Janet Prvu Bettger, ScD, FAHA
Duke Department of Orthopaedic Surgery
Duke Clinical Research Institute
The VERITAS Trial: Virtual Exercise Rehabilitation at the Intersection of Evidence, Implementation, and Policy
Rehabilitation; Virtual physical therapy; Patient outcomes; Physical therapy; Orthopaedic surgery; Total knee replacement; Digital technology; Telehealth
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.
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.
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
The ENGAGES Pragmatic Trial and the Power of Negative Thinking
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.
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.”
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
ICD-Pieces: Lessons Learned in an Ongoing Trial
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
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.
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.
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.
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?
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.
“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).
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
Promoting Effective Advance Care Planning Communication in the Elderly: The ACP-PEACE Trial
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
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.
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.
Niteesh K. Choudhry, MD, PhD
Professor, Harvard Medical School
Executive Director, Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital
Cluster Randomized Trials in Health Care Delivery Systems: Lessons from STIC2IT
STIC2IT; Pragmatic clinical trial; Learning health system; Cluster randomization; Medication adherence; Telepharmacy; Electronic health record; Stakeholder engagement
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.
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.
Renee Mitchell, MT(ASCP), CLS(NCA)
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
MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients
Medical devices; Real-world evidence; Medical Device Epidemiology Network; MDEpiNet; Unique device identifier; UDI
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.
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.
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.