Publications

1. Perform initial risk assessment, and schedule regular risk review, monitor facts about the epidemic.
   If you are just about to start your project, it is strongly advice to do risk assessment. It may lead you to the conclusion to postpone the trial for some period of time, better prepare for challenges, and secure backups of processes. It does not mean you should stop all activities. You still may work on the study set up: protocol, study documentation, qualification of vendors etc. If your study is ongoing this is crucial to reassess the risks and maintain regular review of evidence-based risks.
2. Study a country context of your trial, diverse the location of the research sites
   Although we have a pandemic situation, you still may select the countries that suits better for you study in terms of not only the logistics, but also your protocol indication, and specific design. Diversity of countries may be a key since the situation is dynamic, however it also generates logistic issues (transfer of samples, IMPs, etc.).
3. Prepare a Risk Mitigation Plan and Contingency Plans
   Having plans do not guarantee 100% success, but when new challenge would come – for most of them you will be prepared and will not act in panic.
4. Implement risk-based management and monitoring process
   This risk-based approach, that is becoming more and more popular, sims to be the best in terms of cost effectiveness especially for certain types of studies. In the time of pandemic this approach should be broaden to as many as possible cases of trials. You may consult your risk-based approach to monitoring with you regulatory authority to get some additional ideas and gain more confidence on methods you are going to implement.
5. Whenever possible prepare for implementation of remote monitoring techniques in a broad scale for a certain period of time
   In case you challenge the situation that research sites no longer allow your monitors to visit them, it seems to be the best solution to introduce remote monitoring. Of course, you may delay few visit, and create some backlog, however in such case you lose the oversite on your trial in a difficult time of pandemic. See also recommendation form MHRA
6. Educate thoroughly your staff
   Being well informed for your staff is a key for operations. This is not only how to behave to avoid infection, but also to understand the broad picture of the coronavirus i.e. what the scale of the problem when compared to other diseases or risks, who is at high risk of complications and who is not, which information is evidence based and which is an exaggeration done by social or other media.
7. Secure your study supplies
   This is always necessary to have back up suppliers but during pandemic you need to have a double back up in your risk mitigation and contingency plan including alternative materials if not possible to deliver originally intended for use.
8. Consider decentralization of some processes
   Due to logistic problems you may for example consider such approaches as decentralized, central laboratory. This means a net of regional laboratories having the same identical set up, standard, validation of equipment. Also, QA/QC activities may be decentralized – use of local Project Managers or Line Managers for quality assessment visits, as well local auditors to perform audits at research sites in particular country without traveling to distant locations.

Clinical trial during the pandemic is a challenge for all stakeholders, but with all their engagement, including Patients, and Regulatory Authorities it may be successful. Regulatory Authorities are aware that they may expect more protocol deviations related to patients compliance (rescheduled visits, etc.), some alterations in procedures if not possible to perform the original, due to lack of specific supplies. This of course need to be properly justified and documented, but if not significantly influencing the data integrity, should be accepted.

Author: Michał Ławniczak, DMD, MRQA

Head of Clinical Consulting w CLINMARK – Clinical Research and Consulting