- patients being under the requirement to self-isolate.

Although these deviations should be well-documented internally, the MHRA confirms that an increase in protocol deviations due to coronavirus will not constitute a serious breach unless patients are being put at risk.

• Prospective protocol waivers remain unacceptable.
  
  The eligibility process cannot be bypassed due to issues around assessing trial subjects and carrying out tests. The MHRA strongly stresses that patient safety is the number one priority and therefore patients should not be recruited into a clinical trial unless they meet the inclusion and exclusion criteria. Sponsors and Investigators should be aware that if the safety of a trial subject is at risk because they cannot complete key evaluations, or adhere to critical migration steps, then discontinuing that subject's involvement must be discussed. If the concern around patient safety extends to all subjects, then serious consideration should be given as to whether the entire clinical trial, or recruitment, should be postponed or suspended.
  
  

Comment

There are no easy answers to many of the challenges which the sector is facing at this time, particularly by those responsible for structuring, managing and regulating clinical trials in the UK. However, this further guidance from the MHRA on what is expected of sponsors and investigators is a welcome development, as well as the MHRA's commitment to being as pragmatic and flexible as possible during these unprecedented times.

At VWV we are assisting a number of organisations across the pharmaceutical supply chain in dealing with legal and regulatory issues posed by the coronavirus.

If you would like to get in touch with us please contact a member of our Pharmaceuticals and Life Sciences team, or complete the form below.