Almost one year ago, humanity experienced the first cases of COVID-19. At that time, nobody could have imagined the magnitude of the global consequences it would have. The COVID-19 pandemic changed our reality and influenced nearly all areas of our lives.
In the clinical research world, a lot of trial sites re-organized their activities to enhance patient safety and to stay compliant with protocol requirements. In such unpredictable circumstances, sponsor oversight on site activities became even more crucial than they were in a pre-coronavirus crisis. But one question remained: how would sponsors achieve this level of oversight if monitoring visits to healthcare facilities are significantly restricted?
In a previous contribution to MassBio’s blog, we discussed how remote monitoring could improve the quality of a sponsor’s oversight of trial sites’ activities during the COVID-19 pandemic. One aspect of remote monitoring that causes the most questions is the remote verification of investigator activities related to investigational product (IP) management.
Three Main Challenges in the Remote Monitoring of IP Management
Among the many factors that influence remote monitoring, we identified three peculiarities of IP monitoring activities that caused the most concerns.
First, IP accountability is usually associated with visual control of the IP storage conditions and counting the available IP by the monitor during on-site monitoring.
Next, IP storage (hereinafter, pharmacy) at certain sites is separated from the main site facilities, and coordinating interaction between the pharmacists and the monitor may require additional investigator efforts.
Lastly, IP accountability records and relevant temperature logs are often maintained as a combination of paper and electronic records prepared in different formats (either sponsor or site templates or their mixture). As a result, putting all of them together and converting them into a format convenient for remote sharing may be quite time-consuming.
Overcoming Challenges: Step One
Based on our experience, the most objective and informative source of information about IP management is IP accountability records. With this, main efforts are concentrated on assuring their availability without burdening the site staff.
One possible solution is the implementation of electronic IP accountability records (hereinafter, e-records) compliant with US CFR Title 21 Chapter I, Subchapter A, Part 11 “Electronic Records; Electronic Signatures.” Such e-records may contain information about IP receipt, dispense to/retrieval from subjects, IP return to sponsor, or IP destruction.
By granting remote access to the monitor for e-records on IP accountability, we enable ongoing evaluation of IP handling from the moment it is sent to the site until the moment it is fully utilized. The monitor reconciles data from the e-records with IxRS reports, CRF and trial supplies’ shipment documentation owned by the sponsor. Moreover, the monitor remotely completes IP inventory to ensure that IP supplies to the site are sufficient throughout the trial.
We understand that implementation of e-records on IP accountability may take some time. However, once implemented, this solution will help to significantly decrease time required for on-site IP accountability.
Meanwhile, until e-records are available at all sites, we need to use what we have and to do what we can do. It’s worth remembering that reviewing scanned paper records is still an option.
The first step we need to implement to enable successful remote oversight of IP management is changing our mindsets and the mindsets of Investigators. This will ensure that all involved parties understand that time spent by the site staff for remote sharing of IP accountability records with the monitor (either by scanning paper documents or granting remote access to e-records), is an obligatory step to ensure proper use of the IP which has direct impacts on subjects’ safety.
What Else Can We Do?
Another aspect that requires attention during IP handling monitoring is control of the IP handling temperature conditions.
Here, the simplest solution, in our opinion, is the centralized purchase of temperature loggers for sites with possibility to upload data to PCs for sharing with Site Monitors.
The centralized purchase and distribution of such loggers to sites not only facilitates the Monitor’s remote access to temperature records but also enables a standardized approach to IP temperature control.
Visual Control of IP and Discussion with the Site Staff
After IP accountability and temperature records are reviewed, the monitor may ask site staff for a short call and video tour of the IP location facilities in order to verify physical availability of the IP and to discuss peculiarities of IP handling and possible issues (if any). Based on our experience, such calls do not take much time if all earlier described activities are properly completed by the monitor in advance.
Mindset
Remote monitoring of IP management and site activities is crucial for ensuring proper study conduct when physical access to sites is limited. But even after the restrictions are lifted, we propose including elements of remote verification of IP management to the monitors’ routine practice long-term. This approach makes trial organization more efficient, reduces travel, and supports epidemiological safety measures by decreasing face-to-face contact. William Arthur Ward once said that “The pessimist complains about the wind; the optimist expects it to change; the realist adjusts the sails.” Let’s be realists and adjust our procedures to this current reality.
About the Author:
Tetyana Byelyayeva, MD
Head of Regional Clinical Operation Services, KCR, Trial Execution
Dr. Tetyana Byelyayeva, MD, PhD manages the Regional Clinical Operations team at KCR, the international clinical development solutions provider. Dr. Byelyayeva is an experienced clinical researcher, teacher and physician with Medical Doctor (MD) and Doctor of Philosophy (PhD) degrees in obstetrics and gynecology.
For more: https://www.kcrcro.com/