In this Friday’s PCT Grand Rounds, Dr. Theresa Coles and Dr. Kevin Weinfurt of Duke University will discuss the use of patient-reported outcome measures in clinical trials, using examples from cardiovascular trials.
The Grand Rounds session will be held on Friday, September 24, at 1:00 pm eastern. Join the online meeting.
For webinar recordings and slides from previous Grand Rounds sessions, see the Grand Rounds hub.
Dr. Fan Li, a longtime member of the NIH Collaboratory’s Biostatistics and Study Design Core, has received approval for a $1 million grant award from the Patient-Centered Outcomes Research Institute (PCORI) to develop methods and software for designing cluster randomized trials. Li is an assistant professor of biostatistics in the Yale School of Public Health.
The study, entitled “New Methods for Planning Cluster Randomized Trials to Detect Treatment Effect Heterogeneity,” will contribute new methods, guidance, and user-friendly software for planning parallel and stepped-wedge cluster randomized trials to enable confirmatory “heterogeneity of treatment effect” (HTE) analyses with sufficient statistical power.
HTE occurs when there is systematic variation in treatment effect across predefined patient or provider subgroups that can arise due to diverse practices, varying responses to treatment, or differing vulnerability to certain diseases, among other reasons. While understanding of HTE has been a recognized goal in individually randomized trials, methods for planning cluster randomized trials with HTE analyses are limited. This PCORI-funded study will expand the current cluster randomized design toolbox to accommodate confirmatory HTE analysis and meet a growing interest in better understanding how patient- and provider-level characteristics moderate the impact of new care innovations in pragmatic trials.
The award has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.
Joining Li on the research team are coinvestigators Dr. Patrick Heagerty of the University of Washington, Dr. Rui Wang of Harvard Medical School and the Harvard Pilgrim Health Care Institute, and Dr. Denise Esserman of the Yale School of Public Health. Heagerty and Wang are members of the NIH Collaboratory’s Biostatistics and Study Design Core. The team will work closely with other NIH Collaboratory colleagues and stakeholders, including Dr. Adrian Hernandez of Duke University, Dr. Jerry Jarvik of the University of Washington, and Dr. Richard Platt of Harvard Medical School and the Harvard Pilgrim Health Care Institute.
In the latest episode of the NIH Collaboratory Grand Rounds podcast, Dr. Adrian Hernandez interviews Diana Berrent, JD, founder of Survivor Corps, Nick Guthe, Survivor Corps member and advisor, and Natalie Lambert, PhD, of the Indiana University School of Medicine, around best practices for medical professionals treating patients experiencing the debilitating effects of long-term COVID-19.
The full July 23 Grand Rounds webinar is also available.
Panel:
Amanda Midboe, PhD
Center for Innovation to Implementation
U.S. Department of Veterans Affairs
Chair of the Implementation Science Work Group for the NIH-DOD-VA Pain Management Collaboratory
Anne Trontell, MD, MPH
Associate Director
Clinical Effectiveness and Decision Science Program
Patient-Centered Outcomes Research Institute (PCORI)
Guest Moderator:
David Chambers, DPhil
Deputy Director for Implementation Science
Office of the Director in the Division of Cancer Control and Population Sciences (DCCPS)
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Inclusion of Diverse Participants in Pragmatic Clinical Trials: Maximizing Diversity in PCTs – What Can We Learn From Implementation Trials?
Dissemination research; Implementation research; Participant engagement; Participant diversity; Health equity; PCORI; Ci2i
The study of methods to best implement and disseminate interventions in diverse groups is crucial to the ultimate goal of benefiting population health.
Patient-centered outcomes are important measures to determine the total effectiveness of any health intervention.
By engaging the community in which research takes place and treating patients as partners in the development of implementation strategies, we increase diverse participation and improve patient retention.
Targeted recruitment strategies that leverage administrative data increase diverse study participation.
Are there any ethical issues raised when underserved populations receive monetary incentives to participate in research trials?
What are the challenges of identifying diverse potential participants from the medical record or administrative data?
Do efforts to increase diversity in the study team improve the engagement and retention of a diverse study population?
Read more about methods to increase diversity in implementation trials at the Patient-Centered Outcomes Research Institute (PCORI) and the Center for Innovation to Implementation (Ci2i).
#pctGR, @Collaboratory1
In this Friday’s COVID-19 Grand Rounds session, Diana Berrent, Natalie Lambert, and Nick Guthe of Survivor Corps will present “Long Term COVID Patient Engagement: Best Practices Informed By Patients’ Experiences Seeking Medical Care.” The Grand Rounds session will be held on Friday, July 23, at 1:00 pm eastern. Join the online meeting.
Survivor Corps is an online community of 170,000 patients affected by COVID-19 and their families and friends. The advocacy group is using its members’ collective experience to build a repository of data sets and research tools to support COVID-19 research, including studies of post-COVID conditions, or “long COVID.” The group seeks to fill the gap between real-world evidence and scientific research to advance understanding of the disease and patients’ healthcare options.
“We have been sort of the canary in the COVID coal mine from the beginning,” said Berrent, who founded Survivor Corps in March 2020 after becoming one of the first people in the United States to be diagnosed with COVID-19.
Berrent will be joined during Grand Rounds by Survivor Corps research director Dr. Natalie Lambert and by Nick Guthe, a Survivor Corps member and adviser.
Survivor Corps’s website, which has been selected by the US Library of Congress for inclusion in the nation’s Coronavirus Web Archive, serves as a hub to provide support, information, and education about COVID-19, connect patients to researchers, and facilitate the nation’s COVID-19 response.
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.
Recently published results of the ADAPTABLE study demonstrate no difference in rates of death, hospitalization for heart attack or stroke, or bleeding in those who were assigned to high- versus low-dose aspirin (325 mg versus 81 mg). Trial participants frequently switched their dose, which may have biased the results toward the null: 41.6% of patients who were assigned to take the 325 mg dose switched to 81 mg daily dose. The study, funded by PCORI, is the first randomized controlled trial conducted using PCORnet®, the National Patient-Centered Clinical Research Network, which involves patient representatives during all phases of the trial. It enrolled 15,076 patients with cardiovascular disease at 40 health centers across the United States.
“As interest grows for real-world evidence, the trial provides a demonstration that randomized clinical trials can leverage electronic health record data, direct-to-patient methods, and patient-reported outcomes to address important, patient-centered questions.” —Jones, et al. 2021, New England Journal of Medicine
An accompanying editorial states that this trial represents a step forward for pragmatic clinical trials, demonstrating proof-of-concept for PCORnet. The study and used electronic health record data to identify patients; low-touch recruitment strategies; and a patient portal for consent, collection of patient-reported outcomes, and follow-up.
“ADAPTABLE is a major achievement […] because it has shown a method of conducting trials efficiently and at low cost in the United States, and the method can now be adapted and used more widely. This should allow many more clinical questions to be answered, with obvious benefits to health care consumers.” —Baigent 2021, New England Journal of Medicine.
Read the plain language summary of results and learn more about the ADAPTABLE study.
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
Diverse Representation Among Clinical Trial Participants: Why It Is Important and How Can We Improve
Clinical trials; Health outcomes; Racial disparities; Diverse participant recruitment; Disease burden; Cardiovascular disease
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.
#pctGR, @Collaboratory1
Susanna Naggie, MD, MHS
Associate Professor of Medicine
Duke Clinical Research Institute
Elizabeth Shenkman, PhD
Chair, Department of Health Outcomes and Biomedical Informatics
Co-Director, Clinical and Translational Science Institute (CTSI)
University of Florida
ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications
COVID-19; NIH ACTIV Initiative; Repurposed drugs; Vaccines; Therapeutic agents; Direct-to-participant trials; PCORnet
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) is a public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines. The ACTIV initiative is coordinated by the Foundation for the National Institutes of Health.
ACTIV-6 asks: Are there medications currently approved for other conditions that improve symptoms in nonhospitalized patients with mild-to-moderate COVID-19 symptoms? The study aims to find out how to help patients feel better faster and how to prevent hospitalizations or death in newly diagnosed patients with mild or moderate COVID-19.
All study visits are conducted remotely: Participants use an online system to complete study surveys and report adverse events or changes in clinical status. Participants are assigned randomly to receive either a placebo or one of the treatments, which will be sent to them by mail. If deemed necessary by a study investigator, in-person or remote study visits are possible.
Vaccine hesitancy is still an issue, especially in rural areas; there will continue to be cases of COVID-19.
To ensure diversity in enrollment, the ACTIV-6 study takes a multipronged approach, including making it easy to participate without in-person appointments; partnering with community groups for broad outreach and messaging; and monitoring enrollment numbers closely.
Sites provide participant education and recruitment. The process is straightforward and appeals to both clinicians and patients. Each study site has a primary care physician as a clinical champion.
Read more about ACTIV-6, the NIH’s ACTIV initiative, and the ACTIV master protocols including ACTIV-6.
#pctGR, @Collaboratory1
On April 14 and 15, 2021, more than 100 participants joined the online Steering Committee meeting to discuss important considerations for Collaboratory trials and the embedded pragmatic clinical trial ecosystem at large, including adaptations made due to COVID-19, data sharing models and experiences, barriers encountered, and lessons learned. All presentations are available for download.
To better understand efforts at cultural and linguistic adaptions in clinical trials focused on pain, members of the NIH Collaboratory’s Patient-Centered Outcomes Core recently conducted a survey of the PRISM NIH Collaboratory Trials (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing), which are part of NIH’s Helping to End Addiction Long-term Initiative℠, or NIH HEAL Initiative℠.
"Having culturally valid patient-reported outcome instruments is extremely important to the conduct of embedded pragmatic trials. For the results to be valid, the intended audience needs to understand both the measure and what is being asked of them. This is critical for trials centered on pain because pain-related outcomes are best described by the person who is experiencing the symptoms." —Emily O’Brien, PhD, Co-Chair of the Patient-Centered Outcomes Core
The results are published in the Cultural Adaptation and Linguistic Translation section of the Patient-Reported Outcomes Chapter in the Living Textbook.
For more information on the PRISM projects, study snapshots are accessible from each NIH Collaboratory Trial page and the links below:
Note that the 2 newest PRISM projects, GRACE and BeatPain Utah, are still in the design phase and were not included in this round of interviews.
