Since the COVID-19 pandemic started, it has affected, directly or indirectly, most ongoing and new clinical trials. Based on our experience managing clinical trials during the pandemic, we identified three common challenges in the COVID-19 era:
- Monitoring patient safety during disrupted visits via alternative methods of contact (phone, virtual visits, and/or alternate locations for assessments)
- Changes in study conduct driven by COVID-19 restrictions, exposure, or diagnosis
- Increases in the types and the overall number of protocol deviations
In the current state of uncertainty, sponsors and CROs are likely to continue facing these challenges that could potentially jeopardize trial completion. We asked our Executive Director of Service Strategies to comment on these challenges and share her suggestions on how to overcome them.
Challenge 1: Monitoring patient safety during disrupted visits via alternative methods of contact (phone, virtual visits, and/or alternate locations for assessments)
CROS NT: Now that sponsors, sites, and patients are more comfortable with the decentralized components of clinical trials, we know that most future studies will likely involve activities that are not site-based. Even now, most of our current clients and potential clients are looking to include at least one decentralized component to a trial. ePRO is the most common, but eConsent and home visits are also frequent requests.
If a trial has already started, you can still implement decentralized components, whether required due to COVID, patient ease, or other reasons. Once the administrative requirements for changing patient visits and/or requirements are in place, you can work with your biometrics vendor to implement appropriate changes to the eCRF. These changes could include, for example, local laboratory collection pages, virtual visit contact pages, or a field to the record of consent was obtained via eConsent or traditional methods. One of our ongoing studies was able to implement home nursing visits very quickly at the start of the pandemic, which resulted in very few missed visits. This addition gave us the necessary data to assess the impact of COVID-19 and make adjustments in the analysis of the impacted endpoints.
Data managers also need to understand what additional data sources will be present and include plans for managing and reconciling these sources in the study-specific Data Management Plan. It is also important that these new data sources are transferred in an appropriate format to support both the cleaning and reporting efforts. The data manager should work closely with the biostatistician and programmers to ensure these data requirements are met.
Challenge 2: Changes in study conduct driven by COVID-19 restrictions, exposure, or diagnosis
CROS NT: We know that regulatory agencies are asking for data to support and describe the impact of COVID on ongoing clinical trials. This includes collecting data on exposure and infection, as well as managing the potential increase in concomitant medications and adverse events. Through eCRF amendments, we can develop a system to identify restriction-affected and unaffected data, collect COVID-19 exposure and diagnosis information, and even, perhaps, a symptom tracking sheet specific for suspected COVID-related symptoms to keep them separate from the overall study adverse events. Since our EDC systems are easy to update, with no downtime, it will be a seamless transition for sites to have the new eCRF developed and deployed.
We can also use this additional information during the study to assess if additional medical monitoring reports or formal data safety reviews are needed to support patient safety. We can also use this data during the analysis to assess the impact of COVID-19 on study results. For one of our projects, we were able to assess the impact of COVID-19 on patient participation, primarily through data collected via a wearable device.
Challenge 3: COVID-19 will likely cause an increase in the types and the overall number of protocol deviations
CROS NT: For ongoing studies, we suggested a careful review of the system in place for monitoring protocol deviations along with recommended updates based on this review. Your review could result in increased tracking by the site, perhaps by a specific eCRF page if one is not currently in place. If the EDC system has sufficient reporting capabilities, you may be able to have many deviations automatically tracked. Other deviations will only be able to be identified via manual review or through programming algorithms once the data has been extracted from the EDC system.
At CROS NT, our biometrics teams worked with the clinical and medical monitoring teams to understand the need for and implement any additional or updated listings necessary for data review meetings and DSMBs. Even in the case of unblinded studies, a project team may decide that a formal data review meeting prior to database lock is warranted to assess the overall impact of deviations and determine if there are any additional queries related to the deviations.
For studies still in the planning stage, you have the opportunity to decide in advance exactly how deviations will be monitored, collected, and reviewed. This gives you a tremendous time advantage to consider the above points and include some aspects in the protocol, DMP or SAP, as appropriate.