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

July 2, 2019: New Living Textbook Section on Inpatient Endpoints in Pragmatic Clinical Trials

A new section in the Living Textbook describes the considerations for using “real-world” data for inpatient-based event ascertainment. There are many sources for acquiring this information, and they have different time lags in their availability and varying degrees of error and bias. In order to use inpatient endpoints in pragmatic clinical trials, these factors must be understood during the design, conduct, and analysis phases of an embedded pragmatic clinical trial.

“The pragmatic trial community needs to collectively determine which endpoints are relevant for pragmatic trials, how they can be measured and validated, and how the accuracy of these measurement methods may impact hypothesis testing sample size estimates.” —Eisenstein et al 2019

Topics in the chapter include:

  • Pragmatic trial inpatient endpoints
  • Inpatient event data sources
  • Patient-reported data
  • Secondary data sources: EHR
  • Secondary data sources: claims
  • Case studies: ICD-Pieces, TRANSFORM-HF, ADAPTABLE, and TRANSLATE ACS
  • Data source accuracy

 

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

May 31, 2019: Adapting Clinical Trial Design to Meet the Needs of Learning Health Systems (Harriette Van Spall, MD, MPH)

Speaker

Harriette G.C. Van Spall, MD, MPH, FRCPC
Associate Professor of Medicine
Department of Medicine, Division of Cardiology
Department of Health Research Methods, Evidence, and Impact
McMaster University
Population Health Research Institute

Topic

Adapting Clinical Trial Design to Meet the Needs of Learning Health Systems

Keywords

Learning health system; Pragmatic clinical trial; Patient-Centered Care Transitions in Heart Failure (PACT-HF); Heart failure; Stepped-wedge cluster trial

Key Points

  • Characteristics of a learning health system include:
    • Possessing a culture of knowledge and quality improvement
    • Encouraging research innovation by embedding research into clinical practice and generating knowledge at the point of care
    • Harnessing data from electronic health records and claims/administrative databases
    • Fostering trust between research and clinical teams
    • Engaging patients, clinicians, and key stakeholders
  • The Patient-Centered Care Transitions in Heart Failure (PACT-HF) trial evaluated the effectiveness of a group of transitional care services in patients hospitalized for HF within a publicly funded healthcare system.
  • Challenges of a learning health system include integrating care, intervention, and communications across silos; streamlining workflow; preventing “contamination” of usual care; and the limited interoperability of EHRs and slow updates to claims/administrative datasets.

Discussion Themes

Efficacy in explanatory randomized clinical trials (RCTs) does not equate to effectiveness in real-world settings.

Decisions about implementation of an intervention are not made “live”; you must wait until the study has ended, all the data are available for analysis, and analysis is complete before you can inform decision-maker partners about the risks and benefits of the intervention.

Read more about the PACT-HF study and results in JAMA Network (Van Spall et al. 2019)

Tags

#pctGR, @Collaboratory1

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

May 10, 2019: Treating Data as an Asset: Data Entrepreneurship in the Service of Patients (Eric Perakslis, PhD)

Speaker

Eric D. Perakslis MS, PhD
Rubenstein Fellow, Duke University
Lecturer, Department of Biomedical Informatics
Harvard Medical School

Topic

Treating Data as an Asset: Data Entrepreneurship in the Service of Patients

Keywords

Digital health; Health data; General Data Protection Regulation (GDPR); Data sharing

Key Points

  • The only 100% common element of digital transformation across all industries is data.
  • With data and digital transformation, patients are changing: They are active, connected, informed, and savvy.
  • Security, compliance, and privacy are different things.

Discussion Themes

Is there any hope of data sharing policies helping to bridge the micro and macro silos of healthcare data?

As data starts to flows through institutions, it ends up in multiple places. Part of sharing data is protecting a single source of truth.

If something is relevant to the bedside, it’s worth doing.

Read Dr. Perakslis’s commentary in The Lancet (May 2019).

Tags

#healthdata, #pctGR, @Collaboratory1

April 26, 2019: The VERITAS Trial: Virtual Exercise Rehabilitation at the Intersection of Evidence, Implementation, and Policy (Janet Prvu Bettger, ScD)

Speaker

Janet Prvu Bettger, ScD, FAHA
Associate Professor
Duke Department of Orthopaedic Surgery
Duke Clinical Research Institute

Topic

The VERITAS Trial: Virtual Exercise Rehabilitation at the Intersection of Evidence, Implementation, and Policy

Keywords

Rehabilitation; Virtual physical therapy; Patient outcomes; Physical therapy; Orthopaedic surgery; Total knee replacement; Digital technology; Telehealth

Key Points

  • The VERITAS trial evaluated the effects of physical therapy–supported virtual exercise compared with traditional home- or clinic-based physical therapy after total knee replacement. Outcome measures included 90-day health service use costs; patient-centered outcomes; and differential improvement from 6 weeks to 3 months.
  • The Center for Connected Health Policy found that while most states currently have established telehealth policies for primary care providers, these often do not include physical or occupational therapists.
  • Tele-rehabilitation facilitates communication between the patient and physical therapist in real time. The VERA™ technology provides a virtual physical therapist assistant for patients and clinicians, offering a digital interface that includes patient education, longitudinal functional assessments, telehealth video conferencing, personalized exercises, and remote monitoring of patient progress.

Discussion Themes

Study results support effectiveness and safety hypotheses: that tele-rehabilitation is noninferior to traditional physical therapy with respect to range of motion, walking speed, pain, or rehospitalization. However, it was not shown that the intervention is noninferior with respect to falls after hospital discharge.

Because virtual physical therapy interventions can save total costs, prevent readmissions, and improve mobility, it will be important to expand access to tele-rehabilitation and to advance policies that include physical therapists.

Read more about the VERITAS project and at ClinicalTrials.gov.

Tags

#telehealth, #pctGR, @Collaboratory1

April 5, 2019: The ENGAGES Pragmatic Trial and the Power of Negative Thinking (Michael S. Avidan, MBBCh)

Speaker

Michael S. Avidan, MBBCh
Dr. Seymour and Rose T. Brown Professor of Anesthesiology
Chief, Division of Clinical and Translational Research
School of Medicine, Department of Anesthesiology
Washington University in St. Louis

Topic

The ENGAGES Pragmatic Trial and the Power of Negative Thinking

Keywords

Pragmatic clinical trial; Surgery; Electroencephalography; EEG-guided anesthesia; Postoperative delirium; Older patients; Patient-centered outcomes; ENGAGES

Key Points

  • The ENGAGES pragmatic trial evaluated whether electroencephalogram-guided anesthetic administration decreases postoperative delirium incidence in older patients undergoing major surgery.
  • Delirium is a disturbance in consciousness or change in cognition for a short period of time as a consequence of a medical illness. 25% to 50% of older adults experience delirium after major surgery, and the number is even higher for ICU patients.
  • The ENGAGES trial found that, among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium.

Discussion Themes

Aside from the intensity of patient follow-up and the expertise needed to deliver the EEG-guided protocol, the ENGAGES study fulfilled the criteria for a pragmatic clinical trial as shown in PRECIS-2 ratings.

Clinicians participating in ENGAGES were not researchers but carried out the intervention on the ground. They understood the appeal of it and found it easy to implement.

With respect to study findings, instead of referring to “negative” or “null” findings, why not say, “this is what we found and these are interesting findings.”

Learn more about the results of the ENGAGES trial in JAMA (Feb 2019).

Tags

#delirium, #pctGR, @Collaboratory1, @WUSTL_med

March 29, 2019: ICD-Pieces: Lessons Learned in an Ongoing Trial (Miguel Vazquez, MD, George (Holt) Oliver, MD, PhD)

Speakers

Miguel A. Vazquez, MD
Professor of Medicine
Clinical Chief Nephrology Division
UT Southwestern Medical Center

George (Holt) Oliver, MD, PhD
Vice President Clinical Informatics
Parkland Center for Clinical Innovation

Topic

ICD-Pieces: Lessons Learned in an Ongoing Trial

Keywords

Multiple chronic conditions; Chronic kidney disease; Hypertension; Diabetes; Pieces™; Electronic health record; Parkland Center for Clinical Innovation; Primary care; U.S. Department of Veterans Affairs

Key Points

  • Improving Chronic Disease Management with Pieces™ (ICD-Pieces) is an NIH Collaboratory Demonstration Project that is implementing a novel technology platform (Pieces) to enable the use of electronic health record data in the management of chronic kidney disease, diabetes, and hypertension within primary care practices.
  • The aim of the study is to reduce hospitalizations, emergency department visits, readmissions, and cardiovascular events and deaths for patients with multiple chronic conditions.
  • ICD-Pieces is employing centralized clinical decision support across 4 large, diverse healthcare systems in addition to the use of Practice Facilitators within primary care.

Discussion Themes

In embedded pragmatic clinical trials conducted in real-world settings, it is important to anticipate changes over the course of the study, which could involve changes at every level, from staff turnover to changes in national policies or standards.

As one of the largest healthcare providers in the world for patients with chronic kidney disease, the VA has been an effective healthcare system partner in the ICD-Pieces trial.

When partnering with healthcare systems, it is important to align goals and plan together, minimize disruption, anticipate and adapt to changes, and create a sustainable foundation for future studies.

Learn more about ICD-Pieces on their website.

Tags

#pctGR, @Collaboratory1

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