Within the past week, both the FDA¹ and European Medicines Agency (EMA)²  issued guidance with regards to the conduct of clinical trials during the COVID-19 pandemic. 

This swift action taken by the regulatory agencies was in direct response to global concerns around assuring the safety of clinical trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during this unprecedented time. 

These latest regulatory guidelines permit sites, sponsors, and CROs to adjust their study operations to meet changing conditions for ongoing trials, however there are conditions that must be met in order for new solutions to be considered. 

What you need to know

Both sets of guidance outline important information the clinical trial industry needs to know now about continuing existing clinical trial operations and considerations for new study start-up during the COVID-19 pandemic. 

• Ongoing risk assessment: The EMA legislation states that “safety of the participant is of primary importance, and risks of involvement in the trial, in particular with added challenges due to COVID-19, should be weighed against anticipated benefit for the participant and society.” Both U.S. and European regulatory agencies recognize that local circumstances could lead to a change in risk assessment. Sponsors must use tools available to monitor local markets to ensure that site and patient personnel are safe to continue participating in the clinical trial. 

• Protocol amendments: The FDA says that “changes to the protocol or investigational plan to minimize or eliminate immediate hazards or to protect the life and well-being of research participants (e.g., to limit exposure to COVID-19) may be implemented without IRB approval or before filing an amendment to the investigational new drug (IND) or device exemption (IDE), but are required to be reported afterwards.” On the other hand, the EMA states that it while acknowledges that the COVID-19 situation is likely to introduce more protocol deviations than normal, these deviations should be managed in accordance with the sponsor’s standard operating procedures. They cite that a “proportionate approach will be taken by the GCP inspectors when such deviations are reviewed during inspections,” in the best interest of patient safety. 

• Changes to study conduct: Both FDA and EMA guidance advocate for sponsors to evaluate alternative methods for safety and efficacy assessments, specifically changing physical visits into phone or video visits or providing for alternate locations for assessments, including local labs or imaging centers that are further from a risk zone or closer to the individual’s home. Both also recommend evaluating other ways of getting the study treatment to the participant, such as bringing medicines and equipment to the individual’s home or employing home health services. Implementing video visits or other digital communications could serve as temporary alternate monitoring measures amidst the coronavirus emergency situation. Results of altered monitoring and review measures are required to be reported to sponsors and captured in clinical study reports.

• Communication with sites: The EMA notes that any changes in trial conduct should be “communicated clearly to investigator sites.” Should any of the formerly agreed-upon study conduct rules be amended, the sites should be notified, and implications made clear.

• Reimbursements of expenses: The EMA also notes that if urgent measures for the protection of patients cause expenses to be incurred by the patient, they should be compensated by the sponsor via the investigator. Similarly, if new study conduct causes expenses for the site (such as the use of a delivery service for medication, materials or site personnel), the site should also be reimbursed. These payments should be made in accordance with national legislation and/or guidance.

• Material revisions: Should you implement new approaches to support your study, it’s essential for sponsors, clinical investigators (CIs) and IRBs to update governance documents to showcase new study monitoring methods, travel policies, adverse reaction documentation, and more.

Regulatory agencies no doubt are monitoring the ongoing epidemic and thankfully, are responding to the outbreak with additional guidance. In fact, the FDA just released an appendix to their guidance, with additional information. Key items of note include:

• Ability, desire, and safety of study participants to continue to visit a study site location or pursue at home: The Q&A goes into detail regarding the role a sponsor plays in updating protocol and ensuring that medical delivery is transported appropriately.

• Possibility for securing informed consent from patients in isolation or quarantine due to COVID-19 infection control mandates: Included in the Q&A are flexible options to secure patient consent, including teleconference, e-signature, photograph and more.

• Availability of technology used to support clinical studies: While technology can be used to connect disparate stakeholders and systems, it’s essential to still do due diligence on service providers. The Q&A calls out documenting their processes and procedures, especially with regards to business continuity.

Supporting the clinical trial industry 

These are unsettling times, and a priority for organizations that support clinical trials needs to be to ensure the clinical research community feels educated and supported, by providing reliable information and links in our new COVID-19 Resource Center. 

Despite the global crisis, technology solutions can help keep studies solvent and access to medicines intact. 

Use this time to listen to clients, including CROs, sites, or sponsors, immediate needs-whether that be in client conversations or surveys. This feedback can be used to incubate ideas and innovate on new solutions to help meet the demands of this challenging environment, while adhering to the guidance outlined above. These include:

• Data substantiation: As FDA cited, changes in visit schedules, missed appointments and more may lead to missing information. Solutions can provide valuable insights such as patient visit and reimbursement activity taking place across regions and countries.  

• Alternative travel options: Planes and trains not operational? Let’s shift to car service or Lyft rides. Organizations should be actively working with sponsors and CROs to adjust their travel policies to respond to live and local market conditions. 

• Expense reimbursement and communication: Perhaps now more than ever, patients may have expenses related to their study visits. As the impact of the virus unfolds, we expect to see new categories of out-of-pocket costs, whether that be childcare or new methods of transportation. Solutions offer flexibility and scalability to help ensure that patient access to their study remains unfettered.  

Ensuring that your patients remain safe and enrolled in studies is pivotal, and we all need to do our part and stay committed to ensure that we help sites meet trial goals.

Pete Tarasov is the Senior Director, Quality Assurance & Regulatory Compliance at Greenphire.

References

1.   https://www.fda.gov/media/136238/download

2.   https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf