FDA/EU/MHRA/TGA Clin monitoring suggestions COVID
There are several suggestions, recommendations from different health authorities for sponsors to handle clinical trial aspects during this very challenging time of COVID. Most of them recommended not starting any new studies for time being. For the ongoing studies, below is the compilation from their documents pertaining to Clinical monitoring of ongoing studies:
Remote monitoring for trials
We support remote monitoring where appropriate but consider the following:
- Direct access to patients EHR (Electronic Health Record) away from the site creates issues around confidentiality. Consider where this access takes place, for example will CRAs (Clinical Research Associates) be accessing records in an open plan office, public space or other location where others who are not authorised could view sensitive information
- Trial participants will need to consent to any identifiers leaving the site and be assured that their confidentiality will be protected
- It is likely that there will be increased pressures on clinical staff during this period, so it is important to make sure that extra burdens are not placed on investigators around scanning and uploading many documents.
- The use of alternative means of oversight such as teleconferences/videoconferences is encouraged
Replacing in-person visits with phone calls
Using phone calls instead of protocol-directed in-person study visits is acceptable where possible. This will not constitute a serious breach of the protocol. A substantial amendment to update the protocol will not be required. We would however expect that any protocol deviations are well documented internally.
Changes to monitoring
Certain sponsor oversight responsibilities, such as monitoring and quality assurance activities need to be re-assessed and temporary, alternative proportionate mechanisms of oversight may be required. The extent of on-site monitoring, if it remains feasible, should take into account national and local restrictions, the urgency (e.g. source data verification can often be postponed) and the availability of site staff, and should only be performed as agreed with investigator sites. The burden of the introduction of any alternative measures for the site staff and facilities should also be considered in order to strike an acceptable balance between appropriate oversight and the capacity of and possibilities at the site.
Possible temporary, alternative measures could include:
- Cancelling of on-site monitoring visits and extending of the period between monitoring visit
- Implementing phone and video visits (without unnecessarily increased burden to the investigator site and taking into account trial participant integrity)
- Adapting the on-site monitoring plan when it is impossible to follow, supplementing it with (additional/increased) centralised monitoring and central review of data if possible and meaningful.
Results of adjusted monitoring/review measures should be reported to the sponsor in monitoring reports and in the clinical study report.
It is essential that robust follow-up measures are planned and ready to be implemented when the situation is normalised. This should likely include increased on-site monitoring for a period that is sufficient to ensure that the impact of the reduced monitoring could be rectified and problems resolved or properly documented for reporting in the clinical study report.
So-called remote source data verification (e.g. providing sponsor with copies of medical records or remote access to electronic medical records) is currently not allowed in most member states as it might infringe trial participants’ rights. In addition, provision of redacted/ de-identified pdfs files will not be acceptable as it puts disproportionate burden on site staff.
Nevertheless, since the corona virus emergency situation and containment measures are likely to last for a prolonged period, several NCAs have started to look into possible, temporary solutions related to remote access and conditions for such, providing that methods can be used that restricts access to trial participant records, in line with the principles of necessity and proportionality. This should however also be clarified with other relevant authorities in this area (such as, without limitation, Ethics Committees and data protection agencies) and is consequently not allowed unless a member state has given specific guidance allowing this.
Since trial participants may not be able to come to the investigational site for protocol-specified visits, sponsors should evaluate whether alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for assessment, including local labs or imaging centers) could be implemented when necessary and feasible, and would be sufficient to assure the safety of trial participants. Sponsors should determine if in-person visits are necessary to fully assure the safety of trial participants (for example to carry out procedures necessary to assess safety or the safe use of the investigational product appropriately); in making the decision to continue use or administration of the investigational product, the sponsor should consider whether the safety of trial participants can be assured with the implementation of the altered monitoring approach.
If planned on-site monitoring visits are no longer possible, sponsors should consider optimizing use of central and remote monitoring programs to maintain oversight of clinical sites.
Site monitoring visits
- Remote monitoring visits are encouraged as the first option in all cases and sponsors and institutions should ensure that these are facilitated, taking into account the need to avoid undue burden on hospital or institutional resources. These arrangements must adhere to patient confidentiality protocols already in place. Remote source data verification may be done electronically as long as appropriate security arrangements either are or can be put in place.
- If remote monitoring visits are not feasible, then clinical research associates may continue to undertake on-site monitoring visits as long as they are not symptomatic, have not returned from overseas in the last 14 days or had contact with a known case of COVID-19, in accordance with the most current public health guidance and advice from jurisdictional health departments.