clinical trials

April 8, 2020: NIH Collaboratory COVID-19 Grand Rounds Series Continues With Randomized Trial of Early Hydroxychloroquine Treatment in Hospitalized Adults

Posted on by Damon Seils

The NIH Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency.

In this week’s COVID-19 Grand Rounds session, Dr. Sean Collins will present “Hydroxychloroquine for the Early Treatment of COVID-19 in Hospitalized Adults: A Multicenter Randomized Clinical Trial.” Dr. Collins is professor and executive vice chair of emergency medicine in the Vanderbilt University School of Medicine and director of the Center for Emergency Care Research and Innovation at Vanderbilt University Medical Center. The Grand Rounds session will be held on Friday, April 10, at 1:00 pm eastern. Join the online meeting.

Also coming soon in COVID-19 Grand Rounds:

Previous COVID-19 Grand Rounds:

Recent news announcements:

We will continue to share new research, resources, and guidance as they become available.

April 7, 2020: Support for the PRISM Embedded PCTs From the Health Care Systems Interactions Core

Posted on by Gina Uhlenbrauck

In a recent video interview, Dr. Eric Larson, chair of the Collaboratory’s Health Care Systems Interactions Core, and Leah Tuzzio, research associate, describe ways the Core is supporting the PRISM Demonstration Projects. A priority for conducting embedded PCTs (ePCTs) is establishing strong, sustainable relationships between the study team and health system leadership, clinicians, and staff.

For researchers who are evaluating pain management interventions, the Core advises remaining flexible when integrating the intervention and being mindful of documenting any adaptations made throughout the trial. Other best practices include understanding the context of the health setting, anticipating road blocks, and incorporating the intervention with minimal burden to clinicians and staff.

“Pain is a complicated area. It’s not a specific disease, it’s a state, and it’s a state that everybody experiences.”

For additional suggestions from the Core, read the new chapter in the Living Textbook on how to monitor intervention fidelity and adaptations. Learn more about the Health Care Systems Interactions Core and view interviews with the PRISM Demonstration Projects:

April 3, 2020: Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): Participant-Centered, Rapidly-Deployed, Digitally-Enabled Research (Harlan Krumholz, MD; Bala Hota, MD, MPH; Graham Nichol, MD, MPH)

Posted on by Gina Uhlenbrauck

Speakers

Harlan M. Krumholz, MD
Harold H. Hines Jr. Professor of Medicine, Yale University
Director, Yale New Haven Hospital Center for Outcomes Research and Evaluation
Co-Founder Hugo Health

Bala Hota, MD, MPH
Professor of Internal Medicine, Rush University
Chief Analytics Officer, Rush University Medical Center

Graham Nichol, MD, MPH
Medic One Foundation Endowed Chair for Pre-hospital Emergency Care
Professor of Emergency Medicine
University of Washington

Other Panelists:

Jacqueline Rollin, Administrative Fellow
Rush University Medical Center

Wade Schulz, MD, PhD
Assistant Professor of Laboratory Medicine
Director, CORE Center for Computational Health

Matthew J. Thompson, MB, ChB, DPhil
Helen D. Cohen Endowed Professorship in Family Medicine
Professor of Global Health and Medicine, University of Washington

Deb R. Chromik, Participant Experience
Hugo Health

Dave Hutton, Product Lead
Hugo Health

Topic

Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): Participant-Centered, Rapidly-Deployed, Digitally-Enabled Research

Keywords

Coronavirus; Virus pandemic; INSPIRE Registry; COVID-19 directed research program; SARS-COV-2; Longitudinal data; Hugo Health digital research platform

Key Points

  • In the face of the coronavirus pandemic, there is an urgent need for rapid knowledge generation and actionable insights. Evidence needed includes:
    • The number of cases, including milder ones
    • Risk factors and timing of transmission
    • Severity and attack rate
    • Risk factors for infection and severe outcomes, including death
    • Infectiousness timing and intensity
  • Patients must be considered part of the team; involved, engaged, and respected, with agency over their data.
  • To better understand the experience of people with COVID-19, Rush University Medical Center and Hugo health are piloting the COVID INSPIRE registry. INSPIRE is a rapidly-deployed, digitally-enabled, participant-centered platform to collect longitudinal data and facilitate observational and experimental studies.

Discussion Themes

Even with social distancing, the coronavirus is in a rapid escalation phase; this rapid pace has our attention.

People are interested in participating in research now more than ever. The call to action is to build a human-connected system that treats patients compassionately and supports patients in real time.

Are there existing systems that could be built on or adapted for COVID-19? Are there potential for linkages to other systems?

Tags
#pctGR, @Collaboratory1, @HMKYale, @BalaHota, @GrahamNichol

March 27, 2020: Living Textbook Grand Rounds Series: Part 3-Tips for Putting Together a Successful PCT Grant Application (Wendy Weber, ND, PhD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Wendy Weber, ND, PhD, MPH
Branch Chief, Clinical Research Branch
Division of Extramural Research
National Center for Complementary and Integrative Health (NCCIH)

Topic

Tips for Putting Together a Successful PCT Grant Application

Keywords

Pragmatic clinical trials; Embedded PCTs; Healthcare systems; NIH; Scientific officers; Funding opportunity announcement; Request for application

Key Points

  • Investigators interested in developing a compelling grant application for a pragmatic clinical trial (PCT) should consider these tips:
    • First, confirm that a PCT is the best study design to answer your research question.
    • From the NIH’s 27 Institutes and Centers, find the one that matches your disease area, organ system, or stage of life—and talk with the program official.
    • Also find the right funding opportunity announcement (FOA) and tailor your application to address all the FOA-specific instructions and review criteria.
  • Do not assume that the study panel is going to understand what pragmatic means; they may have a completely different definition. It is important that you get on the same page early in the application.
  • In your application, make sure you justify the research, include pilot data, address potential overlaps, reduce complexity, ensure the aims will advance the field, choose expert personnel for a multidisciplinary team, link data collection and analysis to aims, and justify the use of multiple sites and sample size.

Discussion Themes

For some urgent clinical problems, a PCT may be the only study design that can answer the research question.

Phased awards can be helpful. Determine the key elements of your trial to test in the planning phase. It’s important to “fail quickly”—not in the implementation phase. Applicants should identify milestones in the planning phase that will help convince reviewers their study will be feasible.

Because PCTs take place in changing conditions and real-world healthcare settings, they are not necessarily easier to implement than a traditional efficacy trial.

For more information, visit the Living Textbook’s Developing a Compelling Grant Application.

Tags
#pctGR, @Collaboratory1

March 31, 2020: Engagement in PCTs: Considerations from the Collaboratory’s Ethics and Regulatory Core

Posted on by Gina Uhlenbrauck

A new document from the Ethics and Regulatory Core is available that provides considerations around determining which individuals or groups are engaged in research in pragmatic clinical trials (PCTs). Developed for investigators designing and conducting PCTs as well as institutional review boards overseeing them, the document introduces these questions in relation to research subjects, study team members, and service providers:

  • Which individuals/groups are included in the research?
  • Are these individuals/groups research subjects, study team members, or service providers?
  • Why does it matter how the individuals/groups are categorized for the research?

Download Engagement in Research for Pragmatic Clinical Trials.

 

March 30, 2020: New Living Textbook Chapter Describes Ways to Monitor Intervention Fidelity and Adaptations During the Conduct of ePCTs

Posted on by Gina Uhlenbrauck

The new Monitoring Intervention Fidelity and Adaptations chapter of the Living Textbook was developed to introduce how to evaluate changes that may be encountered while conducting an embedded pragmatic clinical trial (ePCT). For example, a health system might experience competing clinical initiatives; turnover in leadership, clinicians, or staff; changes in technologies; new clinical practice guidelines; or regulatory changes.

The chapter offers strategies for study teams to anticipate, monitor, and document adaptations to the intervention in order to support study analysis and set the stage for dissemination and implementation of successful interventions in other healthcare settings. The chapter was developed by experts from the Collaboratory’s Health Care Systems Interactions Core, along with principal investigators conducting ePCT Demonstration Projects.

Topics include:

  • Anticipating changes that might impact intervention fidelity
  • Frameworks to assist in monitoring fidelity and adaptations
  • Strategies and case examples from the NIH Collaboratory Demonstration Projects
  • Pointers to additional resources

We encourage you to explore this new content.

 

March 24, 2020: Impacts of COVID-19 on the Conduct of Clinical Trials

Posted on by Gina Uhlenbrauck

In a recent PCT Grand Rounds, Drs. Naggie, Hernandez, and Perakslis of Duke University discussed the impacts of the COVID-19 outbreak on the conduct of clinical trials. The panel described the status of COVID-19, its impact on trials currently begin conducted, some key questions to consider, and potential solutions and approaches. A brief Q&A followed the presentation.

View the video and download the slides from the webinar.

Recent news announcements are available at NIH Announces Guidance for Clinical Trials Affected by COVID-19 Emergency and NIH Shares COVID-19 Guidance and Resources for Applicants and Recipients.

March 20, 2020: Clinical Trials in the Time of COVID-19 (Susanna Naggie, MD; Adrian Hernandez, MD, MHS; Eric Perakslis, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Susanna Naggie, MD
Associate Dean for Clinical Research Initiatives and Regulatory Affairs
Duke University School of Medicine

Adrian F. Hernandez, MD, MHS
Professor of Medicine
Vice Dean for Clinical Research
Duke University School of Medicine

Eric Perakslis, PhD
Rubenstein Fellow
Duke University

Topic

Clinical Trials in the Time of COVID-19

Keywords

Infectious disease; Coronavirus; Pandemic response; COVID-19; Population health; Clinical trials; Human subject protections; Contingency measures; Vaccine; Contact tracing

Key Points

Discussion Themes

Do you anticipate that statisticians will need to account for period effect in later analysis of data (pre/post COVID-19)?

Are there lessons learned from the last epidemics, for example H1N1 or Ebola? How can we deal with global pandemics in the future?

What about clinical trials in the elderly population, given that they are the most vulnerable to the coronavirus and may not be as good with technology as younger participants?

Would it be possible to set up a multisite telehealth-based outbreak learning health unit?

Recent news announcements are available at NIH Announces Guidance for Clinical Trials Affected by COVID-19 Emergency and NIH Shares COVID-19 Guidance and Resources for Applicants and Recipients.

Johns Hopkins University maintains a live website of Coronavirus COVID-19 Global Cases.

Tags
#pctGR, @Collaboratory1, @texhern, @snaggie1, @DukeForge, @eperakslis

March 13, 2020: Impact of Regulatory Guidance on Evaluating Cardiovascular Risk of New Glucose-Lowering Therapies to Treat Type 2 Diabetes Mellitus–Lessons Learned and Future Directions (Abhinav Sharma, MD, PhD; Christopher Granger, MD)

Posted on by Gina Uhlenbrauck

Speakers

Abhinav Sharma, MD, PhD
Assistant Professor of Medicine
McGill University

Christopher B. Granger, MD, FAHA, FACC
Professor of Medicine
Director, Cardiac Intensive Care Unit
Duke University Medical Center

Topic

Impact of Regulatory Guidance on Evaluating Cardiovascular Risk of New Glucose-Lowering Therapies to Treat Type 2 Diabetes Mellitus–Lessons Learned and Future Directions

Keywords

Type 2 diabetes; Regulatory; Cardiovascular risk; Food and Drug Administration; FDA; Patient outcomes; Anti-hyperglycemic medications

Key Points

  • The hallmark of type 2 diabetes mellitus is insulin resistance and relative insulin deficiency. Ninety percent of all cases of diabetes are type 2 diabetes, and the diagnosis can occur at any age.
  • While people with type 2 diabetes can often initially manage their condition through exercise and diet, over time most people will require oral drugs or insulin.
  • Strategies are needed reduce the burden of cardiovascular outcomes in patients with diabetes.
  • In 2008, the U.S. Food and Drug Administration (FDA) issued guidelines for sponsors to demonstrate that their anti-hyperglycemic medications do not increase the risk of cardiovascular disease. In March 2020, the FDA updated the guidance in a draft for comment: Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control Guidance for Industry.

Discussion Themes

Is the cardiovascular protection of some anti-hyperglycemic drugs independent of the effect on blood glucose?

How can regulators, industry, academia, payers, and patient advocacy groups assure that evidence generation to improve care is incentivized without undue regulatory burdens?

Should post-marketing studies include comparative effectiveness pragmatic trials in order to improve translation into clinical practice?

Read more on this topic from Sharma and colleagues in a recent publication in Circulation.

Tags
#pctGR, @Collaboratory1

March 12, 2020: Transforming Our Understanding of How to Conduct Research in a Real-World Setting

Posted on by Gina Uhlenbrauck

In a recent video interview, Dr. Helene Langevin, director of the National Center for Complementary and Integrative Health at the NIH, discusses the important work of the NIH Collaboratory in sharing knowledge and lessons learned as well as in harnessing expertise across the 19 Demonstration Projects it supports. “It is very important that we understand how research can be successfully implemented and tested in real-world clinical practice.”

 

 

For more interviews about the HEAL and PRISM projects, check out the February 21 news story.