For patients dealing with rare or difficult-to-treat conditions, access to new, cutting-edge therapies can have vast implications on health outcomes and quality of life. As the industry continues seeking new ways to get promising treatments to patients as quickly as possible, clinical trial sponsors are making their studies more efficient and patient-focused by replacing a trial’s placebo group with existing, real-world data in what’s known as an external control arm.
A new, evidence-driven approach
In a typical clinical trial, patients are placed, or ‘randomized,’ into one of two groups — one receives the investigational treatment, and the other a placebo or other comparative treatment — often the standard-of-care treatment. Although this has been the process for decades, it comes with downsides for both sponsors and patients. “Randomized trials are unwieldy and expensive, which can contribute to increased drug development timelines,” says Amy McKee, Head of Regulatory Oncology at Parexel. Leanne Larson, the company’s Senior Vice President and WW Head, RWE and Access, says that it can be particularly troubling when dealing with rare conditions that aren’t well treated today. “That’s when there’s real urgency to get new treatments out as quickly as possible,” she says.
Trials that use an external control arm work differently. Rather than enrolling two different groups, all patients in the trial receive the treatment being tested, and the placebo (or comparator) group is constructed using data drawn from outside the trial. “Essentially, it’s a control arm that doesn’t exist within the trial itself,” Larson says. “All patients (in the trial) are in the treatment arm, and we’re pulling in the controls from another source.”
The ability to construct these types of external control arms has been driven in part by advances in access to high-quality real-world evidence (RWE). “We can leverage data from an EMR, claims databases, or even sources like genomic databases,” Larson says. “We have tools and processes to rigorously evaluate and analyze those data, transform them into meaningful evidence, and ensure they are relevant and appropriate to the trial.”
“We’re wasting the data if we’re not using them to answer some of our research questions,” adds McKee, who believes the COVID-19 pandemic illustrates the value in leveraging what already exists. “We had to turn to real-world evidence,” she says of early efforts to understand the virus and its progression. “It was the only thing we had.”
Speeding development, improving access
External control arms improve patient access to promising treatments in several different ways. First, an external control arm can make trials more efficient, which might ultimately speed the pace of drug development. “Because (external control arms) can accelerate a trial by not requiring as many people to be enrolled, it can be a much faster study,” Larson says. “That means the product can get through the approval process more quickly, and ultimately, out to patients more quickly.”
But trials that use an external control arm rather than enrolling a placebo or comparator group also offer patients a more immediate and perhaps more concrete benefit — guaranteed access to treatments being tested. ”When I can promise a patient they will receive the active treatment if they participate in a certain trial and not a placebo, that really matters to them,” McKee says. “As an oncologist, it’s something I talk to them about all the time.”
The ability to make that promise has become increasingly important as savvy patients turn to resources like advocacy groups to evaluate different trials. “If you’re looking for a particular treatment, you’ve probably done your research,” says McKee, “You understand how trials work and won’t risk being enrolled in the control arm (placebo group). You want the new thing, because it might be more successful than what’s out there now.” She adds that if trial participants learn they’re receiving a placebo they will sometimes drop out, which can slow trials — and ultimately drug development.
An exciting evolution
McKee and Larson both see external control arms as part of an exciting evolution in clinical research. “We’re becoming a lot more sophisticated in how we gather data and how we analyze it,” McKee says. “And I think it (the external control arm) is going to become another great tool in clinical research.”
“The advances we’re seeing in these (external) control arms highlight the fact that there are other ways to look at how we do things,” adds Larson. “I see it as a new way to answer some of our important questions — a really significant shift in the way we develop drugs — and allows us to do it in a more patient-centric way.”
Ultimately, it all comes back to that focus on patients. “They just want to try to figure out how to get access to the treatments that look the most promising,” McKee says. “They (external control arms) have the power to play an important role… they show us all that there are new, exciting ways for us to do our work.”
For further patient-focused and RWE insights, download Parexel’s eBook, “The new imperatives: adapting oncology drug development to a post-COVID world.”