Pragmatic trials offer benefits in the development of precision medicine for lung cancer

Double-blind randomized clinical trials (RCTs) are the gold standard for evaluating how effective a treatment is as an intervention in a clinical setting. When it comes to understanding how a treatment is or isn’t beneficial in real-world settings, however, pragmatic trials offer advantages that RCTs do not.

Double-blind RCTs have several drawbacks, according to Dr. Nicholas Robert, medical director at Ontada, an oncology technology and insights business supported by McKesson. “RCTs are narrowly focused, expensive, take many years to yield results and take place in strictly controlled settings,” he says. “They require a large enrollment of patients who have been selected in order to minimize attributes that could influence the clinical outcome.”

Pragmatic trials, on the other hand, aren’t examining the effectiveness of a treatment against standard of care. Double-blind RCTs have already answered the question of whether a drug is safe. Instead, pragmatic trials are real-world trials that try to understand what a problem is before trying to solve that problem. Using real-world data, they attempt to answer questions that can’t be addressed in RCTs. That means they leverage patients who are already in treatment by following their journeys via the data in their electronic health records (EHRs).

Pragmatic trials in action

Take, for example, MYLUNG, or “Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium”, a new research study that incorporates pragmatic elements over multiple protocols. The study brings together providers and researchers from The US Oncology Network, US Oncology Research and Ontada, plus life sciences companies and patient advocacy groups to better understand and advance precision medicine for non-small cell lung cancer (NSCLC).

“With MYLUNG, we’ll be observing the real-world data of approximately 12,000 NSCLC patients from across the United States over a five-year period,” says Dr. Robert Coleman, chief scientific officer for US Oncology Research and principal investigator for the program. “This study will help us gain a fuller understanding of the barriers, challenges, risks and opportunities that exist around using molecularly-guided therapies.”

The MYLUNG study won’t be comparing therapies, according to Sarah Alwardt, Ph.D., vice president of operations at Ontada. “We’re not saying, ‘You need to pick this treatment over that one,’ or any comparison like that,” she says. “We’re looking at whether there are interventions that help move the needle on genetic and genomic testing and subsequent adoption of clinically appropriate targeted therapies.”

To get at such questions, pragmatic trial researchers dig through the data in EHRs, such as physician notes, patient progress notes and diagnostic tests such as x-rays and pathology reports. “You observe how they react to the treatment,” Dr. Robert says. “You don't need all the bells and whistles that you need for a randomized trial.”

Statistical rigor

Just because pragmatic trials are not as programmatically complicated as RCTs doesn’t mean they are lacking in rigor. “These trials use actual data from patients’ EHRs, so they are statistically rigorous – they aren’t anecdotal observation,” Alwardt says.

Just as with the RCT process, pragmatic trials go through a series of phases that build on one another with the ultimate goal of providing patients with the best and most effective care. In the MYLUNG example, the first phase of the study examined a large amount of retrospective data to discover what patterns exist around targeted therapy uptake and use, according to Alwardt.

The second phase of the study will establish a baseline from the data captured in the first phase. “We'll start to think through the other things we need to be doing,” Alwardt says. “What are those other pieces that we need to understand? What are the things we can do to improve either appropriate utilization, accessibility, interpretation or any of those things around genetic and genomic testing and targeted therapies?”

The third phase of the study will be to implement interventions aimed at overcoming the barriers or challenges found in the first two phases of the study.

“From a patient standpoint, we believe that we’ll be able to take what we learn and extrapolate that broadly, spanning tumor types and heterogenous practices, and beyond lung cancer,” Alwardt says. “That way, we can really change the ecosystem, putting solutions in place to close the gaps that we find.”