December 20, 2019: Embedded Pragmatic Clinical Trials: From Idea to Funding to Implementation: A Living Textbook Grand Rounds Series

Coming in 2020, the NIH Collaboratory will host a 5-part Grand Rounds Series focused on the Living Textbook. The series will feature Collaboratory expert speakers guiding the audience through the life cycle of an ePCT by way of the textbook—from idea to funding to implementation.

The series begins January 31 with “Pragmatic Clinical Trials: How Do I Start?” and will end June 19 with “Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials.”

See below for the full schedule of sessions and a special message from Dr. Kevin Weinfurt.

Full Schedule of sessions

Title Speakers Date
Pragmatic Clinical Trials:
How Do I Start?
Greg Simon, MD, MPH, KPWHRI

Lesley Curtis, PhD, Duke University

January 31, 2020
Preparing for the Unknown: Conducting Pragmatic Research in Real-World Contexts Jerry Jarvik, MD, MPH, University of Washington

Vince Mor, PhD, Brown University

Leah Tuzzio, MPH, KPWHRI

February 28, 2020
Tips for Putting Together a Successful PCT Grant Application Wendy Weber, ND, PhD, MPH, NCCIH March 27, 2020
Choosing What to Measure
and Making It Happen: Your Keys to Pragmatic Trial Success
Rachel Richesson, PhD, MPH, Duke University

Emily O’Brien, PhD, FAHA, Duke University

May 1, 2020
Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials Liz Turner, PhD, Duke University

Patrick Heagerty, PhD, University of Washington

David Murray, PhD, NIH

June 19, 2020

 

We hope you will join us to learn more about the fundamentals for designing and launching a successful ePCT. Please download the flyer for the Living Textbook Grand Rounds series and share with your colleagues and institution.

December 18, 2019: National Institute on Aging IMPACT Collaboratory Launches Grand Rounds Series and New Website

The National Institute on Aging (NIA) IMbedded Pragmatic Alzheimer’s disease (AD) and AD Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory has launched a new website highlighting the project.

The IMPACT Collaboratory recently invited applications for pilot grant funding for projects that aim to generate preliminary data necessary to design and conduct full-scale embedded pragmatic clinical trials of nonpharmacologic interventions for persons living with Alzheimer’s disease and related dementias and/or their caregivers. Pilot grants will help IMPACT Collaboratory’s mission to build the nation’s capacity to conduct pragmatic clinical trials of interventions embedded within health care systems for people living with dementia and their caregivers.

Since the IMPACT Collaboratory started this September, the program has been hard at work launching its new website, as well as a series of specialized Grand Rounds focused on the topic of pragmatic research in the area of Alzheimer’s disease and related dementias.

IMPACT Collaboratory Grand Rounds occur the 3rd Thursday of each month at 12 noon ET. Join the next webinar on Thursday, December 19, “Stepped Wedge Cluster Trials: What, How, And When?,” by Monica Taljaard, PhD, Senior Scientist, Ottawa Hospital Research Institute and Associate Professor, University of Ottawa from the IMPACT Collaboratory Design and Statistics Core.

Following in the footsteps of the NIH Collaboratory, the IMPACT Collaboratory has also launched a podcast series to correspond with its Grand Rounds Series. Both the Grand Rounds webinar recordings and accompanying podcasts for all the sessions are available on the website.

Those interested in getting updates about the IMPACT Collaboratory can also join the program’s mailing list .

December 18, 2019: NIH Collaboratory Shares New Findings and Fresh Insights in 2019

NIH Collaboratory researchers in 2019 continued to generate new knowledge and research methods in pragmatic clinical trials. Their work included insights from the Coordinating Center and Core Working Groups, large-scale analyses of data from the NIH Collaboratory Distributed Research Network, and results and innovative methodological approaches from the NIH Collaboratory Trials.

So far this year, the NIH Collaboratory has produced nearly 3 dozen articles in the peer-reviewed literature, including the primary results of the ABATE Infection trial, confirmation by the TiME trial of the feasibility of embedding large pragmatic trials in clinical care, and more:

NIH Collaboratory Coordinating Center

NIH Collaboratory Distributed Research Network

ABATE Infection NIH Collaboratory Trial

EMBED NIH Collaboratory Trial

PPACT NIH Collaboratory Trial

PRIM-ER NIH Collaboratory Trial

PROVEN NIH Collaboratory Trial

SPOT NIH Collaboratory Trial

STOP CRC NIH Collaboratory Trial

TiME NIH Collaboratory Trial

TSOS NIH Collaboratory Trial

December 13, 2019: Reissuance of Funding Opportunity Announcement for HEAL Initiative/PRISM Coming January 2020

The National Center for Complementary and Integrative Health (NCCIH), with other NIH Institutes, Centers, and Offices, intends to reissue Funding Opportunity Announcement (FOA) HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain To Reduce Opioid Prescribing (PRISM) (UG3/UH3 Clinical Trial Optional).

This RFA solicits applications for phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications in the health care delivery setting. The re-issuance of the FOA will prioritize the following areas for pragmatic trials to integrate multimodal or multiple interventions that have demonstrated efficacy into health care systems or implement health care system changes to improve adherence to evidence-based guidelines:

  • Pain management in emergency departments, dental clinics, primary care, and hospitals
  • Chronic overlapping pain conditions
  • Pain management in individuals at risk of or with opioid use disorder
  • Pain management in those with co-occurring mental health disorders
  • Noncancer pain management in persons with medical comorbid conditions

The FOA is expected to be published in January 2020 with an expected application due date in March 2020.

The announcement is 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.

 

December 13, 2019: New ePCT Training Materials Focus on Nephrology Research

Presentations from a recent seminar offered by the NIH Collaboratory in partnership with the American Society of Nephrology are now available on the Living Textbook. The seminar, Embedded Pragmatic Clinical Trials: Accelerating Evidence Generation in Nephrology, was held at ASN Kidney Week 2019. The sessions provide an introduction to concepts in the design of embedded pragmatic clinical trials (ePCTs), with a focus on interventions that are relevant to the nephrology research community.

Visit the NIH Collaboratory Training Resources to download the presentations.

December 12, 2019: Two New Studies Highlight Feasibility of Using the Distributed Research Network to Support Pragmatic Trials

Two new studies from the NIH Collaboratory’s Distributed Research Network (DRN) demonstrated the feasibility of using administrative data and claims to define populations, identify outcomes, and generate hypotheses in support of pragmatic clinical trials and other prospective studies.

In an analysis of data for 53,000,000 patients from 3 health insurers, researchers evaluated the feasibility of using claims to identify the incidence of chemotherapy-induced peripheral neuropathy (CIPN). The findings highlight challenges with the administrative codes currently used by clinicians to identify CIPN. The data may also be helpful in generating hypotheses about risk factors and treatment effectiveness in future research.

The study was supported by a grant from the National Cancer Institute and was published online ahead of print in Supportive Care in Cancer.

In another study from the DRN, published last week in PLoS One, researchers used health plan data for more than 750,000 patients to investigate statin use in older adults with and without cardiovascular disease and/or diabetes. Evidence for the appropriateness of statin use in adults older than 75 years is limited. The researchers found that statin initiation was low in the study population, especially for primary prevention of cardiovascular disease, suggesting an opportunity to conduct large pragmatic trials to develop better evidence for clinical guidelines.

Support for both studies was provided within the NIH Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.

November 26, 2019: PRISM Kickoff Meeting Welcomes New NIH Collaboratory Trials to NIH Collaboratory

The NIH Collaboratory welcomed 4 new NIH Collaboratory Trial teams last week during a kickoff meeting in Bethesda, Maryland. These pragmatic clinical trials embedded in healthcare systems are funded through the Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) program, a component of the NIH HEAL Initiative to address the opioid crisis.

PRISM NIH Collaboratory Trial Investigators
Left to right: Kathleen Sluka, PT, PhD (FM TIPS); Andrea Cheville, MD (NOHARM); Karen Sherman, PhD, MPH (AcuOA); Jon Tilburt, MD (NOHARM); Lynn DeBar, PhD, MPH (AcuOA); Leslie Crofford, MD (FM TIPS); and Natalia Morone, MD (OPTIMUM).

In its recently announced role as the PRISM Resource Coordinating Center, the NIH Collaboratory Coordinating Center will provide technical support and pragmatic trial expertise for the new NIH Collaboratory Trials. The projects address a range of questions related to pain management and opioid prescribing. They include:

  • AcuOA: Pragmatic Trial of Acupuncture for Chronic Low Back Pain in Older Adults
  • FM TIPS: Fibromyalgia TENS in Physical Therapy Study
  • NOHARM: Non-pharmacological Options in Postoperative Hospital-Based and Rehabilitation Pain Management
  • OPTIMUM: Group-based mindfulness for patients with chronic low back pain in the primary care setting

Attendees of the PRISM kickoff meeting included the NIH Collaboratory Trial teams, NIH Collaboratory leadership and Coordinating Center faculty and staff, and representatives of several NIH Institutes, Centers, and Offices. The NIH Collaboratory Trial teams presented their studies to the full group for discussion. They then participated in individual breakout sessions with the Core Working Groups to discuss anticipated challenges in design, implementation, analysis, and dissemination.

November 22, 2019: NIH Releases Draft Policy for Data Management and Sharing

The NIH recently released a Draft NIH Policy for Data Management and Sharing and supplemental draft guidance for public comment.

In the draft, the NIH reiterates its commitment to making available the results and products of the research it funds, and acknowledges that data sets come from a variety of sources that may have unique data sharing concerns. Therefore, the draft policy proposes that applicants for research funding submit a plan describing how scientific data will be managed and shared.

 “Under this Policy, individuals and entities would be required to provide a Data Management and Sharing Plan (Plan) describing how scientific data will be managed, including when and where the scientific data will be preserved and shared, prior to initiating the research study.” —Draft NIH Policy for Data Management and Sharing

The elements of the Plan are described in detail in the Draft Policy and will require a description of data type and quantity, a rationale for decisions about data sharing, metadata and associated documentation, and plans for protecting confidentiality.

Comments are due no later than January 10, 2020. Comments may be submitted online.

For information on the NIH Collaboratory Data Sharing Policy, see the Data and Resource Sharing informational document, questionnaire, and checklist.

November 1, 2019: Collaboratory PIs Give Advice to New Pragmatic Trials

The NIH Health Care Systems Research Collaboratory program is welcoming new embedded pragmatic clinical trials (ePCTs) on pain management and reducing opioid prescribing as part of the NIH’s Helping to End Addiction Long-term Initiative (NIH HEAL Initiative). At the same time, many of the Collaboratory’s early NIH Collaboratory Trials are completed and now publishing results. At a recent Collaboratory Steering Committee meeting, we spoke with four of the principal investigators (PIs) of completed trials to glean advice for new trials.

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

Dr. Laura Dember, PI of the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (NCT02019225).

Dr. Dember: “An important message is that progress in making big changes to how trials are conducted is going to be incremental. We need to be aspirational, but we also need to recognize that we’re not going to solve all of the problems with one try. We should not be discouraged by the things that don’t work, but rather keep moving forward by building on what we’ve learned.”

Dr. Lynn Debar, PI of the Collaborative Care for Chronic Pain in Primary Care (PPACT) trial (NCT02113592).

Dr. DeBar: “Regarding stakeholder engagement, recognize that these are really complex adaptive systems, and sometimes, more resources and harder pushing is not the way to accomplish your goal. You have to really think through how to communicate: where and how you push requires thinking about all the stakeholders involved.”

Dr. Beverly Green, Co-PI of the Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) trial (NCT01742065).

Dr. Green: “The collaboration part of bringing the investigators together to figure out the pieces of the puzzle has really been valuable to me. Really try to understand stakeholder engagement, the values of the people involved, and work to align them. This way, when you get it right, embedded pragmatic research can save money, improve health, and be a better experience for staff and patients. It’s a win-win.”

Dr. Susan Huang, PI of the Active Bathing to Eliminate (ABATE) Infection trial (NCT02063867).

Dr. Huang: “Communication is so important because if you have stakeholders at the table, not all of them will have the exact vantage point as you, and you will learn by communicating. And, if you’re learning different things and reaching different forks in the road that require decision-making and troubleshooting, it’s only by talking about them that you get everybody to really understand what the goal is. And in this way, you come up with better solutions than you could come up with yourself.”

What was the biggest lesson learned in conducting your trial?

Dr. Dember:  “It’s important to effectively engage with people on the ground. The extent to which this is possible depends on the setting, but, at least for some interventions, being able to engage with the people who are actually implementing the trial procedures is critical.”

Dr. Huang: “The biggest lesson is the critical nature of the partnership and the investment involved in maintaining it. The strength of our trial, and our ability to conduct it, was dependent on a strong partnership.”

Dr. Debar: “Vertical integration is important: you need high level buy-in, but you also need buy-in from people on the ground who are providing care.”

Dr. Green: “Someone in NIH did the math regarding how much an implementation study costs per participant, and he said, ‘That has to be cheaper.’ This prompted me to think about what things could be answered with embedded research. As a clinician, day to day, I am always making decisions that I don’t really know the answer because there isn’t enough evidence. There are so many questions that need to be answered, and embedded pragmatic research is a great starting point for getting more answers. We’ll never get there by doing this one trial at a time with traditional research.”

Congratulations to all four investigators for their groundbreaking work on their NIH Collaboratory Trials!

October 30, 2019: Baseline Covariate Imbalance Influences Treatment Effect Bias in Cluster Randomized Trials

In a study supported by the NIH Collaboratory, researchers found that imbalance in individual-level baseline covariates influences bias in the observed treatment effect in cluster randomized trials. Using race as an example, the study highlights the importance of reducing covariate imbalance in the design stage of cluster randomized trials and of using statistical analysis techniques to minimize the resulting bias.

The innovative study, published in Contemporary Clinical Trials, used computer simulation models validated by real-data simulations from a large clinical trial to examine the influence of baseline covariate imbalance on treatment effect bias. They found that bias was proportional to the degree of baseline covariate imbalance and the covariate effect size. In the simulations, trials with larger numbers of clusters had less covariate imbalance. Statistical models that adjusted for important baseline confounders were more effective than unadjusted models in minimizing bias.

The authors recommend several design approaches and statistical analysis techniques for both reducing covariate imbalance and minimizing bias. Using the results of available prior data can help researchers identify important baseline confounders when designing cluster randomized trials.

This work was supported within the NIH Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director, and by a research supplement from the NIH Common Fund to promote diversity in health-related research.