Alexander T. Limkakeng and Judd E Hollander discuss how the COVID-19 pandemic is changing the way clinical research is conducted and if these changes can bring about the breakthroughs needed to accelerate clinical research.
Clinical care and research have long depended on in-person interactions, but the COVID-19 pandemic has forced rapid adjustment to virtual modes of communication. Changes made to adapt clinical research during the COVID-19 pandemic could be the disruptive force needed to finally embrace change. These changes, if made permanent, could make the clinical research enterprise more efficient, effective, and inclusive.
Clinical trials are expensive because they require communication between several actors. These communications have occurred primarily through in-person interactions, largely due to inertia and tradition. In response, industry leaders such as former FDA commissioner Robert Califf have called for “disruptive innovation” in the clinical research enterprise. However, changes have been glacial in pace.
In response to the COVID-19 pandemic, regulatory changes to accommodate clinical care occurred rapidly. For example, barriers preventing patient care via telemedicine and digital health rapidly evaporated, at least temporarily. Similarly, the FDA issued guidance for ongoing clinical trials that sponsors should “evaluate whether alternative methods for safety assessments . . . could be implemented”, including virtual visits and assessments. Thus, the clinical research enterprise shifted rapidly to virtual modes of interaction.
“Teleresearch” methods could replace many current landmark events during a clinical trial that traditionally require in-person interactions. Teleconferencing could reduce costs and time associated with protocol planning meetings, investigator meetings, site initiation meetings, and close-out visits. Prior to the initiation of a study at a given site, sponsors often conduct a site qualification visit. Today, most hospitals and other major facilities can provide virtual tours through animation or video conferencing, obviating the need for in-person visits.
Informed Consent in the Post-paper Era
Obtaining valid informed consent is an ethical and legal imperative during clinical trials, and an area where teleresearch methods can greatly improve the patient experience. Arranging an in-person signature of paper informed consent documents for research can be difficult and intrusive for patients and families, particularly if they are suffering from time-sensitive critical illnesses such as COVID-19.
Informed consent processes that use electronic mediums have both economic and ethical advantages. Audio-visual aids increase potential participants’ comprehension of study information during informed consent. Electronic or app-based consent allow potential participants to move through material at their own pace, repeat parts they do not understand, and take quizzes to identify gaps in their comprehension from anywhere. Researchers have also developed virtual environments that allow interactive online discussions with an investigator or artificial intelligence avatar. Teleresearch methods also makes informed consent for large population-health or pragmatic studies possible and is currently the only means by which new studies can enroll.
Extending Research Capabilities
Teleresearch can reduce the need for many in-person clinical patient encounters during the conduct of clinical trials and has been promoted as necessary best practice during the COVID-19 pandemic. Most clinical outcome assessments, including basic physical exams, surveys, and questionnaires can be done telemetrically. Patient-reported outcomes can be done telemetrically and have become more important in assessment of quality of life and early identification of medication side-effects.
Extensive data collected through artificial intelligence smart environments and wearable activity monitors can enhance the amount of data collected on participants. These digital tools can improve clinical trial safety and accuracy through nearly continuous assessment. For example, a study of a heart failure drug could more accurately depict treatment success or failure via full time remote activity monitoring compared to periodic in-person surveys. Geotracking devices on a smart phone can automatically track the quantity of movement as an outcome, or can detect if a patient has returned to a hospital, triggering a search or query for hospital records.
Bringing Products to Market
The impact of teleresearch methods is not limited to enrollment and data collection. Pharmaceutical companies spend millions of dollars monitoring sites for data accuracy. Acknowledging that this is an outsized expense for clinical trials, the International Council for Harmonisation (ICH) proposed Risk Based Monitoring to reduce the amount of in-person monitoring, but there remain several barriers to this approach. The use of telemonitoring to securely and remotely review study documents and records could greatly reduce the cost of drug development through making monitoring less expensive.
Finally, following regulatory approval, pharmaceutical and medical device companies typically hold a large in-person gathering for market launches of their new product. These market launches also could be done via virtual meetings, including use of avatars to create virtual spaces for small group conversations. There could be simultaneous teleconferenced participants worldwide.
The clinical research enterprise has long been awaiting a disruptive catalyst to reassess its processes and adapt to technological advances. That much-needed catalyst may be the COVID-19 pandemic. We can ill afford being unprepared for the next crisis.
Alexander T. Limkakeng Jr., MD, MHSc is an Associate Professor of Emergency Medicine and the Vice Chief of Research for the Duke University Division of Emergency Medicine in Durham, North Carolina, USA. You can follow him on Twitter @alimkakeng.
Judd E. Hollander, MD is Associate Dean for Strategic Health Initiatives at Sidney Kimmel Medical College at Thomas Jefferson University and Professor and Vice Chair of Finance and Healthcare Enterprises in the Department of Emergency Medicine. You can follow him on Twitter @JuddHollander.
Neither authors have any relevant financial conflicts of interest to disclose.
Photo credit: Catherine Bury, MD Division of Emergency Medicine, Duke University