The Grand Rounds session will be held on Friday, April 26, 2024, at 1:00 pm eastern.
Milner is a regulatory policy adviser in the FDA's Office of Clinical Policy. Casey is an assistant professor of medicine and the director of the coordinating center for the Pragmatic Critical Care Research Group at Vanderbilt University Medical Center. Semler is an associate professor of medicine and codirector of the Vanderbilt Center for Learning Healthcare at Vanderbilt University Medical Center.
In an analysis of data from the TSOS study, younger patients and patients who were publicly insured or uninsured were among several subgroups of patients who were at significant risk of missing follow-up outcome assessments. The report was published this week in Injury.
Successful studies of interventions for patients with posttraumatic stress disorder (PTSD) require engaging with injured patients in long-term follow-up. Addressing the needs of patients who are at risk of not engaging in follow-up could improve outcomes and intervention procedures at trauma centers. Yet, many injury survivors are at significant risk for not following up with trauma outcome assessment procedures.
In the new secondary analysis from the TSOS study, the research team examined relationships between patients' clinical and demographic characteristics and rates of follow-up in the study. They found that younger age, public or no insurance, fewer comorbid conditions, and worse mental health function before injury were associated with lack of follow-up. Infrequent cell phone use and lack of internet access were also associated with missing outcome assessments.
The TSOS study, an NIH Collaboratory Trial led by principal investigator Doug Zatzick of the University of Washington, was a stepped-wedge, cluster randomized pragmatic clinical trial testing the delivery of a stepped collaborative care intervention vs usual care for injured patients with PTSD symptoms and comorbid conditions.
TSOS was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Mental Health and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Learn more about the NIH Collaboratory Trials.
During the course of the years-long pragmatic clinical trials supported by the NIH Pragmatic Trials Collaboratory, many unanticipated challenges have occurred, some of which have had profound effects on usual care, trial implementation, data systems, and staff. These unanticipated changes threatened the ability of the trials to address the questions they were designed to answer. A new chapter of the Living Textbook—Navigating the Unknown—describes these challenges and the responses of the study teams.
The chapter describes 3 general categories of challenges, each meriting a different response:
If the challenge is a local or temporary issue (for example, a pandemic temporarily shuts down in-person care, or a partnering health system dissolves or is purchased), but the question is still relevant or important and the trial is still feasible, then a workaround may solve the problem.
If the trial is no longer feasible for some reason (for example, the recruitment process is not feasible, or the intervention cannot be delivered as planned), and the question is still relevant, it is necessary to make significant changes to the protocol.
If the question is no longer relevant or important (for example, new evidence or policy changes make the question no longer relevant), the trial should not continue. For this challenge, it may necessary either to stop the trial or to make fundamental changes to address a different question (since the original question is no longer relevant).
The chapter describes local or temporary challenges some of the study teams faced, such as the COVID-19 pandemic, health system mergers, and changes to the electronic health record (EHR). In these cases, the research questions were still relevant and important and the trial designs were still feasible, so workarounds were created to solve the problems.
Section 2: Study teams responded to staff turnover, leadership changes, and health system acquisitions and mergers.
Section 3: Rapid technology change created unexpected consequences, such as EHR updates causing system changes that affected intervention delivery, and sites switching EHRs systems creating complexities during the trial.
Section 4: COVID-19 had significant impacts on trial activities.
Section 5 of the new chapter addresses barriers that resulted from aspects of the protocol that could have impacted recruitment, retention, or implementation in a way that imperiled the ability of trials to answer the question posed by a research study. In these scenarios, researchers found it appropriate to change the protocol or research question—to pivot—in order to glean meaningful, actionable evidence.
Sections 6 and 7 describe challenges that can fall into either category 1 or 2, and investigators had to decide how to respond in real time.
Section 6: Clinical practice guidelines and policies changed due to new evidence from observational studies, small trials, and shifting expert opinion, and therefore, usual care changed.
Section 7: Quality improvement initiatives were launched to address similar problems, threatening the ability to discern differences between arms of the trial.
The NIH Pragmatic Trials Collaboratory supports pragmatic clinical trials embedded in healthcare systems to test interventions that address urgent public health problems faced by delivery systems. They involve hundreds to thousands of participants and generally include usual care as a control arm. One of the most important lessons learned through the course of these trials is that unexpected change is a given.
The Grand Rounds session will be held on Friday, April 19, 2024, at 1:00 pm eastern.
The YODA Project promotes open science, research transparency, and the sharing of clinical research data to support healthcare research. Through the project, researchers can request access to deidentified participant-level clinical trial data and research reports.
Ross is a professor of medicine and public health at Yale University and codirector of the YODA Project.
The Grand Rounds session will be held on Friday, April 12, 2024, at 1:00 pm eastern.
Grudzen is a professor of emergency medicine at Weill Cornell Medical College and the Fern Grayer Chair in Oncology Care and the Patient Experience and division head of supportive and acute care services at the Memorial Sloan Kettering Cancer Center.
PRIM-ER, an NIH Collaboratory Trial, is a stepped-wedge, cluster randomized trial testing a multidisciplinary primary palliative care intervention in a diverse mix of emergency departments in the United States. The study is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute on Aging. Read more about PRIM-ER.
Dr. Miguel Vazquez, principal investigator for ICD-Pieces
A primary care intervention for patients with coexisting chronic kidney disease, type 2 diabetes, and hypertension did not reduce the hospitalization rate for these patients when compared to usual care, according to the ICD-Pieces study.
The results of the study were published this week in the New England Journal of Medicine.
ICD-Pieces, an NIH Collaboratory Trial, was a cluster randomized, pragmatic clinical trial testing an intervention that used an electronic health record–based algorithm and practice facilitators in 141 primary care practices. The study team randomly assigned more than 11,000 adults to receive either the intervention or usual care. The large, diverse study population—of whom 20% were Black and almost 20% were Hispanic or Latino—was representative of the population with chronic kidney disease, type 2 diabetes, and hypertension in the United States.
In the intervention group, the study team used an algorithm to identify patients in the electronic health record in real time. Practice facilitators then worked with the participating primary care providers and patients to meet blood pressure targets, promote use of appropriate medications, achieve goals for blood glucose control, and engage in other guideline-directed care. The intervention period lasted 12 months, and the primary outcome was hospitalization for any reason.
At the end of the study, the hospitalization rate was similar between the intervention group and the usual care group. Rates of key secondary outcomes, such as emergency department visits and cardiovascular events, were also similar between the groups.
“Although we did not observe a difference in the primary outcome, we believe the study is an important step in advancing our understanding of how to conduct pragmatic trials embedded in healthcare systems,” said Dr. Miguel Vazquez, the principal investigator for ICD-Pieces and a professor of internal medicine at UT Southwestern Medical Center in Dallas.
The study team identified and enrolled a large number of patients, including a large proportion of patients who are members of racial and ethnic groups that are usually underrepresented in clinical trials, Vazquez explained. Moreover, the intervention was delivered across 4 large healthcare systems using a variety of electronic health record systems, there was fidelity in intervention delivery, and there was robust capture of outcomes in a diverse population with multiple chronic conditions.
Vazquez also emphasized the value of conducting the ICD-Pieces study as an NIH Collaboratory Trial.
“The opportunity to work within the NIH Pragmatic Trials Collaboratory was essential for the successful completion of our trial,” Vazquez said. “Access to the expertise from the Coordinating Center and ongoing interactions with investigators from other projects provided critical knowledge to conduct our study embedded in large health systems,” he added.
ICD-Pieces is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases.
Dr. Rosa Gonzalez-Guarda and Dr. Cherise Harrington, cochairs of the Health Equity Core
The NIH Pragmatic Trials Collaboratory’s Health Equity Core developed a written aid to offer guidance on inclusive language and terms to use when referring to specific people, groups, and communities. The Equitable Language Cheat Sheet is available on the Health Equity Core webpage and will be updated as terminology and guidance evolve.
“When collaborating with distinct individuals or communities in the scope of research, it’s important to defer to their personal preferences for identification. This reference guide offers essential guidelines in instances where direct input is not an option,” said Rosa Gonzalez-Guarda, cochair of the Health Equity Core and an associate professor and assistant dean in the Duke University School of Nursing. “We hope that this cheat sheet serves as a valuable tool for researchers and partners striving toward fostering health equity,” she said.
The cheat sheet includes preferred terminology when referring to the following identities:
Age
Race and ethnicity
Gender
Differing abilities
Drug/substance abuse
People who are underserved, at increased risk, or economically marginalized
Partners and populations of focus
The Health Equity Core provides direction for pragmatic trials on how to integrate a health equity lens in pragmatic clinical research, documents barriers to the integration of a health equity lens in pragmatic research, and develops strategies and tools to facilitate a health equity lens in pragmatic trials. This living document supports the Core’s mission in working toward overcoming biases and advancing health equity in the context of pragmatic research.
The Grand Rounds session will be held on Friday, March 27, 2024, at 1:00 pm eastern.
Garg is the associate dean for clinical research at the Schulich School of Medicine and Dentistry and the lead of the provincial Kidney, Dialysis and Transplantation Program of the Institute for Clinical Evaluative Sciences (ICES KDT). Dixon is a biostatistician at the London Health Sciences Centre and the program manager for ICES KDT.
The Patient-Centered Outcomes Research Institute (PCORI) announced the release of its new Foundational Expectations for Partnerships in Research. The resource is an update of the 2014 PCORI Engagement Rubric. It builds on a growing body of evidence about engaging patients and other partners in patient-centered comparative effectiveness research.
A webinar on April 4 will explore the foundational expectations, which PCORI describes as “building blocks for meaningful, effective, and sustainable engagement with patients, communities, and other partners in research.”
The 6 foundational expectations are:
diversity and representation
early and ongoing engagement
dedicated funds for engagement and partner compensation
build capacity to work as a team
meaningful inclusion of partners in decision-making
ongoing review and assessment of engagement
The April 4 webinar will describe the foundational expectations and explore how PCORI will incorporate them into future funding opportunities. This event is intended for current and future applicants for PCORI funding and anyone interested in participating in the healthcare research process. Register for the webinar.
PCORI is an independent, nonprofit organization authorized by Congress and is the nation’s leading funder of patient-centered comparative clinical effectiveness research.
In an analysis of data from the TSOS study, younger patients and patients who were publicly insured or uninsured were among several subgroups of patients who were at significant risk of missing follow-up outcome assessments. The report was 
The Patient-Centered Outcomes Research Institute (PCORI) announced the release of its new Foundational Expectations for Partnerships in Research. The resource is an update of the 2014 PCORI Engagement Rubric. It builds on a growing body of evidence about engaging patients and other partners in patient-centered comparative effectiveness research.