Conducting Clinical Trials amid the COVID-19 Outbreak: FDA Encourages Sponsors to Go Virtual

For pharmaceutical companies, one of the most significant operational impacts of the COVID-19 is on clinical trials. On March 19, 2020, the U.S. Food and Drug Administration (FDA) issued guidance on the conduct of clinical trials during the COVID-19 pandemic. The spotlight of this guidance includes flexibility to implement COVID-19-related clinical protocol changes without prior or institutional review board (IRB) authorization and increased use of telemedicine platforms and virtual clinical sites. 

With numerous lives affected and several countries on lockdown, the COVID-19 pandemic has turned out to be a matter of global concern. The rapid phase at which the virus is spreading has compelled the healthcare community to come out with rapid solutions to treat, diagnose, and prevent the spread of the virus. 

For pharmaceutical companies, one of the most significant operational impacts of the pandemic is on clinical trials. As per a recent survey conducted by Continuum Clinical, COVID-19 will have a ‘big impact’ on one-third of U.S. clinical trial sites. 

Many companies have halted their clinical trials, which, in turn, have ceased the progress of several investigational drugs. In the regions most affected by the pandemic, there are reports of problems in initiating new trials, and the recruitment of new patients into ongoing trials. Healthcare resources are being diverted to deal with COVID-19, and patient visits to hospitals are restricted to prevent the spread of the disease.

Quarantines are one of the critical challenges facing the proper conduct of clinical trials. Enrolled patients are facing difficulties in carrying out the trial visits and, hence, maintain treatment for their conditions. There may also be instances when the trial participants and study personnel are infected with the virus. Such patients would undoubtedly need to be dropped from the trial, which is going to affect the outcomes of the study adversely.

Apart from enrolment and retention challenges, another key aspect is the lack of medical facilities to carry out the trials; medical centers previously utilized by the trials may no longer be easily accessible or safe to use. Interruptions to the supply chain for the investigational product are also a matter of concern.

FDA Guidance on Conduct of Clinical Trials during COVID-19 Pandemic

On March 19, 2020, the U.S. Food and Drug Administration (FDA) issued “Guidance for Industry, Investigators, and Institutional Review Boards on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic”. The FDA guidance outlines considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during the COVID-19 pandemic. The spotlight of this guidance includes flexibility to implement COVID-19 related clinical protocol changes without prior FDA or institutional review board (IRB) authorization and increased use of telemedicine platforms and virtual clinical sites. The FDA states that protocol changes will depend on the particulars of each trial, including participant population, location, and medical products used. 

FDA encourages use of telemedicine platforms and virtual tools as alternative methods for site visits mandated by the protocol

One of the key recommendations of FDA guidance includes the assessment of alternatives such as phone or virtual visits to in-person visits for communication and patient evaluation. FDA urges sponsors to use telemedicine platforms and virtual tools for site visits mandated by the protocol. 

On March 20, 2020, the European Medicines Agency (EMA) released guidance on the management of clinical trials during the pandemic. The EMA also recommends the conversion of physical visits into contact by phone or telemedicine to ensure continuous medical care, identify adverse events, and maintain oversight. 

What are virtual clinical trials or “site-less” clinical trials? 

Virtual clinical trials or decentralized or “site-less” clinical trials are trials conducted through telemedicine and mobile/local healthcare providers, incorporating approaches that vary from the traditional clinical trial model. 

Going virtual would help overcome the pandemic hurdles and avoid disruption in clinical development. A whitepaper by Science 37, a pioneer in decentralized clinical trial technology and design, lists out key considerations for virtual trials in view of the ongoing COVID -19 pandemic. Science 37 suggests the following mitigation strategies which can help reduce the number of in-person clinic visits:

• Employing a trial platform that enables and streamlines virtual visits

• Replacing clinical trial site visits with telemedicine investigators 

• At home nurse visits - Mobile research nurses can be deployed to visit participants at home to collect blood/biospecimens, monitor vital signs, complete protocol-specified procedures, and facilitate data capture.

• Ship study supplies directly to the patient, which eliminates the risk of patients traveling to research sites.

How Easy Will Be the Move to Virtual?

In-person interaction is a crucial aspect for certain trials, and the abrupt shift to new ways of working could be challenging. Sponsors may need to include adequate information to demonstrate that the telemedicine platform is appropriate for clinical research purposes. The use of virtual methods may also raise privacy concerns that could require IRB review or agreements with telemedicine providers; however, most of the telehealth or remote monitoring vendors offer solutions that have pre-existing, standard privacy policies. 

Moving Forward in Uncertainty

While the way-forward is filled with uncertainty, some companies have already initiated ways to carry on with its ongoing trials. Catalyst Pharmaceuticals is one of the first companies to follow a virtual approach to its drug trial. Catalyst Pharmaceuticals is implementing a virtual approach with doctors and company representatives to ensure patients had continued access to its rare neuromuscular disorder drug Firdapse and remained on track to report results from its ongoing late-stage trial in the second quarter. 

Apart from Catalyst, Vertex Pharmaceuticals is also working with clinical trial sites to enable virtual clinic visits and home delivery of study drug to ensure study continuity and medical monitoring, and to facilitate study procedures.

The COVID-19 pandemic will require unprecedented utilization of resources. The rapid spread of the coronavirus will certainly impact trials all around the world; to ensure patient safety and maintain study integrity; it is necessary to incorporate proactive changes to ongoing and planned clinical trials. 

Though challenging, the current situation may turn out to be a revolutionary phase for how clinical trials are executed. Virtual clinical trials will not only allow the adoption of a more patient-centric approach, but it may also have a longer and much wider impact on how trials are conducted in the future.

References:

1. https://www.businesswire.com/news/home/20200316005858/en/Survey-COVID-19-Negatively-Impact-Clinical-Trial-Enrollment/

2. FDA Guidance https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-guidance-conducting-clinical-trials 

3. European Medicines Agency (EMA) released guidance https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf 

4. https://www.science37.com/

5. https://www.reuters.com/article/brief-catalyst-pharmaceuticals-ceo-on-im/brief-catalyst-pharmaceuticals-ceo-on-impact-of-covid-19-says-implementing-virtual-approach-to-guarantee-patients-continual-access-to-firdapse-idUSFWN2BB156

6. https://www.businesswire.com/news/home/20200327005081/en/Vertex-Confirms-Supply-Chain-Continuity-Business-Outlook

About the Author:

Neeta Ratanghayra is a freelance medical writer, who creates quality medical content for Pharma and healthcare industries. A Master’s degree in Pharmacy and a strong passion for writing made her venture into the world of medical writing. She believes that effective content forms the media through which innovations and developments in pharma/healthcare can be communicated to the world."

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