November 28, 2023: Workshop Summary Now Available From ‘Getting the Right Evidence to Decision-Makers Faster’

The workshop summary is now available from the NIH Pragmatic Trials Collaboratory’s recent workshop, “Getting the Right Evidence to Decision-Makers Faster.” The 2-day workshop explored the critical cycle of evidence generation by researchers to decision-making by healthcare system leaders to implement the findings of pragmatic clinical trials conducted within healthcare systems.

The workshop included 4 panels:

  • Panel 1: How Have Health Systems Made Decisions Based on Evidence Collected in PCTs?

    • Panelists: Devon Check, Vincent Mor, Lynn DeBar, Kathryn Glassberg, Douglas Zatzick, Eileen Bulger, Susan Huang, Kenneth Sands, Edward Septimus; Moderator: Gregory Simon
  • Panel 2: How Do We Generate the Right Evidence to Support Decision-Makers?

    • Panelists: Kenneth Sands, Eileen Bulger, Edward Septimus, Amy Kilbourne, Rosa Gonzalez-Guarda, Patrick Heagerty; Moderator: Hayden Bosworth
  • Panel 3: Learning Faster

    • Panelists: Gloria Coronado, Natalia Morone, Corita Grudzen, Kevin Chan, Pearl O’Rourke, Cheryl Boyce, Andrea Cook; Moderator: Kevin Weinfurt
  • Panel 4: Potential Structures and Incentives for Faster Learning

    • Panelists: David Chambers, Wynne Norton, Tisha Wiley, Kenneth Sands, Edward Septimus, Gloria Coronado, Natalia Morone, Corita Grudzen; Moderator: Richard Platt

Access the complete workshop materials, including slides and videocast recordings, as well as the keynote presentation by Andrew Bindman, executive vice president and chief medical officer for Kaiser Permanente.

August 31, 2023: FDA’s Robert Califf and Coauthors Assert More Is Needed to Achieve Learning Health Care

A graphic that includes the cover image from the August 2023 issue of the American Journal of Bioethics. The text in the graphic reads as follows: "American Journal of Bioethics Special issue on pragmatic trials, featuring target articles from the NIH Pragmatic Trials Collaboratory."In an article published this month in the American Journal of Bioethics, FDA Commissioner Robert Califf and coauthors suggest that—despite the potential of embedded pragmatic research to generate information to improve clinical practice and public health policy—it is still relatively uncommon in US healthcare.

“Simply stated, what we are currently doing does not work, and in the face of declining health status we lack answers to critical questions about what we should be doing in health care and public health practice.”

The authors state 3 major obstacles:

  • Inadequate data systems: Electronic health records are not designed for research use, and are driven by billing codes and reimbursement structures.
  • Data sharing malaise: We have failed to develop a convincing paradigm for sharing individual-level data from routine healthcare delivery
  • Current oversight: Research oversight is still not designed to facilitate embedded pragmatic clinical trials or research using real-world evidence.

The authors suggest that achieving a learning health system will require

  • More collaboration between health systems and businesses involved in healthcare
  • More innovative structures for data sharing across institutions
  • Incentives for building the sophisticated infrastructure necessary to enable this work
  • Considerations from the bioethics community about how best to foster this research while respecting all those who participate

This article was part of a special issue of the American Journal of Bioethics on pragmatic clinical trials. Members of the Ethics and Regulatory Core contributed the target articles to this issue regarding investigator obligations and the clinician’s duty to participate in embedded research.

 

June 7, 2022: Reflecting on 10 Years of the Health Care Systems Interactions Core

The NIH Pragmatic Trials Collaboratory Heath Care Systems Interactions Core supports and facilitates productive collaboration between researchers, clinicians, and health system leaders to conduct effective, relevant embedded pragmatic clinical research.

Health Care Systems Interactions Core Co-Chairs Dr. Eric B. Larson and Dr. Gregory Simon discussed the Core’s progress over the last 10 years in an interview at the NIH Pragmatic Trials Collaboratory Steering Committee meeting in April.

Over the last 10 years, the Health Care Systems Interactions (HCS) Core has allowed researchers to learn about working with healthcare delivery systems. Knowledge that is now common, was unknown when the Core was started, such as how dynamic healthcare delivery systems are and how the capabilities of and changes to the electronic health record can impact pragmatic clinical trials.

Through this type of discovery, the HCS Core has helped researchers become more sensitive to and aware of the priorities of healthcare delivery systems, resulting in better collaboration.

“The researchers’ priorities are usually not the same as the priorities of the people we are working with, whether they are patients, providers, or delivery systems. You have to know what other people’s purpose and drivers are and find a way to adapt,” said Larson. “We have learned and taken pretty seriously this idea of a learning health system with bidirectional engagement from research and from elements of the delivery system.”

The work of the HCS Core and NIH Pragmatic Trials Collaboratory has created a safe haven where researchers can share experiences and advance the field with common learning.

Simon sees the HCS Core as having internal and external missions. The internal mission is to support NIH Collaboratory Trials and be a community where researchers can come together, share their trials and tribulations, and experts in the Core can help these projects be successful, he described.

The external mission is focused on generalizable knowledge and advocacy. The HCS Core has shared knowledge with the research community and funders through publications and meetings and is advocating for research that includes the healthcare delivery system perspective.

“The discussion we are having is not just how do I work with healthcare systems to do my research, but how do I engage with healthcare systems about what research we should be doing, what are the right questions we should be asking for the studies that will be happening 5 years from now not the studies that are already underway,” Simon said.

Another lesson the HCS Core has learned is the importance of being flexible and adjusting. This lesson has been particularly relevant during the COVID-19 pandemic.

“COVID-19 is an extreme case of health system overwhelm, but I think we need to recognize that if we are going to serve people that have been traditionally not been well-served by the healthcare system, we will often be dealing with health systems that are chronically overwhelmed,” said Simon. “How do we do research in those settings? There are some really interesting challenges to think about.”

The HCS Core is focused on continued engagement between researchers and healthcare delivery systems that results in implementable new knowledge.

“My belief is that if we have the upstream involvement and are engaged in research projects that matter to the delivery system from the patients all the way up to the executives, we have a much better chance that when a result is valuable it becomes implementable and spreads to benefit everybody,” Larson said.

View the full interview.

See the complete materials from the 2022 Steering Committee meeting.

July 1, 2021: NIH Collaboratory Leadership Asks, ‘Is Learning Worth the Trouble?’

Cover of the New England Journal of MedicineIn an article published today in the New England Journal of Medicine, Drs. Richard Platt, Adrian Hernandez, and Greg Simon of the NIH Collaboratory discuss barriers to healthcare system participation in embedded research and strategies for improvement.

“We advocate creating a robust national [embedded pragmatic clinical trial] capability to generate evidence to guide decisions by patients, clinicians, health systems, and regulators and respond to urgent national health crises, like COVID-19 or the opioid crises,” the authors wrote.

The article recommends a 4-pronged strategy that researchers and funders should consider to increase healthcare system participation in pragmatic clinical trials:

  • Reimburse for the additional costs of trial participation.
  • In some highly engaged systems, support permanent, reusable infrastructure.
  • Offload research-specific tasks to minimize burden on sites (such as IRB oversight, obtaining informed consent, and mailing medications to participants).
  • Assign and promote reputational benefit for these activities.

In another perspective piece by Simon, Platt, and Hernandez published in the April 2020 issue of the journal, the authors explored why randomized A vs B comparisons remain uncommon in clinical trials.

June 24, 2021: New Article Offers Guidance on Accounting for Quality Improvement Activities During Embedded Pragmatic Trials

Cover of the journal HealthcareIn a new article in Healthcare’s special issue on embedded research, Leah Tuzzio and colleagues use experiences from the NIH Collaboratory to describe how quality improvement activities may pose challenges for embedded pragmatic clinical trials (ePCTs), especially if there are overlapping goals and timelines.

For ePCTs to be rigorous, study teams must monitor, adapt, and respond to QI during the design and the trial implementation. Both ePCTs and QI happen within the same context and aim to improve patient care, and they are inherently interconnected. — Tuzzio et al, Healthcare, 2021

ePCTs tend to be larger and more broadly generalizable than quality improvement initiatives and may generate high-quality evidence for care and clinical practice guidelines. Quality improvement initiatives may address the same high-impact health questions, but if they co-occur with ePCTs, they may dilute or confound the ability to detect change. As a result, study teams may need to monitor, adapt, and respond to quality improvement initiatives during the design and conduct of the trial. The authors suggest that routine collaboration with healthcare system stakeholders can help align research and quality improvement to support high-quality, patient-centered care.

Publication of the special issue was supported by AcademyHealth.

For more, see the Living Textbook Chapters on Advice from Health Care System Leadership,  Building Partnerships to Ensure a Successful Trial, and Monitoring Intervention Fidelity and Adaptations.

May 14, 2021: Keynote Session: Diverse Representation Among Clinical Trial Participants: Why It Is Important and How Can We Improve (Clyde W. Yancy, MD, MSc)

Speaker

Clyde W. Yancy, MD, MSc
Vice Dean, Diversity and Inclusion
Professor of Medicine
Chief, Cardiology
Feinberg School of Medicine
Northwestern University

Guest Moderator:
Kanecia Zimmerman, MD
Associate Professor of Pediatrics
Duke University School of Medicine

Topic

Diverse Representation Among Clinical Trial Participants: Why It Is Important and How Can We Improve

Keywords

Clinical trials; Health outcomes; Racial disparities; Diverse participant recruitment; Disease burden; Cardiovascular disease

Key Points

  • The reason we do clinical research is to improve the health of the community. But trials do not represent the full spectrum of the community with respect to elderly patients, minorities, and women. In excluding overlooked populations, trials do not explore—or generate appropriate evidence about—the totality of a health intervention’s benefit.
  • It is urgent that we advance the overall “research IQ” of the populace, thus overcoming a legacy of mistrust of the research enterprise and reducing barriers to participation in clinical trials.
  • Among the steps to advance diversity in clinical trials:
    • Consider economic incentives or penalties by FDA or payers
    • Revisit the design of trials, selection of investigators and sites, and geographic balance
    • Recruit and train more diverse coordinator and investigator research teams
    • Engage with peer investigators outside the U.S. to target more race/ethnicity diversity and gender balance in clinical trial recruitment
    • Incorporate novel digital health technologies to expand the pool of potential research participants

Discussion Themes

In cardiovascular health, having diverse representation in clinical trials is clinically necessary to address ongoing disparities. It’s essential that trialists study the condition in populations that have borne an outsized burden of disease.

To diversify and expand the populations we study, we must think differently and be intentional from the outset. When we start to get truly diverse representation in clinical trials—when we actually study the person who has the condition—there will be robust enthusiasm and a greater sense of purpose throughout the clinical trial ecosystem.

Adaptive trial designs could be used to see if recruitment is on target and then make real-time adjustments to catch missing populations.

In thinking about accountability, what is the role of journals and ClinicalTrials.gov on reporting of race/ethnicity of both participants and investigators?

Read more about how to enhance diversity in clinical trials in recent FDA guidance and in cardiovascular trials in particular in Ortega et al., Circulation, 2019.

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#pctGR, @Collaboratory1

April 16, 2021: Minnesota EHR Consortium COVID-19 Project: A Statewide Collaboration to Inform Vaccine Equity (Paul E. Drawz, MD, MHS, MS; Tyler Winkelman, MD, MSc)

Speakers

Paul E. Drawz, MD, MHS, MS
Associate Professor
Division of Renal Disease and Hypertension
University of Minnesota

Tyler N.A. Winkelman, MD, MSc
Co-Director, Health, Homelessness, and Criminal Justice Lab
Associate Director, Virtual Data Warehouse
Hennepin Healthcare Research Institute

Topic

Minnesota EHR Consortium COVID-19 Project: A Statewide Collaboration to Inform Vaccine Equity

Keywords

COVID-19; Electronic health records (EHRs); Data analysis; Research consortium; Healthcare systems; Population health; Distributed data network; Vaccine equity

Key Points

  • The EHR Consortium’s COVID-19 vaccine project aims to inform policy and practice through data-driven collaboration among members of Minnesota’s health care community.
  • The collaborative network can monitor population-level health metrics and analyze changes over time using aggregations of data to inform public health policy. Sources of data include EHRs, census data, state-wide electronic immunization records, and population data.
  • The COVID-19 vaccine dashboard is updated weekly and provides data at the ZIP level by age categories and race/ethnicity.
  • Minnesotans who have received a COVID-19 vaccine (any source) and had a visit at a consortium site in the last 10 years (~90 percent of the state population) are reflected in the dashboard.

Discussion Themes

How were you able to convene this consortium during a pandemic year?

Was your hashing algorithm home-grown or did you have an outside partner?

In the future, this infrastructure will be expanded to incorporate smaller health systems and additional content expertise around comorbidities, disease prevalence, and identification of disparities in near real-time.

Read more about the MN EHR Consortium at Hennepin Healthcare and the University of Minnesota Clinical & Translational Science Institute.

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#pctGR, @Collaboratory1

April 9, 2021: Taking Research to the Participant: Experiences with TREAT NOW, a No-Touch COVID-19 Trial (Adit Ginde, MD, MPH)

Speaker

Adit Ginde, MD, MPH
Professor and Vice Chair for Research, Department of Emergency Medicine
Director of Clinical Research, Department of Anesthesiology
Director, Colorado CTSI Trial Innovation Network Hub
University of Colorado School of Medicine

Topic

Taking Research to the Participant: Experiences with TREAT NOW, a No-Touch COVID-19 Trial

Keywords

COVID-19; No-touch trial design; Antiviral therapy; Adaptive platform trial; Repurposed drugs; Patient-reported outcomes

Key Points

  • The TREAT NOW trial evaluated the effectiveness and safety of early treatment with antiviral agents (lopinavir/ritonavir) in outpatient adults with COVID-19 for preventing hospitalization and improving clinical outcomes.
  • The trial used an adaptive platform approach with the ability to add or remove agents, and focused on repurposed FDA-approved therapies that are rapidly scalable and easily deployed.
  • The no-touch design required that the entire trial be completed without having any physical interaction with the participant.
  • TREAT NOW shows that no-touch trials are not only feasible but also effective. However, considerable effort was needed to get the smart data systems right. The data system must accommodate many different levels of technical skill, different languages, and different modes of communication.

Discussion Themes

What is the role of a site in a no-touch trial?

What was the most effective recruitment strategy?

What is the demographic breakdown of your participants?

Read more about the TREAT NOW trial on ClinicalTrials.gov.

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#pctGR, @Collaboratory1

April 2, 2021: Lessons from COVID-19: The First Year of the REMAP-CAP Global Adaptive Platform Trial (Derek Angus, MD, MPH)

Speaker

Derek C. Angus, MD, MPH
Chief Healthcare Innovation Officer, University of Pittsburgh Medical Center
Associate Vice Chancellor for Healthcare Innovation, University of Pittsburgh Schools of the Health Sciences
Distinguished Professor and Mitchell P. Fink Endowed Chair
Department of Critical Care Medicine
University of Pittsburgh and UPMC

Topic

Lessons from COVID-19: The First Year of the REMAP-CAP Global Adaptive Platform Trial

Keywords

COVID-19; REMAP-CAP; Adaptive platform trial; Learning health system; Response-adaptive randomization

Key Points

  • REMAP-CAP (Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia) uses a novel adaptive trial design to evaluate a number of treatment options simultaneously and efficiently. This design is able to adapt in the event of pandemics, and increases the likelihood that patients will receive the treatment that is most likely to be effective for them.
  • REMAP-CAP is an international trial with multiple coordinating centers and 300 sites in 19 countries.
  • The REMAP-CAP trial was initially drafted with a prespecified Pandemic Appendix to be activated in the event of an emergent pandemic. In 2020, this mode was activated as REMAP-COVID, which expanded enrollment to include all hospitalized patients with clinically diagnosed or microbiologically confirmed COVID-19.
  • While adaptive platform trials are likely here to stay, there is a need to build comfort with the modeling, inference, and interpretation; build appropriate infrastructure to keep up with the power of the engine; and invest in common data models.

Discussion Themes

It is possible to design adaptive platform trials with a smaller sample size, depending on the research question.

How did you convince study teams to join your effort rather than start their own?

In the future, small trials could be hosted within the REMAP-CAP adaptive platform.

Given the massive inertia in investment to develop adaptive infrastructures, what are your thoughts for funders across institutions and nations?

Read more about REMAP-CAP and how the REMAP-CAP platform was modified to respond to the COVID-19 pandemic.

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#pctGR, @Collaboratory1

February 5, 2021: Generating High-Quality Evidence During a Pandemic: The Brazilian COALITION Experience (Renato Lopes, MD, MHS, PhD)

Speaker

Renato D. Lopes, MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Brazilian Clinical Research Institute

Topic

Generating High-Quality Evidence During a Pandemic: The Brazilian COALITION Experience

Keywords

COVID-19; Patient outcomes; Cardiology; Randomized clinical trials; COALITION; Levels of evidence

Key Points

  • The SARS-CoV-2 infection affects the cardiovascular system and is associated with complications such as myocardial ischemia, myocarditis, arrhythmias, and thromboembolic events. These manifestations result mainly from the intense systemic inflammatory response and disorders of the coagulation system. 
  • The COALITION collaborative includes several major Brazilian hospitals and research networks with the aim of accelerating multicenter randomized controlled trials that generate high-quality evidence to guide the treatment of patients with COVID-19.
  • To move toward a world in which most clinical decisions are supported by high-quality evidence requires structural changes in the clinical trials ecosystem.

Discussion Themes

How did you overcome contractual and regulatory concerns to execute your trials?

Instead of “publish or perish,” it should be “collaborate or perish.” Collaboration is the key to surviving in modern academic medicine.

Read more about the need for high-quality evidence to treat COVID-19 patients in Anticoagulation in COVID-19: It Is Time for High-Quality Evidence (J Am Coll Cardiol, 2020)

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#pctGR, @Collaboratory1