March 13, 2019: PROVEN Publishes Study of Nursing Home Characteristics Associated With Implementation of an Advance Care Planning Video Intervention

The Collaboratory Demonstration Project Pragmatic Trial of Video Education in Nursing Homes (PROVEN) is testing the effectiveness of a novel advance care planning (ACP) video education program in 360 nursing homes within 2 large nursing home healthcare systems. The investigators of PROVEN recently published a study that examines the characteristics of nursing homes associated with implementation of the video. They found that lower quality nursing homes (rated 1 star) had lower offer rates than higher quality nursing homes, suggesting that ongoing support might be necessary in these settings, as well as engagement with a local champion.

ACP is a process by which individuals define their future goals and preferences for medical treatment at the end of life and discuss these goals with their family and healthcare providers. ACP is especially important for nursing home residents, who often receive unnecessary care and experience burdensome transitions at the end of life. The ACP intervention in PROVEN is delivered by an onsite champion at the facility—usually a social worker with structured training in how and when to offer and show the ACP videos to residents and families.

 “These results have implications for future pragmatic trials in the NH [nursing home] setting because ongoing engagement between research and NH staff appears crucial for successful integration of interventions into routine clinical practice. Future research is needed to understand how to best engage NHs in implementation and encourage communication between NHs to share pragmatic strategies for improving clinical practice without the support of research staff.”

– Loomer et al. Journal of the American Medical Directors Association

March 6, 2018: Results of the Active Bathing to Eliminate (ABATE) Infection Trial Published in The Lancet

The Active Bathing to Eliminate (ABATE) Infection trial compared routine bathing to decolonization with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. Similar interventions have been found to reduce multidrug-resistant pathogens and bloodstream infections in intensive care units (ICUs), and this was the first large-scale trial in non-critical-care units. The primary outcome was methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE) clinical cultures attributed to participating units.

“We found that universal decolonization did not reduce infection in the overall population, but in post-hoc analyses of patients with medical devices the regimen was associated with significant reductions in all-cause bloodstream infections and MRSA or VRE clinical cultures.” —Huang et al. The Lancet 2019

The ABATE Infection trial was a large-scale pragmatic trial involving approximately189,000 patients in the baseline period and 340,000 patients in the intervention period across 194 non-critical-care units in 53 hospitals. The trial was one of the first NIH Collaboratory Demonstration Projects, and in keeping with the Collaboratory’s mission, the investigators have helped expand the knowledge base about the design, conduct, and dissemination of pragmatic clinical trials.

March 5, 2019: New Living Textbook Section on Using Death as an Endpoint

Using death as an endpoint in pragmatic clinical trials is challenging because there are no standardized processes for ascertaining patient deaths in the United States. If a patient dies outside of a clinical care system, ascertaining if and how a death has occurred is considerably complicated. There are multiple sources of vital statistics data, each with different amounts of lag time, linking approaches, costs, and specificity of information. For example, some sources include cause of death while others include only fact of death; some have a lag time of a few months and some may take over a year; some charge by the individual file and some have an annual subscription fee.

This section of the Living Textbook describes different death data sources, how to obtain information from them, and the pros and cons of each.

“Death identification and adjudication may be more complicated with pragmatic clinical trials (PCTs) that rely on data collected from the patient’s electronic health record (EHR), medical claims, self-report, or medical devices.” —Eisenstein E, et al. Choosing and Specifying Endpoints and Outcomes: Using Death as an Endpoint. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials.

The sources of data described in this section include the Death Master File, the Medicare Master Beneficiary Summary File, state vital statistics, the Fact of Death File, the National Death Index, and call centers. The section also presents a case study to illustrate a hybrid death identification and verification approach used in the ToRsemide compArisoN with furoSemide FOR Management of Heart Failure (TRANSFORM-HF) PCT (ClinicalTrials.gov Identifier: NCT03296813).

 

March 1, 2019: Approaches to Patient Follow-Up for Clinical Trials: What’s the Right Choice for Your Study? (Keith Marsolo, PhD)

Speaker

Keith Marsolo, PhD
Department of Population Health Sciences
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Approaches to Patient Follow-Up for Clinical Trials: What’s the Right Choice for Your Study?

Keywords

Pragmatic clinical trial; Real-world data; Distributed research network; Electronic health records; EHR; Health data sources; Data standardization; Common data model; Fast Healthcare Interoperability Resources (FHIR); Application programming interface (API)

Key Points

  • Different sites have different capabilities and levels of sophistication around data. Clinical trial investigators should think from the beginning about the questions they want to answer and how much data is needed.
  • From different sources, such as the EHR, claims, or participant, data can be procured and provided in different ways, either by the patient, staff or clinician, or through IT and data experts.
  • PCTs with many sites may require a “patchwork quilt” of approaches for patient follow-up depending on the needs of the trial. Clinician-generated reports, direct from patients, and solutions involving application programming interfaces (APIs) are all good options for data exchange.

Discussion Themes

How do we think through the options for getting patient data where some sites may not be in the distributed research network or use a common data model?

Fast Healthcare Interoperability Resources (FHIR) is a draft standard describing data formats and elements and an application programming interface (API) for exchanging electronic health records. The FHIR interface requests data as an object, and for each defined domain it specifies allowable values and variables and predefines the information that you get out of the system.

Until data are collected/generated using the same standards/formats as the API, there will still be a need to understand the EHR-to-interface mapping.

For more information on using health data in embedded pragmatic clinical trials, visit the NIH Collaboratory’s EHR Core webpage.

Tags

#CommonDataModel, #RealWorldData, #FHIR, #pctGR, @Collaboratory1

February 1, 2019: Promoting Effective Advance Care Planning Communication in the Elderly: The ACP-PEACE Trial (James Tulsky, MD, Angelo Volandes, MD, MPH)

Speakers

James Tulsky, MD
Chair, Department of Psychosocial Oncology and Palliative Care
Dana-Farber Cancer Institute
Professor of Medicine, Harvard Medical School
Chief, Division of Palliative Medicine
Brigham and Women’s Hospital

Angelo Volandes, MD, MPH
Associate Professor of Medicine
Massachusetts General Hospital
Harvard Medical School

Topic

Promoting Effective Advance Care Planning Communication in the Elderly: The ACP-PEACE Trial

Keywords

Pragmatic clinical trial; Advance care planning; ACP PEACE; Dana-Farber Cancer Institute; National Institute on Aging; Palliative care; Video declarations; Goal-concordant care; Patient preferences

Key Points

  • Many people with serious illness die without receiving goal-concordant care, and patients over the age of 65 with cancer experience this disproportionately. Helping patients engage in advance care planning (ACP) can empower them to express and record their goals so that their care can be aligned with their preferences.
  • The ACP PEACE Demonstration Project is a pragmatic, stepped-wedge, randomized trial of a comprehensive ACP program in oncology clinics at 3 health systems. It will involve a combination of 2 evidence-based programs:
    • VitalTalk teaches clinicians important communication skills in having empathic conversations with seriously ill patients.
    • ACP Decisions uses videos to promote planning and decision-making by patients and families.
  • The ACP PEACE study will monitor long-term outcomes to evaluate whether patients received the care they planned for and wanted.

Discussion Themes

The last element of the ACP PEACE trial is a video declaration (ViDec), recorded by a subset of patients. In recording the ViDec, patients are prompted by questions assessing their confidence with their decision, satisfaction, decisional regret, and patient-provider experience.

The ACP PEACE study team has a scaling strategy in place if the intervention proves effective. Implementing the intervention as standard of care will involve a culture shift from what is currently expected in health systems.

Read more about the ACP PEACE Demonstration Project in the Living Textbook.

Tags

#AdvanceCarePlanning, #pctGR, @Collaboratory1 @VitalTalk, @ACPDecisions

January 22, 2019: New Self-Paced ePCT Training Course Available

The NIH Collaboratory is pleased to announce the availability of a new self-paced, 10-module introductory course on how to design, conduct, and disseminate embedded PCTs (ePCTs). This course presents condensed material from the inaugural ePCT Training Workshop held in 2018 and provides users with important things to know and do when designing an ePCT, along with helpful links to additional learning resources within the Living Textbook.

Also available in the Living Textbook are links to videocast workshops hosted by the NIH on a range of ePCT topics including:

  • Embedded PCTs of therapeutic A versus B interventions
  • Unique opportunities for disseminating, implementing, and sustaining evidence-based practices into clinical care
  • Ethical and regulatory issues of PCTs

For these and other ePCT resources, visit the Training Resources webpage.

January 11, 2019: FDA Releases Framework for Evaluating the Use of Real-World Evidence

To help fulfill the requirements of the 21st Century Cures Act by accelerating medical product development and fostering innovation and advances in medicine, FDA recently created a framework for evaluating the use of real-world evidence. The framework is intended to help evaluate trials that use real-world data for the creation of real-world evidence.

  • Real-world data: routinely collected information about a person’s health status in the electronic health record, claims, registries, and other sources, including patient-generated sources.
  • Real-world evidence: reliable, clinical information derived from real-world data about risks, benefits, and burdens of therapies.

This framework will apply to various pragmatic clinical trials embedded in health care systems and conducted as part of routine care (and will not apply to more traditional clinical trials conducted parallel to care).

Three main considerations are included in the framework:

  1. Will the real-world data be fit for use (do they reliably and adequately represent the concept)?
  2. Will the evidence generated by the trial provide adequate evidence to help answer regulatory questions?
  3. Will the conduct of the study meet FDA regulatory requirements?

January 4, 2019: TRANSFORMing Research for Patients With Heart Failure (Robert Mentz, MD, Kevin Anstrom, PhD, Eric Eisenstein, DBA, Stephen Greene, MD, Eric Velazquez, MD)

Speakers

Robert J. Mentz, MD
Associate Professor of Medicine
Duke University School of Medicine

Kevin J. Anstrom, PhD
Professor of Biostatistics and Bioinformatics
Director of Biostatistics, Duke Clinical Research Institute
Duke University School of Medicine

Eric Eisenstein, DBA
Associate Professor in Medicine
Duke University School of Medicine

Stephen J. Greene, MD
Fellow, Division of Cardiology and Duke Clinical Research Institute
Duke University School of Medicine

Eric J. Velazquez. MD, FACP, FACC, FASE, FAHA
Robert W. Berliner Professor of Medicine, Yale University
Chief, Cardiovascular Medicine, Yale New Haven Hospital
Physician-in-Chief, Heart and Vascular Center, Yale New Haven Health

Topic

TRANSFORMing Research for Patients With Heart Failure

Keywords

Pragmatic clinical trial; Heart failure; PRECIS-2; Hospitalization; TRANSFORM-HF; Clinical equipoise; Electronic health records; National Heart, Lung, and Blood Institute (NHLBI)

Key Points

  • The traditional approach to conducting clinical trials is unsustainable in many respects, including operational complexities, low enrollment rates, high costs, and failure to leverage existing resources. Incorporating pragmatic elements in the design of trials may improve efficiencies and conduct.
  • TRANSFORM-HF is a pragmatic trial evaluating torsemide versus furosemide treatment for long-term clinical outcomes among patients hospitalized for heart failure. Study randomization is 1:1, and the primary endpoint is all-cause mortality.
  • Advantages of trials with pragmatic designs include real-world effectiveness; broad patient/provider groups; reduced number and complexity of visits; streamlined data collection; potential for faster results; and results that will be more generalizable.

Discussion Themes

The clinical question involving starting a treatment (Should we start with furosemide or torsemide?) versus switching a treatment (Should we attempt to switch patients from furosemide to torsemide?) would seem to lead to different study designs.

While the peer review process for funding TRANSFORM-HF was challenging and required modifying the approach, it ultimately led to a better design.

Read more about PRECIS-2 domains along the explanatory-pragmatic continuum of a clinical trial in the Living Textbook.

Tags

#HeartFailure, #pctGR, @Collaboratory1, @robmentz, @SJGreene_md, @YaleCardiology, @ericjvelazquez

December 13, 2018: New Living Textbook Chapter: Developing a Compelling Grant Application

A new chapter in the Living Textbook provides expert advice for investigators submitting an application for a pragmatic clinical trial to the NIH. The chapter covers finding the right Program Official and opportunity announcement, writing a strong proposal, addressing review criteria, and award status.

“First and foremost, develop and clearly define a clinical research question with a testable hypothesis and then select an experimental design best suited to answering the research question. The study question drives the research design.” —From Developing a Compelling Grant Application

Dr. Wendy Weber, the Program Officer for the NIH Collaboratory Coordinating Center, and Dr. Marcel Salive, a Program Officer from the National Institute on Aging, contributed to this chapter.

December 11, 2018: Two New NIH Funding Opportunity Announcements for Pragmatic Trials Address the Opioid Crisis

The NIH has announced two new funding opportunity announcements (FOAs) for 7 or more embedded pragmatic clinical trials that address pain management and the opioid crisis. These projects will become part of the NIH Health Care Systems Research Collaboratory as phased UG3/UH3 cooperative research.

The two announcements are:

The announcements are part of the NIH Heal (Helping to End Addiction Long-term) Initiative, which was created in April 2018 in an effort to speed scientific solutions for addressing the national opioid public health crisis.