Clinical Trial Protocol Amendments / Deviations

Sponsor (Q): I need to make amendments in the protocol specified procedures to avoid potential exposure of subjects to COVID-19 infection. Patient safety will be compromised if we wait for the amendment to be approved by IRB/IEC. What shall I do?

Zifo (A): Protocol amendments having significant impact on safety of subjects can be implemented prior to IRB/IEC approval! But do ensure that the approval can and should be obtained post-facto.

Sponsor (Q): In order to ensure that the subjects enrolled in the trial are not infected by COVID-19 while the study is ongoing, it is mandatory to perform Screening Assessments related to COVID-19 during enrolment. I don’t think I can wait till the protocol amendment is done.

Zifo (A): No, it is not necessary that you need to wait. COVID-19 related Screening Assessments can be performed in the trial without amending the protocol.

Sponsor(Q): After lot of deliberations we decided to proceed with the first follow-up through a telephonic visit. This has worked out well with Adverse Events but not much luck with Vital Signs and ECG. Should we capture this deviation at study-level or subject-level?

Zifo (A): Any deviation from the planned course of study due to COVID-19 needs to be recorded at subject-level, summarized and submitted to FDA. Moreover, capturing the deviation at study-level is not advisable, since it can only be listed and not summarized at subject-level.

Informed Consent Form

Sponsor (Q): The ICF process requires an oral communication with the subject and a signed consent for study participation. In this case we would have to call the subjects to the clinical site, discuss with them and get the ICF signed. How to proceed the ICF signature process with the subject during this quarantine?

Zifo (A): Avoid requesting subjects/participants to visit sites, instead you can use other sources to send the ICF document to the client and get their signature. If needed, Video conferencing of ICF explanation involving the subject, investigator and a third-party witness to authenticate the ICF signature is recommended.

Sponsor (Q): We started a Phase III trial on neuropathic pain, and we are in recruitment phase. Due to the ongoing COVID-19 pandemic, it is not possible to get the ICF signed from the new subjects. How can we proceed with this?

Zifo (A): Yeah, ICF is highly critical for subjects to participate in any clinical trial. If the Informed consent form (ICF) cannot be sent to the site, the photo of the attested and signed ICF can be used as a valid ICF document. It is not mandated to comply the conventional methods for obtaining ICF. There are ‘n’ number of validated platforms where we can get the electronic consent signed from subjects. We can use these systems to get the e-consents signed from the subjects directly from their home.

Technology in Clinical Trials

Sponsor (Q): We have ongoing trials in which several subjects are in treatment phase. Sites are closed, and it is not always possible for the subjects to come to clinic for IMP refills. How do we ensure the treatment compliance during this pandemic?

Zifo (A): Home delivery of IMP from sites using online logistics systems can be used. Note that, IMP from sites can be shipped only if it does not require specific storage and handling conditions.

Sponsor / Monitoring CRO (Q): Few of our studies are approaching Database Lock next week. However, there are travel restrictions due to COVID-19 lockdown, and source documents are unable to be transported. Also, monitoring team could not commute to site to perform Source Data Verification. This could delay our submission timelines. How can we perform SDV in this scenario?

Zifo (A): The delay due to SDV completely makes sense. But you can request the sites to support remote monitoring – including remote clinical review and SDV by transferring the source documents electronically with general safety practices. Hope this helps to meet the timelines.

Sponsor (Q): With the current COVID-19 situation, it is unfeasible for subjects to come to the site for visits within the protocol specified window. Is there an alternative to conduct these visits seamlessly?

Zifo (A): Virtual Video Visits using HIPPA-certified online meeting rooms can be used. And, there are few features worth exploring. For instance, you can link the visit dates with the online meeting rooms which will serve as reminders.

Have any thoughts or questions on this? Please email us at info@zifornd.com