CORONAVIRUS AND CLINICAL STUDIES: WHAT TO DO?

20200316 CORONA HOPKINS

By now the Coronvirus outbreak is affecting everyday life worldwide (see latest statistics Johns Hopkins University), and to avoid patient exposure or to reduce the burden on clinical services it also started impacting clinical trials; their execution, monitoring, and publications. Study staff re-allocated to clinical care or requested to stay at home, study participant enrolment and follow-up delayed to limit contact, and monitors being kept out of the hospitals.

With respect to clinical trial management more and more governmental guidance’s are safetyappearing in a hard to keep up pace, indicating what is the best approach with respect to study suspension, protocol amendments, deviations, and study participant recruitment and follow-up. Suggesting for example changing participant site visits to phone calls or paper questionnaires by post where possible, keeping in mind that study participant’s safety has the priority.

In this blog post I would like to address another tool at our disposal for monitoring: Remote (or centralized) monitoring, which depending on the local situation and study security arrangements can be extremely helpful to keep the ‘clinical motor running’ as far as possible given the current situation.

BACKGROUND

Besides training, Site File review, etc., one of the main reasons for the on-site monitoring is proper source data verification (SDV), i.e. the process to ensure that data are verifiable, correct, and complete. On-site monitoring, however, represents at least 15% of the total clinical study budget, and digitization and evolving regulatory insights nowadays allow for remote monitoring (remote evaluation carried out at a location other than the sites at which the clinical study is being conducted),  as well. Although remote monitoring may not be considered the tool of choice for your current clinical trial and/ or described in the study monitoring plan, in the current situation it may be the best tool we have, keeping in mind that remote monitoring is not the same as

RISK BASED MONITORING,

although they do go hand-in-hand, because RBM allows for a lower than 100% SDV and it is extremely difficult to perform 100% SDV with remote monitoring and SDV (see below).

Key is to check whether your study allows for RBM, and what the monitoring plan says about remote monitoring. If it does include RBM, you may just need to adjust your timing or (temporarily) the degree with which you perform remote monitoring, or if it does not include RBM you may want to amend your monitoring plan, notify the applicable Ethics Committee on it (make sure to check their latest ‘Corona’ policy), and train your CRA’s. Especially do not forget the latter, since not all CRA’s are 100% familiar, yet, with remote monitoring procedures.

Good thing in this situation is that the

REGULATIONS

nowadays widely accept a risk-based approach for monitoring, and in parallel to the FDA, ICH-GCP, also the upcoming version of ISO 14155 allows for

“a combination of on-site and where justified, centralized monitoring, as appropriate”,

and see it as additional monitoring capabilities to complement or reduce the extend and frequency of on-site monitoring. So the ‘only’ thing to do is to ensure proper documentation and reporting to the applicable regulatory bodies (Competent Authorities as well as the Ethics Committees) of the ‘why and how’ to ensure you stay compliant with the applicable regulations.

While (temporarily) switching to remote monitoring, a few practical factors should be considered while performing remote monitoring, especially

REMOTE SDV

The study sponsor (eCRF or alternative), but ideally also the concerning sites (electronic patient files), should have electronic systems in place that are remotely accessible in a secured way. Working with a paper study and study staff at home will make remote SDV virtually impossible.

Annet_MarjoleinFor proper SDV the CRA needs to be able to review the patient files. That tends to create challenges due to the fact that most of the hospitals in Europe do not allow for remote (so off-site) viewing of patient files by the sponsor due to (possible) data-protection issues, and in fact most of the Informed Consents do not include permission of sharing of personal not coded data outside the study site.

Since these limitations typically include blockage of web-based tools like WebEx, Skype, GoTo, etc., the best option we have in this respect is that study staff uploads critical coded and signed reports into the study sponsor’s electronic system (eCRF or alternative) making it accessible to the CRA for review. The obvious down-sides being that this places yet a higher burden on the site study staff (so they should not be re-allocated to critical clinical care!), and this concerns a highly selective review of a copy of the source. It would, however, to my opinion be the best option we have for the current situation besides suspending all activities, and is in line with a risk based approach with a reduced amount of SDV.

CONCLUSION

The regulations nowadays allow for combination of remote and on-site monitoring, and given the current situation it seems best to assess the situation for your clinical study, and (re) consider (temporarily) applying remote monitoring, while ensuring ongoing study participant’s safety and well-being, using a risk based approach for SDV.

Annet

About Annet Muetstege - Visscher

My name is Annet Muetstege and I am a clinical research expert, based in The Netherlands, with over 25 years of experience in all aspects of clinical evidence planning and execution especially in medical devices. I am the co-founder of Applied Clinical Services.
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2 Responses to CORONAVIRUS AND CLINICAL STUDIES: WHAT TO DO?

  1. Pingback: Read the latest CEO blog: Coronavirus impacting clinical studies. What options do we have? | – Applied Clinical Services

  2. Pingback: COVID-19 CLINICAL EVIDENCE DOWNTIME: HOW TO MAKE USE OF IT! | Medical Devices Clinical

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