As we all try to navigate the COVID-19 outbreak, it is far from business as usual for clinical trials. Recognizing the disruption to existing clinical trials – from quarantines, site closures, travel limitations, interruptions to the supply chain, infected participants and participant safety – the FDA recently provided guidance that could allow some studies to continue. Given the likelihood of an impact on participants and study staff due to COVID-19 illness or control measures, protocol modifications may be required, and there may be unavoidable protocol deviations.
COVID-19 Related Challenges for Ongoing Clinical Trials
Challenges related to COVID-19 could lead to difficulties in adhering to the protocol, including investigational product administration, adherence to planned visits and laboratory/diagnostic testing. Therefore, the guidance specifically outlines general considerations for ensuring patient safety, maintaining compliance with good clinical practice (GCP) and minimizing risks to data integrity. To enable study continuation, the FDA has suggested greater use of technologies and processes to enable virtual clinical trials.
If you haven’t already downloaded information about the FDA guidance, we’ve included details about it and ways you should respond later in this blog post. First, we wanted to communicate the solutions our software services teams have put in place to help you during this unprecedented time.
Support from Bioclinica
We want to ensure that we are helping our customers to best support the participants of your clinical trials. To facilitate the best decisions around implementing changes to your protocol, we are rolling out exceptions to the pricing of our software services and waiving the fees for changes related to the COVID-19 pandemic for our IRT, CTMS and EDC and data management (DM) services.1 Examples of exceptions to covered changes include:
- Softening visit windows, enabling patients to be dosed outside of a scheduled visit
- Adding depots to the drug delivery algorithms to accommodate protocol procedural changes
- Changes to the MVR template to accommodate remote monitoring visits and extra notes
- Deployment of Bioclinica’s standard Site Contact Summary report
EDC and DM
- Addition of fields on AE/serious adverse event (SAE) or ConMed forms to capture details specific to the pandemic
- Inclusion of forms to collect data from phone assessments in place of site visits
- Adding COVID-19 screening to the CRF
- Adding COVID-19 as a reason for discontinuation
- Related data management activities that result from changes within the EDC system
Below is a summary of the guidance provided by the FDA as of March 27th. Please refer to the original document for more information, and be aware that this guidance may be updated at any time.
Considerations around patient safety
The most important consideration is patient safety. Sponsors should focus on the impact any changes to the clinical trial might have on the safety of trial participants – and consider if patients are best served by:
- Continuing in the study
- Dropping out of the study but continuing the study drug
- Discontinuing the study, by stopping ongoing recruitment or withdrawing participants
If continuing the study is determined to be the best course of action, are alternative monitoring procedures available? Can patients be contacted by phone or virtually? Is it possible to use local labs or imaging procedures?
In cases where the patient no longer has access to the study drug, either because of lack of access or a disruption in the study supply, what safety measures need to be put in place?
First, sponsors and investigators are encouraged to work with their institutional review boards (IRBs) to prospectively determine how to report protocol deviations that may impact the safety of patients.
Then, sponsors should describe any changes in appropriate sections of the clinical study report (or in a separate study-specific document). This includes contingency measures implemented to manage study conduct during disruption of the study as a result of COVID-19 control measures. In addition, document the following:
- Duration of the changes
- A listing of all participants affected by the COVID-19-related study disruption by unique subject number identifier and investigational site
- Description of how the individual’s participation was altered
Because of the increased potential for missing data, from missed or changed visits or patient discontinuation, make sure to capture in the CRF the specific reasons why the data is missing.
Impact of contingency measures
Document any analyses and corresponding discussions that address the impact on the reported safety and efficacy results of implemented contingency measures, such as:
- Discontinuation of the participant from the investigational product and/or study
- Alternative procedures used to collect critical safety and/or efficacy data
Any changes to the statistical plan or data management plan must be explained and documented. Before database lock, describe in the statistical plan how COVID-19-related protocol deviations will be handled in the prespecified analyses.
Alternative methods for drug distribution may need to be considered when scheduled visits at sites will be impacted. This could apply to self-administered drugs or drugs that can be administered via home nurses or alternative non-study-specific locations. However, consideration and documentation for maintaining investigational product accountability are still required.
Centralized, remote monitoring
If centralized, remote monitoring is implemented to maintain oversight of clinical sites, assess and document the methods and impact on the study. The focus can shift to remotely monitoring only that data that is most important for patient safety and data quality. Remote monitoring in the EDC can still help identify eligibility violations, protocol non-compliance and safety concerns via lab data, adverse events (AEs) and other assessments.
It’s important to note that, according to the FDA, health care system-mandated COVID-19 screening procedures do not need to be reported as a protocol amendment, unless that data will be collected as part of the research project.
Other potential effects of the FDA guidance
In addition to the required documentation already described, you might also require a protocol deviation log and explanations of clinical research associate (CRA) monitoring.
Necessary protocol changes could include the:
- Extension of visit intervals
- Ability to perform virtual visits
- Addition of remote monitoring
To support additional data collection needs, the following might be required:
- Modifications to AE forms to assess the relationship of AEs to COVID-19
- New forms for remote data collection
- Modifications to monitoring visit reports (MVRs)
- The addition of COVID-19 as a reason for study discontinuation
Working Together to Adapt and Enable Clinical Trials
Although it might not be business as usual, we want to ensure that our customers have the ability to move forward with current trials to the best of their ability. Thank you for your trust in Bioclinica and in our work to support your teams during this challenging time. Please do not hesitate to reach out to me directly with questions, concerns or escalations that you may have at Guy.Crossley@bioclinica.com.
1Changes that can be made within the existing IRT or EDC configurable features and/or study parameters or that are made to existing MVR templates or standard templates provided by Bioclinica