July 12, 2019: medRxiv: A Paradigm Shift in Disseminating Clinical and Public Health Research (Harlan Krumholz, MD, SM, Joseph Ross, MD, MHS)

Speakers

Harlan M. Krumholz, MD, SM
Harold H. Hines, Jr. Professor of Medicine and Public Health
Yale University

Joseph S. Ross, MD, MHS
Associate Professor of Medicine and Public Health
Yale University

Topic

medRxiv: A Paradigm Shift in Disseminating Clinical and Public Health Research

Keywords

Open science; Clinical research dissemination; Preprints; medRxiv preprint server

Key Points

  • medRxiv (med archive) is a server for health science preprints. It is a free service to the research community, managed in partnership with BMJ and Yale.
  • Benefits of preprints in medicine include early sharing of new information; enabling less “publishable” studies to be more readily available; and facilitating replication and reproducibility studies.
  • medRxiv submissions require:
    • Following ICMJE guidance, including author names, contact info, affiliation
    • Funding and competing interests statements
    • Statement of IRB or ethics committee approval
    • Study registration (ClinicalTrials.gov or other ICMJE approved registry for trials, PROSPERO for reviews) or link to protocol
    • Data sharing availability statement
    • EQUATOR Network reporting guidelines checklists
  • The medRxiv preprint server urges caution in using and reporting preprints, and includes language explaining that preprints are preliminary reports of work that have not been peer-reviewed, should not be relied on to guide clinical practice or health-related behaviors, and should not be reported in news media as established information.

Discussion Themes

Preprint servers do not replace, but rather complement, peer review.

Preprint has the potential for being a vehicle for high-quality but “negative” results. If we teach students that a negative result is also a good result, providing an avenue for us to walk-the-talk more easily via open communication seems largely positive despite the limitations.

Read more about medRxiv.

Tags

#pctGR, @Collaboratory1, @jsross119, @hmkyale

June 28, 2019: Moving Beyond Return of Research Results to Return of Value (Consuelo Wilkins, MD, MSCI)

Speaker

Consuelo H. Wilkins, MD, MSCI
Vice President for Health Equity, Vanderbilt University Medical Center
Executive Director, Meharry-Vanderbilt Alliance

Topic

Moving Beyond Return of Research Results to Return of Value

Keywords

Health outcomes; Research results; Patient preferences; Value of information

Key Points

  • In returning value to research participants, results are shared with added context, are prioritized by each participant, include specific suggestions for relevant actions, and incorporate participant recommendations and preferences.
  • Data captured for research purposes, including EHR data, vital signs, and genetic data, can be repurposed and reoriented for study participants.
  • Participants are more likely to trust research if results are returned—and they are more likely to participate again.

Discussion Themes

We need to return study results that are informed by participants, and we need to design approaches for accessing and understanding results that participants will want to use.

We should think carefully about risk mitigation when returning research results for which there is a clear next step or action for the participant.

Read more about understanding what information is valued by research participants in a recent article by Dr. Wilkins and colleagues in Health Affairs.

Tags

#pctGR, @Collaboratory1, @drchwilkins, @vumchealth

June 14, 2019: Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System (Robert Mentz, MD)

Speaker

Robert J. Mentz, MD, FACC, FAHA, FHFSA
Associate Professor
Director, Duke Cooperative Cardiovascular Society
Associate Program Director, Duke Cardiovascular Disease Fellowship
Duke University Medical Center and Duke Clinical Research Institute

Topic

Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System

Keywords

International Council for Harmonization (ICH); Good clinical practice (GCP); Learning health system; Pragmatic clinical trials; Institutional review board (IRB); Research oversight; Regulatory issues; Quality by design (QbD)

Key Points

  • Good clinical practice (GCP) guidance details the responsibilities, procedures, and recording that are necessary for appropriate trial conduct; for example, conducting the trial in accordance with an IRB-approved protocol with appropriate adverse event monitoring and reporting.
  • There is an urgent need to streamline randomized trials. Key obstacles are lack of transparency, lack of representativeness, and lack of evidence of competence.
  • In the United States, clinical investigators must abide by guidance from FDA, HHS, and ICH-GCP. Yet it is hard for investigators to keep track and to know how GCP applies to their study.
  • GCP as an overall construct is useful, but it does not deal well with issues particular to pragmatic trials or trials outside the FDA-regulated world.

Discussion Themes

With embedded pragmatic trials, informed consent is more nuanced. New considerations and approaches for consent have arisen since ICH GCP first came into effect.

Establishing quality by design will take time, effort, and educating IRBs to understand how QbD can be used to avoid errors in a trial and collect data that is fit-for-purpose.

It’s crucial that trials address an important question, answer that question reliably, and keep participants safe.

Read more about Dr. Mentz’s study of GCP and pragmatic trials.

Tags

#pctGR, @Collaboratory1, @RobMentz

June 7, 2019: In Dreams Begin Responsibilities: Data Science as a Service—Using AI to Risk Stratify a Medicare Population and Build a Culture (Erich Huang, MD, PhD)

Speaker

Erich S. Huang, MD, PhD
Co-Director, Duke Forge
Departments of Biostatistics & Bioinformatics and Surgery
Duke University School of Medicine

Topic

In Dreams Begin Responsibilities: Data Science as a Service—Using AI to Risk Stratify a Medicare Population and Build a Culture

Keywords

Data science; Data liquidity; Data standards; Machine learning; Duke Forge; Application programming interface; Artificial intelligence

Key Points

  • Duke Forge focuses on bringing the best methodological approaches to actionable data problems in health. It is motivated by a framework of value-based healthcare to address societal inequities in health.
  • Essential components to building a data science culture include clinical subject matter expertise, quantitative and methodological expertise, and software architecture and engineering expertise, along with interoperable tools and applications.
  • Like freight shipping containers, health-relevant data needs standardized containers that make any type of data easy to pack, grab, combine, and move around. The aim should be to build a “data liquidity ecosystem” equivalent to freighters, cranes, trains, and trucks that facilitate the logistics of health data transport.

Discussion Themes

If we’re trying to build an ecosystem, then the electronic health record (EHR) platform needs to be evaluated by whether it is truly participatory in this ecosystem. If not, then its deficiencies must be remediated.

The faster we can move to the cloud and use building blocks that “snap” together, the faster we can get answers. We want to be building applications instead of infrastructure.

Algorithms don’t have ethics; some have hidden biases. Algorithms need to be scrutinized and tested for such biases. They also must be secured so they cannot be manipulated.

Read more about Duke Forge and check out articles on the blog.

Tags

#pctGR, @Collaboratory1, @DukeForge

May 17, 2019: The VITamin D and OmegA-3 TriaL (VITAL): Design and Results of a Large Pragmatic Trial (JoAnn E. Manson, MD, DrPH)

Speaker

JoAnn E. Manson, MD, DrPH
Chief, Division of Preventive Medicine, Brigham and Women’s Hospital
Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health
Harvard Medical School
Professor, Department of Epidemiology
Harvard T.H. Chan School of Public Health

Topic

The VITamin D and OmegA-3 TriaL (VITAL): Design and Results of a Large Pragmatic Trial

Keywords

Pragmatic clinical trial; Dietary supplements; Primary prevention; Mail-based randomized clinical trial; Cancer prevention; Cardiovascular disease prevention; vitamin D; Omega-3 fatty acids

Key Points

  • The VITAL pragmatic trial evaluated the effects of dietary supplements (vitamin D and omega-3) on reducing risk for developing cancer, heart disease, and stroke in the general population.
  • Study recruitment involved nationwide and targeted mailings, media reports, advertising, and brochures. Retention included participant newsletters, incentive gifts, and honoraria.
  • Findings included that neither omega-3s nor vitamin D significantly reduced the primary endpoints of major cardiovascular disease events or total invasive cancer. Omega-3s did reduce total myocardial infarction by 28%, with greatest reductions in those with low dietary fish intake and in African Americans.

Discussion Themes

VITAL’s hybrid design—remote or mail-based intervention plus serial in-clinic visits in a sample—has advantages in promoting quality and cost-efficiency.

Next steps for VITAL include continued follow-up for 5 years; genetic studies; and fostering new ancillary studies through nationwide collaborations.  

Visit the VITAL study website and read more about the results of VITAL (Manson et al., New Engl J Med, 2019)

Tags

#dietarysupplements, #pctGR, @Collaboratory1

April 19, 2019: Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims (Doug Zatzick, MD)

Speaker

Doug Zatzick, MD
Professor of Psychiatry
Harborview Medical Center
University of Washington School of Medicine

Topic

Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims

Keywords

Trauma outcomes; Demonstration Project; Hybrid study design; Implementation science; Pragmatic clinical trial; Cluster randomization; Stepped-wedge design; Posttraumatic stress disorder; PRECIS-2; Mental health intervention

Key Points

  • The TSOS Demonstration Project is a cluster-randomized, stepped-wedge trial conducted at 25 U.S. trauma centers. The intervention involves an electronic health record PTSD screen and a baseline PTSD and comorbidity assessment. TSOS is turned on at each site across 4 “waves.”
  • During the course of this hybrid effectiveness-implementation trial, two domains on PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) were scored as more pragmatic and one domain as more explanatory than at the outset of the study.
  • The study team developed a methodology for assessing TSOS implementation aims. Called RAPICE (Rapid Assessment Procedure Informed Clinical Ethnography), the method yielded findings around recurrent intervention and research staff turnover across sites; observations that some patients do not engage in the intervention; and ways to inform a priori secondary hypotheses that suggest per-protocol modifications to the original intention-to-treat analyses.
  • TSOS will present results at the 2020 summit of the American College of Surgeons with the potential to integrate findings into the College’s regulatory and verification processes.

Discussion Themes

Regarding the need to collect outcome data, there may be an important distinction between two aspects of “pragmatic.” That is, while collecting outcome data makes a trial more expensive (one aspect of pragmatic), it doesn’t necessarily affect relevance or generalizability (another, more important, aspect of pragmatic).

Might there be studies which, by design, are not aiming to be on the outer [more pragmatic] spokes of the PRECIS-2 wheel?

Read more about the TSOS Demonstration Project.

Tags

#pctGR, @Collaboratory1, @PRECIS_2

Podcast April 16: Development of Harmonized Outcome Measures for Use in Research and Clinical Practice

Podcast April 16: Development of Harmonized Outcome Measures for Use in Research and Clinical Practice (Michelle Leavy, MPH, Elise Berliner, PhD)

In this episode of the NIH Collaboratory Grand Rounds podcast, Dr. Adrian Hernandez sits down with Dr. Elise Berliner and Michelle Leavy to discuss the Development of Harmonized Outcome Measures for Use in Research and Clinical Practice. In the discussion, Dr. Berliner and Leavy explain the outcome measures framework and harmonizing outcomes in specific clinical areas.

Click on the recording below to listen to the podcast.

Want to hear more? View the full Grand Rounds presentation.

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Read the transcript. 

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April 15, 2019: Registration Now Open for Workshop on the Design & Analysis of Embedded Pragmatic Clinical Trials (ePCT)

The NIH Health Care Systems Research Collaboratory is hosting a one-day workshop on the Design & Analysis of Embedded Pragmatic Clinical Trials (ePCTs) on May 2, 2019, in the Lister Hill Auditorium on the NIH Campus.

The workshop will include a series of moderated discussions that focus on issues of measuring trial outcomes from available data sources, potential randomization strategies, specific ePCT design considerations, and unique challenges associated with ePCTs. Panel discussions will utilize case examples from the Collaboratory repertoire and beyond to illustrate how clinical investigators and biostatisticians work to address research questions posed by specific trials.

The Workshop Website provides information on meeting logistics, agenda, and registration. There is also an option to attend the workshop remotely via the NIH Videoconference Center, and those details are also available at the Workshop Website.

March 8, 2019: Dietary Trials in Heart Failure: SODIUM-HF (Justin Ezekowitz, MBBCh, MSc)

Video not available

Speaker

Justin A. Ezekowitz, MBBCh, MSc
Professor, University of Alberta
Co-Director, Canadian VIGOUR Centre
Cardiologist, Mazankowski Alberta Heart Institute

Topic

Dietary Trials in Heart Failure: SODIUM-HF

Keywords

Multicenter clinical trial; Heart failure; Dietary sodium; Cardiovascular health; Clinical equipoise; Clinical guidelines; SODIUM-HF

Key Points

  • The SODIUM-HF trial is a multicenter, multinational dietary study evaluating the long-term effects of a low-sodium diet in patients with heart failure on a composite clinical outcome of all-cause mortality, cardiovascular (CV) hospitalizations, and CV emergency department visits.
  • The recommended amount of dietary sodium for patients with heart failure varies among the guidelines, ranging from no restriction to <2300mg per day.
  • Among the successes of the study are the important research question, a simple electronic case report form, engaged clinicians and staff, 100% remote monitoring, and a low administrative burden.

Discussion Themes

Sodium restriction is one of the most challenging things for patients to undertake as it affects their lifestyle significantly.

What is your perspective on the importance of a low-sodium diet for patients with heart failure, given that low sodium was shown to be harmful in some studies?

How do you balance wanting a pragmatic/practical intervention versus wanting a rigorous test of your hypothesis?

For more information on this study, visit the SODIUM-HF trial website and ClinicalTrials.gov.

Tags

#HeartFailure, #pctGR, @SodiumHF, @Collaboratory1, @JustinEzekowitz, @CVC_UAlberta