By Deborah Borfitz

February 9, 2022 | A fireside chat on what “fit-for-future” data operations might look like in a post-pandemic world was the topic of a keynote presentation on day two of the Summit for Clinical Ops Executives (SCOPE) in Orlando, Florida yesterday. The risk-benefit ratio on many innovative methodologies and technologies has flipped over the past two years, elevating their value in the “new normal” moving forward, as shared by executives from a trio of leading biopharmaceutical companies.

The pandemic has certainly highlighted the importance of a business continuity plan (BCP) in helping companies keep their portfolio moving forward, says Darren Weston, senior vice president and head of integrated data analytics and reporting and Janssen Clinical Innovation, Janssen R&D. It has also prioritized approaches that consider the needs of patients while also avoiding the need for studies to halt and relaunch.

The challenge is adapting to local conditions by being—by pharma standards anyway—extraordinarily nimble, says Weston. Janssen accomplished this with cross-functional expertise and effort so that few of its over 700 studies were paused by COVID-19.

Cynthia Pan, senior director at Regeneron overseeing the immunology and inflammation therapeutic area, until recently ran the company’s COVID program and that gave her a first-hand view of the awe-inspiring power of collaboration around a common purpose. The focus was on getting hospitalized COVID patients enrolled in a study protocol and dosed with a product within seven days via quick decision-making, troubleshooting, and “doing things in parallel,” she says.

Pfizer paused more of its non-COVID studies than other pharma companies, according to Demetris Zambas, vice president and global head of data monitoring and management. Pandemic-related adjustments were a “test of our processes,” he says. The shift toward remote monitoring began two years ago but required a pivot from ongoing work on a flu vaccine to one targeting the SARS-CoV-2 virus—and wholesale embrace of risk-based monitoring.

Working Remotely

From a change management standpoint, pandemic-associated disruptions were unprecedented, says Weston, requiring new ways of thinking and working over the course of weeks and often days. An early targeted database lock meant quickly sorting out which metrics were truly critical to quality and concentrating on the data queries that mattered.

Almost overnight, the 70/30 ratio of on-site versus remote monitoring completely inverted to a 30/70 mix, he says. In the U.S., remote source verification was also an availed option. In-person investigator meetings, the longtime norm, were “no longer even discussed.” Communications about BCP-related changes went out frequently and from a centralized source.

Remote monitoring and remote (as well as more limited) source data verification—viewed as “impossible or unlikely” in pre-pandemic days—was likewise embraced at Regeneron for lack of any other options when COVID struck, says Pan, especially for COVID studies. In many cases, monitors weren’t allowed on-site at all, so the company created a “fit-for-purpose monitoring plan.” Frequent and short monitoring visits every week or two replaced one- to two-day visits every 16 weeks using new metrics to fit the model.

Implementation was streamlined by cross-functional collaboration with contract research organizations (CROs), Pan notes. The usual vendor model with layers of leadership and review on both sides was replaced by a task-driven functional service provider structure that was “more like a true partnership at all levels.” If need be, she adds, a message could be dropped to a clinical research associate within five minutes.

Instituting change was of course motivated by the existence of a “common [viral] enemy,” says Zambas. At Pfizer, in the time it once took to launch a run-of-the-mill clinical trial the company was able to stage an all-in-one phase 1/2/3 megatrial for a COVID-19 vaccine.

The usual study teams were involved but held “sprint meetings” to plan out how to execute at speed, he continues. The meetings were at least as much about committing to one another on deliverables (and ensuring assumptions were correct) as they were about planning and those pledges “carried us through the whole program.”

It was a similar story at Janssen, says Weston. Relaunch of the clinical portfolio involved a dedicated team who regularly came together to collectively absorb all information as well as standardization of data collection practices while meeting specificity needs of multiple therapeutic areas.

Analytical risk-based monitoring, a huge area of investment for the company six or seven years ago, has evolved from a tool that is nice to have to one everyone—without exception—desperately wants, Weston says. A centralized monitoring dashboard provides data visualization by country and program as well as at the study level. 

Risk-based data monitoring has been impactful for Regeneron as well, says Pan. Rather than outsource study startup to CROs, the company pulled that function inhouse using 10 to 15 small teams any one time who are responsible for informed consent forms, contracts, data collection, and providing administrative support to study sites.

During the pandemic, COVID studies have been launched in as little as 36 hours, Pan says. “On average, even in the summer of 2020, sites were being activated within three weeks.” Strong project management and end-to-end accountability for a single study has been critical on that front, with all eyes on the “low-hanging fruit for the day.”

Data Tracking

A machine learning tool called Smart Data Query that Pfizer introduced at SCOPE in 2020 gained popularity points during the pandemic and is now the “new norm for every single study we put out there,” reports Zambas. It alerts study teams of abnormalities in datasets and does the heavy lifting on redundant back-office tasks, notably data reconciliation.

Data related to the speed of collecting and reviewing clinical data was merged with operational metrics and presented on a new dashboard, Zambas continues. The dashboard lives on and is a critical factor in keeping all studies on track. Data refreshes happen four times daily across the board, he says, specifically citing labs, clinical outcomes assessment devices, and system refreshes.

The suite of analytics being used at Janssen answer key questions, including the spread of COVID and vaccine rollout to inform its continuity plans, says Weston. Site risk analysis and COVID’s impact on data missingness is now routinely monitored in partnership with the company’s statistical group.

Regeneron has been tapping epidemiology data to create heat maps of future disease hotspots, identifying areas where new COVID-related study sites open “just in time” when a surge hits, says Pan. The data has additionally been used to triage where materials in short supply need to be shipped, and for site selection.

‘Conditions For Success’

Decentralizing clinical trials can improve recruitment, broaden the participation pool, and enhance retention and protocol adherence, so Pan says she is optimistic that these new ways of operating will be embraced beyond COVID studies at Regeneron—including rare diseases, her new focus area. Among the options being written into protocols are electronic consent, electronic patient-reported outcomes, wearables, telemedicine, lab tests at local pharmacies and mobile testing sites, and home health nursing.

Using a tree analogy, Zambas says one simple learning from decentralized and hybrid trials is that the mighty oaks are the ones that break and not the bendable pines. Executing on studies at an accelerated speed requires a willingness to adapt rather than being bound by a specific means of working, he says.

Innovation, what Weston calls “change management in disguise,” requires significant investment as well as a dedicated team of individuals creating an “insurance policy for the future,” says Weston. “Now is the time to move on transformational change.”

Longer term, companies will need to carefully map out “conditions for success,” says Weston, using a fleet of car analogy to make his point. Sometimes a Bugatti may be needed, but more often a Chevy Impala will do.

A combination of extra hours and creativity enabled the “crazy speed” of development of a COVID vaccine, says Zambas. But teams at Pfizer are now shifting their focus to what is consistently scalable and financially reasonable.