August 24, 2022: Diuretic Comparison Project, a Point-of-Care Clinical Trial, to Be Featured in PCT Grand Rounds

Head shot of Dr. Areef IshaniIn this Friday’s PCT Grand Rounds, Dr. Areef Ishani of the University of Minnesota will present “The Diuretic Comparison Project: A Large Pragmatic Clinical Trial.” The Grand Rounds session will be held on Friday, August 26, 2022, at 1:00 pm eastern.

The Diuretic Comparison Project is a large, national “point-of-care clinical trial” comparing the effects of 2 thiazide-type diuretics, hydrochlorothiazide and chlorthalidone, on cardiovascular outcomes in older veterans with hypertension. The study is funded by the US Department of Veterans Affairs Cooperative Studies Program.

A point-of-care trial is an operational approach to the conduct of clinical trials—whether explanatory or pragmatic—that “centers on enhancing key clinical trial operations (including patient screening, consent, randomization, and data collection) and incorporating clinical trial processes into routine care to make clinical trials more accessible to broader and more diverse populations” (Propes et al 2022).

Dr. Ishani is the director of the Minneapolis Primary Care and Specialty Care Integrated Care Community at the Minneapolis VA, director of the VA Midwest Health Care Network, and a professor of medicine at the University of Minnesota.

Join the online meeting.

March 9, 2022: PCT Grand Rounds to Feature MIPACT Study and THRIVE Pragmatic Trial

Headshots of Dr. Sachin Kheterpal, Dr. Jessica Golbus, and Nicole Pescatore
Dr. Sachin Kheterpal, Dr. Jessica Golbus, and Nicole Pescatore

In this Friday’s PCT Grand Rounds, Dr. Sachin Kheterpal, Dr. Jessica Golbus, and Nicole Pescatore of the University of Michigan will present “Understanding a Patient’s Daily Experience Through Mobile Devices and Wearables: Lessons Learned From the 8000 Patient MIPACT Study and Implementation in a National Pragmatic Trial.” The Grand Rounds session will be held on Friday, March 11, at 1:00 pm eastern.

The Michigan Predictive Activity and Clinical Trajectories (MIPACT) study is a prospective observational study exploring whether data collected on an Apple Watch, combined with home blood pressure measurements and other health information, can provide insights into health and disease. The Trajectories of Recovery After Intravenous Propofol vs Inhaled Volatile Anesthesia (THRIVE) trial is a pragmatic trial of of intravenous vs inhalational general anesthesia in patients undergoing elective noncardiac surgery.

Join the online meeting.

April 30, 2021: ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications (Susanna Naggie, MD, MHS; Elizabeth Shenkman, PhD)

Speakers

Susanna Naggie, MD, MHS
Associate Professor of Medicine
Duke Clinical Research Institute

Elizabeth Shenkman, PhD
Chair, Department of Health Outcomes and Biomedical Informatics
Co-Director, Clinical and Translational Science Institute (CTSI)
University of Florida

Topic

ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications

Keywords

COVID-19; NIH ACTIV Initiative; Repurposed drugs; Vaccines; Therapeutic agents; Direct-to-participant trials; PCORnet

Key Points

  • Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) is a public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines. The ACTIV initiative is coordinated by the Foundation for the National Institutes of Health.

  • ACTIV-6 asks: Are there medications currently approved for other conditions that improve symptoms in nonhospitalized patients with mild-to-moderate COVID-19 symptoms? The study aims to find out how to help patients feel better faster and how to prevent hospitalizations or death in newly diagnosed patients with mild or moderate COVID-19.

  • All study visits are conducted remotely: Participants use an online system to complete study surveys and report adverse events or changes in clinical status. Participants are assigned randomly to receive either a placebo or one of the treatments, which will be sent to them by mail. If deemed necessary by a study investigator, in-person or remote study visits are possible.

Discussion Themes

Vaccine hesitancy is still an issue, especially in rural areas; there will continue to be cases of COVID-19.

To ensure diversity in enrollment, the ACTIV-6 study takes a multipronged approach, including making it easy to participate without in-person appointments; partnering with community groups for broad outreach and messaging; and monitoring enrollment numbers closely.

Sites provide participant education and recruitment. The process is straightforward and appeals to both clinicians and patients. Each study site has a primary care physician as a clinical champion.

Read more about ACTIV-6, the NIH’s ACTIV initiative, and the ACTIV master protocols including ACTIV-6.

Tags

#pctGR, @Collaboratory1

March 11, 2021: TSOS Study Intervention Reduces PTSD Symptoms in Injured Patients at Level I Trauma Centers

Photo of Dr. Doug Zatzick
Dr. Doug Zatzick

A collaborative care intervention for injured patients at trauma centers can reduce symptoms of posttraumatic stress disorder (PTSD), according to the results of the Trauma Survivors Outcomes and Support (TSOS) study. The results were published online this week in JAMA Surgery.

The TSOS study, an NIH Collaboratory Demonstration Project, was a stepped-wedge, cluster randomized pragmatic clinical trial testing the delivery of a stepped collaborative care intervention vs usual care for 635 injured patients with PTSD symptoms and comorbid conditions at 25 level I trauma centers in the United States.

Patients in the control group received usual care plus nurse notification about the patient’s high level of distress. Patients in the intervention group received collaborative care consisting of evidence-based medication, cognitive behavioral therapy, and case management. Patients in the intervention group whose PTSD symptoms persisted after initial treatment received stepped-up care, such as medication adjustments or additional psychotherapeutic elements.

After 6 months, the intervention group experienced a significant reduction in PTSD symptoms as compared with the control group. The treatment effect was greater for patients with higher baseline PTSD risk.

“Our study shows that a brief, approximately 2-hour collaborative care intervention delivered by frontline trauma center providers can significantly reduce PTSD symptoms in diverse injury survivors, including survivors of firearm injuries,” said Dr. Doug Zatzick of the University of Washington School of Medicine, the TSOS study’s principal investigator. “Collaborative care may therefore be an optimal treatment approach for trauma-exposed patients treated in acute care medical settings,” he said.

Figure from the TSOS main outcomes paper
Source: JAMA Surg. 2021 Mar 10. doi: 10.1001/jamasurg.2021.0131.

The study also included an implementation process assessment to allow the investigators to examine how the quality of each site’s implementation of the protocol affected study outcomes. The effect of the intervention on PTSD symptoms was greater at trauma centers with good or excellent protocol implementation.

“The upfront integration of an implementation process assessment into the TSOS pragmatic trial design allowed us to identify sites with good/excellent versus fair/poor protocol implementation, a key characteristic in discriminating patient-level PTSD treatment effects,” Zatzick said.

Overall, reduction in PTSD symptoms did not differ significantly between the study arms at 3 and 12 months, and there was no effect on secondary outcomes. However, the subgroup of patients who had firearm injuries and who were treated at sites with good or excellent implementation had among the largest 6-month treatment effects and demonstrated significant treatment effects at 12 months.

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 Demonstration Projects.

October 9, 2020: Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) (Myles Wolf, MD)

Speaker

Myles Wolf, MD, MMSc
Division of Nephrology, Department of Medicine
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)

Keywords

End-stage renal disease; Hemodialysis; Serum phosphate; Patient-centered outcomes; NIDDK; Electronic health record; Cluster randomization; eConsent

Key Points

  • High serum phosphate is a ubiquitous complication in end-stage renal disease (ESRD), a serious illness that affects ~500,000 people in the United States. However, evidence is lacking for the best approach to reducing high phosphate that benefits survival in patients.
  • The hemodialysis setting is ideal for conducting a pragmatic trial because of an accessible study population, frequent clinical encounters, granular and uniform data collection via electronic health record (EHR), and the many unanswered questions about major aspects of dialysis care.
  • Pragmatic features of HiLo include:
    • Real-world setting
    • Cluster randomization
    • Broad entry criteria
    • Electronic informed consent
    • No traditional on-site study staff
    • Remote site monitoring
    • Outcomes based on EHR with no adjudication

Discussion Themes

The HiLo Ambassadors, a patient advisory group, have contributed to HiLo study materials including the protocol, informed consent form, eConsent script, informational videos, FAQs, flyer, and website content. They are providing strategies to help patients successfully participate and stay in the trial.

Dieticians are critical to the success of HiLo as they directly interact with dialysis patients and are among the most motivated caregivers on dialysis teams.

The onset of the COVID-19 pandemic came after the first week of HiLo site activation, causing a pause of trial activities and enrollment at the dialysis facilities.

What will success look like for the HiLo trial? A clear, proven answer to the question of higher versus lower target.

Read more about HiLo trial at the study website and the NIH Collaboratory Trials page.

Tags

#pctGR, @Collaboratory1

October 2, 2020: Driving Toward Health Impact: Our Journey and Path Forward (Nakela Cook, MD, MPH)

Speaker

Nakela L. Cook, MD, MPH
Executive Director
Patient-Centered Outcomes Research Institute (PCORI)

Topic

Driving Toward Health Impact: Our Journey and Path Forward

Keywords

PCORI; Health outcomes; Health disparities; Patient-centered research; Comparative clinical effectiveness; COVID-19; Maternal health

Key Points

  • Despite improvements in health, disparities and variation in care remain—especially underscored by the unprecedented COVID-19 pandemic.
  • PCORI funds studies that can help patients and those who care for them make better informed healthcare choices.
  • PCORI has funded the HERO Registry to assess COVID-19 exposure responses and outcomes within the community of healthcare workers. Other research support is targeted toward vulnerable populations, healthcare delivery, and emerging health trends.
  • With PCORI 2.0, new funding will be available for large-scale, high-impact comparative effectiveness trials. Each study will include an initial phase to determine the feasibility and viability of the study and maximize the likelihood of success during the full-scale phase.

Discussion Themes

What are your observations regarding COVID-19’s impact on health, healthcare, and research that you think will be critical for PCORI's strategy? What will bring about the necessary innovations to the system?

Addressing maternal health disparities is a high priority in PCORI 2.0. The next phase will also expand PCORI’s role in collecting and generating relevant evidence and focusing on a deliberate and transparent process for implementation.

How will PCORI broaden its reach to reduce outcome disparities among people with disabilities?

Read more about PCORI.

Tags

#pctGR, @Collaboratory1

September 30, 2020: PCORI’s Nakela Cook to Offer a Look Ahead in PCT Grand Rounds

Photograph of Dr. Nakela CookDr. Nakela Cook, executive director of the Patient-Centered Outcomes Research Institute (PCORI), will present “Driving Toward Health Impact: Our Journey and Path Forward” during the NIH Collaboratory’s PCT Grand Rounds.

The Grand Rounds session will be held on Friday, October 2, at 1:00 pm eastern. Join the online meeting.

Since 2010, PCORI has funded more than $2 billion in research to help patients, caregivers, and clinicians make informed healthcare decisions and to improve healthcare delivery and outcomes.

May 4, 2020: TSOS Study Team Draws Lessons From Early COVID-19 Experiences in Washington State

Clinicians and researchers at Seattle’s Harborview Medical Center documented their experiences in the early weeks of the COVID-19 outbreak in King County, Washington. Their report offers lessons from clinical and research personnel, patients, and peer interventionists during the evolving pandemic response in an early US COVID-19 epicenter.

The article, published online in Psychiatry, presents a case series of experiences of frontline clinical and research teams in incorporating COVID-19 prevention strategies in the context of an ongoing comparative effectiveness trial of multidisciplinary, peer-integrated care coordination for patients with severe injury. The report also describes key themes from qualitative data collected during daily team meetings for the Trauma Survivors Outcomes and Support (TSOS) study, a pragmatic clinical trial also underway at Harborview. TSOS, an NIH Collaboratory Trial, is a stepped-wedge, cluster randomized pragmatic trial testing the delivery of screening and intervention strategies for patients with posttraumatic stress disorder and comorbid conditions at 24 level I trauma centers in the United States.

The case series offers evidence that primary and secondary prevention strategies can be integrated into ongoing clinical and research interventions during pandemic response. Procedures can also be developed to support team members who are adapting to rapidly changing individual, organizational, and societal demands.

This work was supported in part by the Patient-Centered Outcomes Research Institute (PCORI). TSOS is 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.

For more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

January 16, 2020: NIH Collaboratory Investigators Describe Key Elements of Successful Distributed Research Networks

Members of the NIH Collaboratory Distributed Research Network (DRN) have helped build DRNs for the Sentinel System, the NIH Collaboratory, and the National Patient-Centered Clinical Research Network (PCORnet). In a new article published online in Contemporary Clinical Trials Communications, they describe the key elements of successful DRNs, as well as methods, challenges, and solutions encountered in using DRNs to support different phases of randomized, multisite clinical research.

“…[DRNs] are a vital component for trials that use real-world data to generate real-world evidence. Given their access to larger and more diverse populations, as well as health systems with a variety of care practices, DRN-based trials have the potential to produce more generalized results.” —Marsolo et al. 2020

DRNs enable the use of real-world data by repurposing electronic health record (EHR) and claims data for research. However, the use of these data to create evidence is “complicated by lack of uniformity in data collection, a fragmented healthcare system, and the imperative to protect research participants.”

The NIH Collaboratory DRN can support observational studies of comparative effectiveness and safety, prospective data collection, and randomized clinical trials. For more, see the list of publications and presentations.

October 11, 2019: Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials (Michelle Meyer, PhD, JD)

Speaker

Michelle N. Meyer, PhD, JD
Assistant Professor & Associate Director, Research Ethics
Center for Translational Bioethics & Health Care Policy
Faculty Co-Director, Behavioral Insights Team
Steele Institute for Health Innovation, Geisinger

Topic

Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials

Keywords

A vs B trials; Comparative effectiveness research; Clinical equipoise; Randomization; Learning health system

Key Points

  • Healthcare delivery systems often have an ethical obligation to experiment in order to determine the effects of their policies and treatments on stakeholders. A/B experiments conducted within health systems are intended to increase quality and safety, decrease waste or lower costs, and reduce inequity and injustice.
  • The “A/B effect” is the approval of untested policies or treatments (A or B) being universally implemented but disapproval of randomized experiments (A/B tests) to determine which of those policies or treatments is superior.
  • Experimentation aversion may be an important barrier to evidence-based practice.

Discussion Themes

Do you think the objection to random assignment is related to a sense that it is not “random?”

A potential solution to the “A/B effect” is to let patients be partners in improving healthcare by explaining that “we don’t know if A or B is better. Would you be willing to help us find out?”

Read Dr. Meyer and colleagues’ open access article in the journal Proceedings of the National Academy of Sciences (May 2019): Objecting to experiments that compare two unobjectionable policies or treatments.

Tags
#pctGR, @Collaboratory1