Article featured in One Nucleus' Annual Review & Directory
The impact of COVID-19 on clinical trials has been a trending topic over the last few months and will continue to be a point of discussion as ongoing trials are disrupted and the initiation of new trials is delayed.
On 2nd September, One Nucleus hosted a BioWednesday Webinar entitled ‘How Will COVID-19 Influence Site Selection for Future Trials?’.
Key considerations discussed included the disruptions experienced in ongoing trials, and the potential plans for future trials, with a focus on building in resilience to the design and implementation of new trials.
When considering the impact of COVID-19 on clinical trials, the following aspects must be considered; ongoing trials, opening a new trial, opening a new trial site in an existing trial, ongoing recruitment and continued involvement of participants in the trial, and the Risk-Benefit Assessment for the trial (particularly in trials where healthy subjects who do not derive clinical benefit).
The evaluation of the potential impact of COVID-19 on a trial should take into account national recommendations, including travel restrictions and confinements of trial participants, the resource available at the sites to perform visits and data entry into the Case Report Form (CRF), the notification of serious adverse events and, more generally, ensuring the safety of trial participants.
Phase 1 units have continued conducting studies throughout the COVID-19 pandemic, enabled by the use of rapid turn-around COVID-19 PCR testing, whereby subjects are only allowed into the facility for screening when they have had a negative test result. This testing requirement is used for all study visits to the study site. Site staff also have regular COVID-19 PCR tests to minimise any transmission to study participants.
In phase 2 and 3 trials, we have seen positive changes to study designs, e.g. where a trial participant is unable to attend the site, other measures, such as home nursing, , or contact via phone or telemedicine, may be utilised to dose patients, identify adverse events and ensure continuous medical care and oversight. In future, when writing protocols for these studies, flexible study visit schedules should be considered. A balance is needed to ensure that any flexibility built into the trial design maintains data integrity.
Some trials are clearly affected more than others, with oncology trials becoming difficult when dosing and investigations such PET/MRI/CT scans and tumour biopsies are part of the study protocol rely on limited trial resource at the study sites. When attendance at the study site is mandatory for the patient, help with transport (e.g. offering taxis rather than public transport) could be considered.
From a regulatory perspective, the EMA acknowledge that the COVID-19 situation is likely to result in larger numbers of protocol deviations. It is expected that the Sponsor will escalate and manage such deviations in accordance with their standard procedures. A proportionate approach will be taken by the regulatory authorities when such deviations are reviewed during inspections, to ensure in all cases that the best interests of the participant have been maintained, and that the participant has not been put at risk.
Remote monitoring of study data is becoming more common but on-site data monitoring is still required for most trials.
This pandemic has accelerated the shift from traditional ‘site based’ trials to ‘online’ home-based trials with e-consent/e-data collection, web meetings, telemedicine and wearable devices to record real-time data.
In summary while a pragmatic approach should be adopted by Sponsors, investigators and study participants during this pandemic there are exciting advances in clinical trial technology that will benefit us into the future.