April 16, 2020: Why Randomized A vs B Comparisons Remain Uncommon in Clinical Trials

In an article published today in the New England Journal of Medicine, NIH Collaboratory investigators Drs. Greg Simon, Rich Platt, and Adrian Hernandez describe why it has been so challenging to meet the National Academy of Medicine’s 2020 goal for the development of a learning health system. If the goal had been met, 90% of clinical decisions would be based on accurate evidence gathered from health systems that continually learn from data collected as part of routine care.

Absent such evidence, the type of care provided is determined by the haphazard influences of financial incentives, clinicians’ anecdotal experiences, and patients’ or clinicians’ exposure to marketing messages. — Simon et al, New England Journal of Medicine, April 16, 2020

Most pragmatic trials, including the NIH Collaboratory Demonstration Projects and clinical trials conducted through the National Patient-Centered Clinical Research Network (PCORnet), have compared 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 rarely done.

The authors describe both the barriers and the potential solutions for the development of more A vs B pragmatic clinical trials in pursuit of a learning health system.

“Achievement of the NAM’s goal of basing 90% of clinical decisions on accurate evidence remains distant, and meaningful progress will involve engagement by many parties,” write Simon and colleagues. “It will require health system leaders to consider rigorous evidence generation a core function of ordinary health care, research funders to prioritize practical questions relevant to population health and to support infrastructure for embedded research, research regulators to align consent procedures with incremental risks of research, and researchers to ask real-world questions that patients, caregivers, and clinicians want answered. But the first step is for everyone involved to honestly acknowledge the lack of evidence supporting the majority of common medical decisions and the urgent need for more relevant and efficient clinical research,” the authors continue.

The impetus for the article was an NIH Collaboratory workshop, Embedded Pragmatic Clinical Trials of Therapeutic A vs B Interventions. The workshop explored challenges and strategies for planning and implementing embedded pragmatic clinical trials that compare 2 or more therapeutic medical regimens.

The authors of the article are Adrian F. Hernandez, MD, MHS, professor of medicine and vice dean for clinical Research in the Duke University School of Medicine; Gregory E. Simon, MD, MPH, of the Kaiser Permanente Washington Health Research Institute; and Richard Platt, MD, MSc, of the Harvard Pilgrim Health Care Institute. All 3 institutions are part of the NIH Collaboratory Coordinating Center.