EMBED

December 15, 2025: A Year of Trial Results and Innovations From the NIH Pragmatic Trials Collaboratory

Posted on by Damon Seils

A collage of journal covers with the label "NIH Pragmatic Trials Collaboratory 2025 Publications Roundup"In 2025, NIH Pragmatic Trials Collaboratory investigators published new study designs and trial results, shared insights from program leadership, and developed innovative methods in the design, conduct, implementation, and dissemination of pragmatic clinical trials. Their work included perspectives from the Coordinating Center, best practices from the Core Working Groups, and results from the NIH Collaboratory Trials.

The program contributed 45 articles to the peer-reviewed literature this year, including the primary results of the ACP PEACE, BackInAction, HiLo, INSPIRE, and PRIM‑ER trials. Cross-Core and cross-Trial collaborations led to the sharing of important lessons from the conduct of multiple NIH Collaboratory Trials.

The total number of published articles from the program reached 386.

Coordinating Center

Cross-Core and Cross-Trial Collaborations

Distributed Research Network

Core Working Groups

Biostatistics and Study Design Core

Community Health Improvement Core

Electronic Health Records Core

Ethics and Regulatory Core

Health Care Systems Interactions Core

Patient-Centered Outcomes Core

NIH Collaboratory Trials

ABATE Infection

ACP PEACE

ARBOR-Telehealth

BackInAction

BeatPain Utah

BEST-ICU

EMBED

FM-TIPS

GGC4H

GRACE

HiLo

I CAN DO Surgical ACP

IMPACt-LBP

INSPIRE

iPATH

LIRE

MOMs Chat & Care Study

NOHARM

Nudge

OPTIMUM

PRIM-ER

SPOT

TAICHIKNEE

April 22, 2025: New Report Highlights Value of Informing Participants About Research Conducted Under a Waiver of Consent

Posted on by Karen Staman

Even in minimal-risk studies that do not use the standard consent process, there may be value in informing participants about the research. Such notifications should be considered the default for clinical trials conducted under a waiver of informed consent, argue the authors of a new report from the NIH Pragmatic Trials Collaboratory.

The open-access article was published online ahead of print this week in Learning Health Systems.

Pragmatic clinical trials conducted in the context of routine healthcare often meet the regulatory criteria for a waiver or alteration of the standard informed consent process. In such cases, researchers and reviewers might assume there is no reason to communicate information about the study to participants. However, providing information to participants, even in minimal-risk research conducted with a waiver of consent, can promote important ethical values.

Experts from the NIH Collaboratory’s Ethics and Regulatory Core teamed up with investigators from several of the NIH Collaboratory Trials to describe methods of informing participants in minimal-risk research.

The investigators used a variety of notification approaches in their studies, including letters and email campaigns, posters in waiting rooms and other common areas, conversations with clinicians, and presentations at staff meetings. The amount of information provided to participants ranged from a general statement that research was being conducted at the institution to detailed information about the study in question.

“When a study is approved with a waiver of research consent, investigators and review committees should consider on a case-by-case basis what information, if any, to disclose to participants, and how it will be disclosed,” the authors wrote. The costs, benefits, and feasibility of these approaches vary from study to study.

Communicating information to participants can promote several important goals:

  • The ethical principle of respect for persons
  • Participants’ understanding of the study and of research in general
  • Participants’ understanding of their contributions to the research
  • Participants’ ability to voice and discuss any concerns about the study
  • Participant engagement in research
  • Trust in research and researchers

“Providing information to the participants should thus be the default for trials conducted under a waiver of research consent,” the authors wrote.

Read the full report.

December 12, 2024: A Year of Innovations and Insights From the NIH Pragmatic Trials Collaboratory

Posted on by Damon Seils

A graphic showing a collection of journal covers.In 2024, experts from the NIH Pragmatic Trials Collaboratory published the results of newly completed studies, shared insights from program leadership, and developed innovative methods in the design, conduct, and analysis of pragmatic clinical trials. Their work included perspectives from the Coordinating Center, best practices from the Core Working Groups, and results from the NIH Collaboratory Trials.

The program contributed more than 30 articles to the peer-reviewed literature this year, including the primary results of the ICD-Pieces and Nudge trials. Several cross-Core and cross-Trial collaborations led to the sharing of important lessons from the conduct of multiple NIH Collaboratory Trials.

The total number of published articles from the program surpassed 340.

Coordinating Center

Cross-Core and Cross-Trial Collaborations

Core Working Groups

Biostatistics and Study Design Core

Electronic Health Records Core

Ethics and Regulatory Core

Community Health Improvement Core

Implementation Science Core

Patient-Centered Outcomes Core

NIH Collaboratory Trials

ABATE Infection

BackInAction

BeatPain Utah

EMBED

FM-TIPS

GGC4H

GRACE

I CAN DO Surgical ACP

ICD-Pieces

LIRE

NOHARM

Nudge

OPTIMUM

PRIM-ER

PROVEN

SPOT

STOP CRC

TSOS

June 22, 2023: EMBED Team Documents Rise in Fentanyl-Associated Overdose Deaths

Posted on by Damon Seils

EMBED logoResearchers from EMBED, an NIH Pragmatic Trials Collaboratory Trials, found a sharp rise in out-of-hospital overdose deaths in the early years of the COVID-19 pandemic, attributable largely to increasing involvement of fentanyl.

The findings were published online ahead of print this week in the New England Journal of Medicine.

EMBED was a cluster randomized trial across 21 emergency departments in 5 healthcare systems in the United States. The trial evaluated a clinical decision support system for initiating buprenorphine in emergency department settings. Since completing the trial, the research team has pursued multiple health services research studies to describe the environment in which the EMBED clinical decision support tools are being implemented.

Using data from the National Center for Health Statistics from 2016 through 2021, the research team compared overdose deaths outside the hospital in the years before the COVID-19 pandemic to those in the early years of the pandemic. Out-of-hospital overdose deaths increased significantly during the early pandemic period and were driven primarily by deaths associated with fentanyl.

Read the full report.

EMBED was supported within the NIH Collaboratory by a cooperative agreement from the National Institute on Drug Abuse and received logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about EMBED in the Living Textbook, and learn about the other NIH Collaboratory Trials.

May 22, 2023: EMBED Finds Racial and Ethnic Differences in Buprenorphine Initiation for Opioid Use Disorder

Posted on by Damon Seils

EMBED logoIn a secondary analysis from the EMBED pragmatic clinical trial, Black patients with opioid use disorder were less likely than White patients to be initiated on buprenorphine in the emergency department.

The study’s findings were published recently in Academic Emergency Medicine.

EMBED, an NIH Collaboratory Trial, was a cluster randomized trial across 21 emergency departments in 5 healthcare systems in the United States. The trial evaluated a clinical decision support system for initiating buprenorphine in emergency department settings.

The racial disparity in buprenorphine initiation remained after adjustment for patient, clinician, and site characteristics. Even in emergency departments in academic hospitals, where rates of buprenorphine were higher overall, Black patients received proportionally less buprenorphine initiations than White patients. Hispanic patients were more likely to receive buprenorphine than non-Hispanic patients in both community and academic emergency departments. However, adjustment for discharge diagnosis attenuated the association between ethnicity and buprenorphine initiation.

“Attention should be focused on identifying continued disparities in [emergency department] treatment of opioid use disorder by race and ethnicity,” the authors concluded, “as well as the barriers and inequities that continue to limit patients’ ability to access the [emergency department] for treatment of opioid use disorder.”

EMBED was supported within the NIH Collaboratory by a cooperative agreement from the National Institute on Drug Abuse and received logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about EMBED in the Living Textbook, and learn about the other NIH Collaboratory Trials.

Read the full report.

May 15, 2023: EMBED Offers Lessons for Intervention Adoption, Implementation, and Maintenance

Posted on by Damon Seils

EMBED logoOrganizational culture, clinician training and support, the ability to link patients to ongoing treatment, and the ability to tailor implementation to each clinical site were key determinants of successful implementation of an intervention to promote buprenorphine initiation in emergency departments, according to a qualitative study conducted as part of the EMBED pragmatic clinical trial.

The study’s findings were published recently in Implementation Science Communications.

EMBED, an NIH Collaboratory Trial, was a cluster randomized trial across 21 emergency departments in 5 healthcare systems in the United States. The trial tested the effectiveness of a clinical decision support tool integrated into the electronic health record in improving rates of buprenorphine initiation in the emergency department for the treatment of opioid use disorder. The intervention led to a modest increase in buprenorphine initiation and little impact on patient outcomes.

A secondary aim of the study was to identify determinants of adopting, implementing, and maintaining the clinical decision support tool at the trial sites. Among the key determinants were:

  • establishing buprenorphine initiation as a cultural norm within healthcare organizations;
  • organizational commitment to implementing and sustaining the intervention;
  • clinician training and support on opioid use disorder and buprenorphine initiation in emergency departments;
  • availability of referral resources to link patients who were initiated on buprenorphine in the emergency to ongoing treatment; and
  • the ability to tailor the intervention to clinic workflows that fit the resources and characteristics of the local clinic.

EMBED was supported within the NIH Collaboratory by a cooperative agreement from the National Institute on Drug Abuse and received logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about EMBED in the Living Textbook, and learn about the other NIH Collaboratory Trials.

Read the full report.

July 18, 2022: New Article Offers Recommendations for Pragmatic Trials in Emergency Medicine

Posted on by Elizabeth Mccamic

Dr. Edward Melnick, Co-PI of EMBED, and Dr. Corita Grudzen, PI of PRIM-ER
(From left) Dr. Edward Melnick, Co-PI of EMBED, and Dr. Corita Grudzen, PI of PRIM-ER

Investigators planning emergency department (ED)­–based pragmatic clinical trials (PCTs) face multiple decisions during the planning phase to ensure robust and meaningful study findings in this unique setting; however, there is no guide for planning and conducting these studies.

A new article in Academic Emergency Medicine fills the gap by providing recommendations for the design of PCTs in emergency settings. Among the authors are investigators from EMBED and PRIM-ER, both NIH Pragmatic Trials Collaboratory Trials.

The authors recommend that investigators planning ED-based PCTs should strongly consider the use of the PRECIS-2 wheel diagram during the study design phase to increase chances that the results of the trial are generalizable across the intended practice settings. The PRECIS tool was developed to help investigators work through study design decisions to avoid designing a trial that does not meet their own intentions.

The authors expand upon the 9 domains within the PRECIS-2 framework to identify points for investigators to consider in the design of ED-based PCTs, and they provide examples of successful studies. Using the PRECIS-2 framework can help investigators navigate unique challenges in the ED setting, including time-sensitive conditions, limited availability of electronic health data for the patient population, and added complexity surrounding capacity and consent for certain vulnerable ED populations with mental illness or substance use disorder.

The authors also address special considerations for randomization, human subjects concerns, and electronic health record integration.

Finally, the authors provide an analysis that highlights the advantages, disadvantages, and rationale for the use of 4 common randomized PCT study design types and examples of similar trials set in the ED.

Read the full text of the article.

July 14, 2022: Solving Unexpected Challenges in Pragmatic Trial Data Collection

Posted on by Elizabeth Mccamic

Headshot of Dr. Keith MarsoloDuring the NIH Pragmatic Trials Collaboratory Steering Committee meeting and 10th anniversary celebration, Dr. Keith Marsolo, Co-chair of the Electronic Health Records Core, moderated a panel on “Barriers and Challenges: Data Collection and Merging Datasets.” Four panelists shared their experiences collecting and aggregating data from diverse data sets and how they solved unexpected challenges.

The panelists included Drs. Ted Melnick (EMBED), Holt Oliver (ICD-Pieces), Margaret Kuklinski (GGC4H), and Andrea Cheville (NOHARM).

During the discussion, panelists shared lessons learned from collecting electronic health record (EHR) data during large pragmatic clinical trials across multiple health systems. Common challenges included:

  • Privacy concerns and not having the ability to collect deidentified patient or clinician demographic information
  • Working across health systems that use different EHR platforms and collecting data consistently across sites
  • Turnover of IT staff at participating sites and changes in site data agencies during the study period
  • Updates to the EHR that affect study algorithms and other issues with algorithms not identifying data as expected
  • Overcoming technical barriers with practice workflows and integrating with IT systems

The panelists shared solutions and possible best practices for future studies, including the need for planning, coordinating, and testing before study launch, the importance of being able to pivot and change directions as problems arise, being open to alternative data collection methods such as surveys to augment findings, and having the right team at the right time to be responsive to problems, which for one study meant having informaticists and expert EHR builders embedded in the trial team.

Panelists identified two key policy and infrastructure changes that would help trials be successful in the future. These changes include development of a national unique patient identifier across health systems and incentivizing EHR vendors to find common ground to better support research.

The Electronic Health Records Core continues to learn from experiences of the program’s NIH Collaboratory Trials and shares emerging information, resources, and EHR-related recommendations to improve future pragmatic research.

View slides from the discussion panel.

Learn more

View video collection that highlights advances in Electronic Health Records for pragmatic research.

Watch the August 2021 Interview with Electronic Health Record Core leaders Drs. Rachel Richesson and Keith Marsolo

June 27, 2022: EMBED Publishes Results From Study of Buprenorphine Initiation in Emergency Departments

Posted on by Elizabeth Mccamic

Headshots of Dr. Edward Melnick and Dr. Gail D'Onofrio
Dr. Ted Melnick and Dr. Gail D’Onofrio, co–principal investigators of EMBED

Implementation of a user-centered clinical decision support tool did not increase the rate of patients receiving buprenorphine for treatment of opioid use disorder in the emergency department (ED) when compared to usual care.

When the tool was used, it was associated with high rates of buprenorphine initiation, and the tool increased the number of physicians who provided ED-initiated buprenorphine and naloxone prescriptions.

The findings of EMBED were published in the BMJ on June 27.

From November 2019 to May 2021, researchers conducted EMBED, an NIH Pragmatic Trials Collaboratory Trial, in 18 clusters across 5 healthcare systems in 5 states, representing the Northeast, Southeast, and Western regions of the United States.

The 18 clusters included 21 EDs, with 3 sites paired with a second ED within the same healthcare system due to low patient volume or high physician crossover rates between the 2 sites. Each cluster received either the intervention or maintained usual care.

The study sample was made up of all patient visits to the ED during the study period. Eligible patient encounters were identified using criteria in the electronic health record. For patients with multiple ED visits during the trial, only the first ED visit was included in the analysis.

ED attending physicians caring for patients who met the trial’s inclusion criteria were the primary study subjects, but all ED clinicians practicing at intervention sites had access to the EMBED tool for all patients in their care at that site. A total of 5,047 patients (2,787 intervention and 2,260 usual care) were eligible for analysis along with the 599 physicians who cared for them (340 intervention, 259 usual care).

The intervention did not affect the patient-level rate of ED-initiated buprenorphine (which was 12.5% in the intervention arm and 12.0% in the usual care arm). The proportion of physicians who initiated buprenorphine in the ED at least once was higher at intervention sites compared to usual care sites (44.4% vs 34.0%).

In the intervention arm, the EMBED tool was launched by physicians for 261 of 2,787 eligible patients. When the tool was launched, buprenorphine was ordered for 161 patients (67% of 261 encounters).

“We built tools that work within the electronic health record that make it easier for clinicians to treat patients with addiction, using medications that physicians may initially find complex and unfamiliar,” said Dr. Edward Melnick of Yale University, co–principal investigator of the study. “We’ve tried to make that easier for clinicians to allow this practice to be adopted into routine care.”

“EMBED offers a major opportunity to accelerate adoption by offering a simple, automated, rapid solution to initiating treatment and referral for people suffering from opioid use disorder,” said Dr. Gail D’Onofrio of Yale University, co–principal investigator of the study. “Additional prompts and interventions will be needed to increase more universal implementation into the routine care of ED patients with opioid use disorder.”

Watch Dr. Melnick discuss the EMBED project in this NIH Pragmatic Trials Collaboratory interview from April 2022.

EMBED was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute on Drug Abuse and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.

January 28, 2022: EMBED Trial Results: Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder

Posted on by terren.green@duke.edu

Speaker

Edward R Melnick, MD, MHS
Associate Professor of Emergency Medicine, Yale School of Medicine
Associate Professor of Biostatistics (Health Informatics), Yale School of Public Health
Program Director, Yale-VA Clinical Informatics Fellowship Program

Gail D’Onofrio, MD, MS
Albert E. Kent Professor of Emergency Medicine
Yale School of Medicine
Professor of Public Health, Chronic Disease & Epidemiology
Yale School of Public Health

 

 

Keywords

EMBED; Opioid use disorder; Buprenorphine; EHR workflow

 

Key Points

  • The epidemic of opioid misuse continues to escalate with almost 70 thousand deaths attributed to prescription and illicit opioids in 2020.
  • Medications for opioid use disorder, including Buprenorphine, are available and can be prescribed to patients in the emergency department, but less than 30% of patients who are eligible for BUP receive the medication. Buprenorphine/naloxone (BUP) is safe, effective, decreases withdrawal, and decreases opioid overdose events.
  • EMBED was started to address the barriers and promote the facilitators to initiating BUP in the emergency department. Common barriers included complex protocols, knowledge gaps, and poor usability of health IT systems. Promoting a proper learning tool was a helpful facilitator for initiating BUP.
  • EMBED was an 18-month pragmatic, parallel, group randomized trial conducted in 18 emergency department clusters in 5 healthcare systems.
  • EMBED created a user centered design to simplify the clinician’s role in initiating BUP to an automatic 5-minute process that included diagnosing opioid use disorder, assessing withdrawal severity, motivating patients to accept treatment, and an automatic EHR workflow for prescribing and referral.
  • EMBED increased Naloxone prescriptions at discharge for intervention patients (18.6%) compared with control patients (6.0%). Of the patients eligible, BUP was initiated using EMBED for 42.5%. Physicians in the intervention group initiated BUP (39.7%) and prescribed naloxone (52.1%) at a higher rate than physicians in the control group (initiated BUP 30.1%; prescribed naloxone, 27.4%).
  • EMBED increased provider adoption of complex, unfamiliar evidence-based practices in the emergency department. EMBED can help improve consistency and quality of care for patients with opioid use disorder.

Discussion Themes

– Gentle nudges to encourage clinicians to use the health IT, may increase use. Incentives to use the health IT may also lead to greater use.

– The explosion of health information, especially with regard to emergency department care, has increased acceptance of the use of health IT pathways that give the most updated evidence for care.

 

Learn more about the EMBED project and read about the findings from EMBED.

Tags

#pctGR, @Collaboratory1