How Cerevel Therapeutics Put Hybrid Trials Into Practice
By Deborah Borfitz
March 31, 2021 | Cerevel Therapeutics is looking at new studies in a different way after test-driving an assortment of virtual trial options when the pandemic hit. Remote site initiation visits and remote monitoring will be permanent fixtures moving forward, and the incorporation of home health visits also appears promising, according to Laura Whitmore, director of clinical operations oversight, during a presentation on operationalizing hybrid trials at the recent Summit for Clinical Ops Executives (SCOPE).
The two-year-old biotech company is focused on therapies for central nervous system disorders. Currently, Cerevel is conducting several phase 1 studies in addition to two phase 2 proof-of-concept studies and four phase 3 studies, Whitmore says. The phase 2 and 3 studies are all being conducted globally.
COVID-19 caused the company to temporarily stop enrollment into all its studies in the spring of 2020. It was “between cohorts” with its phase 1 studies and no randomization had started for its phase 2 and 3 studies, so the timing could have been worse, she says.
Decisions about where and when to restart the studies was entrusted to a cross-functional task force and based on an assessment of public and private data at the macro, regional, and site level, says Whitmore. The private data sources include global advisory group meetings, site-level contacts, and questionnaires sent to investigators.
The job of the task force was not only the timetable for study restarts, but also identifying the necessary tools and processes to mitigate COVID-19 risk, she adds. A trial execution team was assembled to research, evaluate, and recommend potential technology and innovative trial processes to meet needs in the COVID-19 era.
The group did a deep dive on all studies in the portfolio to assess the risk based on the patient population, trial design, and length, and, most importantly, any safety concerns, Whitmore says. For every visit and assessment, they would consider the impact of a patient not being able to get to the site for any reason—be it a government shutdown, an individual site closure, a patient exposure or testing positive for COVID-19, or a patient worried about a local outbreak and not wanting to travel to the site.
Once risks were understood, the team began looking at virtual trial solutions that could mitigate them under a tight deadline and without knowing how long the pandemic would last, says Whitmore. “We also determined that all of our [solutions] needed to be on demand; they would only be used when necessary. Based on our protocols, on-site visits were optimal, and we wanted to maximize those. Some visits had to occur on site; there were no virtual workarounds.”
Workstreams were broken up into four areas based on study and program needs, Whitmore says. The workstream specific to patient access and safety focused on ensuring patients could complete a trial safely. If they could not, the trial would need to be brought to them. Potential solutions identified here were telemedicine, home health visits, patient travel, eConsent, and wearable devices. eConsent was already being used in phase 2 and 3 studies, she notes, and that helped get new consents quickly out to patients.
In the workstream for investigational medicinal products (IMP), study supplies and labs, the focus was on how to get IMP to patients and how to handle lab sample collection, Whitmore continues. For the latter, home health ended up being the solution.
Knowing site access for CRAs would be an issue, the monitoring and data quality workstream evaluated tools for remote monitoring, source data verification, and any enhanced analytics for monitoring site progress to identify issues early, she says. The support workgroup was responsible for documentation and communication for the site, patient, and study team and the goal here was “to build things so they’d be turnkey whenever possible.”
The groups did extensive research quickly and in parallel, she says. “We had different solutions moving through our process at different times.”
Two different remote monitoring solutions were evaluated but, in the end, Cerevel did not contract with either vendor, says Whitmore. “We were able to identify a solution that connected to our eTMF [electronic trial master file], and that required sites to contract directly with that vendor,” she explains. “We also received feedback from many sites that they had solutions in place that would allow for remote source data verification.”
A request-for-proposal (RFP) was received from one of two direct-to-patient IMP vendors evaluated, with whom a contract was signed, Whitmore says. Vendors for other services, such as curbside delivery, were also identified that could meet site and patient needs.
Capabilities presentations were made by four home health services providers and RFPs were sent to three of them, she continues. An agreement was ultimately signed with one vendor to service all six of the company’s phase 2 and 3 studies.
Many vendors were researched for remote data collection (e.g., sensors, wearables), but only six were invited to make capabilities presentations, Whitmore says. “We focused on safety data specifically, vitals and cardiac solutions.”
A contract was signed with only one of those vendors, she says. “This is definitely a challenging area because the data we collected had to be comparable to site data. We ran into a lot of solutions that were not yet validated or did not capture the same data that we needed.” Additionally, startup timelines were often prohibitive for vendors, “much longer than we really had to invest.”
Telemedicine providers were heavily researched, and the thinking initially was that Cerevel would identify a single solution for all its studies. The company had five capabilities presentations but decided not to request any proposals because feedback from sites and others in the industry was that most sites had solutions in place or would only use those that integrated with their internal system, she explains. Although the company let sites know it could recommend telemedicine vendors if the need arose, no such requests have come in, she adds.
Money discussions were paramount given that Cereval Therapeutics does not yet have a product on the market, says Whitmore. Budget models were built so it could better understand what the new interventions were going to cost. “We built models around three different scenarios based on the projected patients’ impact, and we modeled out costing for year one , year two , as well as the full life of the trial.”
Costs were broken down by startup, monthly maintenance fees, per-patient fees, and per-visit fees, she says. “This took a long time, and these are very complicated models; however, they were incredibly valuable and made it very easy to switch numbers around and make changes, so we are going to be able to use these models on an ongoing basis for budgeting clinical trial solutions.” The projections have proven to be “pretty much on target,” she adds.
The main budget drivers were the number of countries (15 in one study), sites, patients, and visits, as well as total months using a new solution, along with any start-up costs, says Whitmore. Detailed trackers helped the company follow progress, understand timelines, and keep senior management apprised of every intervention for every study.
As the contracting process started last summer, Cerevel simultaneously restarted its studies, she says. Solutions were available for sites to use immediately as those agreements were signed.
All study teams and sites have been trained on the new capabilities and using the interventions when needed, says Whitmore, but actual deployment has been limited to less than 5% of randomized patients. To date, three countries have used telemedicine, direct-to-patient IMP delivery, paper-based remote scales, and home health visits. In addition, the company has seen high adoption of remote monitoring since many study sites continue to discourage on-site monitoring.
For studies conducted from now on, says Whitmore, remote site initiation visits will be the norm because it is the “preferred option” by sites and also effective from Cerevel’s perspective. Remote monitoring is being built into “every study where it makes sense... we think it’s better for us but also better for the sites.” Use of eConsent will also continue.
Home health visits are a feature of a new trial that is starting soon, she adds, which is expected to make the study “much more attractive to patients.” The same vendor used for mitigation purposes will be providing those services as an extension of the relationship.
Cerevel is actively evaluating wearables and home-based data collection tools to add to what the company is currently using, says Whitmore. “We’re really excited about the possibilities and the integrations these offer.”