To date numerous guidances, blogposts, webinars have been published addressing what one must and cannot do in the process of clinical evidence collection due to the COVID-19 pandemic (for overviews see here and here), and with this post I have no intention repeating that, but rather want to focus on the things we CAN do and actually use this downtime to increase the quality of our clinical evidence base.
With my medical device background, I cannot help but address the fact that following the Coronavirus pandemic the MDR date of application is likely to be delayed with one year (mind you, the IVDR DoA still stands, with an even bigger clinical evidence challenge, or quoting Erik “another crisis in the making”), and as (hopefully) known, an important activity concerns (re)assessment and updating your device clinical evaluation(s). The extension of the deadline does not only give you more time to do a better, more thorough, job updating your clinical evaluation report(s) (after all, literature and database searches, and writing can still be done), but also, if recently discovered that your (accessible) clinical evidence base is too small (maybe the equivalence did not work out that well, or the available clinical data of the equivalent device is not as good as expected, or…, basically something you should have assessed much earlier), it gives you more time (3-6 months or so, also see below) to collect and process your own clinical data on the safety & performance of your device, and depending on the specific situation in a pre- or post-market setting.
Over the years I have been mentioning that the clinical investigation start-up process is like getting a baby, didn’t I? Roughly the study start-up process will take 9 month from conception (idea) to birth (FPI) (anything faster thumbs up!), so when near to, or in the process of initiating a clinical trial, now is the time for a thorough discussion (video, phone, e-mail, …) with your (candidate) study PI’s, steering committees, etc, on the details of your study design and endpoints, write-up the corresponding documentation, and initiate the applicable EC/ IRB, R&D Committee, Competent Authority approval routes.
In absence of the usual pressure to get that done (in the current situation every-one including management will understand that FPI takes more time than usual), you now can take the time needed, thereby enhancing quality and reducing mistakes, and consequently the number of protocol amendments with related consequences in the course of the study.
Indeed, in the current situation EC & CA review takes more time than usual due to coronavirus trial priorities and people involved working remotely, but everyone is getting used to it by now, and the process is still ongoing (actually even better since processes are more tweaked towards fully digital submissions instead of using paper), so there is nothing to keep you from submitting your clinical trial package for review.
If well timed, you will be ready for study kick-off as soon as the pandemic is under control.
Excluding coronavirus related trials, the execution of clinical investigations and specifically patient enrolment has come to a grinding halt, and several companies actually put their trials for that reason on hold.
Provided there is study personnel available, however, participant visits can be converted from a physical visits into a phone or video visit. In times like these study participants tend to be even more open to (extra) attention, and by phone you will be able to capture key parameters, obviously not with the details as when the subjects are on site, but for sure you will capture big events (Safety!), and with a little luck some other key parameters on your study, while also keeping the participants engaged for the remainder of the study when it picks up speed again when the pandemic is under control.
In addition, this to my opinion is also THE moment to apply and gain experience with risk-based and centralized monitoring. As mentioned in my preceding blog on this topic, options for remote SDV are limited, especially when there is no dedicated study personnel able to give insights into study participant source data, but partially due to the fact that there will be little to no new data coming in, the timing for the other aspect of it centralized monitoring, i.e. checking for consistency, data completeness & trends, identification of sites with high (or low for that matter) PD and AE rates, is excellent. So review and (internally) discuss your study data and follow-up with the concerning sites, if possible, now, or otherwise right after the coronavirus downtime is over, thereby enhancing the quality of your data.
Being in the wrap-up phase of your clinical investigation, on-site close-out visits will hardly be possible at the moment, but (provided you have digital study files) you can still prepare for it by performing a TMF reconciliation, making sure all files are in order at sponsor’s as well as site’s end when performing the on-site close-out visit after the coronavirus downtime is over. Alternatively, when the reconciliation shows the files are in order, and site data review is finished, you could consider performing the close-out by phone.
In case you are in the ‘fortunate’ situation that final (or interim for that matter) and clean study data are available, you can also use the downtime to prepare the final/ interim study report and publication, and subsequently ensure the applicable regulatory bodies submissions/ notifications are done. The latter is still a neglected child as I unfortunately know from experience, in spite of the fact that (timely) reporting of the study results is an ethical and scientific duty partially imposed by GCP standards. So what better way to use this clinical evidence collection downtime than to write your reports when stuck at the (home) office?
In short, depending on the phase of clinical evidence collection process you are in, I believe there are several things we can still do to keep the processes reasonably on track. Limiting the amount of time lost and picking up speed once the pandemic is under control, and actually using this down-time to increase the quality of your clinical evidence base, working on your clinical evaluations, clinical study start-up documentation, performing centralized monitoring, and writing clinical study reports and publications where possible.
Annet
Westervoort, April 13, 2020