June 27, 2022: Special Edition of Contemporary Clinical Trials Offers New Perspectives on Pragmatic and Virtual Clinical Trials

Contemporary Clinical TrialslsA special series of articles addressing pragmatic and virtual trials appears this week in the journal Contemporary Clinical Trials and offers practical approaches to the many challenges clinical trials face.

The 14 articles bring together leaders, researchers, biostatisticians, and bioethicists—including members of the NIH Pragmatic Trials Collaboratory—who are rethinking key aspects of the development, conduct, and oversight of clinical trials.

The articles include recommendations and real-world experience on how clinical trials can be done better while maintaining high-quality results using digital technology, direct-to-participant methods, and electronic health records.

The special issue can be found on the Contemporary Clinical Trials website.

Adrian F. Hernandez, MD, MHS, a co-principal investigator for the NIH Pragmatic Trials Collaboratory Coordinating Center, and Tammy Reece, MS, PMP, CCRA, the program’s project director, served as the issue co-editors. Dr. Hernandez is also vice dean and executive director of the Duke Clinical Research Institute and professor of medicine at Duke University. Ms. Reece is a Senior Project Leader in the Government Trials and Networks Group at the Duke Clinical Research Institute.

Following an introduction written by Hernandez, the remaining 13 articles focus on topics including simplification by design, digital technologies and clinical trials, iterative approaches to the use of electronic health records data for large pragmatic studies, ethics and regulatory considerations, and lifestyle and behavioral modification trials.

This body of work offers pragmatic approaches to overcoming the many reasons clinical trials are underperforming, such as high financial costs, long duration, administrative complexity, low recruitment and retention of participants, and difficulty translating knowledge to actual medical care.

“The articles in this issue recognize advances in evidence generation while sharing the challenges and gaps that still need to be addressed,” Hernandez said. “Ultimately, the clinical research ecosystem must improve, not only to keep pace with the advances in science, but to improve public health in meaningful ways.”

“The NIH Pragmatic Trials Collaboratory has been working to re-engineer clinical trials for a decade, yet there is still progress to be made,” Reece said. “Sharing knowledge and innovations across disciplines is critical to continue the momentum of transformation toward a learning health system.”

February 25, 2022: The Next Generation of Patient-Centered Trials – No Site Visits, Home-delivery of Meds and Patient-reported Outcomes – The CHIEF-HF Trial (John Spertus, MD, MPH, FACC, FAHA)

Speaker

John Spertus, MD, MPH, FACC, FAHA
Daniel Lauer/Missouri Endowed Chair and Professor
University of Missouri – Kansas City
Clinical Director of Outcomes Research
Saint Luke’s Mid America Heart Institute

Keywords

Heart failure; Canagliflozin; INVOKANA; Kansas City Cardiomyopathy Questionnaire (KCCQ); tele-health; tele-trials

Key Points

  • The CHIEF-HF trial (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) was a double blind randomized clinical trial of the medication Canagliflozin for heart failure.
  • CHIEF-HF was designed to learn if patients have fewer symptoms after 3 months of treatment with Canagliflozin.
  • CHIEF-HF used a novel trial design that involved no site-visits and electronic monitoring of patient engagement. The follow up rate for this study was over 97%.
  • The Total Symptom Score on the KC Cardiomyopathy Questionnaire was the key outcome measure in the CHIEF-HF Trial.
  • Heart failure patients treated with Canagliflozin experienced a statistically significant improvements in symptoms.
  • Sites in the study chose recruitment methods that worked best for them. More personalized recruitment strategies were most successful.
  • Difficulties of electronic trials include the technology limitations of the participants, and electronic consent concerns from regulatory agencies. Positives of electronic trials are high enrollment and completion rates.

Discussion Themes

How do technology heavy studies enroll diverse and underserved populations who may not have access to smartphones and wearable technology?

Virtual studies such as this that enrolled at 6 to 8 times the rate on a traditional trial can save quite a bit of money on overhead expenses.

 

Read more about the CHIEF-HF trial.

 

Tags

#pctGR, @Collaboratory1

January 27, 2022: Grand Rounds Podcast Now Available, Featuring Dr. Chris Lindsell on Selecting Outcomes for Outpatient Trials

Headshot of Dr. Christopher John LindsellIn the latest episode of the NIH Collaboratory Grand Rounds podcast, Dr. Christopher Lindsell and Dr. Adrian Hernandez continue the discussion about research outcomes and the importance of understanding stakeholder perspectives in choosing the correct outcomes for outpatient trials.

The full January 14 Grand Rounds webinar with Dr. Lindsell is also available.

January 14, 2022: Searching for a Unicorn: Understanding Stakeholder Perspectives When Selecting Outcomes for Outpatient Trials (Christopher Lindsell, PhD)

Speaker

Christopher Lindsell, PhD
Professor of Biostatistics and Biomedical Informatics
Director, Vanderbilt Institute for Clinical and Translational Research (VICTR) Methods Program
Codirector, Vanderbilt Health Data Science (HEADS) Center

Topic

Searching for a Unicorn: Understanding Stakeholder Perspectives When Selecting Outcomes for Outpatient Trials

Keywords

Research outcome; Outpatient clinical trials; Patient-reported outcomes; Researcher-observed outcomes; Pragmatic trials; ACTIV-6; Days of benefit; Mean time unwell

Key Points

  • A research outcome is the main piece of data used to decide if the research intervention has failed or succeeded.
  • If the incorrect outcome is chosen, the question of whether the intervention has succeeded can’t be answered accurately. Finding the correct outcome requires asking the question ‘What matters?’
  • In studies that are designed to help you feel better faster, we may need to prioritize symptoms and signs (patient reported outcomes) over objective measures (researcher observed outcomes).
  • Outcomes should be chosen based on the purpose of the study.
  • Researchers need to balance sensitivity and specificity when choosing an outcome measure.
  • The ACTIV-6 study uses an overall symptom outcome scale to determine if patients ‘feel better faster.’
  • ACTIV-6 uses Days of Benefit and Time to Recovery/hospitalization and death as an outcome to determine if the intervention is successful.

Discussion Themes

It’s important to strive to complete the most powerful and efficient studies that we can do.

Having multiple medicines available that balance risk and benefit differently gives patients options for their treatment. Individual patients have differing levels of risk tolerance and different ideas about what is the most beneficial outcome.

 

Learn more about the ACTIV-6 study.

 

Tags

#pctGR, @Collaboratory1

Grand Rounds January 28: EMBED Trial Results: Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder

Speakers:
Edward R Melnick, MD, MHS
Associate Professor of Emergency Medicine, Yale School of Medicine
Associate Professor of Biostatistics (Health Informatics), Yale School of Public Health
Program Director, Yale-VA Clinical Informatics Fellowship Program

Gail D’Onofrio, MD, MS
Albert E. Kent Professor of Emergency Medicine
Yale School of Medicine
Professor of Public Health, Chronic Disease & Epidemiology
Yale School of Public Health

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

Date: Friday, January 28, 2022, 1:00-2:00 p.m. ET

Meeting Info: To check whether you have the appropriate players installed for UCF (Universal Communications Format) rich media files, go to https://dukemed.webex.com/dukemed/systemdiagnosis.php.

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December 3, 2021: Primary Care-Based Behavioral Treatment for Long Term Opioid Users with Chronic Pain: Primary Results and Lessons Learned from the PPACT Pragmatic Trial (Lynn DeBar, PhD MPH)

Speaker

Lynn DeBar, PhD MPH
Senior Scientist
Kaiser Permanente Washington Health Research Institute
Seattle, WA

Keywords

PPACT, Chronic pain, Opioid use, Patient reported outcome data, Patient-centered research, Cognitive behavioral therapy

Key Points

  • Chronic Pain is responsible for far more years lived with disability than a large number of other diseases and injuries, such as COPD, diabetes, dementia, stroke and others, combined.
  • PPACT was a cluster randomized study aimed at integrating interdisciplinary pain management methods into primary care to improve care for patients with chronic pain.
  • Participants had been prescribed long-term opioids for mixed chronic pain conditions.
  • Study intervention lasted 12 weeks and included cognitive behavioral therapy, yoga-based exercises, physical therapy, a medication review, and support from a primary care provider.
  • Participants in the treatment group of the PPACT study showed a modest reduction of pain that was sustained over a 12 month period.
  • The PPACT intervention was cost effective versus usual treatment methods.

Discussion Themes

An in-person enhanced enrollment session was conducted to give potential subjects a comprehensive overview of the study procedures. This enrollment session led to fewer people enrolling in the study, but of those that did, more completed the study.

The key to successful CBT is an interactive patient-centered approach.

 

Read more about the PPACT study.

 

Tags

#pctGR, @Collaboratory1

November 19, 2021: Exploring Approaches in Using Digital and Mobile Health in Patient-oriented Research: Pearls and Pitfalls (Anish K. Agarwal MD, MPH MS)

Speaker

Anish K. Agarwal MD, MPH MS
Assistant Professor of Emergency Medicine
Clinical Innovation Manager, Penn Medicine Center for Health Care Innovation
University of Pennsylvania, Perelman School of Medicine

Topic

Exploring Approaches in Using Digital and Mobile Health in Patient-oriented Research: Pearls and Pitfalls

Keywords

Mobile health; Digital health; Patient-oriented research; Study design

Key Points

  • Digital and mobile health is a rapidly evolving field that integrates with the electronic health records in both low and high tech ways.
  • Dr. Agarwal conducted a randomized control trial of overweight veterans who had daily access to a smartphone or tablet. These participants were sent a wearable device to collect step count data.
  • An important consideration for studies using mobile health technology is participant access to a smart or mobile device. 85% of Americans have access to a Smartphone where 97% have access to a mobile device that can receive texts. 20% use a smartwatch.
  • Mobile methods are just tools to support overall study design.
  • Dr. Agrawal conducted a study on post-operative opioid prescribing and use. Data was gathered from participants via text messaging systems.
  • Simple text messages that are more conversational in nature are received better by the participant. Links in text messages should be limited. It’s important for participants to understand the privacy and security of their communications and data. Nudge a participant with a text at the right time to avoid being overbearing.

Discussion Themes

Let patients know that SMS is not secure, and frame questions to avoid patients sending HIPAA covered data via text.

A good relationship with your institutions Privacy and Safety office is fundamental to navigating IRB regulations for research with digital and mobile devices.

 

Read more about Dr. Agarwal’s studies using mobile health devices: Effect of Gamification With and Without Financial Incentives to Increase Physical Activity Among Veterans Classified as Having Obesity or Overweight: A Randomized Clinical Trial and Patient-Reported Opioid Consumption and Pain Intensity After Common Orthopedic and Urologic Surgical Procedures With Use of an Automated Text Messaging System.

 

Tags

#pctGR, @Collaboratory1

November 12, 2021: Using Financial Incentives to Increase COVID-19 Vaccine Uptake (Charlene Wong, MD MSHP; Noel T. Brewer, PhD)

Speakers

Charlene Wong, MD MSHP
Associate Professor of Pediatrics and Public Policy
Duke University School of Medicine
Chief Health Policy Officer for COVID-19
North Carolina Department of Health and Human Services

Noel T. Brewer, PhD
Gillings Distinguished Professor in Public Health
Department of Health Behavior
Gillings School of Global Public Health
University of North Carolina
Member, Lineberger Comprehensive Cancer Center
University of North Carolina

Topic

Using Financial Incentives to Increase COVID-19 Vaccine Uptake

Keywords

COVID-19; Vaccine; Incentive; North Carolina DHHS

Key Points

  • The Summer Cash Card incentive program, run by the North Carolina Department of Health and Human Services from May 26 to June 8, 2021, offered $25 gift cards as an incentive to receive a COVID-19 vaccination and an additional $25 gift card to anyone transporting individuals to a vaccination site.
  • During the time period that the Summer Cash Card incentive program was running, 2 in 10 people indicated that they were likely to get vaccinated, but remained unvaccinated for reasons such as lost wages, lack of child care, and lack of transportation.
  • Other incentive programs used in North Carolina included drawings for larger cash prizes or college scholarships for teens.
  • Recipients of $25 gift cards completed a survey asking the importance of getting the $25 gift card in their decision to get vaccinated or drive someone to get vaccinated.
  • Results from the survey showed that the financial incentive was particularly important to Hispanic individuals and individuals with an annual income below $40,000.
  • During times when vaccine administration fell, incentive sites did not see the same drop in vaccination rates.
  • Incentives are effective if they are known, valued, contingent, certain, and immediate.

Discussion Themes

For many individuals cost or transportation issues are the main barrier to vaccination.

Financial incentives could be considered coercive, but the benefits to the individual and the community are broad and the risks low. The $25 incentive is a fair amount to cover the costs of lost wages and transportation that it takes to get to the vaccine clinic.

Focus for incentives is still on the remaining people who are not vaccinated at all rather than on those who need booster vaccines.

 

Read more about the North Carolina DHHS financial incentive program for COVID-19 vaccines. Read the JAMA paper published in October 2021.

 

Tags

#pctGR, @Collaboratory1

November 5, 2021: Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services: The BEST-MSU Study (James C Grotta, MD)

Speaker

James C Grotta, MD
Director Stroke Research and Mobile Stroke Unit
Memorial Hermann Hospital-Texas Medical Center
Houston, Texas

Topic

Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services: The BEST-MSU Study

Keywords

Stroke; BEST-MSU study; Mobile Stroke Unit; Patient-centered outcome; tPA

Key Points

  • We can improve stroke outcomes by giving tPA in the first hour after stroke onset, but to do this, we have to bring the treatment to the patient.
  • The Mobile Stroke Unit (MSU) is an ambulance equipped with a CT scanner and other medical care equipment necessary to treat stroke.
  • The BEST-MSU Study was a partially randomized trial that examined outcomes of patients who were treated by the MSU versus in the hospital emergency department.
  • The BEST-MSU study compared the diagnosis of telemedicine and onboard neurologists, and they agreed that the patient was having a stroke 88% of the time, which is the same as the agreement rate of two neurologists in the hospital setting.
  • For every 100 patients treated with the MSU rather than the standard medical practice in a hospital emergency setting, 27 will have less final disability and 11 more will be disability-free.

Discussion Themes

Consent to deliver treatment wasn’t necessary in this case because the treatment delivered was the standard of care. Consent to use the patient’s data was obtained in the emergency department after the patient had stabilized. Very few patients refused to consent.

Implementation of the MSU with the local fire departments was straight forward, but the politics of the area served was a challenge for implementation.

One barrier to treating stroke quickly with the MSU is the patient’s hesitancy to call 911. Calling emergency services needs to be made less threatening and less expensive to promote better patient outcomes.

 

Read more about The BEST-MSU study here and in the paper publish in September 2021 “Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.”

 

Tags

#pctGR, @Collaboratory1

November 9, 2021: PPACT Study Finds Benefits of Cognitive Behavioral Therapy in Reducing Chronic Pain and Pain-Related Disability

Photo of Dr. Lynn DeBar
Dr. Lynn DeBar, principal investigator of PPACT

Patients who participated in a cognitive behavioral therapy (CBT) intervention as part of their regular care for chronic pain showed improved function and reduced pain compared to standard treatment, according to the results of the Pain Program for Active Coping and Training (PPACT) study. Although CBT did not reduce opioid use, patients who participated in a 12-week course on pain self-management led by primary care providers showed modest but sustained benefits that persisted for 12 months after the intervention.

Study results were published this month in the Annals of Internal Medicine.

The PPACT study, an NIH Collaboratory Trial, was a pragmatic, cluster randomized trial that enrolled 850 patients receiving long-term opioid therapy for chronic pain. Patients in the intervention group participated in 12 weekly, 90-minute group sessions that taught skills of muscle relaxation, guided imagery, cognitive restructuring, and yoga-based adapted movement. Patients in the usual care group continued to receive pharmacologic and nonpharmacologic treatment.

Figure from PPACT main outcomes paper
Source: Annals of Internal Medicine 2021 Nov 2. doi: 10.7326/M21-1436

Patients were followed for 12 months with primary outcome measures of pain impact on enjoyment of life, activity levels, and sleep. Researchers also assessed secondary outcome measures of pain-related disability and opioid use.

Compared to usual care, the CBT intervention reduced self-reported pain and pain-related disability and increased satisfaction with primary healthcare providers. Opioid use and dose remained the same in both the intervention group and the usual care group.

PPACT was supported within the NIH Collaboratory by the NIH Common Fund, the National Center for Complementary and Integrative Health (NCCIH), and the National Institute of Neurological Disorders and Stroke (NINDS). Learn more about the NIH Collaboratory Trials.