December 11, 2018: Two New NIH Funding Opportunity Announcements for Pragmatic Trials Address the Opioid Crisis

The NIH has announced two new funding opportunity announcements (FOAs) for 7 or more embedded pragmatic clinical trials that address pain management and the opioid crisis. These projects will become part of the NIH Health Care Systems Research Collaboratory as phased UG3/UH3 cooperative research.

The two announcements are:

The announcements are part of the NIH Heal (Helping to End Addiction Long-term) Initiative, which was created in April 2018 in an effort to speed scientific solutions for addressing the national opioid public health crisis.

November 13, 2018: Summary of Workshop on Pragmatic Trials of Therapeutic A vs B Interventions Now Available

The NIH Collaboratory recently convened a workshop to explore embedded pragmatic clinical trials comparing two or more therapeutic medical interventions. These “A vs B” trials are meant to test existing, viable treatment alternatives where there is uncertainty about which treatment is best in which populations. There are unique barriers that make these types of pragmatic trials especially challenging to implement. For the workshop, a panel of experts gathered to discuss challenges and solutions regarding partnering with healthcare systems to conduct the trials, unique legal and ethical issues, and design and operational considerations. The summary of the workshop is now available: Workshop Summary: Embedded Pragmatic Clinical Trials of Therapeutic A vs. B Interventions

 

Additional Resources:

Embedded pragmatic clinical trials of therapeutic A vs. B interventions workshop videocast.

 

October 1, 2018: Dr. Greg Simon Uses a Pie Eating Contest Analogy to Explain the Intraclass Correlation Coefficient

In a new video, Dr. Greg Simon explains the intraclass correlation coefficient (ICC) with an analogy to a pie eating contest. The ICC is a descriptive statistic that measures the correlations among members of a group, and it is an important tool for cluster-randomized pragmatic trials because this calculation helps determine the sample size needed to detect an effect.

Greg Simon from NIH Collaboratory on Vimeo.

“When we randomize treatments by doctors, clinics, or even whole health systems, we need to think about how things cluster, and the intraclass correlation coefficient is the measure of that clustering. When we think about sample sizes in pragmatic clinical trials, it’s important to understand what an intraclass correlation coefficient actually is.”

For most pragmatic trials, the ICC will be between 0 and 1. If the outcomes in a group are completely correlated (ICC=1), then all participants within the group are likely to have the same outcome. When ICC=1, sampling one participant from the cluster is as informative as sampling the whole cluster, and many clusters will be needed to detect an effect. If there is no correlation among members of the groups (ICC=0), then the available sample size for the study is essentially the number of participants.

For more on the ICC, see the Intraclass Correlation section in the Living Textbook or this working document from the Collaboratory’s Biostatistics and Study Design Core.

September 14, 2018: Tips for Submitting a Pragmatic Trial Application to NIH

In a new video, Dr. Wendy Weber, the Program Officer for the NIH Collaboratory Coordinating Center, provides some expert advice for investigators who are considering submitting an application for a pragmatic clinical trial to the NIH.

“Don’t assume that the study panel is going to understand what pragmatic means. They may have their own completely different definition than you, and it’s important that you get on the same page early on in your application.” —Wendy Weber, PhD, Acting Deputy Director, National Center for Complementary and Integrative Health (NCCIH)

September 10: NIH Collaboratory Launches New ePCT Training Resources

The NIH Collaboratory is pleased to announce new training resources available on the Living Textbook. These resources are being shared with the research community to provide guidance about building partnerships with health systems and overcoming the challenges of conducting embedded pragmatic clinical trials (ePCTs). The materials reflect the knowledge, insight, and best practices acquired by the NIH Collaboratory program and its Demonstration Projects.

Resources include:

  • Materials from the inaugural ePCT Training Workshop held in February 2018 to provide training to mid- and senior-level investigators interested in conducting ePCTs
  • A slide presentation of the NIH Collaboratory’s goals and organizational structure along with a brief introduction to each Demonstration Project
  • An infographic introducing the elements of the NIH Collaboratory program and the value of engaging in pragmatic research
  • A slide presentation and worksheet on essential things to think about and do when designing, conducting, and disseminating ePCTs
  • An introductory video from NIH Collaboratory leadership on the rationale and aims for the ePCT training resources

“The workshop reinforced that there is a demand for these kinds of training opportunities across the clinical research community.” Lesley Curtis, PhD

Visit the new training resources webpage.

September 7, 2018: Spotlight on a New Demonstration Project: HiLo

Kidney transplantation is the preferred treatment for patients with end-stage renal disease (ESRD), but an insufficient organ supply renders dialysis the only viable treatment option for most patients. Though clinical outcomes among patients receiving dialysis have improved modestly in recent years, annual rates of hospitalization and mortality remain unacceptably high, and quality of life is poor. Poor outcomes are driven primarily by increased risk of cardiovascular disease (CVD), but interventions that improve outcomes in the general population by targeting traditional CVD risk factors have mostly failed in patients with ESRD. Current clinical practice guidelines advocate aggressive treatment of high serum phosphate to near-normal levels using dietary phosphate binders and restrictive diets. The benefits of this approach, however, are unproven, the optimal serum phosphate target remains unknown, and potential harms of aggressive treatment have not been definitively identified.

The Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) plans to address these clinically important questions in a large, pragmatic, cluster-randomized trial that will evaluate the effects of liberalizing the serum phosphate target (“Hi”) versus maintaining aggressive phosphate control (“Lo”) for patients receiving treatment with maintenance hemodialysis.

 “The question at hand is something we grapple with on a daily basis in every dialysis facility across the country. Either answer will be important new information that will help us do a better job taking care of patients and hopefully improve their quality of life.”

HiLo is led by Myles Wolf, MD, of Duke University with support from the National Institute of Diabetes and Digestive and Kidney Diseases. Read more about HiLo.

September 6, 2018: Spotlight on a New Demonstration Project: ACP PEACE

Because many clinicians do not have the skill set to engage patients in conversations about advance care planning (ACP), many older Americans with advanced cancer receive aggressive interventions at the end of life that do not reflect their values, goals, and preferences. The ACP PEACE trial is investigating whether a comprehensive approach to ACP improves patient outcomes. The program will combine two evidence-based complementary interventions: clinician communication skills training (VitalTalk) and patient video decision aids (ACP Decisions). The goal is to provide both patients and clinicians with communication skills and tools so they can make informed decisions about end-of-life care.

“We’re doing an intervention where we include videos for patients about what the possible interventions are, and we’re also training the clinicians, the oncologists and their teams to have better communication about their goals of care and about treatment planning.” —James Tulsky, MD, Co-Principal Investigator of the ACP PEACE trial.

ACP-PEACE is one of the new NIH Collaboratory Demonstration Projects and is led by Drs. James A. Tulsky and Angelo Volandes with support from the National Institute on Aging. Read more about ACP PEACE.

James Tulsky from NIH Research Collaboratory on Vimeo.

 

September 5, 2018: Spotlight on a New Demonstration Project: GGC4H

Before the end of high school, more than half of all adolescents will use an illicit drug, about a quarter will meet the criteria for depression, and many others will engage in behaviors such as delinquency and violence. Guiding Good Choices is a universal evidence-based anticipatory guidance curriculum for parents of early adolescents that has been shown to reduce adolescent alcohol, tobacco, and marijuana use; depression; and delinquent behavior. Evidence-based parenting interventions shown to prevent these behavioral health concerns could improve adolescent health trajectories if implemented widely in pediatric primary care.

The Pragmatic Trial of Parent-Focused Prevention in Pediatric Primary Care: Implementation and Adolescent Health Outcomes in Three Health Systems (GGC4H: Guiding Good Choices for Health) is a cluster-randomized trial that will partner with pediatric primary care clinics to offer the training in three large, integrated healthcare systems serving socioeconomically diverse families.

“We already have an effective intervention, so we’re not trying to test whether it works or not; it’s really about getting the intervention into a population.”  —Richard Catalano, PhD, co-Principal Investigator of the GGC4H trial.

GGC4H is led by Richard Catalano, PhD, Margaret Kuklinski, PhD, and Stacy Sterling, DrPH, with support from the National Center for Complementary and Integrative Health. Read more about GGC4H.

August 9, 2018: New Interview with Dr. David Shurtleff about the NIH Collaboratory

In a recent video interview, Dr. David Shurtleff, acting director of the National Center for Complementary and Integrative Health (NCCIH), discusses the unique work of the Collaboratory in bringing together multiple NIH Institutes and Centers to develop best practices, methods, guidance, and tools for conducting rigorous pragmatic research.

“The Collaboratory has been transformative in how it’s developed a novel, supportive infrastructure to conduct pragmatic research in a way that allows it to be embedded within healthcare systems.” David Shurtleff, PhD

April 9, 2018: PPACT Study Design Paper Published

Congratulations to Dr. Lynn DeBar and the investigators of the Collaborative Care for Chronic Pain in Primary Care pragmatic trial for recently publishing their study design paper. One of the NIH Collaboratory Demonstration Projects, the trial is designed to test whether a primary care–based behavioral intervention the Pain Program for Active Coping and Training (PPACT)—will provide a “more effective, safer, and more satisfactory alternative to opioid-based chronic pain treatment” than usual care for patients on chronic opioid treatment (Debar et al 2018). Learn more about this innovative trial in the article in Contemporary Clinical Trials. You can also download a trial snapshot.

Full Citation: DeBar L, Benes L, Bonifay A, et al. Interdisciplinary team-based care for patients with chronic pain on long-term opioid treatment in primary care (PPACT) – Protocol for a pragmatic cluster randomized trial. Contemporary Clinical Trials. 2018;67:91-99. doi:10.1016/j.cct.2018.02.015