informed consent

January 20, 2021: New Article Explores Ethical Obligation to Monitor Signals of Behavioral and Mental Health Risk in Pragmatic Trials

Posted on by Karen Staman

In a new Contemporary Clinical Trialslsarticle, members of the Ethics and Regulatory Core of the NIH Pragmatic Trials Collaboratory explore the ethical obligation of investigators to address signals of behavioral and mental health risk in pragmatic clinical trials.

The article was published online ahead of print in Contemporary Clinical Trials and will appear in a forthcoming special issue on pragmatic and virtual trials.

Some pragmatic trials collect sensitive data that could signal distress, such as suicidal ideation, opioid use disorder, or depression. Investigators have an ethical obligation to monitor these signals and identify in advance if, when, and how such signals will trigger a response. Using examples from the NIH Collaboratory Trials, the authors offered preliminary recommendations and identified opportunities for future work.

The NIH Collaboratory Trials discussed in the article are supported by the PRISM program—Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing. The projects are studying the real-world effectiveness of nonpharmacologic interventions to improve pain management and reduce reliance on opioids.

Read the full article.

The PRISM program is a part of the Helping to End Addiction Long-Term Initiative℠, or NIH HEAL Initiative℠. The NIH Pragmatic Trials Collaboratory Coordinating Center serves as the PRISM Resource Coordinating Center.

January 7, 2022: D-PRESCRIBE-AD: A Pragmatic Trial to Educate and Sensitize Caregivers and Healthcare Providers to Reduce Inappropriate Prescription Burden in Persons Living with Dementia (Jerry H. Gurwitz, MD; Richard Platt, MD, MSc)

Posted on by terren.green@duke.edu

Speaker

Jerry H. Gurwitz, MD
Chief, Division of Geriatric Medicine
University of Massachusetts Medical School and UMass Memorial Medical Center
Executive Director, Meyers Health Care Institute
A joint endeavor of University of Massachusetts Medical School, Fallon Health, and Reliant Medical Group

Richard Platt, M.D., M.Sc.
President, Harvard Pilgrim Health Care Institute

Topic

D-PRESCRIBE-AD: A Pragmatic Trial to Educate and Sensitize Caregivers and Healthcare Providers to Reduce Inappropriate Prescription Burden in Persons Living with Dementia

Keywords

Distributed Research Network; Dementia; Alzheimer’s Disease; Deprescribing

Key Points

  • The Distributed Research Network, with 45 million members currently accruing new data, facilitates the conduct of multi-center research requiring access to full text medical records and the collection of patient-generated data.
  • Inappropriate prescribing can increase the likelihood of adverse drug events and may have a heightened impact for Alzheimer’s patients.
  • D-PRESCRIBE-AD study is a randomized educational intervention to improve medication safety among Alzheimer patients by discontinuing potentially inappropriate prescriptions.
  • The D-PRESCRIBE-AD study found incidents of prescribing cascades to be less common than expected in the AD population, but prescription of high-risk medications were relatively high.
  • The challenges of the D-PRESCRIBE-AD study are deciding who should receive the provider letter and who is the appropriate caregiver of the patient.

Discussion Themes

One challenge of a study of this nature is getting buy-in from primary care providers.

Randomization was attempted at the level of Metropolitan Statistical Areas, but challenges with this idea proved too great. Randomization was instead done at an individual level.

Multiple arms of the study were necessary to answer questions about primary care doctor buy-in for this type of study.

 

Learn more about partnering with the DRN.  Read more about. Read more about the D-PRESCRIBE-AD study.

 

Tags

#pctGR, @Collaboratory1

November 29, 2021: New Article From the NIH Collaboratory Examines Use of Incentives and Payments in Pragmatic Clinical Trials

Posted on by Damon Seils
Head shot of Dr. Andrew Garland
Dr. Andrew Garland

Members of the NIH Collaboratory’s Ethics and Regulatory Core examined the use of incentives and payments to patients included in pragmatic clinical trials. Their findings and preliminary recommendations are published in the December issue of Clinical Trials.

Incentives and payments to patients are used in both pragmatic trials and conventional explanatory trials. However, because pragmatic trials typically evaluate interventions in the context of “real-world” clinical settings, the use of incentives and payments can raise logistical, ethical, and regulatory challenges.

Dr. Andrew Garland, a postdoctoral fellow at the Johns Hopkins Berman Institute of Bioethics who works in the Ethics and Regulatory Core, and who is the lead author of the article, reviewed 9 NIH Collaboratory Trials that used incentives and other payments to patients. Garland and coauthors Dr. Kevin Weinfurt and Dr. Jeremy Sugarman used these examples to describe how the standard conceptual framework for ethical payments and incentives may not always be appropriate for pragmatic trials.

Read the full report.

This work was supported within the NIH Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. This work was also supported by the NIH through the NIH HEAL Initiative.

June 22, 2021: Diversity Workshop Continues With Meeting Participants Where They Are

Posted on by Damon Seils

The NIH Collaboratory is using its popular ePCT Grand Rounds platform for a special webinar series on diversity in pragmatic clinical trials.

In this Friday’s session—“Meeting Participants Where They Are – Outreach, Trust, and Consent to Maximize Diversity”—Dr. Wendy Weber of the National Center for Complementary and Integrative Health will host a panel of investigators for a discussion about strategies for maximizing participant diversity in pragmatic clinical trials by improving outreach and building trust.

The panel will include:

  • Dr. Jonathan Jackson, executive director of the Community Access, Recruitment, and Engagement (CARE) Research Center at Massachusetts General Hospital and Harvard Medical School
  • Dr. Judith Schlaeger of the University of Illinois at Chicago, co–principal investigator of GRACE, an NIH Collaboratory Demonstration Project
  • Dr. Stacy Sterling of the Kaiser Permanente Division of Research, Northern California, co–principal investigator of GGC4H, an NIH Collaboratory Demonstration Project

The Grand Rounds session will be held on Friday, June 25, at 1:00 pm eastern. Join the online meeting.

Other upcoming sessions in the diversity workshop series include:

All sessions are free and open to the public; no registration is required. Recordings will be archived on the Grand Rounds website.

Headshots of Emily O'Brien, Jonathan Jackson, Judith Schlaeger, and Stacy Sterling
Left to right: Drs. Emily O’Brien, Jonathan Jackson, Judith Schlaeger, and Stacy Sterling

April 23, 2021: COVID Clinical Trials: The Intermountain Healthcare Experience (Samuel M. Brown, MD, MS)

Posted on by Gina Uhlenbrauck

Speaker

Samuel M. Brown, MD, MS
Associate Professor and Director of Pulmonary/Critical Care Research
Intermountain Healthcare
Associate Professor, University of Utah

Topic

COVID Clinical Trials: The Intermountain Healthcare Experience

Keywords

COVID-19; Public health; Integrated health system; COVID-19 treatment trials

Key Points

  • Intermountain Healthcare is a nonprofit, community-based healthcare system that maintains an academic referral center and several hospitals in Utah.
  • During the pandemic, the health system was able to integrate COVID-19 research with urgent clinical, operational, and public health needs. The health system currently supports 15 randomized clinical trials in COVID-19 research, investigating immunologic and virologic therapies.
  • Collaboration and communication across divisions were essential elements to the successes achieved.
  • Among the challenges of conducting the COVID-19 trials, there remains a wish for a comprehensive risk management solution and regulatory reform.

Discussion Themes

Could we establish a robust program that provides better training and pay for study coordinators? These staff have direct contact with participants for recruitment and retention and can make or break a trial.

What aspects of institutional culture contributed to the success of conducting these trials?

What is needed is a clinical research ecosystem that appropriately balances regulatory oversight with the agility to answer urgent health questions.

Read more about Intermountain Healthcare’s experiences with COVID-19 clinical trials in these recent publications:

Tags

#pctGR, @Collaboratory1

October 9, 2020: Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) (Myles Wolf, MD)

Posted on by Gina Uhlenbrauck

Speaker

Myles Wolf, MD, MMSc
Division of Nephrology, Department of Medicine
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)

Keywords

End-stage renal disease; Hemodialysis; Serum phosphate; Patient-centered outcomes; NIDDK; Electronic health record; Cluster randomization; eConsent

Key Points

  • High serum phosphate is a ubiquitous complication in end-stage renal disease (ESRD), a serious illness that affects ~500,000 people in the United States. However, evidence is lacking for the best approach to reducing high phosphate that benefits survival in patients.
  • The hemodialysis setting is ideal for conducting a pragmatic trial because of an accessible study population, frequent clinical encounters, granular and uniform data collection via electronic health record (EHR), and the many unanswered questions about major aspects of dialysis care.
  • Pragmatic features of HiLo include:
    • Real-world setting
    • Cluster randomization
    • Broad entry criteria
    • Electronic informed consent
    • No traditional on-site study staff
    • Remote site monitoring
    • Outcomes based on EHR with no adjudication

Discussion Themes

The HiLo Ambassadors, a patient advisory group, have contributed to HiLo study materials including the protocol, informed consent form, eConsent script, informational videos, FAQs, flyer, and website content. They are providing strategies to help patients successfully participate and stay in the trial.

Dieticians are critical to the success of HiLo as they directly interact with dialysis patients and are among the most motivated caregivers on dialysis teams.

The onset of the COVID-19 pandemic came after the first week of HiLo site activation, causing a pause of trial activities and enrollment at the dialysis facilities.

What will success look like for the HiLo trial? A clear, proven answer to the question of higher versus lower target.

Read more about HiLo trial at the study website and the NIH Collaboratory Trials page.

Tags

#pctGR, @Collaboratory1

September 22, 2020: New Article Highlights Ethical and Regulatory Challenges of Conducting PCTs

Posted on by Gina Uhlenbrauck

Cover of Ethics & Human ResearchA recent article in Ethics & Human Research describes the experience and management of regulatory noncompliance during the conduct of a large, multisite embedded pragmatic clinical trial (ePCT). The Trauma Survivors Outcomes and Support (TSOS), an NIH Collaboratory Trial, was a stepped-wedge, cluster-randomized clinical trial of a collaborative care intervention for injured patients with symptoms of posttraumatic stress disorder in 25 level 1 trauma centers in the United States. The article, Ethical and Regulatory Concerns in Pragmatic Clinical Trial Monitoring and Oversight, was coauthored by members of the TSOS study team, the Collaboratory’s Ethics and Regulatory Core, and colleagues.

The authors describe how the study encountered variabilities in participant tracking across sites, which led to a study-wide internal audit and corrective action. The study team implemented a revision of the participant tracking system and retrained site staff in new procedures. Based on the lessons learned, the authors offer recommendations for future PCTs and relevant stakeholders, including institutional review boards, data safety and monitoring boards, institutions, and trial sponsors.

Among the recommendations:

  • Use a single IRB of record to streamline regulatory processes and reduce variability among research sites.
  • Standardize research procedures but allow for real-world flexibility; this could include real-time, workflow-integrated study logging that captures and documents provider turnover and regulatory training compliance.
  • Implement thorough, specific, and practical training in procedures, especially around participant enrollment and tracking.
  • Ensure that research procedures, monitoring and oversight plans, and training are study specific to account for unique issues, contexts, and needs.

Thoughtful planning, communication, and development and dissemination of standardized procedures remain hallmarks of successful research operations both to advance biomedical research and to ensure appropriate safeguards for its participants. –Roberts et al.

April 24, 2020: The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19 (Martin Landray, PhD, FRCP)

Posted on by Gina Uhlenbrauck

Speaker

Martin Landray, PhD, FRCP
Professor of Medicine & Epidemiology
Nuffield Department of Population Health
University of Oxford, UK

Topic

The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19

Keywords

Coronavirus; Virus pandemic; COVID-19; SARS-CoV-2; RECOVERY Trial; Randomized trial; Epidemiology

Key Points

  • Between March 10 and April 3, 2020, the RECOVERY team developed the protocol, obtained regulatory and ethics approval, and enrolled 1,000 patients.
  • COVID-19 presents an unprecedented clinical challenge to the health system, staff, and patients. Even moderate effects from this study will be worthwhile in the generation of robust evidence.
  • RECOVERY follow up will involve linkage to national data sources for vital status and death certificates; coded hospital episode statistics (diagnoses, procedures); intensive care audit data and SARS-CoV-2 PCR laboratory results; and primary care and national outpatient prescribing data.

Discussion Themes

Informed consent for participants in the RECOVERY trial consists of a 2-page information sheet and single form written in plain language.

The urgency of this pandemic requires everyone to focus on what matters and leave orthodoxy, habits, and traditional practices behind. Our mindset has been altered by the COVID-19 disruptions and this public health crisis of extraordinary proportion.

For more information, visit the RECOVERY Trial website.

Tags
#pctGR, #COVID19, @Collaboratory1

April 22, 2020: New Article Details the Design of ADAPTABLE, PCORnet’s First Pragmatic Trial

Posted on by Damon Seils

A new article in JAMA Cardiology discusses the design of ADAPTABLE, a pragmatic clinical trial (PCT) which strives to answer a three-decade-old question with great potential significance for public health. ADAPTABLE is the first PCT to use many of the data-driven and patient-centric capabilities of the National Patient-Centered Clinical Research Network (PCORnet).

Researchers in ADAPTABLE pursued the unanswered question of whether a low dose or high dose of aspirin is optimal for secondary prevention of atherosclerotic cardiovascular disease. Complexities of running a randomized clinical trial and the expenses associated with it have previously prevented researchers from answering this question.

The capabilities of PCORnet have aided in this research. Though not all randomized clinical trials can be designed as PCTs, ADAPTABLE demonstrates the possibility of incorporating pragmatic elements into future studies with the goal of producing real-world evidence.

A key objective of involving PCORnet in ADAPTABLE was the ability for large-scale recruitment (15,000 participants) using electronic health records and electronic informed consent. The PCORnet component permitted complete electronic participation, from randomization to data collection. Patients reported their own data during scheduled electronic follow-ups, which replaced conventional follow-up visits.

NIH Collaboratory Coordinating Center co–principal investigator Dr. Adrian Hernandez also serves as co–principal investigator of ADAPTABLE and contributed to the article.

See the accompanying editorial describing lessons learned from the design features of ADAPTABLE.

March 31, 2020: Engagement in PCTs: Considerations from the Collaboratory’s Ethics and Regulatory Core

Posted on by Gina Uhlenbrauck

A new document from the Ethics and Regulatory Core is available that provides considerations around determining which individuals or groups are engaged in research in pragmatic clinical trials (PCTs). Developed for investigators designing and conducting PCTs as well as institutional review boards overseeing them, the document introduces these questions in relation to research subjects, study team members, and service providers:

  • Which individuals/groups are included in the research?
  • Are these individuals/groups research subjects, study team members, or service providers?
  • Why does it matter how the individuals/groups are categorized for the research?

Download Engagement in Research for Pragmatic Clinical Trials.