UK MHRA: COVID-19 To Spark Rise In Clinical Trial-Related Deviations
Executive Summary
The UK’s Medicines and Healthcare products Regulatory Agency says that any increase in clinical trial protocol deviations in relation to coronavirus outbreak will not constitute a serious breach.
The UK medicines regulator says it expects to see a rise in protocol-related deviations in ongoing clinical trials as a result of disruptions caused by the COVID-19 outbreak, which the World Health Organization declared a pandemic on 11 March.
The Medicines and Healthcare products Regulatory Agency has clarified that any increase in protocol deviations in relation to coronavirus “will not constitute a serious breach” and should not be reported to the agency, unless there is a risk to patients. Companies should ensure that all deviations are well documented to enable appropriate evaluation for the trial, the agency said.
The MHRA said it was aware of challenges arising in relation to coronavirus and the effect this was having on the conduct of clinical trials. As a result of the outbreak, patients may be advised to stay away from hospitals and GP sites, or they may be reluctant to travel or they may be advised to self-isolate, which may result in them being unable to undertake required clinical trial activities. In addition, organizations managing and sponsoring clinical trials may be experiencing a higher proportion of staff working from home during this period.
“This has led to reports of protocol and standard operating procedure deviations due to missed visits, or changes in processes… Wet-ink signatures have also been difficult to obtain in a timely manner if staff are not in the office, and this can delay some clinical trial processes,” the MHRA said.
To manage the situation, the agency suggests that companies should consider:
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- Reassessing certain oversight duties in hospital settings, such as monitoring and quality assurance activities, and introduce alternative proportionate mechanisms of oversight, such as phone calls, video calls etc, to ensure ongoing subject safety and well-being. The MHRA recommends a brief risk assessment and documentation of the impact of this, with consideration of prioritization of critical activities such as safety reporting.
- Introducing remote monitoring while ensuring this does not place an extra burden on trial sites. The trial subjects should consent to sharing of their personal information outside the trial site.
- Adopting alternative methods of demonstrating approvals (in place of wet-ink signatures) such as email confirmation. The MHRA said its inspectors would take a pragmatic approach to this, but companies should consider a standard operation procedure (SOP) deviation to cover this in the interim.
Prospective Protocol Waivers Unacceptable
Disruptions by COVID-19 can also impact recruitment to ongoing trials. In this context, the MHRA clarified that it remains strictly opposed to “prospective protocol waivers,” which are memos that sponsors sometime issue allowing a trial site to enrol a patient who does not meet all inclusion or exclusion criteria, or to give a site pre-approval to deviate from protocol-defined visit windows.
The UK regulator told companies that prospective protocol waivers are unacceptable as “we would not expect you to bypass the eligibility process due to difficulties in assessing subjects and carrying out tests.” Similarly, if the safety of a trial subject is at risk because they cannot complete key evaluations or adhere to critical mitigation steps, then consideration to discontinuing that subject must be discussed.
The MHRA noted that the sponsor and investigator have the authority to use “urgent safety measures” or even temporarily halt a trial, or halt recruitment, where necessary. Companies must ensure that any temporary halt, including for logistical reasons such as trial team unavailability, needs to be submitted as a substantial amendment to ensure the MHRA has complete oversight.