Sharpening the pencil: Rethinking trial design with the patient at the center
New medicines are at the core of clinical research. Historically in clinical research, these experimental medicines move from a warehouse to a clinical research site, where they are administered to a study participant. But what happens when a pandemic strikes and patients can’t access their trial site?
“When COVID hit, everything kind of stopped for a second.” said Kim Boericke, President of Commercialization and Outcomes at ICON plc. “Our first worry as an organization was how to protect the safety of patients and the integrity of our trials. Where were the risks and how could we mitigate them?”
Focus quickly turned to access to the medicines for ongoing trials. ICON began their COVID response by exploring what services could be implemented right away to ensure patients received medicines. The result was the implementation of direct delivery mechanisms, ensuring that drugs reached patients.
But delivery is only part of the equation. Experimental medicines present challenges for proper administration, patient monitoring and more. Through Symphony, an ICON company division which provides in-home nurse visits, ICON was able to work directly with patients to continue their treatment, ensure safety and collect data. Other systems enabled patient engagement over the phone to collect information on outcomes, rather than visiting a trial location.
Although regulators were receptive to alternatives to patients going to sites, it was difficult to immediately implement because most trials weren’t designed with this degree of remote monitoring in place. Protocols needed to be rewritten, endpoints and biostatistical analyses reassessed, followed by IRB and regulatory approval of modifications. These pivots were most easily implemented where there was already access to electronic medical records (EMR), which enabled remote monitoring of the study. COVID sparked flexibility with regulators, allowing more remote monitoring, in a way that offers insight into the future of clinical research. After 6 months of not being able to go on site, the industry has demonstrated it can advance new medicines in a hybrid approach without always deploying in-person monitors.
Genuine patient centricity
A COVID-inspired acceleration toward hybrid and decentralized trials is also decreasing the burden on patients. “Patients want to be part of finding the solution to diseases,” said Boericke. But there can be a heavy burden of time and effort of being in a trial, which can decrease enrollment and drive dropout. COVID has sparked protocol design shifts that incorporate more Real World Data (RWD), with the aim of finding a bigger pool of patients that can commit to fully participate in clinical research.
Boericke explains that clinical trials have often been in search of “the healthy, dying patient” – participants with exactly the narrow disease state of interest, and no other comorbidities. This type of “white unicorn” patient population can reduce the complications of figuring out efficacy and safety amidst a slew of biological complexity. “What we’ve seen with COVID is that it’s harder to find these unicorns because they never really existed. We need to be testing medicines in a real environment where we have real people.” Trials of the future will need more and better data to understand real patients and what is ‘good enough” to recruit the right population and achieve a study’s goals.
Early indicators of change
Retrenchment in remote monitoring has already been seen. Because studies that started pre-COVID didn’t have that level of remote monitoring built in, there has been some return to what regulators agreed on for that study. Boericke doesn’t expect remote monitoring to decrease to the pre-COVID levels, but that studies will strike a more remote-heavy balance.
With new studies, some sponsors are already asking for “no onsite” solutions. Most are still looking for a balanced approach, however, with a mix of remote and onsite monitoring, home visits and onsite patient engagement. This is expected to decrease patient burden, but also accelerate the pace of change. “We’re a ‘fast following’ industry. Sponsors are reluctant to jump in with both feet until the FDA or EMA bless something, and then they all dive in right after.”
Sharpening the pencil to reduce development time
“The one thing we need to learn from COVID is that drug development takes too long. As an industry, we have to figure out how to sharpen that pencil. Even in the face of a pandemic, we still can’t react as quickly as people would like us to.” Boericke sees that reducing cycle times – shortening phases or merging phases and reducing dead time – as ripe for innovation.
Another source of delays in R&D is the speed of recruitment. Rethinking trial design and planning for the real world, rather than the unicorns, can improve development time. The last six months has demonstrated that reducing site obstacles makes it easier for a patient to want to contribute and be part of a solution.
COVID has allowed ICON to be much more creative and edgy when implementing solutions that integrate diverse data sources and focus on the patient experience. Those lessons point the way to the future of clinical research. When trials generate more meaningful data with greater speed, they help much-needed solutions reach a population in need.
Kim Boericke, President, ICON Commercialization and Outcomes Services