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 21, 2019: Living Textbook Offers New Content on Design and Analysis of Pragmatic Clinical Trials

Members of the NIH Collaboratory’s Biostatistics and Study Design Core contributed 3 new sections to the Living Textbook exploring issues in the design and analysis of pragmatic clinical trials. The new sections offer insights into emerging issues in embedded pragmatic clinical trials and lessons learned from the NIH Collaboratory’s first round of Demonstration Projects.

  • The Designing to Avoid Identification Bias section addresses a type of selection bias that can occur in pragmatic clinical trials that use information from electronic health records to determine study population eligibility and in which the study intervention influences who undergoes screening or receives a diagnosis in clinical care.
  • The Alternative Cluster Randomized Designs section describes alternative design choices for cluster randomized trials and their implications for statistical power and sample size calculations. Modified cluster randomized designs, such as cluster randomization with crossover, may reduce the sample size required for a pragmatic clinical trial and may be particularly feasible in trials embedded in healthcare systems with electronic health records.
  • Case Study: STOP CRC Trial explores challenges in design and analysis that were faced in the Strategies and Opportunities to Stop Colorectal Cancer in Priority Populations (STOP CRC) trial, one of the NIH Collaboratory Demonstration Projects. The case study illustrates how the study team dealt with pragmatic issues during the planning and conduct of the trial.

In addition to contributing content to the Living Textbook, the Biostatistics and Study Design Core works with the NIH Collaboratory Demonstration Projects to address challenges in their statistical plans and study designs during the planning phase and to develop guidance and technical documents related to study design and biostatistical issues relevant to pragmatic clinical trials.

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 7, 2018: Cluster Randomized Trials in Health Care Delivery Systems: Lessons from STIC2IT (Niteesh K. Choudhry, MD, PhD)

Speaker

Niteesh K. Choudhry, MD, PhD
Professor, Harvard Medical School
Executive Director, Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital

Topic

Cluster Randomized Trials in Health Care Delivery Systems: Lessons from STIC2IT

Keywords

STIC2IT; Pragmatic clinical trial; Learning health system; Cluster randomization; Medication adherence; Telepharmacy; Electronic health record; Stakeholder engagement

Key Points

  • STIC2IT, a pragmatic, cluster-randomized trial, evaluated a telepharmacy intervention to improve medication adherence for people with chronic diseases.
  • Pragmatic aspects of STIC2IT included outcomes assessed using routinely collected data, cluster randomization by physician practice, intention-to-treat analysis, and use of the EHR to collect research data.
  •  While medication adherence did improve in the STIC2IT intervention group, secondary clinical outcomes did not improve. Future trials within health systems should incorporate multilevel engagement across the health system, physicians and staff, and patients.

Discussion Themes

It is important to do ongoing outreach at the health system leadership level to ensure understanding and commitment to the study and keep providers aware of the trial. Study teams should be mindful of the priorities of their partner health system.

Using the EHR for research data required some upfront work building special modules and generating custom reports.

For more information on conducting PCTs in health delivery systems, visit the Living Textbook chapter on engaging stakeholders and building partnerships.

Tags

@Collaboratory1, #pctGR, #HarvardMed, #telepharmacy

November 2, 2018: EMBED Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder (Ted Melnick, MD, Gail D’Onofrio, MD)

Speakers

Ted Melnick, MD, MHS
Assistant Professor of Emergency Medicine
Program Director, ACGME Clinical Informatics Fellowship
Yale School of Medicine

Gail D’Onofrio, MD
Professor and Chair of Emergency Medicine, Yale School of Medicine
Physician-in-Chief of Emergency Services Yale-New Haven Hospital

Topic

EMBED: Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder

Keywords

EMBED; Embedded PCT; Pragmatic clinical trial; Opioid use disorder; Clinical decision support; Emergency department; Buprenorphine

Key Points

  • The EMBED pragmatic trial is evaluating a clinical decision support tool designed to automatically identify and facilitate management of eligible patients with opioid use disorder in the emergency department (ED).
  • From July 2016 to Sep 2017, there was a 30% increase in visits to the ED for opioid overdose (Morbidity and Mortality Weekly Report, March 9, 2018).
  • With medication-assisted treatment, patients are 2 times more likely to be engaged in addiction treatment at 30 days.
  • EMBED’s user-centered design aims to streamline workflows, address barriers to adoption, embed ED-initiated buprenorphine into routine ED care, and optimize adoption, dissemination, implementation, and scalability.

Discussion Themes

Poor usability of health information technology (HIT) is major source of frustration for clinicians. Electronic health record usability is a fundamental barrier to implementation of evidence-based medicine.

The science of usability in healthcare is still in the early stages. The EMBED study wants to improve the HIT experience.

How much does the study rely on EHR data for outcomes, and how detailed are the pilot outcomes data requested from each system? How do you plan to verify the accuracy of those data?

For more information on treatment of opioid use disorder in the emergency department, visit the National Institute on Drug Abuse (NIDA) website’s Initiating Buprenorphine Treatment in the Emergency Department.

Tags

@Ted_Melnick, @DonofrioGail, @yaleem2, @YaleMed, @Collaboratory1, #pctGR, #EmergencyMedicine

October 29, 2018: NIH Collaboratory Distributed Research Network Used to Analyze Abnormal Cancer Screening & Follow-up Rates in >6 Million People

In a new article in the Journal of General Internal Medicine, over 100 million person-years of curated claims data were evaluated to assess new rates and follow-up procedures for colorectal, breast, and cervical cancer. These observational data were collected from national and regional insurers participating in the NIH Collaboratory distributed research network. The proportion of abnormal screening results was consistent with rates reported from a cancer-specific screening consortium (1.8–7.7 for colorectal cancer, 23.8–26.0 for breast cancer, and 9.5–18.2 for cervical cancer).

“A strength of this analysis is its employment of a reusable analysis program executing against standardized and curated, routinely collected electronic data from various institutions to enable rapid, privacy-protecting, cost-efficient assessment of practice.” —Raman et al. JGIM 2018

October 12, 2018: MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients (Renee Mitchell, MT, CLS, Terrie Reed, MSIE, Roseann White, MA)

Speakers

Renee Mitchell, MT(ASCP), CLS(NCA)
Regulatory Affairs
Boston Scientific Corporation, Inc.

Terrie Reed, MSIE
Senior Advisor for UDI Adoption
U.S. Food and Drug Administration (FDA)

Roseann White, MA
Director of Innovative Clinical Trial Statistics
Duke Clinical Research Institute

Topic

MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients

Keywords

Medical devices; Real-world evidence; Medical Device Epidemiology Network; MDEpiNet; Unique device identifier; UDI

Key Points

  • In partnership, clinicians, device developers, and FDA can benefit from the use of real-world evidence on medical devices:
    •  Clinicians can contribute to the generation of real-world evidence.
    •  Device manufacturers can use real-world evidence to evaluate and release new devices and expand indications.
    •  Regulatory bodies can increase the use of patient-level data for device approval.
  • Unique device identifiers (UDIs) make it possible to follow medical devices longitudinally, advancing the quality of real-world evidence and allowing more sophisticated analyses.

Discussion Themes

The vision for the future is that registries will transform into big data solutions using multiple sources and will be more robustly integrated with electronic health records (EHRs). Both EHRs and registries will play a role.

More organizations as partners brings greater diversity, advancing better data and results. When stakeholders work together, learning curves can be accelerated toward a transformational approach to real-world evidence.

Tags

#MedicalDevices, #pctGR, @PCTGrandRounds, @Collaboratory1, @MDEpiNet_ppp

August 28, 2018: Spotlight on a New Demonstration Project: Nudge

More than half of patients with prescriptions for cardiovascular medications do not take their medications as prescribed. These patients are at greater risk of death and comorbid conditions and have higher healthcare costs. Strategies to improve medication adherence have had mixed results. Meanwhile, advances in mobile and digital technologies for health promotion and disease self-management offer new opportunities to influence patients’ health behaviors and improve health outcomes.

“One of the real benefits of using technology is that it can be widely disseminated. Studying that dissemination process is really where we are in the field. So a pragmatic trial makes a lot of sense.” — Sheana Bull, PhD, MPH

The NIH Collaboratory is pleased to welcome the Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications (Nudge) study to its portfolio of Demonstration Projects. The Nudge study will use mobile phone text messages and an artificial intelligence chatbot to deliver behavioral “nudges” to patients to improve medication adherence. The study will access population-level pharmacy data in 3 integrated healthcare delivery systems to test the effectiveness of the nudges on adherence and outcomes among patients with chronic cardiovascular conditions who take medications to treat hypertension, atrial fibrillation, coronary artery disease, diabetes, or hyperlipidemia.

The Nudge study is led by co–principal investigators Drs. Sheana Bull and Michael Ho of the University of Colorado with support from the National Heart, Lung, and Blood Institute. Watch a video interview with Drs. Bull and Ho, and read more about Nudge.

 

August 20, 2018: Spotlight on a New Demonstration Project: EMBED

The NIH Collaboratory is pleased to introduce the Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder (EMBED). Led by co–principal investigators Dr. Ted Melnick and Dr. Gail D’Onofrio of Yale University, and supported by the National Institute on Drug Abuse, EMBED is a pragmatic, multicenter, group-randomized trial that will implement and evaluate a user-centered clinical decision support tool to facilitate the initiation of buprenorphine/naloxone therapy for opioid use disorder in emergency departments.

The intervention consists of computerized treatment guidance for emergency department physicians and is embedded in the existing care delivery workflow. By conducting the study under real-world conditions and employing passive collection of structured data from the electronic health record, EMBED will use an innovative approach to address public health concerns about opioid use in the United States. Watch a video interview with Dr. Melnick, and read more about EMBED.

“This is an area where there is already good efficacy data for the practice of ED-initiated buprenorphine treatment for patients with opioid use disorder, but the practice is not part of routine care right now.” — Ted Melnick, MD, MHS

 

EMBED is 1 of 6 new large-scale clinical trials launched by the NIH Collaboratory in 2018. The Demonstration Projects are multicenter pragmatic trials that engage healthcare delivery systems in research partnerships to gather real-world evidence and answer clinical questions of major public health importance. Learn more about the Demonstration Projects.