clinical outcomes

December 14, 2021: A Year of New Insights From the NIH Collaboratory

Posted on by Damon Seils

Collage of journal coversNIH Collaboratory researchers in 2021 shared study results, generated new knowledge, and developed innovative research methods in pragmatic clinical trials. Their work included insights from the Coordinating Center and Core Working Groups, analyses from the NIH Collaboratory Distributed Research Network, and results and methodological approaches from the NIH Collaboratory Trials.

So far this year, the NIH Collaboratory has produced 3 dozen articles in the peer-reviewed literature, including the primary results of the PPACT and TSOS trials, the study design of the Nudge and OPTIMUM studies, insights into the COVID-19 pandemic from the EMBED and ACP PEACE studies, and more:

NIH Collaboratory Coordinating Center

NIH Collaboratory Distributed Research Network

ACP PEACE NIH Collaboratory Trial

BackInAction NIH Collaboratory Trial

EMBED NIH Collaboratory Trial

GRACE NIH Collaboratory Trial

HiLo NIH Collaboratory Trial

LIRE NIH Collaboratory Trial

Nudge NIH Collaboratory Trial

OPTIMUM NIH Collaboratory Trial

PPACT NIH Collaboratory Trial

PRIM-ER NIH Collaboratory Trial

PROVEN NIH Collaboratory Trial

SPOT NIH Collaboratory Trial

TSOS NIH Collaboratory 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.

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

May 7, 2021: Online Recruitment in the Era of COVID-19: Pitfalls and Progress (Megan L. Ranney, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Megan L. Ranney, MD, MPH, FACEP
Director, Brown-Lifespan Center for Digital Health
Warren Alpert Endowed Associate Professor of Emergency Medicine, Brown University
Associate Dean of Strategy and Innovation, School of Public Health, Brown University
Chief Research Officer, AFFIRM
Co-founder, GetUsPPE

Topic

Online Recruitment in the Era of COVID-19: Pitfalls and Progress

Keywords

COVID-19; Online trial recruitment; Clinical trials; Emergency medicine; Digital health technologies; Remote interventions; Electronic informed consent

Key Points

  • The Center for Digital Health at Brown University is a research and education hub that explores innovative solutions to urgent health challenges. The Center has supported studies involving the use of digital health technologies for recruiting participants and delivering behavioral health interventions.
  • Due to disruptions caused by the COVID-19 pandemic, many research studies pivoted from in-person contact toward the use of digital technologies such as smartphone apps and remote telehealth.
  • To advance clinical trials in a post-pandemic world, we will need to establish best practices for digital health technologies—and recognize when online recruitment is appropriate and when it is not. Hybrid recruitment models offer a solution.

Discussion Themes

It remains clear that the relationship between study staff and participants is essential to forming positive alliances and determines the likelihood of follow up.

For social media advertising, it’s possible that an IRB could approve a group of images, headlines, and content that study teams can combine in different ways to optimize the advertising over the course of a study.

The Pew Research Center provides recent data on which social media platforms are used most by Americans. Read more about digital health science at the Center for Digital Health.

Tags

#pctGR, @Collaboratory1

April 30, 2021: ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications (Susanna Naggie, MD, MHS; Elizabeth Shenkman, PhD)

Posted on by Gina Uhlenbrauck

Speakers

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

Topic

ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications

Keywords

COVID-19; NIH ACTIV Initiative; Repurposed drugs; Vaccines; Therapeutic agents; Direct-to-participant trials; PCORnet

Key Points

  • 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.

Discussion Themes

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.

Tags

#pctGR, @Collaboratory1

April 23, 2021: COVID Clinical Trials: The Intermountain Healthcare Experience (Samuel M. Brown, MD, MS)

Posted on by Gina Uhlenbrauck

Speaker

Samuel M. Brown, MD, MS
Associate Professor and Director of Pulmonary/Critical Care Research
Intermountain Healthcare
Associate Professor, University of Utah

Topic

COVID Clinical Trials: The Intermountain Healthcare Experience

Keywords

COVID-19; Public health; Integrated health system; COVID-19 treatment trials

Key Points

  • Intermountain Healthcare is a nonprofit, community-based healthcare system that maintains an academic referral center and several hospitals in Utah.
  • During the pandemic, the health system was able to integrate COVID-19 research with urgent clinical, operational, and public health needs. The health system currently supports 15 randomized clinical trials in COVID-19 research, investigating immunologic and virologic therapies.
  • Collaboration and communication across divisions were essential elements to the successes achieved.
  • Among the challenges of conducting the COVID-19 trials, there remains a wish for a comprehensive risk management solution and regulatory reform.

Discussion Themes

Could we establish a robust program that provides better training and pay for study coordinators? These staff have direct contact with participants for recruitment and retention and can make or break a trial.

What aspects of institutional culture contributed to the success of conducting these trials?

What is needed is a clinical research ecosystem that appropriately balances regulatory oversight with the agility to answer urgent health questions.

Read more about Intermountain Healthcare’s experiences with COVID-19 clinical trials in these recent publications:

Tags

#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)

Posted on by Gina Uhlenbrauck

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.

Tags

#pctGR, @Collaboratory1

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

Posted on by Gina Uhlenbrauck

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.

Tags

#pctGR, @Collaboratory1

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

Posted on by Gina Uhlenbrauck

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.

Tags

#pctGR, @Collaboratory1

March 26, 2021: The Path to Preventive Genomics (Robert C. Green, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Robert C. Green, MD, MPH
Professor of Medicine (Genetics), Harvard Medical School
Director, Genomes2People Research Program and Preventive Genomics Clinic
Mass General Brigham, Ariadne Labs, Broad Institute

Topic

The Path to Preventive Genomics

Keywords

Preventive genomics; Whole genome sequencing; Return of results; Risk stratification; Precision medicine

Key Points

  • The goal of the Genomes2People research program is to bring genomics into evidence-based patient care. The program conducts empirical research in translating genomics into health, including the first rigorous trials to provide comprehensive genome sequencing to adults and newborn infants.
  • Twenty percent of healthy people are carrying a monogenic disease risk variant. The number of people carrying variants for monogenic diseases depends on how many genes are analyzed.
  • Polygenic risk is the chance of developing certain health conditions based on a large number of genetic variants across the genome.

Discussion Themes

People are interested in medical information about themselves. It’s up to the healthcare system and physicians to create nuanced communication about genetic information that helps people understand its role in health.

Is there a diversity of families seeking out genomic screening services?

Should genetic variants of unknown significance (VUS) be reported to the individual?

Read more at Genomes2People and Brigham Preventive Genomics Clinic.

Tags

#pctGR, @Collaboratory1, @genomes2people