NIH Collaboratory Trials

June 29, 2022: Pragmatic Trials Experienced Significant Impacts of COVID-19 on Trial Activities

Posted on by Damon Seils
Headshot of Dr. Emily O'Brien
Lead author Dr. Emily O’Brien

Pragmatic clinical trials experienced significant impacts of COVID-19 on trial activities, according to a survey of NIH Pragmatic Trials Collaboratory Trials published last month in Trials.

Since the beginning of the COVID-19 pandemic in March 2020, many of the NIH Collaboratory Trials have had to postpone recruitment, alter methods of participant engagement, and modify tools for research assessment and intervention delivery. Trial delays often created statistical challenges, especially for those using stepped-wedge designs.

Most of the study teams were able to work closely with healthcare system partners to adapt their study interventions. Some of the adaptations resulted in better participant outreach and the ability to study virtual intervention delivery methods. All of the NIH Collaboratory Trials were able to adapt to pandemic-related changes.

In a recent video interview, lead author Dr. Emily O’Brien praised the study teams.

“We certainly did see some degree of disruption, but I was impressed by the flexibility in the ability to adapt that all of our NIH Collaboratory Trial teams showed,” said O’Brien. “Some of them mentioned the support of having the [Core Working Groups] and consultations with experts in real time to be able to make adjustments,” she said.

The NIH Collaboratory published a tool last year to assist investigators in identifying impacts of the COVID-19 pandemic on ongoing pragmatic trials. The Statistical Analysis Plan Checklist for Addressing COVID-19 Impacts summarizes impacts on trial conduct that study teams should document, measure, analyze, and report.

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.

June 16, 2022: ICD-Pieces Credits Communication and Collaboration for a Successful Trial

Posted on by terren.green@duke.edu

ICD-Pieces, an NIH Pragmatic Trials Collaboratory NIH Collaboratory Trial, aims to improve care for patients with a triad of co-existing conditions: chronic kidney disease, diabetes, and hypertension. Dr. Miguel Vazquez, principal investigator of the ICD-Pieces project, discussed the study in an interview after the NIH Collaboratory’s annual Steering Committee meeting.

 

 

ICD-Pieces uses a novel information technology platform to identify patients and deliver evidence-based interventions to improve patient outcomes. Vazquez explained the goal of the study is to reduce emergency department visits, cardiovascular events, and deaths in this patient population. ICD-Pieces has finished enrollment and data collection and is currently analyzing data for its final outcomes.

ICD-Pieces faced several challenges during the course of the study. Vazquez explained, “in the area of recruitment, we enlisted the collaboration of the different sites in helping to enroll more patients.” He said it was important to “have a regular conversation with the different health systems” in order to identify eligible patients. Turnover within the health systems also presented a challenge for the study. “The most important step was to maintain the dialogue with the local health systems and identify local champions to help us to move forward.”

“One of the most important and immediate accomplishments of this study was to advance the research infrastructure that can now be used for other embedded pragmatic trials,” Vazquez said. The ICD-Pieces study was successful in identifying patients with chronic kidney disease, diabetes, and hypertension. “In this day and age it is so important that we include in our trials the patients who actually have the conditions that we want to study.”

Reflecting on the course of the ICD-Pieces study, Vazquez said, “there were some things that we could not have anticipated in terms of planning.” He acknowledged the importance of the NIH Pragmatic Trials Collaboratory in “providing the critical mass of other investigators and trials that are addressing the same questions so we can learn from each other. The Collaboratory was one of the most valuable resources that we had to be able to not only plan, but conduct our study.”

View the full video.

Headshot of Dr. Miguel Vazquez

June 13, 2022: Nudge Trial Overcomes Challenges, Completes Enrollment

Posted on by Elizabeth Mccamic

Michael Ho, MD, PhD
Michael Ho, MD, PhD

In an interview at the NIH Pragmatic Trials Collaboratory Steering Committee meeting and 10th anniversary celebration, we asked Drs. Sheana Bull and Michael Ho to update us on the Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications (Nudge) NIH Collaboratory Trial. Nudge is using population-level pharmacy data to deliver nudges via cell phone text messaging and artificially intelligent interactive chat to improve medication adherence and patient outcomes in 3 integrated healthcare delivery systems.

What is the current status of the Nudge trial?
The Nudge study has completed enrollment at all 3 of its participating healthcare systems (VA Eastern Colorado Health Care System, Denver Health, and UCHealth, Aurora, Colorado). Follow-up has been completed for the VA, Denver Health follow-up was completed on May 27, and UCHealth follow-up will continue until April 11, 2023. A pharmacist and research staff continue to engage with questions from participants at UCHealth. Data for final analysis will be pulled for the VA and Denver Health sites in fall 2022.

What challenges have you faced, and how have you dealt with them?

Sheana Bull, PhD, MPH
Sheana Bull, PhD, MPH

The onset of COVID-19 greatly delayed enrolling at the UCHealth site since there were not enough resources to devote to implementing the intervention. Additionally, there were administrative difficulties at UCHealth in adding participants via SureScripts due to concerns about time management and payment for IT professionals.

What impact do you hope your trial will have on real-world healthcare?
Text messaging is increasingly becoming part of standard of care for many health care systems. We hope our trial will encourage more healthcare systems to integrate text messaging and chatbots specifically for medication adherence and other health behaviors. Participants have engaged more with messages that are more personalized and include a chatbot, which may mean patients feel more empowered to discuss their medication needs when a mechanism seems more invested in their well-being.

How has being part of the NIH Pragmatic Trials Collaboratory shaped your project?
It was very helpful to have the NIH Pragmatic Trials Collaboratory weigh in on our IRB and statistical plan during the UG3 [planning] year. In the UH3 [implementation] phase, it has been helpful to participate in the various NIH Pragmatic Trials Collaboratory Core calls and share our experiences and learn from others.

May 25, 2022: NOHARM Aims to Change How Patients Manage Pain After Surgery

Posted on by Elizabeth Mccamic

NOHARM, an NIH Pragmatic Trials Collaboratory Trial, is a cluster-randomized, stepped-wedge trial of a bundled intervention that relies heavily on the electronic health record to encourage perioperative patients to consider using nonpharmacologic approaches to manage their postoperative pain. The goal is to diminish patients’ reliance on opioids after surgery and, as a result, reduce rates of inappropriate and prolonged use of opioids.

Dr. Andrea L. Cheville, Co-PI of the Non-pharmacological Options in postoperative Hospital-based And Rehabilitation pain Management (NOHARM) project, discussed the study in an interview during the NIH Pragmatic Trials Collaboratory’s Steering Committee meeting in April.

NOHARM includes 5 steps with 22 clusters randomized to each step. The clusters are defined by surgical type as well as site. The project includes 4 health systems that fall under the Mayo enterprise and share a common electronic health record.

“We have now gone live with 2 of our steps, a total of about 10 clusters, and the surgical types that are included are transplant, cardiac, pulmonary, gynecologic, C-section, orthopedic, and colorectal surgeries,” said Cheville. “The statisticians from the Collaboratory were truly vital allies in parameterizing our choice of procedures and the stepped-wedge so I really cannot call them out enough.”

In May, the project was set to go live with a third step, the automated assignment of a portal-delivered conversation guide to patients.

“The goal of the guide is to educate patients that they are likely to have pain, that it’s important to take seriously and plan for, the benefits and the potential harms of opioid use, and the availability of equally effective, safer nonpharmacologic options that have additional benefits with respect to function and anxiety and sleep quality,” Cheville said.

NOHARM has engaged more than 36,000 patients with a target of roughly 100,000 patients total. Cheville said the project has learned that patients’ receptivity to different pain management options is dynamic over the course of their perioperative journey.

NOHARM, like other trials, has faced challenges related to COVID-19, and the fact that sites may experience surges at different times. A COVID-19 surge at one site can mean that nurses trained in the intervention are deployed elsewhere or that their ability to ingest new information and change practice patterns is stressed and challenged.

“We are trying to find a happy medium between advancing the trial, ensuring high-fidelity delivery, and consistent implementation across all of our clusters while being very respectful to the taxing demands imposed by the COVID-19 epidemic on all of the stakeholder groups,” Cheville said.

Cheville said being part of the NIH Pragmatic Trials Collaboratory has been extremely beneficial for NOHARM, particularly having access to experts who are available to help with methodology, informatics, the electronic health record, parameterization, and statistics.

“If I had to pinpoint one attribute of the Collaboratory it would be the freedom to share our weaknesses, our fears, the things that keep us up at night, with colleagues who are grappling and troubleshooting exactly the same issues in parallel, who truly are walking the walk. Feeling part of a community, that’s been vital for our own psychosocial well-being,” Cheville said.

View the full video here.

May 24, 2022: FM-TIPS Seeks More Treatment Options for Patients With Fibromyalgia

Posted on by terren.green@duke.edu

FM-TIPS, an NIH Collaboratory Trial, is studying real-world implementation of transcutaneous electrical nerve stimulation (TENS) therapy along with physical therapy to treat patients with fibromyalgia. Dr. Kathleen Sluka, Co-PI of the FM-TIPS project, and Dr. Emine Bayman, biostatistician for the project, discussed the study in an interview after the NIH Collaboratory’s annual steering committee meeting.

 

 

Sluka was excited to share an update on the project. “We are currently enrolling in the study thanks to a fantastic team,” she said. “The team has worked really hard to keep the participating clinics engaged.” With 6 healthcare systems and 30 active centers, the project has enrolled 115 patients.

The study faced several challenges during the startup phase, the biggest of which was the COVID-19 pandemic. Some of the smaller clinics participating in the study don’t have the staffing capacity to remain open when staff contract COVID-19. “When this happened,” said Sluka, “we did have significant reductions in recruitment.”

The electronic health record (EHR) has also presented challenges for the study. “Each of our healthcare systems is using different EHR systems,” said Bayman. In many clinics, the clinician or physical therapist is responsible for inputting data into the EHR. For busy healthcare staff who may not have training in the EHR system, this extra task can be difficult. The FM-TIPS project found creative ways around this challenge. Bayman said, “One of our most important exploratory outcomes was turned into a patient reported outcome. We will be collecting this data from the patients.”

Despite these challenges, FM-TIPS is making progress toward its goals and hopes to give patients with fibromyalgia more options to manage their pain on a day-to-day basis.

View the full video.

FM-TIPS is supported by the NIH through the NIH HEAL Initiative under an award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

April 11, 2022: TSOS Implements Suicide Assessment and Monitoring Method in Pragmatic Clinical Trial

Posted on by terren.green@duke.edu

The Trauma Survivors Outcomes and Support (TSOS) trial, an NIH Pragmatic Trials Collaboratory Trial, successfully implemented a large-scale suicide assessment and monitoring method in a pragmatic clinical trial focused on collaborative mental healthcare for traumatic injury survivors. Study intervention and monitoring methods are detailed in a recent publication in Psychiatry.

TSOS researchers analyzed data collected at 25 trauma centers from 635 patients experiencing posttraumatic stress disorder (PTSD) as the result of a traumatic injury. The study used a randomized stepped-wedge design and assigned 370 patients to a control group and 265 to an intervention group.

Patients in the intervention group received proactive injury care management, psychopharmacology, and psychotherapy for PTSD and depression. All patients in both groups were evaluated at 4 timepoints: baseline and 3, 6, and 12 months after injury.

Study personnel interacting with patients participated in a 1-day training workshop to learn study methods and skills for the management of acute suicidal ideation or suicidal intent. Among other measures to assess PTSD symptoms, alcohol use, and physical function, the study team administered the Patient Health Questionnaire (PHQ-9) to screen for suicidal ideation and depression.

Source: Psychiatry. 2022; Spring. doi:10.1080/00332747.2021.1991200.

Patients from both the intervention and control groups who indicated suicidal ideation on the PHQ-9 received calls, texts, and voice messages from study personnel and referral for additional care from a clinician. Study personnel reached out to 161 control and 107 intervention group patients.

The intervention group showed a small but not significant reduction in suicidal ideation compared to the control group.

Lack of a significant treatment effect may be due to the outreach and additional care received by patients in the control group. This level of additional care could be considered a minor intervention for the control group.

Future studies may learn more about treatment differences between control and intervention groups by incorporating implementation process assessments into the design of pragmatic trials.

TSOS was supported within the NIH 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.

March 31, 2022: GRACE Trial Has New Study Snapshot, Updated Ethics and Regulatory Documentation

Posted on by Damon Seils

GRACE Trial logoA downloadable study snapshot and updated ethics and regulatory documentation are now available for the GRACE trial, an NIH Pragmatic Trials Collaboratory Trial.

GRACE transitioned from the planning phase to the implementation phase in September. As part of the transition, the study team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core. The study is a hybrid effectiveness–implementation trial of guided relaxation and acupuncture for pain associated with chronic sickle cell disease in 3 large healthcare systems.

  • Read the updated ethics and regulatory documentation, including information about the study team’s approach to inclusion and exclusion criteria, informed consent, and collection of patient-reported outcome data.
  • Also available is a new study snapshot for GRACE. This downloadable handout summarizes the study’s aims, lessons from the planning phase, and links to other resources from this innovative pragmatic clinical trial.

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

March 30, 2022: Two Weights Make a Wrong: New Article From the Biostatistics and Study Design Core

Posted on by Karen Staman

Contemporary Clinical TrialslsIn a new article from the NIH Pragmatic Trials Collaboratory Biostatistics and Study Design Core, the authors share analytic considerations for cluster randomized trials with hierarchical nesting of participants within clusters. The authors illustrate the problem using theoretical derivations, a simulation study, and data from the STOP CRC NIH Collaboratory Trial as an example.

“We conclude that an analysis using both an exchangeable working correlation matrix and weighting by inverse cluster size, which may be considered the natural analytic approach, can lead to incorrect results. That is, two weights make a wrong. The bias is minimal when there is homogeneity of treatment effects according to cluster size but unacceptable when there is heterogeneity of treatment effects according to cluster size. In addition, we show that only an analysis with an independence working correlation matrix and weighting by inverse cluster size always provides valid results for the UATE [unit average treatment effect] estimand.”

Read the full article.

March 25, 2022: A Telehealth-Delivered Pragmatic Trial of Mindfulness for Persons with Chronic Low Back Pain (Natalia Morone, MD, MS)

Posted on by terren.green@duke.edu

Speaker

Natalia E. Morone, MD, MS
Associate Professor of Medicine
Boston University/Boston Medical Center

Keywords

Chronic pain; Mindfulness; Stress Reduction; Low back pain; OPTIMUM; The Pain, Enjoyment of Life and General Activity (PEG) Scale; HEAL Initiative

Key Points

  • Chronic back pain is very common across all racial and ethnic groups. Doctors treat chronic back pain with non-pharmacologic methods before resorting to pharmacologic treatments.
  • Optimizing Pain Treatment in Medical Settings Using Mindfulness (OPTIMUM) is a randomized study of mindfulness for low back pain operating in 3 health settings: Boston Medical Center; UPMC, Pittsburgh, PA; and University of North Carolina, Chapel Hill in partnership with Piedmont Health Services.
  • Participation in the OPTIMUM study requires 8 weekly 90 minute group-based sessions of mindfulness meditation training delivered in primary care through a telehealth medical visit with follow up assessments at 6 and 12 months.
  • Four methods of mindfulness meditation are taught: Walking meditation, body scan, breath focused meditation, and mindful stretching.
  • The OPTIMUM study uses the PEG scale as the main outcome measure at the 6 and 12 month follow up assessments.
  • Group tele-health visits provide a variety of benefits for patients including more time with a clinician, better medication adherence, and more patient satisfaction.

Discussion Themes

Primary care usually consists of 1 provider and 1 patient, but family medicine evolved to see patients in a group. This group setting model may have unexpected benefits.

OPTIMUM is part of the PRISM project and is collecting data on participant use of opioids along with all PRISM projects.

Recruiting minority participants has been a priority in the OPTIMUM trial. Targeting recruitment advertisements to zip codes where more minorities live makes a difference in recruiting a diverse population.

 

Read more about the OPTIMUM trial.

 

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