Could COVID-19 be a catalyst for virtualizing clinical trials?

The virtualization of clinical trials has long been technically feasible, but cultural and regulatory barriers have prevented implementation. With over 1200 clinical trials worldwide being discontinued due to the SARs-CoV2 pandemic ¹, the potential benefits and opportunities of virtualizing clinical trials have been highlighted.

A recent survey based study of 65 institutions focused on randomized control trials (RCTs) and single arm studies reported that, following COVID-19, trial enrollment was suspended at 78% of sites ². Additionally, 75% of sites put new trials on hold. Importantly, this survey highlighted the slow uptake of virtual elements pre-pandemic, with 40% of sites not having any protocols in place for remote consent.

As such, US and EU Regulatory agencies have demonstrated support for virtualizing aspects of clinical trials. The FDA published comprehensive guidance encouraging sponsors to adopt innovative approaches to clinical trials e.g. switching to virtual visits were possible, permitting remote consent, and even shipping medications directly to patient homes. Suggested protocol modifications include educating patients to record their own vital signs and providing reminders and alerts via mobile devices to ensure trial participants take their medication ³. Similarly, the EMA has permitted translation of physical visits into video or phone calls and has allowed remote consent via email. However, the EMA explicitly notes that these changes will only be accepted during the COVID-19 outbreak and will be revoked once the pandemic is over ⁴.

How can virtualization support clinical trials?

To begin with, enrolling patients into trials can be a major problem; many patients agree to enroll but are presented with logistical challenges that prevent their participation e.g. difficulty traveling to research sites ⁵. Virtualization decreases the number of on-site visits necessary, as patients can record their own vital signs and avoid long distance travel to collect their treatment. This greatly reduces the burden of trials for the patient, improving patient satisfaction and participation. Furthermore, this could offer an opportunity to access a much wider pool of patients e.g. those living in rural areas or those unable to travel long distances. Retaining trial participants and expanding the recruitment pool could accelerate clinical trial timelines.

A further advantage of minimizing on-site visits is reduced infection exposure risk, in for example, often highly immunocompromised cancer patients ⁶. A recent study showed that lung cancer patients treated with chemotherapy within three months of a COVID-19 diagnosis were reportedly at higher risk of dying from the infection ⁷. Furthermore, there is evidence to suggest that patients with progressing cancer could be at a higher risk of death or serious health complications from COVID-19 infection compared to those in remission. The danger of hospital-acquired infections (HAI) existed long before the SARS-CoV2 pandemic where patients on immunosuppressive treatment have always had an increased risk for HAIs, particularly with multi drug resistant bacteria ⁸. Reducing non-essential clinic visits by switching to phone calls or video conferencing reduces the patient’s overall risk of getting infected.

What tools can be used?

Virtual tools like mobile apps may increase compliance by navigating patients through complex treatment decisions and trial guidelines, as well as providing alerts and reminders to ensure an adequate treatment schedule is maintained. The integration of these apps with wearable health monitors offers the opportunity to collect continuous, accurate health data in real time ⁹. This remote data collection and adherence tracking could, not only improve operational efficiencies, but result in significant cost savings. A University of Arizona study noted that the FDA’s first remote monitoring clinical trial, comprising multiple sclerosis patients taking lisinopril, saved approximately 3.5 million US dollars by integrating vital sign monitors into the study ¹⁰. Moreover, researcher bias could be reduced, with a more uniform and automated alternative to data collection ¹¹.

Several wearable devices have recently been developed to take patient measurements. One example is BioSticker, which is placed on a patient’s chest and continuously monitors vital signs and symptomatic events including respiratory rate, resting heart rate, skin temperature, gait, body position and more. BioSticker provides the opportunity to monitor patients remotely, allowing doctors to take action even before the patient recognizes they are sick ¹². In oncology trials, wearable technologies are increasingly being used to obtain objective measures of physical activity. Gresham et al. identified 41 oncology trials involving wearable activity monitors between 2005 and 2016 ¹³. Commonly, physical activity assessments rely on self-reported questionnaires, which are limited by recall and response biases.

Mobile apps could also enhance patient recruitment. TROG ClinTrial Refer, for example, is an app through which patients and clinicians can access information regarding cancer research trials, allowing users to filter by their disease type and location ¹⁴.

Could virtualization be expanded post-COVID?

There has been a significant shift towards virtualization and decentralization of clinical trials during the COVID-19 pandemic. According to the Tufts Centre for the Study of Drug Development, as of May, one third of sponsors have switched to virtual or decentralized models ¹⁵. In April and May 2020, clinical data specialist ERT surveyed clinical trial professionals to find out how the demands of the pandemic were affecting their use of virtual trial technologies ¹⁶. Out of 114 triallists, 82% stated that their organizations were incorporating virtual elements to their trials due to the pandemic; a significant increase from 33% prior to COVID-19 ^{16, 17}. Furthermore, the survey seems to indicate that this shift may continue even after this crisis; only 9% of responders believe there is no need to take virtual approaches to clinical testing ¹⁷.Nevertheless, with increased adoption comes increased concern in multiple areas. While supportive devices may be as accurate as recordings taken by a qualified health professional, the entire patient is not being assessed i.e. the device can only detect what it is told to detect. Additionally, despite being able to record patient progress throughout treatment, there is a lack of standardization across device types, which could hamper data comparisons across trials. Furthermore, the use of sophisticated medical devices to record patient data gives rise to privacy and security concerns and may require the use of special informed consents, a potential regulatory barrier. Lastly, while virtual trials are arguably more patient-centric, certain trial participants, particularly the older population, may be apprehensive and prefer maintaining face-to-face interactions. Providing options such that patients and physicians can choose how they participate in a study is crucial in order for virtualized and decentralized clinical trials to be efficient and effective for all parties ¹⁵.

Conclusion

In summary, there are several potential benefits to virtualizing at least some aspects of clinical trials, namely faster and cheaper trials with potentially reduced infection rates. We are already seeing accelerated adoption of virtualization. In the US, virtualization has become the new normal for non-urgent care, marking a dramatic shift in the US healthcare delivery system. For example, at the NYU Langone, there has been a 4000% increase in non-urgent care visits delivered over tele-health ¹⁸. On the other hand, the EMA’s guidelines still suggest that COVID-19 virtualization allowances will be revoked once normal service resumes, suggesting regulators remain to be convinced. Hybrid models, in which some procedures are carried out on-site, while others are done remotely, may provide the perfect balance. However, expansion into wider therapeutic areas will always be indication-dependent and device capabilities and data privacy will continue to be important considerations.

¹   “Over 1,200 clinical trials worldwide have ground to a halt due to COVID-19.” https://www.transparimed.org/single-post/2020/05/08/Discontinued-clinical-trials-COVID (accessed Sep. 11, 2020).

² A. T. Rai et al., “Neuroendovascular clinical trials disruptions due to COVID-19. Potential future challenges and opportunities,” J NeuroIntervent Surg, vol. 12, pp. 831–835, 2020, doi: 10.1136/neurintsurg-2020-016502.

³ “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency Guidance for Industry, Investigators, and Institutional Review Boards,” 2020. Accessed: Aug. 05, 2020. [Online]. Available: https://www.fda.gov/regulatory-.

⁴ “GUIDANCE ON THE MANAGEMENT OF CLINICAL TRIALS DURING THE COVID-19 (CORONAVIRUS) PANDEMIC.” Accessed: Aug. 19, 2020. [Online]. Available: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-.

⁵ IQVIA, “Adopting Virtual Approaches in Oncology Trials: Patient-centric trial delivery during COVID-19 and beyond.” https://event.on24.com/eventRegistration/EventLobbyServlet?target=reg20.jsp&mode=login&loginemail=cfairley%40alacrita.com&eventid=2371360&sessionid=1&key=C5F9E3701A0D63174A220AD54A12C73F&regTag=&sourcepage=register (accessed Aug. 05, 2020).

⁶ “Common Questions About COVID-19 and Cancer: Answers for Patients and Survivors | Cancer.Net.” https://www.cancer.net/blog/2020-06/common-questions-about-covid-19-and-cancer-answers-patients-and-survivors (accessed Aug. 10, 2020).

⁷ “ASCO20 Virtual Scientific Program: The Global Impact of COVID-19 on People With Cancer | Cancer.Net.” https://www.cancer.net/blog/2020-05/asco20-virtual-scientific-program-global-impact-covid-19-people-with-cancer (accessed Aug. 10, 2020).

⁸ P. Cornejo-Juárez, D. Vilar-Compte, A. García-Horton, M. López-Velázquez, S. amendys-Silva, and P. Volkow-Fernández, “Hospital-acquired infections at an oncological intensive care cancer unit: Differences between solid and hematological cancer patients,” BMC Infect. Dis., vol. 16, no. 1, Jun. 2016, doi: 10.1186/s12879-016-1592-1.

⁹ “The Growing Availability of Wearable Devices: A Perspective on Current Applications in Clinical Trials.” https://www.appliedclinicaltrialsonline.com/view/growing-availability-wearable-devices-perspective-current-applications-clinical-trials (accessed Aug. 10, 2020).

¹⁰ N. D. Panayi, M. M. Mars, and R. Burd, “The promise of digital (mobile) health in cancer prevention and treatment,” Futur. Oncol., vol. 9, no. 5, pp. 613–617, doi: 10.2217/fon.13.42.

¹¹ “FDA gives go ahead for Phase 2 trial using remote monitoring for MS drug.” https://medcitynews.com/2012/12/fda-gives-go-ahead-for-phase-2-trial-using-remote-monitoring-for-multiple-sclerosis-drug/?goback=.gde_2914634_member_198015756&rf=1 (accessed Aug. 19, 2020).

¹² “Remote patient monitoring sticker gets vitals from home - UCHealth Today.” https://www.uchealth.org/today/remote-patient-monitoring-sticker-gets-vitals-from-home/ (accessed Aug. 25, 2020).

¹³ G. Gresham et al., “Wearable activity monitors in oncology trials: Current use of an emerging technology,” Contemporary Clinical Trials, vol. 64. Elsevier Inc., pp. 13–21, Jan. 01, 2018, doi: 10.1016/j.cct.2017.11.002.

¹⁴ “Cancer Trial App - TROG Cancer Research.” https://www.trog.com.au/Download-our-app (accessed Aug. 10, 2020).

¹⁵ “Five Steps to Guide Successful Risk-Based Decentralized Clinical Trials – Endpoints News.” https://endpts.com/sp/five-steps-to-guide-successful-risk-based-decentralized-clinical-trials/ (accessed Sep. 16, 2020).

¹⁶ “Virtual Trials and the State of Clinical Research | ERT.” https://virtualtrials.ert.com/virtual-trials-clinical-research-report/#report (accessed Aug. 25, 2020).

¹⁷ “COVID-19 driving adoption of virtual trials -.” https://pharmaphorum.com/news/covid-19-driving-adoption-of-virtual-trials/ (accessed Aug. 25, 2020).

¹⁸ “Telemedicine soars amid COVID-19: Will virtual healthcare be the new normal? - TechRepublic.” https://www.techrepublic.com/article/telemedicine-soars-amid-covid-19-will-virtual-healthcare-be-the-new-normal/ (accessed Sep. 14, 2020).

About Alacrita

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