The N3C initiative aims to build a centralized national data resource that researchers can use to study COVID-19 and identify potential treatments as the pandemic continues to evolve. N3C is a partnership among the Clinical and Translational Science Awards Program hubs and the National Center for Data to Health, with overall stewardship by the National Center for Advancing Translational Sciences (NCATS).
The goals of N3C are to:
Rapidly collect and aggregate clinical, lab, and imaging data from hospitals, health plans, and CMS at the peak of the COVID-19 pandemic and as it evolves
Provide a longitudinal dataset to understand acute hospital and recovery phases
Understand pathophysiology of disease
Support clinical trials by identifying patients who might wish to participate in trials
Ken Gersing, MD Director of Informatics, NCATS National Institutes of Health
Robert A. Star, MD Director, Division of Kidney, Urologic, and Hematologic Disorders, NIDDK Chief, Renal Diagnostics and Therapeutics Unit, NIDDK National Institutes of Health
Topic
COVID Open Science Collaborative Analytics Platform: National COVID Cohort Collaborative (N3C)
Keywords
COVID-19; Coronavirus; Pandemic; Data exchange; Data use agreement; Phenotypes; Data harmonization; Common data model; Fast Healthcare Interoperability Resources (FHIR); Synthetic data
Key Points
The National COVID Cohort Collaborative (N3C) initiative aims to build a centralized national data resource that the research community can use to study COVID-19 and identify potential treatments as the pandemic continues to evolve.
Rapidly collect and aggregate clinical, lab, and imaging data from hospitals, health plans, and CMS at the peak of the COVID-19 pandemic and as it evolves
Provide a longitudinal dataset to understand acute hospital and recovery phases
Understand pathophysiology of disease
Support clinical trials by identifying patients who might wish to participate in trials
Discussion Themes
The N3C analytics platform is cloud-based and provides a secure data enclave. Data can be received via multiple data models and transformed into a common analytic model for research.
As a centralized data model, N3C complements existing federated data models like PCORnet and OMOP. The tool does not replace the need for randomized controlled trials.
NCATS, FDA, and NCI are working together on common data model (CDM) harmonization so that data will be publicly available and reusable in human and machine-readable formats.
Susan L. Mitchell, MD, MPH Senior Scientist Hebrew SeniorLife Hinda and Arthur Marcus Institute for Aging Research Professor of Medicine Harvard Medical School
Topic
A Cluster Randomized Pragmatic Trial of an Advance Care Planning Video Intervention in Long-Stay Nursing Home Residents: Main Findings from the PROVEN Trial
Keywords
Embedded pragmatic trial; PROVEN; Advance care planning; Nursing homes; Video intervention; Medicare; Care preferences; Decision support tool; Minimum data set; Intention to treat
Key Points
The PROVEN trial was the first large-scale embedded pragmatic trial conducted in nursing homes.
The advance care planning (ACP) video intervention in PROVEN was meant as an adjunct to first-person discussions with the clinical care provider.
The levels of care preferences described in the ACP videos were life prolongation, limited care, and comfort care.
PROVEN’s primary outcome was the number of transfers to the hospital from the nursing home.
Discussion Themes
Widely adoptable, effective interventions to improve ACP in nursing homes remain elusive.
Of the challenges of conducting PCTs embedded in nursing homes, it is important not to overlook the real-world priorities of stakeholders. A high level of endorsement, from C-suite to frontline care providers, is needed before attempting such a trial.
While a priority for nursing home administrators is the number of residents who transfer to the hospital, an essential question for patients and palliative care experts is whether patients receive care that matches their goals and preferences. This is hard to ascertain in a pragmatic way.
Read more about the PROVEN trial, and learn about a new research initiative built on the success of the NIH Collaboratory: the National Institute on Aging’s IMPACT Collaboratory, which is directly funding pilots of embedded PCTs across diverse healthcare settings to improve the care of patients with dementia and their caregivers.
Guest Moderator Wendy Weber, ND, PhD, MPH Branch Chief, Clinical Research in Complementary and Integrative Health Division of Extramural Research National Center for Complementary and Integrative Health, NIH
Panel Jeffrey (Jerry) G. Jarvik, MD, MPH LIRE NIH Collaboratory Trials Professor of Radiology, Neurological Surgery and Health Services Adjunct Professor of Pharmacy and Orthopedics & Sports Medicine Co-Director, Comparative Effectiveness, Cost and Outcomes Research Center Director, UW CLEAR Center for Musculoskeletal Disorders University of Washington School of Medicine
Lynn DeBar, PhD, MPH PPACT NIH Collaboratory Trials Senior Scientist Kaiser Permanente Washington Health Research Institute
Doug Zatzick, MD TSOS NIH Collaboratory Trial Professor, Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine
Vince Mor, PhD PROVEN NIH Collaboratory Trial Florence Pirce Grant University Professor and Professor of Health Services, Policy and Practice Brown University School of Public Health
Topic
Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Experiences from the Collaboratory PCTs
Lessons and experiences from the NIH Collaboratory Trials include:
Pilot the intervention at the partnering health systems and work closely with site programmers who know the systems best.
Monitor the trial’s implementation at regular intervals to detect breakage.
Keep both the intervention and the outcomes as simple as possible.
Choose endpoints that matter to patients and providers and that are captured reliably as part of routine clinical care.
Enabling rapid outcome ascertainment in large pragmatic trials can be a game changer.
The Emergency Department Information Exchange (EDIE) in Washington state is an innovative technology platform that can help with the collection of population-level administrative data for acute care follow-up and ongoing care plans.
It might be better to uncouple some types of patient-reported outcome (PRO) data collection from the routine clinical care visit.
Discussion Themes
A common theme throughout all the NIH Collaboratory Trial PCTs is how dynamic and ever-changing health care delivery settings are. The reality is that the trial as planned is often not the trial as piloted or conducted.
What type of education is most effective about how to use a PRO to inform care plans and decision-making?
There is nothing like a crisis (eg, the coronavirus pandemic) for people to do things that were before thought impossible. Now, the concept of a “visit” is changing, and there will likely be more uncoupling.
Derek C. Angus, MD, MPH, FRCP Distinguished Professor and Mitchell P. Fink Endowed Chair Department of Critical Care Medicine University of Pittsburgh and UPMC Health System
Topic
Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial
Keywords
Adaptive study design; REMAP-CAP; Community-acquired pneumonia; Embedded research; Learning health system; Pandemic; Response-adaptive randomization; Global adaptive platform; COVID-19
Key Points
The Randomised, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) aims to determine and continuously update the optimal set of treatments for community-acquired pneumonia.
An important aspect of adaptive trial designs is that already accrued data are used to increase the likelihood that patients within the trial are randomized to treatments that are beneficial.
With the onset of the COVID-19 pandemic, the REMAP study made use of an adaptive sub-platform called REMAP-COVID, which is studying multiple questions around COVID treatment simultaneously.
Discussion Themes
The COVID-19 pandemic requires us to do two things at once: learn and do. An integrated approach finds the optimal balance to treat patients as well as possible and learn as fast as possible.
Adaptive randomization is potentially more comfortable for physicians, where patients are preferentially assigned to the best therapy over time.
Read more about REMAP-CAP and Dr. Angus’ research in Optimizing the Trade-off Between Learning and Doing in a Pandemic (JAMA, March 2020).
The Healthcare Worker Exposure Response & Outcomes (HERO) Registry invites both clinical and nonclinical healthcare workers to share their life experiences in order to understand the perspectives and problems faced by those on the COVID-19 pandemic frontlines. HERO Registry participants could have the opportunity to participate in future research studies to improve the understanding of COVID-19 and beyond, generating evidence to help healthcare workers stay safe and healthy.
The HERO Registry is open to all healthcare workers, including nurses, therapists, physicians, emergency responders, food service workers, environmental service workers, interpreters, transporters — anyone who works in a setting where people receive health care.
Guest Moderator: Patrick J. Heagerty, PhD Professor, Department of Biostatistics, University of Washington
Panel: Jacqueline Corrigan-Curay, JD, MD Director of CDER’s Office of Medical Policy (OMP) U.S. Food and Drug Administration (FDA)
Joshua C. Denny, MD, MS, FACMI Chief Executive Officer, All of Us Research Program, NIH
Topic
Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions
Keywords
Electronic health records; Real-world evidence; RWE; Real-world data; RWD; FDA; All of Us; Phenotypes; Regulatory; Fit-for-use data; Digital heath
Key Points
To create quality clinical/research records, we must design for multiuse by integrating standards-based tools in the EHR to bring together health care and research.
Quality real-world evidence cannot be built without quality real-world data. With greater efficiencies in data capture, randomization with real-world data provides a pathway for reliable—and persuasive—real-world evidence.
Discussion Themes
Patient-generated health data is part of FDA’s MyStudies Application, designed to facilitate the input of real-world data directly by patients, which can be linked to electronic health data supporting traditional clinical trials, pragmatic trials, observational studies, and registries.
In assessing data quality we can ask, How does a data element travel from clinical care to a research data set?
The NIH’s All of Us program is building a diverse database that can inform thousands of studies on a variety of health conditions.
The All of Us study is tracking COVID-19 in its patients. Sites have identified their COVID-19 participants and relevant labs. Consent is obtained for future sharing of data.
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
Recording June 30, Available July 7, 2020: Podcast: Summary Expert Panel Discussion (Patrick J. Heagerty, PhD; Keith Marsolo, PhD; Wendy Weber, ND, PhD, MPH; Moderator: Lesley H. Curtis, PhD)
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?
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.
