Pragmatic clinical trials experienced significant impacts of COVID-19 on trial activities, according to a survey of NIH Collaboratory Trials published in Trials (O’Brien et al. 2022). All of the trials were able to adapt to pandemic-related changes. In a video interview, lead author Dr. Emily O’Brien praised the study teams.

“We certainly did see some degree of disruption, but I was impressed by the flexibility in the ability to adapt that all of our [study] teams showed,” said O’Brien. “Some of them mentioned the support of having the [Core Working Groups] and consultations with experts in real time to be able to make adjustments,” she said.

One key finding from the survey was that healthcare operations and social distancing resulted in project delays, and some trials even needed to start over (O’Brien et al. 2022). For example, in an interview with Karen Sherman, Co-PI of BackInAction in 2022, she stated, “Our biggest challenges have been associated with COVID-19 impacts. Given the higher risk and vulnerability for our older adult target population and the requirement for in-person treatment (acupuncture), we delayed the start of recruitment by many months to ensure that those outreached had ample opportunity to be vaccinated beforehand and have also paused recruitment commensurate with regional surges of COVID variants at one or more of our clinical sites as needed. We also vetted the community acupuncturists who provide acupuncture to our study participants to ensure adequate COVID-safe office practices.”

Trial delays often created statistical challenges, especially for those using stepped-wedge designs. To help address this problem, NIH Collaboratory’s Biostatistics and Study Design Core Working Group developed a tool to assist investigators in identifying impacts of the COVID-19 public health emergency on ePCTs. The Statistical Analysis Plan Checklist for Addressing COVID-19 Impacts summarizes impacts on trial conduct that study teams should document, measure, analyze, and report.

The leaders of the Biostatistics Core, Dr. Patrick Heagerty and Dr. Liz Turner, spoke in an interview about the impacts of the pandemic on the NIH Collaboratory Trials.

Resources: Statistical Analysis Plan Checklist for Addressing COVID-19 Impacts.

In addition to delays, changes to the intervention, implementation plans, and data collection strategies were often necessary (O’Brien et al. 2022).

Pandemic-related modifications resulted in some benefits, including expanded outreach capabilities and the use of virtual interventions (O’Brien et al. 2022). For example, the intervention for Guiding Good Choices for Health Study (GGC4H) is a group-based program for parents and caregivers of adolescents. The GGC4H study found that virtual parenting support coinciding with COVID-19 helped families deal with the impact of the pandemic; the intervention was delivered with high fidelity across cohorts, sessions, and sites; and parents were satisfied with the virtual program, with parents valuing the flexibility, connection, and community.

As another example, the ACP PEACE trial, which studied advanced care planning, modified their intervention, including texting patients a video to view before their clinic visits. This enabled the team to reach a wider population and to study virtual intervention delivery (O’Brien et al. 2022; LaVine et al. 2023). Finally, the OPTIMUM study was initially designed to provide group-based mindfulness to people with chronic low-back pain. Due to the pandemic, the trial pivoted to a telehealth intervention, and used input from participants in the pilot to help make sure that the information was accessible and appropriate, while maintaining fidelity to the original intervention.

The COVID-19 pandemic provides an example of an unanticipated change that had enormous ripple effects across the trials.  Other unexpected external events are likely to happen, and ePCT investigators can take the lessons learned from the pandemic and apply them to other situations. As seen in the examples, close collaboration with healthcare systems leaders and other partners is critical. It is also important to remain adaptable to change throughout the process to allow for a pivot, if needed.