clinical trials

July 9, 2021: COVID-19 Vaccine Efficacy Studies: Challenges and Successes (Hana El Sahly, MD)

Posted on by Gina Uhlenbrauck

Speaker

Hana El Sahly, MD
Professor of Molecular Virology and Microbiology
Baylor College of Medicine

Topic

COVID-19 Vaccine Efficacy Studies: Challenges and Successes

Keywords

COVID-19; Vaccines; Clinical endpoints; Phase 3 trials

Key Points

  • The design of Phase 3 clinical trials varies—from individual randomized clinical trials (RCTs) within sites, multiple arm trials within sites, parallel cluster RCTs, and stepped-wedge cluster RCTs—and each design produces different efficiencies and potential for evaluating the vaccine’s effectiveness.
  • The primary endpoints of vaccine trials are infection, disease, and severe disease; however, a study with a primary endpoint that captures all the endpoints of public health importance is likely not feasible.
  • A principle of clinical trials is that the study population should represent the vaccine target population. Yet, clinical trial participants traditionally are predominantly Caucasian, whereas COVID-19 disproportionately affects minorities, including a higher incidence and higher mortality.

Discussion Themes

Conducting effectiveness studies is essential to understanding how vaccines affect severe disease.

What are the arguments for or against human challenge trials?

Based on your experience during the past year, and the success of the COVID-19 vaccine trials, what applications do you see for future viruses outside a pandemic?

While some successes have been achieved, we do not know everything yet; it will be important to study other pathogens on other platforms to find approaches that ensure reliability.

Read more about Operation Warp Speed, a federal collaboration that has supported the acceleration of testing, supply, development, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

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#pctGR, @Collaboratory1

July 13, 2021: Diversity Workshop Continues With Lessons From Implementation Trials

Posted on by Damon Seils

The NIH Collaboratory is using its popular ePCT Grand Rounds platform for a special webinar series on diversity in pragmatic clinical trials.

In this Friday’s session—“Maximizing Diversity in PCTs – What Can We Learn From Implementation Trials?”—Dr. David Chambers of the National Cancer Institute (NCI) will facilitate a discussion about lessons from implementation science for maximizing participant diversity in pragmatic clinical trials. Dr. Chambers is deputy director for implementation science in the Office of the Director in the NCI’s Division of Cancer Control and Population Sciences.

The panelists will include:

  • Dr. Amanda Midboe of the US Department of Veterans Affairs, chair of the Implementation Science Work Group for the NIH-DOD-VA Pain Management Collaboratory
  • Dr. Anne Trontell, associate director in the Clinical Effectiveness and Decision Science Program at the Patient-Centered Outcomes Research Institute (PCORI)

The Grand Rounds session will be held on Friday, July 16, at 1:00 pm eastern. Join the online meeting.

Other upcoming sessions in the diversity workshop series include:

All sessions are free and open to the public; no registration is required. Recordings will be archived on the Grand Rounds website.

Headshots of Drs. David Chambers, Amanda Midboe, and Anne Trontell
Left to right: Drs. David Chambers, Amanda Midboe, and Anne Trontell

July 7, 2021: COVID-19 Grand Rounds Continues With Vaccine Efficacy Studies

Posted on by Damon Seils

Headshot of Dr. Hana El Sahly
Dr. Hana El Sahly

In this Friday’s COVID-19 Grand Rounds session, Dr. Hana El Sahly of the Baylor College of Medicine will present “COVID-19 Vaccine Efficacy Studies: Challenges and Successes.” The Grand Rounds session will be held on Friday, July 9, at 1:00 pm eastern. Join the online meeting.

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.

For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

June 25, 2021: Inclusion of Diverse Participants in Pragmatic Clinical Trials: Meeting Participants Where They Are – Outreach, Trust, and Consent to Maximize Diversity (Emily O’Brien, PhD; Jonathan Jackson, PhD; Judith Schlaeger, PhD; Stacy Sterling, DrPH)

Posted on by Gina Uhlenbrauck

Speakers

Panelists:

NIA IMPACT Collaboratory
Jonathan Jackson, PhD
Executive Director
Community Access, Recruitment, and Engagement (CARE) Research Center
Massachusetts General Hospital and Harvard Medical School

GRACE
Judith Schlaeger, PhD, CNM, LAc, FAAN
Associate Professor, Department of Human Development Nursing Science
University of Illinois Chicago

GGC4H
Stacy Sterling, DrPH, MSW, MPH
Research Scientist
Kaiser Permanente Division of Research, Northern California

Guest Moderator:

Emily O’Brien, PhD
Associate Professor, Department of Population Health Sciences
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Inclusion of Diverse Participants in Pragmatic Clinical Trials: Meeting Participants Where They Are – Outreach, Trust, and Consent to Maximize Diversity

Keywords

Participant diversity; Health equity; Outreach strategies; GRACE; Guiding Good Choices for Health (GGC4H); NIA IMPACT Collaboratory; Implementation science

Key Points

  • Health equity is a matter of scientific integrity. Health equity must be front and center when trials are designed and implemented because, without it, access may be undermined and effectiveness could be misrepresented.
  • Study enrollment bias occurs at every level of selection, beyond the participant level. “Healthy worker bias” can occur at the level of the healthcare system too.
  • Health equity is a crucial and unique aspect of embedded PCTs (ePCTs). While the PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) domains show how pragmatic a trial design is, the tool does not identify biases in the design. For research that is truly effective and generalizable, it is vital to implement PRECIS-2 through an equity lens.
  • Among the many practices that can maximize diversity in trial enrollment:
    • Tailored, personalized outreach and community connections
    • Bilingual, bicultural staff
    • Balancing fidelity with feasibility and relatability
    • Cultural and linguistic adaptation
    • Flexible scheduling
  • Incorporating a community-based participatory research model in the design of the study can assist in addressing barriers and build trust.

Discussion Themes

Concerns about racism and bias can affect the emotions and behaviors of study participants. Can these topics be incorporated into the curriculum?

What role do broad stakeholder organizations, such as funders and insurance providers, have in advancing outreach and building trust?

Implementation science offers ways to think about the complex aspects of an intervention that may not be captured in the protocol.

Read more about the GRACE and GGC4H NIH Collaboratory Trials, and visit the NIA IMPACT Collaboratory.

Tags

#pctGR, @Collaboratory1

June 22, 2021: Diversity Workshop Continues With Meeting Participants Where They Are

Posted on by Damon Seils

The NIH Collaboratory is using its popular ePCT Grand Rounds platform for a special webinar series on diversity in pragmatic clinical trials.

In this Friday’s session—“Meeting Participants Where They Are – Outreach, Trust, and Consent to Maximize Diversity”—Dr. Wendy Weber of the National Center for Complementary and Integrative Health will host a panel of investigators for a discussion about strategies for maximizing participant diversity in pragmatic clinical trials by improving outreach and building trust.

The panel will include:

  • Dr. Jonathan Jackson, executive director of the Community Access, Recruitment, and Engagement (CARE) Research Center at Massachusetts General Hospital and Harvard Medical School
  • Dr. Judith Schlaeger of the University of Illinois at Chicago, co–principal investigator of GRACE, an NIH Collaboratory Demonstration Project
  • Dr. Stacy Sterling of the Kaiser Permanente Division of Research, Northern California, co–principal investigator of GGC4H, an NIH Collaboratory Demonstration Project

The Grand Rounds session will be held on Friday, June 25, at 1:00 pm eastern. Join the online meeting.

Other upcoming sessions in the diversity workshop series include:

All sessions are free and open to the public; no registration is required. Recordings will be archived on the Grand Rounds website.

Headshots of Emily O'Brien, Jonathan Jackson, Judith Schlaeger, and Stacy Sterling
Left to right: Drs. Emily O’Brien, Jonathan Jackson, Judith Schlaeger, and Stacy Sterling

June 4, 2021: Inclusion of Diverse Participants in Pragmatic Clinical Trials: Planning for Diversity – Stakeholder Engagement and Site Selection to Maximize Diversity (Wendy Weber, ND, PhD, MPH; Julie Fritz, PhD, PT; David Wetter, PhD, MS; Gloria Coronado, PhD; Amanda Petrik, MS)

Posted on by Gina Uhlenbrauck

Speakers

Panelists:

BeatPain Utah  
Julie Fritz, PhD, PT
Associate Dean for Research, College of Health
Adjunct Professor, Orthopaedic Surgery
Distinguished Professor, Physical Therapy & Athletic Training
Adjunct Professor, Orthopaedic Surgery Operations
University of Utah  

David Wetter, PhD, MS
Professor, Population Health Sciences
Adjunct Professor, Psychology
University of Utah  

STOP CRC  
Gloria Coronado, PhD
Distinguished Investigator Mitch Greenlick Endowed Scientist for Health Disparities
Kaiser Permanente Center for Health Research  

Amanda Petrik, MS
Sr. Research Associate Center for Health Research
Kaiser Permanente Northwest

Guest Moderator:

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

Topic

Inclusion of Diverse Participants in Pragmatic Clinical Trials: Planning for Diversity – Stakeholder Engagement and Site Selection to Maximize Diversity

Keywords

Participant diversity; Stakeholder engagement strategies; STOP CRC; BeatPain Utah; Health equity; Community health centers; Plan-Do-Study-Act

Key Points

  • Disparities in pain prevalence and pain management are well established. In particular, odds of receiving opioids for pain management are greater, and odds of nonpharmacologic care lower, in rural, low income, and Latinx communities.
  • It is essential that communities and researchers come together to create long-term solutions to prevent cancer, chronic and infectious disease, and improve health among underserved populations. Research projects should be driven by the priorities of community partners.
  • Study advisory boards can include health center leaders, patient advocates, legislators, and community organization leaders. These boards provide local context and, in the case of STOP CRC, they identified policy changes that were needed around access to colorectal cancer screening.

Discussion Themes

Sharing information and resources with community partners—and responding to their needs and building their capacity—helps to build trust around medicine and research.

To what extent is it important to show evidence of interest in and respect for the community beyond the specific focus of your initiative? For example, participating in important community activities and developing a deeper understanding of the culture.

We must design and plan for sustainability at the outset, and we must make targeted, specific efforts to ensure the inclusion of diverse populations in clinical trials.

Another way to increase diversity is to prepare and train more scientists and investigators from diverse populations.

Read more about the BeatPain Utah and STOP CRC Demonstration Projects.

Tags

#pctGR, @Collaboratory1

June 3, 2021: Town Hall Will Introduce ACTIV-6 Study to Potential Sites and Investigators

Posted on by Damon Seils

Leaders of the ACTIV-6 study, featured recently during NIH Collaboratory Grand Rounds, will hold a town hall Wednesday, June 9, to share information about the study with interested stakeholders, including sites and investigators that may want to participate. The leadership team will describe the rationale for ACTIV-6, share an overview of the platform and objectives, and provide information about how to join and contribute to the study.

Contact DCRI-ACTIV6@dm.duke.edu if you would to receive a calendar invitation the event. The town hall will be recorded for those who are unable to attend.

ACTIV-6, part of the NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, is a platform trial that will test whether several already approved medications can be repurposed for treating symptoms of mild to moderate COVID-19 in nonhospitalized patients.

View the April 30 Grand Rounds webinar.

June 2, 2021: Diversity Workshop Continues With Strategies for Site Selection and Stakeholder Engagement

Posted on by Damon Seils

The NIH Collaboratory is using its popular ePCT Grand Rounds platform for a special webinar series on diversity in pragmatic clinical trials.

In this Friday’s session—“Planning for Diversity – Stakeholder Engagement and Site Selection to Maximize Diversity”—Dr. Wendy Weber of the National Center for Complementary and Integrative Health will host investigators from 2 of the NIH Collaboratory Demonstration Projects for a discussion about strategies for site selection and stakeholder engagement to maximize diversity.

  • In BeatPain Utah, Dr. Julie Fritz, Dr. David Wetter, and their team are designing interventions in federally qualified health center (FQHC) clinics to overcome barriers specific to rural and lower-income communities through innovative use of telehealth resources.
  • In STOP CRC, Dr. Gloria Coronado, Amanda Petrik, and their team worked with FQHC clinics to improve colorectal cancer screening rates in racial/ethnic minority and low-income populations.

The Grand Rounds session will be held on Friday, June 4, at 1:00 pm eastern. Join the online meeting.

Other upcoming sessions in the diversity workshop series include:

All sessions are free and open to the public; no registration is required. Recordings will be archived on the Grand Rounds website.

May 21, 2021: The PRINCIPLE Adaptive Platform Trial for Community Treatment of COVID-19: Innovation in Trial Design and Delivery (Chris Butler, MD; Ben Saville, PhD)

Posted on by Damon Seils

Speakers

Chris Butler, MD
Nuffield Department of Primary Care Health Sciences
University of Oxford

Ben Saville, PhD
Berry Consultants

Topic

The PRINCIPLE Adaptive Platform Trial for Community Treatment of COVID-19: Innovation in Trial Design and Delivery

Keywords

COVID-19; Adaptive platform trial; PRINCIPLE; Master protocols; Direct-to-participant trial; Repurposed drugs

Key Points

  • Adaptive platform trials focus on a specific disease, asking: What is the best treatment for a unique patient with this disease? Such trials involve making adaptations to accruing data and conducting frequent interim analyses. Multiple interventions can be evaluated at the same time, and study arms can be staggered.

  • An adaptive platform is well suited to studying COVID-19 interventions. The PRINCIPLE trial aims to evaluate whether repurposed drugs can make a difference with early intervention for patients with COVID-19 symptoms. It is a nationwide (UK) clinical study from the University of Oxford to find treatments for recovery at home.

  • Adaptive platform trials have the potential to evaluate treatments quickly (to determine early superiority or futility) and the flexibility to add or remove treatments during the ongoing study. The use of “response adaptive randomization” allocates more patients to interventions having better outcomes.

  • Because most people with COVID-19 are managed in the community, community treatments may have the widest reach and impact. PRINCIPLE takes “research to the patient,” with online consent, study materials that are sent directly to patients, and patient self-sampling. Participation in the trial is not limited to where people receive healthcare.

Discussion Themes

The “inverse research participation law” (proposed by Julian Tudor Hart) posits that access to research is often inversely proportional to a participant’s potential contribution and to where the research findings should be most applicable.

A pragmatic trial should ensure that the comparator group is as close to usual care as possible. So while the trial design does not allow an understanding of the mechanisms behind any observed effect, it is the best design to find out what would happen if the treatment were used in the real world.

The PRINCIPLE study team was able to do intensive remote monitoring of patients online, by telephone, trial partner, or using routinely collected data.

Read more about PRINCIPLE and adaptive platform trials.

Tags

#pctGR, @Collaboratory1

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)

Posted on by Gina Uhlenbrauck

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.

Tags

#pctGR, @Collaboratory1