Sponsors Should Expect Trial Recovery to Be Driven Regionally
Clinical trial activity picking back up will likely be dependent on regional factors and sponsors should not expect to see a “day one” for recovery — but they should keep an eye out for certain recovery indicators.
“There’s simply no guessing when this is going to be over, and we need to be very careful about it, but there’s going to be some leading indicators on how we would be able to start to approach in a localized way that we might be able to start to recruit patients, or the active patients are going to start to come into the clinic again,” Jill Johnston, WCG Clinical president of study planning and site optimization, said during a WCG webinar last week.
She anticipated that even after the outbreak is over, there won’t be a “return to normal,” but rather, “a new and improved normal” made by the pandemic. She said that there’s been an increased acceptance of risk-based approaches to trials, digital tools and telemedicine, which she viewed as positive.
“We know there’s been a jolt. This has been a really great opportunity for us to see forward progress on virtual and decentralized trials,” she said. “We would expect to see more and more virtual clinical trials or procedures in clinical trials.”
Johnston said to also look for lead measures — “things that we can see that patients are starting to go back and look for standard care, healthcare again, being able to see them going back and trying to manage their care in a very forthcoming way.” She noted that it’s still unclear when patients will start to return to institutions after a recovery is seen.
She recommended a “pragmatic approach” that sponsors should start considering now, outlining the rough draft of a five-step recovery preparation plan.
Approaches won’t be one-size-fits-all for studies or sites, she said. Instead, they will be “rigorous, portfolio planning prioritization[s]” of what sponsors require for each trial and when patients will be released to come back into the institution. Sponsors should consider key areas, including clinical supplies needed, expiration dates, regulatory impact, data flow, individual investigator sites and their staff, third-party vendors like labs and imaging centers, and the management of safety.
Sponsors should also prioritize studies and localize recovery efforts; Johnston noted that trials won’t open across the board. Instead, she predicted that trials will restart relatively slowly and in a localized way.
They should also know their trigger points. “We should be planning for trigger points. If we see those early indicators locally, what is the next step that should take place in order for us to start moving progression forward?”
The fourth step is taking action, she said. Once trigger points are reached, sponsors should be prepared to communicate.
“Communication is key. You cannot over-communicate enough. Transparency is the name of the game here, being open in communication and transparent about what’s going on in all ways, both with the sponsor, with the CRO and the site,” she said.
Lastly, Johnston advised sponsors to figure out how to measure if their plans are working or not, calling for flexibility and multiple backup plans if they experience problems.
As for trials that are underway now, Kathryn King, Aptinyx senior vice president of clinical development, said that remote monitoring of trials under COVID-19 conditions requires a more refined, risk-based strategy to make sure that source data verification and quality review focus on the factors most important to patient safety and trial success.
Sponsors should be thinking carefully about remote monitoring strategies and cautiously considering reduced and targeted source data verification. Ongoing trials, suspended trials and trials planned for the future all should be evaluated for risk-based monitoring approaches, King said.
“You might think that it’s not possible to do source data review remotely, but I think we are finding that there are possibilities for that, leveraging technology that protects both patient privacy information and also the security of the data that’s being shared,” she said during the WCG webinar.
She stressed the importance of “collaborative and creative” thinking for enabling data review and source data verification when on-site availability may not be possible. It’s also important to consider limitations that arise when monitors can’t be on site. For example, monitors may not be able to see information in the source when monitoring remotely, and these cases need to be factored into data integrity and quality considerations.
Additionally, monitoring of the study drug supply may not be possible; depending on its importance in the protocol and the specifics of the investigational drug, sponsors may need to consider how to get it done remotely or once on-site monitoring becomes possible. They should also consider the burden remote monitoring of supplies may place on site staff when they aren’t in the office or are focused on other things like patient care.
King also recommended sponsors consider centralizing site monitoring, which would allow remote access to data and the application of statistical methods across all of a trial’s sites and help identify data outliers at individual sites. Centralized monitoring can contribute significantly to data quality, she said. It can also help identify deviations and variations from investigational plans, ensure they’re tracked and reported, and enable collection of such information in datasets to be factored into the trial’s final data analysis.
Remote patient visits also present a challenge for collection of safety data, King said. Site staff may be able to connect with patients via web-based or telephone communication, but protocol safety parameters must be minded. If remote patient visits are conducted, it’s important that they don’t impact or underreport safety in the clinical trial, she said, noting that sponsors need to consider the patient population being worked with, the stage of development and other risks before opting for a remote visit approach.
In every case, data collection and analysis plans must be adjusted appropriately, meaning that sponsors will likely have to add new fields to their electronic data collection systems or case report forms and make changes to their statistical analysis plans, she said.