Clinical Researcher—August 2020 (Volume 34, Issue 7)

DATA-TECH CONNECT

Lisa Hafer, MPH, CCRP; Kelly Dunsky, MS, CCRC; Paula Smailes, DNP, RN, MSN, CCRP, CCRC

With the onset of the COVID-19 pandemic, there has been a significant push for research teams to do work remotely. That translates to working electronically while still attempting to accomplish workflows that otherwise would be done face-to-face. This is no easy feat for sites not equipped or prepared for this transition.

Obtaining Informed Consent

The heart of clinical research is direct patient interaction, and it is during this time that perhaps the most important function researchers must do is obtain consent. With the transition to telework due to COVID-19, researchers were scrambling to re-consent or obtain initial consent without having the patient in the same room. Another related scenario has been consenting patients in isolation due to possible or confirmed COVID-19 infection. What is the best way to capitalize on technology and continue the forward progress of clinical research?

Transitioning a workflow from a traditional paper-based process to an electronic process becomes challenging while maintaining compliance with 21 CFR Part 11 of the Code of Federal Regulations. If the research is regulated by the U.S. Food and Drug Administration (FDA), the consent process is a necessary consideration, but if it is not an FDA-regulated study, it becomes less important. FDA forms and documents requiring signatures need them in either scanned or digital format.{1} Specific enforceable provisions related to 21 CRF Part 11 include, but are not limited to:

System access only by authorized persons
Operational, authority, and device checks
Education, training, and experience of those who are assigned to develop, maintain, and use these systems
Documentation controls
Requirements related to electronic signatures{2}

Electronic tools such as Docusign®, REDCap®, and electronic health records all have the capability to meet 21 CFR Part 11 compliance for electronic consent (eConsent). For example, DocuSign’s Part 11 module was created to be incorporated as part of an “open system” as defined in Section 11.3(b)(9), in which there is electronic communication among multiple people with system access extending to those who are not part of the organization that operates the system.{3}

Despite these add-on abilities for compliance, not every organization makes an investment in this type of technology. The absence of these features may leave researchers scrambling for solutions.

Electronic consent can be further complicated by the idea of remote consent. These two very different concepts can be a source of confusion for research study staff. Remote consent occurs when a research participant and the study team member obtaining consent are not in the same location during the consent discussion and form completion. This differs from eConsent, which includes electronic presentation of the information contained in the consent form and an electronic signature with a date and time stamp placed by the electronic system. eConsent could occur in person or through a remote consent process.

For a study regulated by the FDA, the study team should ensure it utilizes a Part 11-compliant electronic signature system that includes authentication of the research participant’s identification, as the signing of the informed consent form cannot be witnessed in person. It is recommended, and often requested from sponsors, for sites to have a standard operating procedure on electronic consent.

In response to the challenges investigators are facing in obtaining informed consent for patients under isolation precautions and those unable to travel to outpatient clinics, the FDA announced that its MyStudies app was being made available for free to investigators.{4} The MyStudies app provides a Part 11-compliant means for obtaining informed consent securely from patients interested in clinical research when face-to-face contact is not possible or advised due to COVID-19 restrictions.

Conducting Virtual Visits

Consenting is just one aspect of the research study visit. What about all the other study procedures that need to take place for data collection? While telehealth has been expanding for healthcare organizations in a standard of care capacity, it has seen slow adoption within clinical research. However, virtual study visits can serve as a means of collecting some patient safety and efficacy data while still complying with COVID-19 restrictions.

Virtual visits take full advantage of technology using online platforms to conduct clinical research from the comfort and safety of a patient’s home. This could include everything from recruitment and informed consent, to measuring patient endpoints and assessing adverse events.{5}

As the pandemic has progressed, it is apparent that patients are in favor of research opportunities that allow them flexible study participation in a convenient way, including 61% in favor of telehealth services.{6} Technology that captures behavior and physiologic measures has been on the rise for clinical research since the turn of the century, with a 34% increase in product usage from 2000 to 2017.{7} Capitalizing on these tools can further facilitate the transition to virtual studies.

It is recommended that study sites now making the transition to virtual visits should over-communicate with their patients who are on studies to mitigate concerns related to safety, equipment availability, logistics, and any other related stressors from COVID-19 and the patient’s condition.{8} Keep in mind that, while virtual visits allow for safe participant assessment and data collection, there are still some shortcomings to this method; clinical laboratory measures, imaging, and other study procedures simply cannot be completed in a remote fashion.

For example, research participants who are unable to come in for onsite laboratory testing may need to use local facilities for safety labs. In such cases, investigators should consider guidance from sponsors (if applicable), institutional review boards (IRBs), as well as site policies and procedures to determine which “in-person” visits are essential to the safety of the research subject, despite the potential risks of conducting in-person study activities during the COVID-19 pandemic.

Regulatory Maintenance and IRB Review Considerations

As site procedures change dramatically from the pandemic, communication with IRBs becomes essential. Most studies will likely need some changes in response to COVID-19 restrictions; this could lead to overwhelmed IRBs if all protocol changes require review and approval. If remote study operations are temporary and do not pose significant risk to the patient, it may be that these operational changes do not need IRB review.

While virtual communications do pose some risks in terms of confidentiality breaches, those risks weighed against the possibility of a COVID-19 infection are minimal. By reducing the number of protocol changes requiring IRB review in response to COVID-19 restrictions, IRBs could avoid being overwhelmed by the volume of submissions.

Investigative sites conducting COVID-19 research need to work quickly through study start-up processes in order to offer investigational COVID-19 treatments to their patients. In support of this, the FDA issued guidance in June 2020 providing key considerations and recommendations to allow for shorter review timelines for IRBs reviewing submissions for patient access to investigational drugs for treating COVID-19 infections.{9}

The maintenance of essential documents is also impacted by teleworking. Getting signatures on essential documents, such as delegation logs and financial disclosure forms, is challenging remotely, where we once again revisit the best way to obtain electronic signatures. For fillable FDA forms, the FDA prefers that Adobe Sign be used.{1}

Training

Transitioning to remote working and virtual study operations can be challenging for research staff. It is important to provide them with the support, training, and tools they need to continue to operate effectively. For example, research sites within larger organizations may need to investigate applicable institutional policies, such as for data management, that staff should be aware of while conducting research remotely.

An additional consideration is onboarding new hires during the pandemic. Providing newly hired staff with the training they need to be independent, both during and after the pandemic, is a challenge in a remote work setting. However, providing effective training to new staff is key to their individual success, as well as to the overall success of the research team.

Conclusion

Through the challenges of conducting clinical research under COVID-19 restrictions, electronic and remote processes have been discovered and implemented that can be more efficient than some traditional onsite processes. It is important that we use this pandemic as a catalyst for change for the conduct of clinical research.

For example, research still is heavily dependent on paper-based documentation, especially when considering consent. As we see clinical research procedures in a new light, it is easy to envision the potential for growth in long-term adoption of electronic processes and continued exploration of new technologies that may make conducting research more efficient.

We have grown and are learning how to survive in the remote environment of a pandemic. It is crucial that regulatory bodies and all members of the research community continue to collaborate and provide support to sites as they explore the adoption of new technologies and electronic processes, even beyond COVID-19.

References

Lisa Hafer, MPH, CCRP, has more than 15 years of clinical research experience across several disciplines including neurology, cardiovascular imaging, and dermatology. Her role is an Assistant Director of Operations for the Clinical Trials Management Organization at The Ohio State University.

Kelly Dunsky, MS, CCRC, is a Clinical Research Manager for the Clinical Trials Management Organization at The Ohio State University, working with non-oncology clinical researchers in the College of Medicine. She has more than eight years of experience in clinical research, with previous roles as a clinical research coordinator and float clinical research coordinator.

Paula Smailes, DNP, RN, CCRP, CCRC, has been in the clinical research field for more than 17 years, with a decade of experience as a research nurse and seven years educating researchers on the electronic medical record at The Ohio State University Wexner Medical Center. She is a Visiting Professor at Chamberlain College of Nursing and currently serves on the Content Advisory Committee of ACRP.

ACRP Learning Update

What COVID-19 Teaches Us About Conducting Clinical Research Remotely and Electronically

Obtaining Informed Consent

Conducting Virtual Visits

Regulatory Maintenance and IRB Review Considerations

Training

Conclusion

References

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Back to Basics with Research Education