A paper authored by the DCRI’s Adrian Hernandez, MD, MHS, and colleagues calls for major changes in the research ecosystem to enable pragmatic trials, especially those comparing different treatments in order to generate evidence needed to guide decisions in clinical practice.
Reducing uncertainty in clinical practice will require a move toward a learning health system in which research is embedded in clinical care, write the authors of a recent Perspective piece published in the New England Journal of Medicine.
The DCRI’s Adrian Hernandez, MD, MHS, Professor of Medicine and Vice Dean for Clinical Research for the Duke University School of Medicine, was one of the authors for this publication, which comments on a goal set in 2010 by the National Academy of Medicine (NAM). The goal outlined that by 2020, “90 percent of clinical decisions will be supported by accurate, timely, and up-to-date clinical information, and will reflect the best available evidence.” The paper’s authors argue that uncertainty still abounds in clinical practice, with little or no evidence in many cases and “haphazard, arbitrary selection” guiding treatment decisions.
While data from observational studies and health records can fill some of these gaps, randomization “remains the best tool for the unbiased comparison of many alternative treatments,” the authors write. However, traditional randomized clinical trials are slow to provide much-needed evidence, and because of highly specific inclusion criteria, results are often not generalizable to a wider population.
To address this problem, the authors recommend major changes in the ecosystem to enable clinical trials that are embedded into clinical practice and address common decisional dilemmas for clinicians. The majority of current pragmatic trials compare current clinical practice to proposed improvements rather than comparing two or more treatments to determine which results in better outcomes. The NIH Health Care Systems Research Collaboratory and PCORnet®, the National Patient-Centered Clinical Research Network, are two entities that work on pragmatic clinical trials, and the DCRI serves as a coordinating center for both entities. The paper’s authors draw on their experience working with both organizations to identify the challenges of conducting pragmatic trials especially designed to study head-to-head comparisons. The authors’ observations include:
- There is a false impression of certainty in clinical practice, and more transparency is needed around uncertainty.
- Meaningful engagement with stakeholders is necessary, as research “should focus on questions and outcomes that are important to patients, clinicians, and health care systems.”
- Health systems that have established infrastructure and the resources needed to conduct pragmatic trials and implement a learning health system are more likely to be successful.
Navigating these challenges will require buy-in from many stakeholders, including:
- Health system leaders must place value on rigorous evidence generation and consider it “a core function of ordinary health care.”
- Research sponsors must support infrastructure for embedded research and fund projects that answer questions that can make an impact on population health.
- Regulators must consider aligning consent procedures with research risk, as randomization is no more risky than the guesswork that occurs in today’s uncertain clinical practice environment.
- Researchers must ask real-world questions that are important to patients, caregivers, and clinicians.
Although the NAM’s goal for evidence-based decisions remains distant, the authors write, progress will only begin when all of these parties recognize that the current evidence is not sufficient and come together to institute change.
Other authors of the paper include Gregory Simon, MD, MPH, of the Kaiser Permanente Washington Health Research Institute and Richard Platt, MD, MSc, of the Harvard Pilgrim Health Care Institute. Both of these institutes serve as part of the NIH Collaboratory coordinating center along with the DCRI.