June 25, 2019: GGC4H Awarded Continuation From Planning to Implementation Phase

The investigators of Guiding Good Choices for Health (GGC4H), an NIH Collaboratory Demonstration Project, have received approval to move from the planning phase to the implementation phase of their study. Congratulations to the GGC4H study team for their excellent work!

At the May 2019 NIH Collaboratory Steering Committee meeting, we talked with Drs. Stacy Sterling, Margaret Kuklinski, and Richard Catalano to hear about progress and challenges during the UG3 planning phase. The goal of GGC4H is to test the feasibility and effectiveness of implementing Guiding Good Choices—a universal evidence-based anticipatory guidance curriculum for parents of early adolescents—in 3 large, integrated healthcare systems serving socioeconomically diverse families.

“Guiding Good Choices is a tested and proven intervention in community and school-based settings. We think primary care is an ideal implementation setting because pediatricians have parents’ trust, and the AAP recommends that they offer anticipatory guidance to parents. Community and school settings do not often have the same advantages.” — Rico Catalano, Co-PI of GGC4H

In the UG3 phase, the study team partnered with 5 pediatric primary care clinics in Kaiser Permanente Northern California, Kaiser Permanente Colorado, and Henry Ford Health System, finalized the trial protocol, obtained IRB approval, and presented UG3 and pilot study findings at 2 recent national meetings: the Society for Prevention Research and the National Academy of Medicine Collaborative for Healthy Parenting in Primary Care.

Were there any surprises during the study’s planning phase?

“I’ve been pleased and surprised to see the near universal excitement for Guiding Good Choices across the 3 healthcare systems and in multiple clinics. My previous work has been with adolescents who have already started to develop problems and are clearly at risk. Often when you are engaging those teens and their parents, they are coming from a place of crisis and have a lot of anxiety and worry. With Guiding Good Choices, we’re offering it to all families of young adolescents in the pediatric clinics, and we’re heartened to see pediatricians and parents welcoming this.

“The parents and kids were so enthusiastic and excited in our pilot. It’s been extremely heartening, and I think it bodes well for the reception we’re going to get.” — Stacy Sterling, Co-PI of GGC4H

What is an example of a challenge that you were able to overcome with the help of a Core Working Group?

Our study has two core questions: Will Guiding Good Choices improve adolescent behavioral health when offered in a health care setting? Will parents in a health care setting actually enroll in Guiding Good Choices and to what degree? Our initial study design attended more to the second question, and in doing that, raised problems for the valid assessment of effectiveness. These issues could have prevented us from transitioning to the implementation phase, so we needed a good design for assessing both effectiveness and implementation. Our original plan would have included all adolescents who had well visits, but at some clinics, 25% of teens don’t have them. Our new design, developed with the IRB chair and the Biostatistics and Study Design Core, includes everyone who receives care at the pediatric clinic. Although we may enroll some people who don’t engage with the intervention, this will make the study results more generalizable and valid for both effectiveness and implementation.

What words of advice do you have for investigators conducting their first embedded PCT?

“It’s a really fasted-paced year. I think we have complementary strengths across the leaders at our sites, and that is important. Pay attention to the qualities of your team and how they can help you hit the ground running and eventually help you get across the finish line to the UH3 phase.”  — Margaret Kuklinski, Co-PI of GGC4H

GGC4H is supported within the NIH Collaboratory by a cooperative agreement from the National Center for Complementary and Integrative Health and receives logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about GGC4H in the Living Textbook, and learn more about the NIH Collaboratory Demonstration Projects.

June 7, 2019: Meeting Materials from the 2019 NIH Collaboratory Steering Committee Meeting

The Collaboratory has made available all the presentations from their recent Steering Committee meeting held in Bethesda May 1-2, 2019.

Highlights of Day 1 included updates on the progress and sustainability of the NIH Collaboratory, perspectives on the landscape of embedded PCTs (ePCTs) and the need for real-world evidence, challenges and lessons learned from the UH3 Demonstration Projects, updates on progress and transition plans from the UG3 Demonstration Projects, and discussions on data sharing policy and planning. Day 2 featured an intensive workshop hosted by the NIH with the goal of starting discussions on statistical issues with ePCTs.

View or download the meeting materials on the website.

May 16, 2019: NIH Collaboratory Investigators Author Recommendations for Responding to Guideline or Policy Changes That Affect Ongoing Pragmatic Trials

A new perspective article by NIH Collaboratory investigators describes the unique, unexpected challenges researchers face when clinical practice guidelines and policies change during the conduct of a pragmatic clinical trial (PCT). The article was published online this week in Clinical Trials.

The NIH Collaboratory Demonstration Projects are PCTs that test interventions to address urgent public health problems. They involve hundreds to thousands of participants and generally include usual care as a control arm. During the course of these years-long trials, clinical practice guidelines and policies changed due to new evidence from observational studies, small trials, and shifting expert opinion. Such changes can have profound effects on usual care and, therefore, threaten the ability of the PCTs to address the questions they were designed to answer. Investigators must strike a balance between the primary ethical obligation to protect patients by adhering to new best-practice guidelines and policy and the secondary, yet crucial, obligation to develop high-quality evidence to improve care.

“PCTs are an important means of producing high-quality evidence needed to better inform clinical practice. However, when guidelines or reimbursement policies change during the conduct of a PCT, the ethical obligation to gather information to develop evidence-based practices may conflict with the primary ethical obligation to participants.” — Curtis et al, Clinical Trials, 2019

Based on their aggregate experience with the NIH Collaboratory, the authors provide broad recommendations and strategies for overcoming these challenges, including protecting the well-being of patients; involving stakeholders, health system leaders, and the entity charged with data and safety monitoring; and actively monitoring changes and site-level responses to them. If changes to the standard of care are merited, investigators should provide equal opportunity and support for the recommended changes. Finally, during the design phase, investigators should communicate with the entities charged with creating guidelines to see what is needed and to anticipate possible future changes.

“The ability to appropriately address the tension between modifications to clinical guidelines and the need to generate quality evidence to support those guidelines is a crucial consideration for the fulfilment of a learning health system.” — Curtis et al, Clinical Trials, 2019

May 8, 2019: Dr. Greg Simon Receives National Suicide Prevention Award

At the Lifesavers Gala in New York last night, Dr. Greg Simon received the American Foundation for Suicide Prevention (AFSP’s) Research Award for his contributions to suicide prevention. Dr. Simon leads the Suicide Prevention Outreach Trial (SPOT), an NIH Collaboratory Demonstration Project that builds on previous work demonstrating that patients who answer “yes” to thoughts of self-harm on routinely administered PHQ-9 questionnaires at primary care visits are more likely to attempt suicide. For these high-risk patients, SPOT explores different modes of outreach (care management or online skills training versus usual care) to prevent suicide.

“There’s a conspiracy of silence around suicidal thoughts, because it’s awkward to discuss. So we’ve found that we have to incorporate talking about it into our standard care. Our suicide prevention work is a great example of how research and care keep influencing each other to improve our patients’ health. When research springs from clinicians’ and patients’ questions, ‘learning health systems’ can put results into practice much faster than the oft-cited 17-year lag.” — Dr. Greg Simon, from the Kaiser Permanente Washington Health Research Institute Press Release

Dr. Simon and his colleagues are also studying how machine-learning models can be used to predict risk of suicide. The models combine the PHQ-9 mental health questionnaire responses with information from electronic health records, including prior suicide attempts and mental health and substance use diagnoses. In a blog post regarding his research (and recent publication) on machine learning, Dr. Simon compares machine learning to warning lights on cars:

Our paper prompted many questions from clinicians and health system leaders about the practical utility of risk predictions:

“Are machine learning algorithms accurate enough to replace clinicians’ judgment?” our clinical partners asked.

“No,” I answered, “but they are accurate enough to direct clinicians’ attention.”

The AFSP also honored four others, including Anderson Cooper, a CNN and 60-minutes correspondent, and Kate Snow, an NBC news correspondent, for their work raising public awareness of suicide prevention.

Read more about what inspired Dr. Simon to study mental health.

May 2, 2019: Cost-Effectiveness Analysis of STOP CRC Trial Finds Wide Variation Across Health Centers

A cost-effectiveness analysis of the Strategies and Opportunities to Stop Colorectal Cancer in Priority Populations (STOP CRC) trial, an NIH Collaboratory Demonstration Project, revealed wide variation across participating health centers. The study’s findings reflect the complexity of implementing an intervention in pragmatic research involving community health clinics with diverse patient populations, clinic structures, and resources.

The study was published recently in Preventive Medicine.

The STOP CRC trial tested a program to improve colorectal cancer screening rates in 26 clinics within 8 federal qualified health centers in California and Oregon. Intervention clinics embedded a tool in the electronic health record to identify patients who were overdue for screening and mailed a fecal immunochemical test (FIT) kit to these patients. Screening rates were higher overall in intervention clinics than in clinics that practiced usual care, despite low and highly variable rates of implementation of the program among participating clinics.

In the subsequent cost-effectiveness study, variability in program implementation was likewise a key factor in the results. Intervention delivery costs were highly variable across health centers, and the incremental cost-effectiveness of the intervention was diminished somewhat because usual care clinics generated more colonoscopies than intervention clinics after abnormal FIT results.

The study has implications for the design of implementation strategies in pragmatic trials that are embedded in diverse community health centers.

The STOP CRC trial was supported within the NIH Collaboratory by a cooperative agreement from the National Cancer Institute and received logistical and technical support from the NIH Collaboratory Coordinating Center. Download a study snapshot of the STOP CRC trial, and learn more about the NIH Collaboratory Demonstration Projects.

April 19, 2019: Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims (Doug Zatzick, MD)


Doug Zatzick, MD
Professor of Psychiatry
Harborview Medical Center
University of Washington School of Medicine


Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims


Trauma outcomes; Demonstration Project; Hybrid study design; Implementation science; Pragmatic clinical trial; Cluster randomization; Stepped-wedge design; Posttraumatic stress disorder; PRECIS-2; Mental health intervention

Key Points

  • The TSOS Demonstration Project is a cluster-randomized, stepped-wedge trial conducted at 25 U.S. trauma centers. The intervention involves an electronic health record PTSD screen and a baseline PTSD and comorbidity assessment. TSOS is turned on at each site across 4 “waves.”
  • During the course of this hybrid effectiveness-implementation trial, two domains on PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) were scored as more pragmatic and one domain as more explanatory than at the outset of the study.
  • The study team developed a methodology for assessing TSOS implementation aims. Called RAPICE (Rapid Assessment Procedure Informed Clinical Ethnography), the method yielded findings around recurrent intervention and research staff turnover across sites; observations that some patients do not engage in the intervention; and ways to inform a priori secondary hypotheses that suggest per-protocol modifications to the original intention-to-treat analyses.
  • TSOS will present results at the 2020 summit of the American College of Surgeons with the potential to integrate findings into the College’s regulatory and verification processes.

Discussion Themes

Regarding the need to collect outcome data, there may be an important distinction between two aspects of “pragmatic.” That is, while collecting outcome data makes a trial more expensive (one aspect of pragmatic), it doesn’t necessarily affect relevance or generalizability (another, more important, aspect of pragmatic).

Might there be studies which, by design, are not aiming to be on the outer [more pragmatic] spokes of the PRECIS-2 wheel?

Read more about the TSOS Demonstration Project.


#pctGR, @Collaboratory1, @PRECIS_2

April 22, 2019: TiME Trial Confirms Feasibility of Embedding Large Pragmatic Trials in Clinical Care

Laura Dember

The primary results of the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial, an NIH Collaboratory Demonstration Project, were published online this month in the Journal of the American Society of Nephrology. The study confirmed the feasibility of embedding a large pragmatic clinical trial in clinical care delivery.

Although maintenance hemodialysis has long been a staple of care for patients with end-stage renal disease, there are limited data from clinical trials to inform optimal approaches, including the optimal duration of hemodialysis sessions. The TiME trial investigators, in partnership with 2 large dialysis provider organizations, evaluated the effects of a longer hemodialysis session duration on mortality and hospitalization rate among more than 7000 patients receiving care in 266 dialysis facilities.

The TiME trial was discontinued early (median follow-up, 1.1 years) because there was an insufficient difference in mean hemodialysis session duration between the intervention group and the usual care group. The investigators observed no reduction in mortality or hospitalization rate in either group.

Despite ending early, the trial met important objectives for informing the implementation of large pragmatic clinical trials embedded in health care systems. In a large multicenter study with no onsite research personnel, the investigators quickly and efficiently enrolled a large number of participants using an opt-out consent approach. The study data were obtained entirely from the electronic health and administrative records of the partnering dialysis provider organizations and were generated from routine clinical care delivery.

“The TiME trial provides an important foundation for future pragmatic trials in dialysis as well as in other settings,” said Dr. Laura M. Dember of the University of Pennsylvania Perelman School of Medicine, the principal investigator of the TiME trial.

The TiME trial was supported within the NIH Collaboratory by a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases and received logistical and technical support from the NIH Collaboratory Coordinating Center. Download a study snapshot about the TiME trial, and learn more about the NIH Collaboratory Demonstration Projects.

April 9, 2019: EMBED Awarded Continuation From Planning to Implementation Phase

The investigators of EMBED, an NIH Collaboratory Demonstration Project, have received approval to move from the planning phase to the implementation phase of their study. Congratulations to Dr. Ted Melnick, Dr. Gail D’Onofrio, and the EMBED study team for their excellent work!

“The opioid crisis is taking a devastating toll on Americans, their families, and their communities. The EMBED project leverages the urgency of our nation’s opioid crisis to bring together leaders in human-centered design, clinical informatics, data coordination, emergency medicine, and addiction medicine to provide an integrated, user-friendly solution to emergency clinicians caring for people with opioid addiction.”   —Dr. Edward Melnick, Co-PI of EMBED

EMBED (Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder) is designed to evaluate the effect of computerized clinical decision support on rates of emergency department-initiated buprenorphine/naloxone (BUP), which is a well-established outpatient treatment for people with opioid use disorder. BUP can only be prescribed by appropriately trained physicians. Although patients with opioid use disorder often seek medical care in emergency departments, the practice of initiating BUP in the emergency department is not common.

“Initiating buprenorphine in the emergency department has the potential to improve and save so many lives, but currently adoption rates are close to 0%. We believe that the EMBED intervention will be a crucial part of getting this evidence-based practice into routine emergency care.”   —Dr. Edward Melnick, Co-PI of EMBED

NIH Collaboratory Demonstration Projects begin with a 1-year, milestone-driven planning phase. Projects become eligible to move to the implementation phase after an administrative review of progress toward scientific milestones and feasibility requirements.

In the planning phase, the EMBED study team developed the clinician decision support tools intended to facilitate the management of people with untreated opioid use disorder who seek care in emergency departments. In the next phase, the team will implement the trial and test the effect of the clinical decision support tool compared to usual care on outcomes in patients with opioid use disorder who seek care in emergency departments.

EMBED was supported within the NIH Collaboratory by a cooperative agreement from the National Institute on Drug Abuse. The study also received logistical and technical support from the NIH Collaboratory Coordinating Center through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.


April 1, 2019: Pre-Conference Seminar on Essentials of ePCTs Offered at AcademyHealth’s June 2019 Annual Research Meeting in D.C.

The NIH Collaboratory is partnering with AcademyHealth to offer a full-day pre-conference seminar at the 2019 Annual Research Meeting in Washington, D.C. Essentials of Embedded Pragmatic Clinical Trials will provide an introduction to the investigative opportunities for embedded health systems research, along with strategies for conducting clinical trials that provide real-world evidence necessary to inform both practice and policy. Firsthand ePCT experiences and case studies from the NIH Collaboratory will support and illustrate the topics presented. Speakers will include program officers and senior staff from NIH Institutes and Centers and senior investigators from the Collaboratory Demonstration Projects and Coordinating Center.

Learning objectives include:

  • To clarify the definition of ePCTs and explain their utility.
  • To introduce attendees to the unique characteristics and challenges of designing, conducting, and implementing ePCTs within diverse health care systems.
  • To increase the capacity of health services researchers to address important clinical questions with ePCTs.
Seminar Details & Registration
Saturday, June 1, 2019
8 am to 5 pm
Walter E. Washington Convention Center
Washington, D.C.

March 13, 2019: PROVEN Publishes Study of Nursing Home Characteristics Associated With Implementation of an Advance Care Planning Video Intervention

The Collaboratory Demonstration Project Pragmatic Trial of Video Education in Nursing Homes (PROVEN) is testing the effectiveness of a novel advance care planning (ACP) video education program in 360 nursing homes within 2 large nursing home healthcare systems. The investigators of PROVEN recently published a study that examines the characteristics of nursing homes associated with implementation of the video. They found that lower quality nursing homes (rated 1 star) had lower offer rates than higher quality nursing homes, suggesting that ongoing support might be necessary in these settings, as well as engagement with a local champion.

ACP is a process by which individuals define their future goals and preferences for medical treatment at the end of life and discuss these goals with their family and healthcare providers. ACP is especially important for nursing home residents, who often receive unnecessary care and experience burdensome transitions at the end of life. The ACP intervention in PROVEN is delivered by an onsite champion at the facility—usually a social worker with structured training in how and when to offer and show the ACP videos to residents and families.

 “These results have implications for future pragmatic trials in the NH [nursing home] setting because ongoing engagement between research and NH staff appears crucial for successful integration of interventions into routine clinical practice. Future research is needed to understand how to best engage NHs in implementation and encourage communication between NHs to share pragmatic strategies for improving clinical practice without the support of research staff.”

– Loomer et al. Journal of the American Medical Directors Association