Remote Research and Clinical Trial Integrity During and After the Coronavirus Pandemic

Abstract

Approximately 1 year ago, in March 2020, clinical trials were suddenly and severely disrupted by the COVID-19 pandemic. Pandemic-related restrictions that limited or prevented in-person visits resulted in unprecedented obstacles to clinical trial enrollment, data collection, and intervention delivery for many clinical trials. 1 As of April 21, 2021, ClinicalTrials.gov listed 1773 suspended clinical trials, with many trials identifying the COVID-19 pandemic as the primary reason for suspension. Ongoing trials that were not suspended are likely to be experiencing challenges with enrollment and fidelity to aspects of study protocols that require in-person contact, including interventions and outcome assessment.Many clinical trial investigators replaced in-person interactions with alternative approaches conducted remotely. 2 A survey of 245 clinical trial investigators reported that the proportion of participant interactions conducted remotely increased from 9% in January 2020 to 57% in May 2020. 2 Remote interactions with participants implemented in response to the pandemic included mailings or drop-off of devices, such as physical activity monitors or pulse oximeters for outcome measurements, and mail delivery or drop-off of pills or devices for trial interventions. 3,4 Additional activities implemented to avoid in-person visits included use of telephone, web-based or video interactions, home visits, or outdoor visits to collect outcomes or administer interventions. [3][4][5] These remote activities facilitated clinical trial progress during the pandemic.Embedded trials build data collection for a clinical trial into essential clinical care and represent another alternative to in-person clinical trial interactions. An example is the ongoing Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE) trial (NCT04262206), in which 20 000 participants 75 years or older are randomized to atorvastatin 40 mg daily or placebo and followed up with the electronic health record for outcomes of disability-free survival and cardiovascular events. Medications are mailed to participants' homes. Outcomes that are not part of routine clinical care, including detailed cognitive assessments and physical performance testing, are collected at participants' homes by trained research staff. A visit to a research laboratory is required to collect blood for a biorepository of red blood cells and DNA.An example of a fully remote trial was a randomized, double-blind, clinical trial conducted in St Louis, Missouri, that evaluated whether fluvoxamine, compared with placebo, improved outcomes in 152 outpatients newly diagnosed with COVID-19. 4 Eligibility screening was conducted by email and telephone and COVID diagnosis was confirmed using electronic health record

Impact of potential modifications to Alzheimer’s disease clinical trials in response to disruption by COVID-19: a simulation study

“…The results of our simulations demonstrate the potential utility of various adaptations that might be made to maintain the validity and integrity of treatment trials disrupted by COVID-19 [ 9 ], including the use of remote outcome measures and interventions [ 10 ]. Clearly, continuing a trial after a pause is a substantially better option than prematurely ending it and analyzing truncated trial data, even in the face of increased dropouts, medication disruptions, missing outcomes, and other exigencies.…”

Participant views and experiences of sexual health research: The Contraception Choices online trial

“… 5 Automated online recruitment was much quicker and less resource-intensive than face-to-face recruitment and is highly appropriate in the context of the coronavirus pandemic. 19 The credentials of a research team are important to participants, 20 and should feature on online recruitment adverts.…”

Adapting to the Pandemic: Protocol of a Web-Based Perinatal Health Study to Improve Maternal and Infant Outcomes (Preprint)

“…Despite study challenges related to the pandemic, including time and effort adapting to a remote protocol, remote recruitment and remote visits for this study were found to constitute a successful approach. We also recognize the potential advantages to participants in accessing our study remotely, including lessening the burden of time, costs, and inconvenience associated with traveling for in-person visits at the clinic [14]. It is important to note, however, that there are limitations to remote delivery of study visits, which may pose challenges for generalizing to other research studies or clinical settings that may not offer remote care.…”

“…In this paper, we highlight the ways in which our study team has adapted our research protocol and study procedures so that we can continue recruitment, assessment, and intervention remotely during the COVID-19 pandemic. Remote study participation may have potential advantages for participants, including lessening the burden of travel time, costs, and inconvenience associated with in-person visits [14].…”