GRACE

October 12, 2026: GRACE Trial Links Depression and Catastrophizing to Worse Pain Outcomes in Sickle Cell Disease

Posted on by Damon Seils

GRACE Trial logoAmong participants in the GRACE trial with sickle cell disease, depressive symptoms were associated with worse pain outcomes both directly and indirectly through pain catastrophizing. The study is the first to observe the mediating role of catastrophizing between depression and pain outcomes in adults with sickle cell disease and chronic pain.

The report was published online ahead of print in General Hospital Psychiatry.

Adults with sickle cell disease often have chronic pain and experience symptoms of depression more frequently than the general population and other patients with chronic pain. Depression and pain catastrophizing are known to exacerbate pain outcomes. However, the mediating role of catastrophizing between depression and pain outcomes is less well studied.

Using baseline data from the GRACE trial, researchers confirmed that depression was common in adults with sickle cell disease and chronic pain and was associated with worse pain outcomes. They also found that pain catastrophizing partly linked depressive symptoms to worse pain outcomes. The findings suggest that integrated pain-focused interventions that target both depression and catastrophizing may be useful.

Read the full article.

GRACE, an NIH Collaboratory Trial, is a pragmatic clinical trial embedded in 3 large healthcare systems to assess the effectiveness of guided relaxation and acupuncture treatments to improve pain control for patients with sickle cell disease. GRACE is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative by a grant administered by the National Center for Complementary and Integrative Health. Learn more about GRACE.

August 10, 2026: NIH Collaboratory Trials Offer Lessons in Using Computable Phenotypes With Real-World Data

Posted on by Damon Seils

The journal cover image of JAMIA Open alongside a screenshot of the first page of the article.Members of the NIH Pragmatic Trials Collaboratory’s Electronic Health Records (EHR) Core Working Group recorded the experiences of pragmatic trial investigators in using computable phenotypes in their studies.

The article was published online in JAMIA Open.

Using real-world data for research poses many challenges, including variations in data documentation practices. Researchers use computable phenotypes—data queries that use specified codes and logical parameters—to standardize the capture of characteristics of interest from real-world data sources, such as EHRs.

The NIH Collaboratory’s EHR Core collected examples from 4 of the NIH Collaboratory Trials to illustrate how computable phenotypes are developed and used in pragmatic trials. Based on these experiences, the Core made several recommendations:

  • Develop computable phenotypes as part of a team with multiple areas of expertise
  • Use appropriate validation procedures
  • Disseminate salient details about phenotype creation
  • Capture and report any modifications made to phenotypes during the conduct of the trial

Read the full report.

July 14, 2026: Investigators for Closing Pragmatic Trials Reflect on NIH Collaboratory Experience

Posted on by Damon Seils

Three studies from the first cohort of NIH Collaboratory Trials in pain management supported through the NIH HEAL Initiative are nearing completion. At the NIH Collaboratory’s 2026 Annual Steering Committee Meeting, we asked investigators Natalia Morone, Andrea Cheville, and Ardith Doorenbos to reflect on their experiences in the program and to share lessons for other researchers starting their own pragmatic trials.

“A commonality across our trials was the effort we put into collecting outcomes, the shared prioritization of how critical this is, guiding each other in ways to maximize our response rates,” said Cheville, co–principal investigator for the NOHARM trial and a professor of physical medicine and rehabilitation at the Mayo Clinic. “Also, I think our trials share an experience of using tele-care, sometimes unplanned because of the pandemic, and experiencing the benefits and the limitations of that.”

NOHARM is testing an electronic health record–embedded, bundled intervention comprised of patient- and clinician-facing decision support components that enable patients to integrate nonpharmacologic pain care into their perioperative management.

Go to the full video.

“The best advice I got…was to be flexible, and I really took that to heart,” said Morone, associate professor of medicine at Boston University and the principal investigator for the OPTIMUM trial. OPTIMUM studied the addition of mindfulness-based group telehealth visits to usual care for patients with chronic low back pain. The trial’s primary results were published last month in JAMA Internal Medicine.

“Especially with pragmatic trials, I think there are more challenges that may arise and more questions as far as how flexible you can be,” added Doorenbos. “Emphasize relationships, value your relationships, and identify the pain points, the opportunities for synergism, how to give back to the sites that are hosting the trials,” she said.

Doorenbos is a co–principal investigator for the GRACE trial and the Harriet H. Werley Endowed Chair for Nursing Research at the University of Illinois Chicago. GRACE is assessing the effectiveness of guided relaxation and acupuncture treatments to improve pain control for patients with sickle cell disease.

OPTIMUM, NOHARM, and GRACE are supported within the NIH Collaboratory through the NIH HEAL Initiative by grants awarded by the National Institute of Neurological Disorders and Stroke and administered by the National Center for Complementary and Integrative Health (OPTIMUM and GRACE) and the National Institute on Aging (NOHARM).

In the coming weeks, we will share more highlights from the 2026 Annual Steering Committee Meeting. Access the complete meeting materials.

Video still from an interview with Drs. Natalia Morone, Andrea Cheville, and Ardith Doorenbos
Dr. Natalia Morone, Dr. Andrea Cheville, and Dr. Ardith Doorenbos

January 26, 2026: New Findings From GRACE Trial Highlight Strategies for Integrating Acupuncture and Guided Relaxation Into Sickle Cell Disease Clinics

Posted on by Damon Seils

GRACE Trial logoNew qualitative findings from the GRACE trial reveal critical barriers and facilitators for incorporating complementary and integrative health interventions into routine clinical care. The study emphasizes that successful integration requires participatory approaches and significant adjustments to clinic workflows.

The article was published online ahead of print in Pain Management Nursing.

GRACE, an NIH Collaboratory Trial, is a pragmatic clinical trial embedded in 3 large healthcare systems to assess the effectiveness of guided relaxation and acupuncture treatments to improve pain control for patients with sickle cell disease. While clinical guidelines promote nonpharmacological treatments to reduce reliance on opioids, integrating therapies like acupuncture and guided relaxation into standard practice remains challenging.

The researchers conducted in-depth interviews with 13 hematologists, nurses, and pharmacists at GRACE trial sites. Two primary themes emerged: the variable impact on clinic operations, and the requirements for introducing complementary and integrative health interventions into clinical practice.

Participants noted that even minor changes can disrupt complex clinic workflows. Specifically, they identified the need for flexible or extended clinic hours to accommodate multiweek courses of acupuncture, as well as space for administering treatments without interrupting other patient visits. Participants also noted that clinics would benefit from streamlined ordering processes to avoid administrative burdens.

The study highlighted a significant need for patient and clinician education. While evidence exists for complementary and integrative health interventions, many clinicians remain hesitant to recommend them due to knowledge gaps. Patients may also feel wary of new therapies, necessitating clear, accessible educational tools like videos, apps, and brochures.

GRACE is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative by a grant administered by the National Center for Complementary and Integrative Health. Learn more about GRACE.

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

August 11, 2025: New Living Textbook Chapter Explores Implementation in Pragmatic Clinical Trials

Posted on by Karen Staman

The NIH Pragmatic Trials Collaboratory Implementation Science Core, led by Devon Check and Hayden Bosworth, has developed a new chapter on implementation to assist study teams with the complex process of using and studying implementation strategies to help implement research findings into clinical care. The chapter includes sections on:

Case studies are used to illustrate how pragmatic clinical trials embedded in healthcare systems use implementation frameworks, including examples from RAMP, BEST-ICU, STOP CRC, TSOS, ABATE, STEP-2, and GRACE.

For more, see our collection of chapters on Dissemination and Implementation, which includes chapters on Dissemination to Different Stakeholders, Data Sharing and Embedded Research, and End-of-Trial Decision-Making.

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

September 24, 2024: GRACE Team Identifies Barriers to Integrating Acupuncture Into US Healthcare System

Posted on by Damon Seils

Cover of the Journal of Integrative and Complementary Medicine (JICM)In a systematic review of the literature, researchers from the GRACE trial identified and categorized barriers and facilitators related to integrating acupuncture into the US healthcare system.

The review was published online ahead of print in the Journal of Integrative and Complementary Medicine.

Acupuncture is widely practiced in the United States and has been shown to be effective in multiple clinical applications for a variety of conditions. Yet, its integration into the healthcare system has been uneven.

In their review of the existing evidence, the authors found:

  • Understanding and addressing individual patients’ needs, awareness, concerns, and financial constraints is essential
  • Healthcare providers play an important role in communicating information about acupuncture to their patients and building trust
  • Organization-level changes are needed to address lack of space in healthcare facilities, lack of referral systems, and lack of credentialing and privileging procedures
  • Policies related to payment by both private and public insurers have been slow to change

Read the full report.

The authors stress that studies testing implementation of acupuncture interventions in real-world settings can help to address barriers to integration.

“Results of this study can be used to optimize strategies to effectively implement acupuncture into clinical practice, and ultimately influence policy changes,” they wrote.

GRACE, an NIH Collaboratory Trial, is a pragmatic clinical trial testing real-world implementation of acupuncture and guided relaxation for patients with pain associated with sickle cell disease. The trial is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative under an award administered by the National Center for Complementary and Integrative Health. Learn more about the GRACE trial.

October 12, 2023: GRACE Team Shares Lessons About Monitoring Signals of Suicidality in Pragmatic Clinical Trials

Posted on by Karen Staman

In a new article published this week in Contemporary Clinical Trials Communications, the GRACE DNIH Collaboratory Trial team recommends that suicidality should be monitored in pragmatic clinical trials that measure depression as an outcome. The work builds on their experience conducting research involving patients with sickle cell disease and on previous work from the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core.

The authors offer 7 recommendations to address ethical considerations in the development of protocols, procedures, and monitoring activities related to suicidality in depressed patients in a pragmatic clinical trial.

Recommendations:

  • Understand our responsibility to act
  • Define triggers for action
  • Examine responsibilities for action
  • Protect patient autonomy and privacy
  • Identify indirect and collateral participants
  • Mitigate the risk of bias
  • Integrate responses within the clinical practice and understand the sociotechnical considerations.

Severe depression symptoms such as suicidal ideation can be assessed in patients using the PHQ-9, a validated self-report instrument used to score depression severity by inquiring about the  presence and severity of depression, passive thoughts of death, and active ideas of self-harm.

For more, read the full article or the article Responding to Signals of Mental and Behavioral Health Risk in PCTs from the Ethics and Regulatory Core.

The GRACE is supported by the NIH through the NIH HEAL Initiative under an award administered by the National Center for Complementary and Integrative Health. Learn more about the GRACE trial.

Community-Based Participatory Research Practices in the GRACE Trial

Posted on by Damon Seils

Community-Based Participatory Research Practices in the GRACE Trial

Description

Building trust in communities is critical for long-term partnerships between patients and researchers. In this video, Dr. Judith Schlaeger, Co-PI of the GRACE Trial, describes her team's efforts to engage patients and community-based organizations.

Biography

Headshot of Dr. Judith Schlaeger

Judith Schlaeger, PhD, CNM, LAc, FACNM, FAAN
Associate Professor, University of Illinois Chicago
GRACE NIH Collaboratory Trial co-PI

 

Related

Deciding Who to Engage

View the full Grand Rounds video