clinical trials

May 5, 2020: Dr. Robert Califf Discusses Next Steps for Reforming the Evidence Generation Ecosystem After COVID-19

Posted on by Gina Uhlenbrauck

In case you missed the May 1 keynote address by Robert M. Califf, MD, MACC, you can now listen to the recorded webinar and Q&A. Dr. Califf, head of strategy and policy for Verily Life Sciences and Google Health, kicked off the Collaboratory’s Grand Rounds workshop series, Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials.

His presentation outlined several opportunities to drive change and rebuild clinical research in the aftermath of COVID-19, including:

  • Evaluate what has and has not worked in the changes that have been made in response to the crisis
  • Allocate a significant part of recovery funding to transition issues in evidence generation, especially at the interface of medicine and public health
  • Do everything possible to fix the “purposefulness issue”:
    • Create methods for deciding the most important questions
    • Reward behavior that gets important questions answered quickly
  • Develop inclusive networks driven by people with the health problems of interest; increase incentives for clinicians and investigators that lead to reliable and faster evidence generation (balance financial focus with purpose); and automate mapping of EHR data beyond individual systems

“The effective use of digital information such as electronic health records, telehealth, applications, and patient-reported outcomes should free up effort to fix the human components that are holding us back.” – Dr. Robert Califf

View the full presentation for more insights from Dr. Califf.

Stay tuned for these upcoming presentations in the series:

May 1, 2020: Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Keynote-Can the COVID-19 Crisis Lead to Reformation of the Evidence Generation Ecosystem? (Robert Califf, MD, MACC)

Posted on by Gina Uhlenbrauck

Speaker

Robert Califf, MD, MACC
Head of Strategy and Policy
Verily Life Sciences and Google Health

Topic

Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Keynote-Can the COVID-19 Crisis Lead to Reformation of the Evidence Generation Ecosystem?

Keywords

Electronic health records; Digital health; Mobile health; Coronavirus; COVID-19; Ecosystem; Clinical trials; Evidence generation

Key Points

  • The HERO Registry and RECOVERY Trial are good examples of a rapid clinical research response to the urgent COVID-19 health crisis.
  • Among the essential steps to move the evidence generation system in the right direction:
    • Evaluate what has and has not worked in the changes made in response to the crisis
    • Allocate a significant part of recovery funding to transition issues in evidence generation, especially at the interface of medicine and public health
    • Increase purposefulness by creating methods for deciding the most important questions and rewarding behavior that gets those questions answered quickly

Discussion Themes

The COVID-19 pandemic has shone a spotlight on disparities in our current healthcare delivery system. How can we avoid leaving the most vulnerable of society behind?

Telemedicine can be a framework for the integration of research and clinical care. But the digital element must be integrated with the human element. The routine and effective use of digital information should free up effort to fix the human components that are holding us back.

We’ve been trying to modernize clinical trial design for decades (factorial/sequential/adaptive designs for example). While some positive movement in the past month has been made, the research enterprise remains largely conservative when it comes to design modernization. How do we make more rapid progress?

Tags

#pctGR, #COVID19, @Collaboratory1, @Califf001

April 29, 2020: Materials from the Collaboratory Steering Committee’s Virtual Meeting Now Available

Posted on by Gina Uhlenbrauck

On April 22 and 23, 2020, more than 90 participants joined the online Steering Committee meeting to hear about the evolution of the embedded PCT (ePCT) ecosystem, discuss how to strengthen partnerships across the ecosystem, and identify approaches and lessons that will help inform and broaden the ecosystem. All presentations are available for downloading.

April 24, 2020: The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19 (Martin Landray, PhD, FRCP)

Posted on by Gina Uhlenbrauck

Speaker

Martin Landray, PhD, FRCP
Professor of Medicine & Epidemiology
Nuffield Department of Population Health
University of Oxford, UK

Topic

The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19

Keywords

Coronavirus; Virus pandemic; COVID-19; SARS-CoV-2; RECOVERY Trial; Randomized trial; Epidemiology

Key Points

  • Between March 10 and April 3, 2020, the RECOVERY team developed the protocol, obtained regulatory and ethics approval, and enrolled 1,000 patients.
  • COVID-19 presents an unprecedented clinical challenge to the health system, staff, and patients. Even moderate effects from this study will be worthwhile in the generation of robust evidence.
  • RECOVERY follow up will involve linkage to national data sources for vital status and death certificates; coded hospital episode statistics (diagnoses, procedures); intensive care audit data and SARS-CoV-2 PCR laboratory results; and primary care and national outpatient prescribing data.

Discussion Themes

Informed consent for participants in the RECOVERY trial consists of a 2-page information sheet and single form written in plain language.

The urgency of this pandemic requires everyone to focus on what matters and leave orthodoxy, habits, and traditional practices behind. Our mindset has been altered by the COVID-19 disruptions and this public health crisis of extraordinary proportion.

For more information, visit the RECOVERY Trial website.

Tags
#pctGR, #COVID19, @Collaboratory1

April 22, 2020: New Article Details the Design of ADAPTABLE, PCORnet’s First Pragmatic Trial

Posted on by Damon Seils

A new article in JAMA Cardiology discusses the design of ADAPTABLE, a pragmatic clinical trial (PCT) which strives to answer a three-decade-old question with great potential significance for public health. ADAPTABLE is the first PCT to use many of the data-driven and patient-centric capabilities of the National Patient-Centered Clinical Research Network (PCORnet).

Researchers in ADAPTABLE pursued the unanswered question of whether a low dose or high dose of aspirin is optimal for secondary prevention of atherosclerotic cardiovascular disease. Complexities of running a randomized clinical trial and the expenses associated with it have previously prevented researchers from answering this question.

The capabilities of PCORnet have aided in this research. Though not all randomized clinical trials can be designed as PCTs, ADAPTABLE demonstrates the possibility of incorporating pragmatic elements into future studies with the goal of producing real-world evidence.

A key objective of involving PCORnet in ADAPTABLE was the ability for large-scale recruitment (15,000 participants) using electronic health records and electronic informed consent. The PCORnet component permitted complete electronic participation, from randomization to data collection. Patients reported their own data during scheduled electronic follow-ups, which replaced conventional follow-up visits.

NIH Collaboratory Coordinating Center co–principal investigator Dr. Adrian Hernandez also serves as co–principal investigator of ADAPTABLE and contributed to the article.

See the accompanying editorial describing lessons learned from the design features of ADAPTABLE.

April 21, 2020: NIH Collaboratory COVID-19 Grand Rounds Series Continues With the RECOVERY Trial

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, Prof. Martin Landray of the University of Oxford will present “The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised With COVID-19.” This new trial is randomly assigning patients to standard care alone or standard care plus one of a variety of potential treatments for COVID-19. The Grand Rounds session will be held on Friday, April 24, at 1:00 pm eastern. Join the online meeting.

Previous COVID-19 Grand Rounds:

Recent news announcements:

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

April 17, 2020: The HERO Program: PCORnet® at Work to Create a Healthcare Worker Community for Rapid Cycle Evidence (Nakela Cook, MD, MPH; Josie Briggs, MD; Susanna Naggie, MD; Emily O’Brien, PhD; Russell Rothman, MD; Chris Forrest, MD, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Nakela Cook, MD, MPH
Executive Director
PCORI

Josie Briggs, MD
Acting Chief Science Director
PCORI

Susanna Naggie, MD
Principal Investigator, HERO-HCQ Clinical Trial
Duke University

Emily O’Brien, PhD
Principal Investigator, HERO-Registry
Duke University

Russell Rothman, MD, MPP
Chair, HERO Steering Committee
Vanderbilt University

Chris Forrest, MD, PhD
Chair, HERO Registry
Children’s Hospital of Pennsylvania

Topic

The HERO Program: PCORnet® at Work to Create a Healthcare Worker Community for Rapid Cycle Evidence

Keywords

Coronavirus; Virus pandemic; COVID-19; PCORI; Patient-Centered Outcomes Research Institute; Frontline health workers; Hydroxychloroquine; Healthcare systems; HERO-HCQ

Key Points

  • With the onset of the coronavirus pandemic, the U.S. healthcare system faces an unprecedented stress test to adapt to meet new demands.
  • Those on the frontline of caring for patients—healthcare workers—are at risk of developing or transmitting COVID-19. Evidence is urgently needed to keep healthcare workers and their families safe and healthy, which ultimately will help protect us all.
  • The HERO (Healthcare Worker Exposure Response & Outcomes) Program has three broad focus areas to develop rapid evidence around healthcare workers’ outcomes related to COVID-19:
    • Emphasis on the adaptations in how healthcare is delivered
    • Emphasis on vulnerable populations
    • Emphasis on the well-being of the healthcare worker
  • HERO will consist of a registry study of healthcare workers and a randomized controlled trial called HERO-HCQ that will evaluate the safety and efficacy of hydroxychloroquine to prevent COVID-19 clinical infections in healthcare workers.

Discussion Themes

The goal of the HERO registry is to understand all aspects of healthcare workers’ lives—those with direct impact and those with indirect impact.

What mechanisms are you envisioning for new study proposals that would be conducted via the HERO platform?

Serologic testing will have a significant role in understanding prior infection and potential immunity.

The HERO Registry is open to any healthcare worker to join at https://heroesresearch.org/. Enrollment takes only a few minutes; participation is free and voluntary. It is not restricted by profession. All data are kept confidential.

Tags
#HeroRegistry, #pctGR, @Collaboratory1, @PCORI, @PCORnetwork, @HeroesResearch

April 16, 2020: Why Randomized A vs B Comparisons Remain Uncommon in Clinical Trials

Posted on by Damon Seils

In an article published today in the New England Journal of Medicine, NIH Collaboratory investigators Drs. Greg Simon, Rich Platt, and Adrian Hernandez describe why it has been so challenging to meet the National Academy of Medicine’s 2020 goal for the development of a learning health system. If the goal had been met, 90% of clinical decisions would be based on accurate evidence gathered from health systems that continually learn from data collected as part of routine care.

Absent such evidence, the type of care provided is determined by the haphazard influences of financial incentives, clinicians’ anecdotal experiences, and patients’ or clinicians’ exposure to marketing messages. — Simon et al, New England Journal of Medicine, April 16, 2020

Most pragmatic trials, including the NIH Collaboratory Demonstration Projects and clinical trials conducted through the National Patient-Centered Clinical Research Network (PCORnet), have compared standard care with proposed improvements to standard care, or “A vs A-plus trials.” Trials that compare 2 alternative treatments that are in current use, or “A vs B trials,” are rarely done.

The authors describe both the barriers and the potential solutions for the development of more A vs B pragmatic clinical trials in pursuit of a learning health system.

“Achievement of the NAM’s goal of basing 90% of clinical decisions on accurate evidence remains distant, and meaningful progress will involve engagement by many parties,” write Simon and colleagues. “It will require health system leaders to consider rigorous evidence generation a core function of ordinary health care, research funders to prioritize practical questions relevant to population health and to support infrastructure for embedded research, research regulators to align consent procedures with incremental risks of research, and researchers to ask real-world questions that patients, caregivers, and clinicians want answered. But the first step is for everyone involved to honestly acknowledge the lack of evidence supporting the majority of common medical decisions and the urgent need for more relevant and efficient clinical research,” the authors continue.

The impetus for the article was an NIH Collaboratory workshop, Embedded Pragmatic Clinical Trials of Therapeutic A vs B Interventions. The workshop explored challenges and strategies for planning and implementing embedded pragmatic clinical trials that compare 2 or more therapeutic medical regimens.

The authors of the article are Adrian F. Hernandez, MD, MHS, professor of medicine and vice dean for clinical Research in the Duke University School of Medicine; Gregory E. Simon, MD, MPH, of the Kaiser Permanente Washington Health Research Institute; and Richard Platt, MD, MSc, of the Harvard Pilgrim Health Care Institute. All 3 institutions are part of the NIH Collaboratory Coordinating Center.

April 15, 2020: NIH Collaboratory COVID-19 Grand Rounds Series Continues With Discussion of HERO Program for Healthcare Workers

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, leaders of the Patient-Centered Outcomes Research Institute (PCORI) and investigators from the Healthcare Worker Exposure Response and Outcomes (HERO) registry and the HERO-HCQ randomized clinical trial will present “The HERO Program: PCORnet® at Work to Create a Healthcare Worker Community for Rapid Cycle Evidence.” The Grand Rounds session will be held on Friday, April 17, at 1:00 pm eastern. Join the online meeting.

Previous COVID-19 Grand Rounds:

Recent news announcements:

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

April 10, 2020: Hydroxychloroquine for the Early Treatment of COVID-19 in Hospitalized Adults: A Multicenter Randomized Clinical Trial (Sean Collins, MD, MSc)

Posted on by Gina Uhlenbrauck

Speaker

Sean Collins, MD, MSc
Professor and Executive Vice Chair
Department of Emergency Medicine
Director, Center for Emergency Care Research and Innovation
Vanderbilt University Medical Center

Topic

Hydroxychloroquine for the Early Treatment of COVID-19 in Hospitalized Adults: A Multicenter Randomized Clinical Trial

Keywords

Coronavirus; Virus pandemic; COVID-19; Randomized controlled trial; Acute respiratory distress syndrome (ARDS); Hydroxychloroquine; FDA; Emergency Use Authorization; ORCHID study

Key Points

  • Hydroxychloroquine is a biologically plausible agent for early treatment of acute respiratory distress syndrome in patients with COVID-19, but its effects remain to be evaluated in a high-quality, multicenter, blinded, placebo-controlled trial.
  • In an Emergency Use Authorization, the FDA has encouraged the conduct and participation in randomized controlled clinical trials that may produce evidence concerning the effectiveness of hydroxychloroquine in treating patients with COVID-19.
  • Trial results of the effects of this agent will be informative, whether showing benefit or harm.

Discussion Themes

The study team for this trial determined that one-to-one randomization would yield the best data quickly.

Efficacy and safety of hydroxychloroquine must be closely monitored in a health setting.

This is not the only study of chloroquine going on around the world; is there any collaboration with other studies?

Because of the urgency of the pandemic, people are collaborating on a level never seen before. We have a common goal and must maintain momentum through accelerating clinical trials with large teams of parallel studies.

Read more about this COVID-19 study at NCT04332991.

Tags
#pctGR, @Collaboratory1