From left: NIH Collaboratory Coordinating Center co–principal investigators Lesley Curtis, Adrian Hernandez, and Kevin Weinfurt
With the NIH Pragmatic Trials Collaboratory entering its second decade, we are expanding our presence on the LinkedIn social media platform to promote research that advances the design, conduct, and dissemination of pragmatic clinical trials.
If you are active on LinkedIn, we invite you to follow our page for the latest news about our innovative NIH Collaboratory Trials, tools and resources from the Core Working Groups, upcoming sessions of our weekly Rethinking Clinical Trials Grand Rounds webinar series, and fresh content from the Living Textbook of Pragmatic Clinical Trials.
We also look forward to highlighting news and content from our investigators, collaborators, and partner organizations, many of whom are active on LinkedIn.
In an interview at the annual NIH Pragmatic Trials Collaboratory Steering Committee meeting in Bethesda, Maryland, Richard Platt, MD, MS (co–principal investigator) and Shruti Gohil, MD, MPH (lead investigator) of the INSPIRE NIH Collaboratory Trial shared the status of the trials, discussed recent lessons learned, described the impact they hope their trials will have on the future of healthcare, and reflected on the impact the NIH Collaboratory has had on their trials thus far.
Status Update
Richard Platt, MD
Shruti Gohil, MD, MPH
INSPIRE (or Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection for Patients) is implementing 2 separate cluster-randomized trials to study the effectiveness of a patient/infection/hospital-specific clinical decision support program in improving antibiotic prescribing for non–critically ill patients who are hospitalized with abdominal infections or skin and soft tissue infections. The purpose of the trials is to reduce unnecessary broad-spectrum antibiotic use in non–intensive care unit inpatients.
The 12-month trial is currently in month 5, and the team has already seen a downward inflection in broad-spectrum antibiotic use.
Lessons Learned
Due to the urgent public health threat of antibiotic resistance, healthcare systems are actively seeking ways to support clinicians in judicious antibiotic prescribing. As a result, although the target recruitment was 60 hospitals out of approximately 200, 92 hospitals at HCA Healthcare requested enrollment.
"We have the privilege of being with a health system that has a strong leadership structure that is patient-safety oriented, and quality improvement is a top-notch priority," Gohil said, describing the unusual overenrollment.
The INSPIRE team determined that the trial could be shortened from 18 months to 12 by using all 92 hospitals.
"We determined that the higher number of hospitals wanting to participate gave us the opportunity to understand the usefulness of this decision support tool as quickly as possible and honor the commitment of the partner health system," Platt said. "Their view is, if it works, we want to use it everywhere as soon as possible," he said.
Impact of the Trial on Real-World Healthcare
Dr. Gohil explained that she hopes not only to reduce unnecessary prescribing of broad-spectrum antibiotics, but also to learn about how digital health can transform healthcare and its delivery.
“We have a tool that not only flags a low-risk patient, but is doing it based on data from the [electronic medical record] system, and is calculating risk specific to a patient, specific to a disease, and specific to a type of bacteria, and one that is unique to a hospital. It captures all that information and presents it to a clinician to make good judgments about antibiotic selection,” Gohil said. She hopes this work will be a step towards future systems that could be “savvy enough and real-time enough deliver high precision care tailored for individual patients as part of an embedded learning system.”
Impact of the NIH Pragmatic Trials Collaboratory on INSPIRE
The INSPIRE intervention includes a clinical decision support tool to help clinicians make a guideline-concordant decision on antibiotic use based on a patient's personalized risk. At the time of the trial’s launch, the FDA introduced a new guidance on Clinical Decision Support Software to support determinations regarding whether a software would be considered a device and therefore subject to FDA oversight.
“It was really helpful to have the Ethics and Regulatory Core do a deep dive with us on the FDA guidance on clinical decision support and help determine that our software was not considered a device,” Platt said.
The INSPIRE NIH Collaboratory Trial is supported within the NIH Pragmatic Trials Collaboratory by a grant from the National Institute of Allergy and Infectious Diseases (NIAID).
All of the materials from the 2023 Steering Committee meeting are now available.
In an interview at the NIH Pragmatic Trials Collaboratory Steering Committee’s annual meeting in April, Dr. Lesley Curtis, Dr. Adrian Hernandez, and Dr. Kevin Weinfurt discussed the program’s plans for the future.
“The NIH Pragmatic Trials Collaboratory is developing the fundamental knowledge necessary to build a learning health care system,” said Hernandez. “The Collaboratory is learning how to embed clinical trials as part of healthcare delivery to accelerate evidence generation.”
Curtis, Hernandez, and Weinfurt are co-principal investigators of the NIH Pragmatic Trials Collaboratory Coordinating Center at Duke University.
In August 2022, the program plans to add 2 Core Working Groups, one focused on health equity and the second on implementation science.
“Health equity is an issue that is front-and-center for all of us,” Curtis said. “To have a group of experts in the field who can consult with new NIH Collaboratory Trials to give them guidance about best practices for addressing health equity will be fabulous.”
As the NIH Collaboratory moves forward, the program will focus its efforts on bringing in more diverse researchers and trainees into the program.
When asked about how the NIH Collaboratory has fulfilled its mission over the last 10 years, Weinfurt said, “Toward the broad goal of improving our national capacity to do embedded trials, we have improved the knowledge base that future trialists can use to develop new trials. We’ve generated tools and approaches to solve challenges that arose, trained and increased the number of researchers who are familiar with embedded pragmatic trials, and encouraged trials to develop their own networks to continue conducting these embedded trials.”
“We’ll know we’ve succeeded when all of the barriers and challenges that we’ve been working on over the last 10 years have run out,” said Curtis.
The co–principal investigators of the NIH Pragmatic Trials Collaboratory Coordinating Center at Duke University—Drs. Adrian Hernandez, Dr. Lesley Curtis, and Dr. Kevin Weinfurt—will share lessons from the network’s portfolio of NIH Collaboratory Trials and discuss priorities for future research.
The NIA IMPACT Collaboratory is supported by a grant from the National Institute on Aging. Its mission is to advance care for persons with dementia and their caregivers in real-world settings by building national capacity to conduct pragmatic clinical trials that test interventions embedded in healthcare systems.
In a new NIH Collaboratory study, 20 NIH Collaboratory Trials responded to a survey about challenges encountered when using the electronic health record (EHR) for pragmatic clinical research. The goal of the study was to elucidate challenges and develop solutions—or prerequisites for pragmatic research—to enable healthcare system leaders, policy makers, and EHR designers to improve the national capacity for generating real-world evidence.
The article was published in the Journal of American Medical Informatics Association (JAMIA).
The challenges identified by the projects fell into 6 broad themes, including inadequate collection of patient-centered data, lack of functionality for structured data collection, lack of standardization, lack of resources to support customization, difficulties aggregating data from multiple sites, and difficult and inefficient access to EHR data.
Researchers from the NIH Collaboratory’s EHR Core and colleagues from the Patient-Centered Outcomes and the Health Care Systems Interactions Core Working Groups discussed the issues and iterated possible solutions. The authors developed the following prerequisites for the conduct of pragmatic research:
Integrate collection of patient-centered data into EHR systems
Facilitate structured research data collection by leveraging standard EHR functions, usable interfaces, and standard workflows
Support creation of high-quality research data by using standards
Ensure adequate IT staff to support embedded research
Create aggregate, multidata type resources for multisite trials
Create reusable and automated queries
The authors argue for the ability to tailor EHR systems to enable the collection of patient-centered outcomes and the extraction of high-quality, standardized data. Although the primary uses of the data are for clinical care and billing, high-quality data from the EHR also have the potential to improve clinical care and population health by providing reliable evidence and to support pragmatic research and learning within and across healthcare systems.
This work was supported within the National Institutes of Health (NIH) Health Care Systems Research Collaboratory by the NIH Common Fund through cooperative agreement U24AT009676 from the Office of Strategic Coordination within the Office of the NIH Director. This work was also supported by the NIH through the NIH HEAL Initiative under award number U24AT010961.
Gregory Simon, MD, MPH
Senior Investigator
Kaiser Permanente Washington Health Research Institute
Susan M Shortreed, PhD
Senior Investigator, Biostatistics Unit
Kaiser Permanente Washington Health Research Institute
Affiliate Professor, Department of Biostatistics
University of Washington
Keywords
Care Management; Dialectical Behavior Therapy; Patient engagement; Suicide prevention
Key Points
The SPOT trial was a pragmatic randomized clinical trial comparing care management and dialectical behavioral therapy skills training to usual care in adults at risk of self-harm or suicidal behavior.
Dialectical Behavior Therapy skills training (DBT) was delivered online and supported by coaching.
A care management intervention was intended to facilitate and maintain engagement in effective outpatient care.
Adult outpatients who reported suicidal ideation on a mental health questionnaire were randomized to one of 3 study groups: continued usual care, offer of Care Management program, offer of DBT skills Training program.
Patients were sent a message expressing care and concern through an online system and invited to participate in the study.
Patients were followed for 18 months and fatal or non-fatal self-harm events were recorded as the primary outcome measure.
Interim analysis detected a signal of possible serious outcome in April/May 2019, but upon analysis rerun, the signal dropped below threshold and the DSMB recommended the trial continue.
Patients offered care management had no reduction in Risk of self-harm behavior compared to usual care. Patients offered DBT had significantly increased risk of self-harm compared to usual care.
Discussion Themes
Real-time feedback from potential subjects is important to ascertain if recruitment efforts or intervention is affecting patients negatively.
The inclusion of the usual care group allowed us to determine more than just care management works better than DBT.
In a recent interview, Dr. Wendy Weber shared that the National Advisory Council for Complementary and Integrative Health has approved a concept for the NIH Collaboratory to continue with the support of NIH Institutes and Centers, as the program completes its term as an NIH Common Fund initiative.
“We’re quite excited for some new directions in where we’re going to head with this program, and really excited that we’ve identified a number of partners across the NIH as different Centers, Institutes, and Offices that want to continue this program and want to continue to do research embedded in healthcare systems,” Weber said.
Weber is the branch chief for the Clinical Research in Complementary and Integrative Health Branch in the Division of Extramural Research at the National Center for Complementary and Integrative Health (NCCIH) and serves as the program officer for the NIH Collaboratory.
“I think one new direction for us is looking at how do we address health disparities in healthcare systems, what types of interventions can actually improve those disparities and improve the quality of care so that we have less differences in the way patients are treated within the healthcare delivery system,” Weber said.
We interviewed Weber after the NIH Collaboratory’s annual steering committee meeting, along with Dr. Robin Boineau, the project scientist for the NIH Collaboratory, and Dr. Kevin Weinfurt, a professor in population health sciences at Duke University and a co–principal investigator for the NIH Collaboratory Coordinating Center. View the full interview.
The 3 leaders talked about the program’s newest NIH Collaboratory Trials—BeatPain Utah and GRACE—and their role in advancing the goals of the NIH Collaboratory. They also discussed focus areas for the coming year, including greater attention to implementation science outcomes, diversity in pragmatic trials, and lessons from the COVID-19 pandemic.
“[BeatPain Utah and GRACE] are helping the Collaboratory to learn how to design, analyze, and interpret adaptive designs,” said Weinfurt. “These are our 2 first trials where we’re using adaptive designs. One of the goals of the Collaboratory is to generate generalizable knowledge about how to do pragmatic trials, so we like these types of learning opportunities,” he said.
Boineau highlighted the Diversity Workshop Grand Rounds Series, which began in May and is ongoing. The series is focused on strategies for improving diversity in pragmatic clinical trials and is “an important next step to really think together about where we can go and what we can do to really build this community of investigators and participants,” Boineau said.
Dr. Wendy Weber of NCCIH, program officer for the NIH Collaboratory
The Health Care Systems (HCS) Interactions Core of the NIH Collaboratory has created a new guidance document: Resources for Frequently Asked Questions. The document compiles common questions from researchers and points to resources that provide potential solutions, including Living Textbook chapters and journal articles. The topics include evaluation strategies, anticipating and adapting to changes, dissemination and implementation, and stakeholder engagement.
Drs. Adrian Hernandez, Greg Simon, and Rich Platt of the NIH Collaboratory have authored two new sections of the Living Textbook as part of an ongoing commitment to sharing resources and data.
This section calls for a revision of the appointment, promotion, and tenure (APT) process to incorporate effective data sharing into decision-making and to recognize and credit creators of data sets that gain meaningful use by others.
This section describes how to prepare for data and resource sharing throughout the embedded PCT (ePCT) lifecycle, including during grant submission, trial registration, conduct, and dissemination.
“For all the Demonstration Projects, primary data sets should be made available with the publication of the primary results paper. The Collaboratory policy also recognizes that there are additional considerations that must be incorporated into the policy because data sets are derived from the electronic health records of partnering healthcare systems, and additional precautions might be relevant to making these data sets available.” —Cathy Meyers, MD
The PRISM (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) Demonstration Projects are part of the HEAL Initiative to address the national opioid crisis. The special requirements for these pragmatic trials include:
All publications must be open access so the public has immediate access to the results of the trials.
The underlying primary data must be shared through a repository, which will be set up for all of the projects funded through the HEAL Initiative.
To support sharing, the NIH Collaboratory Data and Resource Sharing Page on the Living Textbook holds links to datasets and data dictionaries, study tools, ethics and regulatory documentation, computable phenotypes and analytic code, data collection forms, study design papers, main outcomes papers, and other information from the Demonstration Projects that might be useful to others.
