The COVID-19 pandemic has resulted in unfortunate disruptions of some clinical trials. The Medicines Healthcare and Products Regulatory Agency (MHRA) has published guidance outlining various actions that Sponsors should take in order to build resilience into clinical trial design and help avoid future disruptions for the benefit of trial participants.
The actions include:
The creation of Standard Operating Procedures with training/guidance to staff covering, for example, telemedicine; direct-to-patient supply of the Investigational Medicinal Product (IMP); and the capture of data from remote home visits where necessary.
To support the move to decentralization of clinical trials, Sponsors should set up vendors and conduct due diligence on providers, including home care providers.
In order to reduce the need for substantial amendments to the clinical trial authorization, Sponsors should:
- include a shelf life extension proposal in the IMP Dossier;
- reduce the complexity of the protocol; for example, consider what endpoints are really needed to answer the research question and build flexibility into the protocol;
- consider digital/virtual elements in a study; and
- where clinical visits are unavoidable, ensure they are consolidated and include social distancing requirements.
A risk-based approach is supported by the MHRA, including the documentation of protocol deviations. Deviations that have an impact on participant safety and the reliability of results should be identified, documented, and taken into account when the data are analysed. Minor protocol deviations identified can be documented at a trial level, rather than an individual level.
A risk assessment should be performed by the Sponsor in order to determine if and which trial modifications are necessary to protect trial participant safety and minimise impact on study integrity, and should include assessment of the impact of the pandemic on:
- participant enrolment over time;
- adherence to study treatment and use of concomitant medication;
- ability to monitor and report safety data;
- ability to monitor/verify source data for critical parameters; and
- validity of the methods for measuring primary (or surrogate for the primary endpoint) and secondary endpoints, if measured differently than what was originally intended.
The sponsor should implement a risk-based monitoring program to identify and prioritize at the onset the most important information to be collected, in order to assess the primary endpoint(s). It also helps ensure that key data can be reviewed to meet the study completion deliverables.
The review of ongoing clinical trials in this context and also completing these actions for future clinical trials should speed up trials generally, as well as reduce disruptions for patients and improve trial integrity.
