Sites Overwhelmed by Cost and Trial Complexity, Need Sponsor Help to Bear the Burden
Dwindling clinical trial financial resources caused by COVID-19 and declining investigator participation are clashing with sponsors’ demand for more — and more complex — trials, creating a “perfect storm” of pressure that threatens to overwhelm the research industry if sites and sponsors don’t work together to adjust to the realities of life in a pandemic.
Sites have been under significant financial and resource pressure since long before COVID-19, Nicholas Slack, WCG Clinical executive vice president and chief commercial officer, said. “They were before the pandemic and those issues are being exacerbated by the pandemic. … And so we have to wonder,” Slack said, “will the volume [of trials] overwhelm the system if something doesn’t change?”
Slack said that when you dig into the financial data, you realize that trials aren’t even a break-even operation. “Actually, trial costs, research program costs aren’t covered by the program itself; rather they’re largely subsidized to the tune of 38 percent,” Slack told attendees at a WCG Clinical webinar last week.
At the same time, new investigator participation had been significantly declining in the years before COVID-19 appeared, he said. Data from WCG Clinical’s KnowledgeBase show that the rate of new investigators entering the research field has dropped 60 percent in the past five years.
The number of trials registered with ClinicalTrials.gov has increased by 44 percent in the same period, Slack said. Data from the Tufts University Center for the Study of Drug Development show phase 3 trials have experienced a 70 percent increase in trial procedures and an 86 percent jump in the number of endpoints.
To ensure that sites can adjust to growing financial and staffing pressures, sponsors need to find innovative ways to relieve their burden, he said, pointing to one sponsor’s two-year relationship-building effort as a model.
Sanofi’s SMILE (Sanofi Making Investigators’ Lives Easier) program began in 2018 as a conversation with the sponsor’s site partners about their needs. “The theme always resonated around complexity, around burden,” said Vicky DiBiaso, Sanofi vice president and head of global strategy and collaboration. “So at that point, we really felt let’s address burden,” DiBiaso said. “How do we focus on that, where do we even start?”
The company’s focus on improving site relationships was spurred by a disappointing 11th place finish on the 2017 CenterWatch Global Site Relationship Benchmark report, DiBiaso said.
The resulting five-point plan put the company in a position to help their sites survive when the COVID-19 pandemic hit in late 2019, DiBiaso said. “I can honestly say one of the things that we’re proud of is that we have not had to stop any of our studies for enrollment,” she said. “We are still starting new studies because of a lot of the things that we addressed early on in this.”
Sanofi began by considering protocol optimization, using digital and real-world evidence to “pressure- test” their trial templates and make them adaptable to unanticipated events, such as a worldwide viral infection.
When planning new studies, “if we have to apply some flexibility, whether it’s in a remote procedure, whether it’s in direct-to-patient drug shipments,” she said, “that is already built in to avoid an amendment, to avoid the slowdown in continuing the trial.”
“A lot of times you may have a protocol that’s developed through science,” added Karri Venn, president of research at LMC Manna, one of Sanofi’s partners, “but not thought about the clinic perspective. And so I think the minute you get those two together, you realize what is that “must-have” vs. the “wish list.”
“The concept is not to go back every time as a site to feed back the same information,” Venn said. “But to have that information embedded into protocols as they move forward, become the standardization, makes it easier.”
DiBiaso said speed was essential in reacting to the pandemic. “If you have patients that all of a sudden, with very little notice, as we’ve all seen with COVID, cannot get to the clinic, [then] there’s a smooth transition to remote capabilities.”
LMC Manna conducted a virtual trial experiment with Sanofi in 2016 that proved the point, Venn said, giving it the site intelligence needed to pivot quickly to telemedicine when the pandemic hit. “It took literally over a weekend and our sites were comfortable, our [quality management system] team was comfortable creating these processes,” she said. “We had many years prior to COVID hitting so that we were ready to run with it.”
The second area Sanofi addressed was finance and contracts. “When we started SMILE,” DiBiaso said, “some of the feedback we were getting is that payments perhaps weren’t as timely as sites would like to see.” The company instituted a policy of a two-week payment turnaround to help alleviate sites’ concerns about cash flow, a move that has proven very helpful to partners trying to weather the current economic downturn.
Sites need monthly payments, Venn agreed. “If they’re only getting paid quarterly in a time where there’s a cash crunch, it becomes very meaningful to see that month-over-month cash.”
And more transparent negotiation procedures have helped sites understand the payment structure more clearly, increasing startup time and allowing faster site reimbursement without hold-backs.
The third focus, Sanofi’s site partnership approach, has improved relationships, DiBiaso said. “We’re trying to be much more transparent with the portfolio so that sites know what studies are coming and when.”
As part of the partnership, the company has established dedicated points of contact for each site to help keep them in the loop and offer feedback. “A lot of our site partnerships are the first sites that we turn to for feedback on our protocol design, as part of the optimization for the real world,” DiBiaso said.
Recruitment also is a partnership function, she said. The company’s global recruitment capacity and focus on patient feedback has allowed it to achieve two to four times more enrollment per site than previously.
CRA empowerment is the fourth prong of the SMILE program, featuring enhanced training and motivation to help reduce monitor turnover. “These CRAs are the face of the sponsors,” DiBiaso said. “So we want to make sure that our CRAs feel empowered and part of our team, and that they’re really equipped with the knowledge and the skills to do the job easily.”
As the fifth step in the plan, Sanofi improved its overall study support through such methods as gathering site feedback on case report form design. And the company’s virtual site selection and investigator meeting innovations placed it well when the pandemic hit.
“We have all of that ready to go because of SMILE, and so we’re able to adjust very, very quickly,” DiBiaso said.
Venn agrees. “We’ve moved 10 years in the research industry in literally six months.”
The SMILE program paid off in higher ratings from sites on the most recent CenterWatch survey. From a disappointing 11th place in 2017, the company jumped 10 places to top the list in 2019.