Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory

Abstract

BackgroundThe clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped.MethodsTo strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design.ResultsIn this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs.ConclusionA planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I‐PICC) Study

“…17,18 These characteristics allow for the ready transition of PCTs into existing healthcare infrastructures and make them particularly appealing to comparative effectiveness research 19 and the evidence-based mission of "learning healthcare systems." 20 As calls for more real-world evidence are made to support the clinical adoption of genomics innovations in health care, PCTs are poised to play an increasingly important role in precision medicine outcomes research. 7,8 Thus, it is timely for precision medicine researchers, clinicians, and policymakers to become familiar with the underlying principles and design features of PCTs.…”

“…In addition, the embedding of PCTs into routine clinical practice may result in greater efficiency and lower costs compared with some explanatory trial designs . These characteristics allow for the ready transition of PCTs into existing healthcare infrastructures and make them particularly appealing to comparative effectiveness research and the evidence‐based mission of “learning healthcare systems.”…”

Protocol for a Noninferiority Comparative Effectiveness Trial of Home-Based Palliative Care (HomePal)

“…This is especially true for care of patients with serious illness. 6,[33][34][35] Implementation challenges for the study fall under four domains: (1) clinician readiness and openness to integrating video visits in their practice, (2) participant enrollment and data collection, (3) HBPC program staffing and resources, and (4) the evolving telehealth landscape. These challenges and corresponding mitigation strategies are described briefly here and summarized in Table 5.…”

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

“…The model they describe, however, does not truly expand the traditional approach to drug evaluation and retains the longstanding emphasis on standard safety/efficacy endpoint collection and regulator-mediated evaluation and decision making. Novel clinical trial designs and settings (e.g., the National Institutes of Health Collaboratory), large-scale health record analysis (e.g., Million Veterans Program), and new patient-engaged networks (e.g., PCORnet) have also been cited as potential opportunities to generate RWE [44][45][46]. As these are all relatively new programs (less than 3 years), their impacts are not yet defined.…”