In an interview during the NIH Pragmatic Trials Collaboratory’s 2024 Annual Steering Committee Meeting, Tracy Wang of the Patient-Centered Outcomes Research Institute (PCORI) discussed challenges of conducting A vs B pragmatic clinical trials of approved drugs in routine clinical practice. Wang joined Adrian Hernandez, co–principal investigator of the NIH Collaboratory Coordinating Center, and Pearl O’Rourke, cochair of the program’s Ethics and Regulatory Core.
“There are a couple of key challenges, the first of which is, who’s going to pay for the drug, especially if the [drugs being compared] have differential drug costs,” Wang said. “The other aspect is, how do we preserve the rigor of that comparison, [such as] the need for blinding, which is not as pragmatic in routine practice,” she said.
Most pragmatic trials, including the NIH Collaboratory Trials and those conducted through the National Patient-Centered Clinical Research Network (PCORnet), compare standard care with proposed improvements to standard care, or “A vs A-plus trials.” Trials that compare 2 alternative treatments that are in current use, or A vs B trials, are rare.
The problem of A vs B pragmatic trials was the subject of an NIH Collaboratory workshop, as well as an article from the Coordinating Center in the New England Journal of Medicine.
Wang, a cardiologist and clinical researcher, is PCORI’s chief officer for comparative clinical effectiveness research. Hernandez is a professor of medicine and the vice dean and executive director of the Duke Clinical Research Institute in the Duke University School of Medicine. Prior to her retirement, O’Rourke was the director of human research affairs at Partners HealthCare Systems in Boston and an associate professor of pediatrics at Harvard Medical School.
Access the complete meeting materials from the 2024 Annual Steering Committee Meeting.