Reducing disruptions of cardiovascular trials and ensuring trial integrity during a global pandemic

New trial starts have been halted or delayed, and enrollment in ongoing trials has stalled. Continuity of participation in active studies has necessitated adaptations and creative solutions to ensure adherence and retention. What’s more, because patient populations are particularly vulnerable to infection and COVID-19, sponsors are expected to be extra vigilant to ensure patients stay safe. Here we report on measures that can be implemented to reduce the disruption of CV trials, while maintaining patient safety.

Developing an integrated solution to keep clinical trials on track during COVID-19

To overcome operational challenges, clinical trial stakeholders need to adapt how they manage CV trials in response to constantly changing pandemic-related restrictions. Specifically, they should start by developing an integrated solution that is tailored to meet the needs of each individual study. This would include the following:

• Track latest information on the pandemic: Track the impact of COVID-19 on a country and individual site level in real-time. To mitigate delays in site activation and screening, use the data generated from the tracking to redeploy study resources where appropriate. 
• Initiate remote trial monitoring: Remote source data verification, remote source data review and remote/central monitoring should be employed to ensure that protocol compliance, and accurate and timely data collection are being performed where on-site monitoring is no longer feasible.  
• Employ direct-to-subject shipping and home healthcare: When sites cannot directly dispense study medication to participants, arrangements should be made for secure direct-to-subject shipping. In situations where a laboratory test result is needed to authorise the dispensation of a study drug, home healthcare nurses can be used to ensure that dosing is not disrupted. Further, local travel restrictions, limited access to sites, and trial subject concerns for potential exposure to the coronavirus have increased the probability of missed study visits. Therefore, sponsors should consider using alternative means such as telemedicine. Also, when possible, home health services should be employed to increase compliance and reduce the need for subjects to travel to sites.
• Communicate change: Maintaining regular contact with participants to communicate protocol changes and to facilitate compliance and study retention is particularly crucial during this pandemic. When needed, urgent operational changes in study conduct should be promptly communicated to research staff, participants and local institutional review boards before protocol amendments can be implemented. 

Sponsors who utilise a fully integrated approach driven by an overarching COVID-19 regulatory guidance will be well positioned to adapt to the challenges of the evolving pandemic, ensure patient safety, reduce disruptions to trial timelines and stay compliant.

Trial committees, core labs, and endpoint adjudication

In addition to overcoming the operational challenges during the pandemic, maintaining a sense of continuity with regard to trial committees, core labs and endpoint adjudication is essential to the successful continuation of the trial. 

Trial committees composed of key opinion leaders and independent experts are commonly employed in CV trials to monitor patient safety and provide scientific insight, and to ensure data quality, integrity and operational oversight. These committees are ever more critical in light of the pandemic. However, committee members may have transitioned to working remotely, which could impact their participation. Therefore, it is best to work with a third party who can manage the logistics for these committee members and facilitate remote meetings. 

Core labs often provide unbiased and consistent analyses in CV trials. Data is typically transferred to the core lab in an electronic and secure environment. To facilitate timely analyses, developing a compliant platform to provide high-quality images for review and an efficient communications system for relaying information is critical for those reviewers who must work remotely. Proactive communication with sites and reviewers ensures “reads” have been performed on a timely basis and information has been relayed back to sites promptly.

Endpoint adjudication committees are commonly used in CV trials. They are made up of expert cardiologists who render a decision regarding a clinical cardiac event in accordance with a prespecified event definition. 

During this pandemic, a number of COVID-19-related cardiac events have been reported in persons hospitalised with the virus. In these situations, it will be necessary to collect additional source documentation — including COVID-19 testing results — to adjudicate a cardiac event, and attribute causality, especially in the case of death. Finally, one will need to factor in these cardiac events when interpreting the effect of an investigational treatment on adjudicated cardiac events (e.g., the primary endpoint of a trial).

Deploy connected devices and mobile health solutions

Connected devices and mobile health solutions can help to minimise COVID-19-related disruptions to CV clinical trials and can be incorporated into future trials. For example, when an echocardiogram is required, but the patient is unable or unwilling to go to a study centre for the procedure, several options can be considered beyond extending the visit window. One alternative is to perform the study at a more accessible site. Another may be to use high-end mobile echocardiogram equipment, with trained sonographers conducting the echocardiogram in the subject’s home. The use of this equipment can not only minimise physical patient contact with healthcare providers, but also enable the collection of important safety and efficacy data outside the centre in real time. 

Future direction

The lessons learned during the COVID-19 pandemic will enable a more efficient and, hopefully, a greater number of hybrid trial designs to further ease site and patient burdens, and facilitate responses to unforeseen risks to study execution. Additionally, the use of digital health technologies, along with home healthcare visits and telehealth, may improve monitoring of clinical trial participation. 

Learn more about ICON’s cardiovascular expertise in our white paper: Mitigating the impact of COVID-19 on cardiovascular trials at ICONplc.com/CVTrials