informed consent

June 14, 2023: IMPACt-LBP and INSPIRE Have Updated Study Snapshots, Ethics and Regulatory Documentation

Posted on by Damon Seils

Updated study snapshots and ethics and regulatory documentation are now available for the IMPACt-LBP and INSPIRE trials, both NIH Pragmatic Trials Collaboratory Trials.

Logo for the IMPACt-LBP NIH Collaboratory TrialIMPACt-LBP transitioned from the planning phase to the implementation phase in August. As part of the transition, the study team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core. The study is a cluster randomized trial evaluating the effect of first-contact patient referral to physical therapists and doctors of chiropractic for the treatment of low back pain. IMPACt-LBP is supported within the NIH Collaboratory under an award from the National Center for Complementary and Integrative Health.

Logo for the INSPIRE NIH Collaboratory TrialINSPIRE joined the NIH Collaboratory at the beginning of its implementation phase. The study team held its initial consultation with the Ethics Regulatory Core to review their approach their approach to consent, data privacy, and the applicability of recent FDA guidance regarding clinical decision support software functions. INSPIRE consists of 2 cluster randomized trials that are using personalized clinical decision support to improve judicious antibiotic prescribing for non–critically ill patients hospitalized with abdominal infections or skin and soft tissue infections. The project is supported within the NIH Collaboratory under an award from the National Institute of Allergy and Infectious Diseases.

Grand Rounds Ethics and Regulatory Series February 10, 2023: Informing and Consenting: What Are the Goals? (P. Pearl O’Rourke, MD; David S. Wendler, PhD, MA; Miguel Vazquez, MD; P. Michael Ho, MD, PhD)

Posted on by Elizabeth Mccamic

Speakers

Pearl O’Rourke, MD (retired)
Harvard Medical School

David S. Wendler, PhD, MA
Senior Researcher
Head, Section on Research Ethics
Department of Bioethics
NIH Clinical Center

Miguel Vazquez, MD
Professor of Internal Medicine
UT Southwestern Medical Center

Michael Ho, MD, PhD
Professor of Medicine
University of Colorado School of Medicine

 

 

Keywords

Ethics and Regulatory, Consent, Waiver of Consent, Notification

 

Key Points

  • Using informed consent addresses two of the Belmont Principles, respect for persons by informing and autonomy by allowing choice. The regulations recognize that consent is not always possible and allow for alteration, where some of the required elements of informed consent can be altered or not included, and waiver of consent, where no consent is required.
  • It is not uncommon to see waivers of consent in pragmatic clinical trials because many trials meet minimal risk criteria and involve numerous institutions and thousands of subjects. There are also concerns that obtaining consent could alter the “real-world” medical care being studied, may introduce an alteration of routine care, may introduce bias or make research impossible to conduct.
  • Informed consent is not the only way to inform. Think about methods of notification, from detailed study-specific information to a general statement that research is being conducted. There are consequences of notification, such as logistics and cost. If you are notifying, when do you offer an opt-out option and what do you do when potential subjects have questions or do not want to be in the research?
  • ICD-Pieces studied patients with chronic kidney disease (CKD), diabetes and hypertension. The intervention was to facilitate delivery of guideline-based care. The study had a waiver of informed consent. The study used a patient-information sheet to inform patients about the research, how patient data would be handled, and an option to opt-out of including their data in the study.
  • The Nudge Study is a pragmatic clinical trial seeking to improve medication adherence to patients’ already-prescribed cardiovascular medications through a series of theory-based text or voice messages that served as “nudges.” The study mailed patients an opt-out packet that included an introductory letter from the site PI, a FAQ sheet and opt-out form. If they did not opt-out within a month, we would monitor their prescription refills and send a nudge if one went unfilled for more than 7 days.
  • Participants always know some things and agree to some extent. When not getting full regulatory consent, the relevant questions are: What should they know? What should they agree (not object) to?

 

Discussion Themes

– How did the various types of notifications in the ICD-Pieces study impact opt-outs? The patient population and geography across sites was very different. The opt-outs were also very different. It was up to individuals how to deliver or make information about the study available than other sites in the study. It would be difficult for us to say a poster or letter is better.

– Whichever type of notification was used, did you tell people they could opt-out and explain how they could opt-out and give them assurance that opting-out would not impact care? For ICD-Pieces, there was a bullet that stated clearly that patients could opt-out and a phone number to opt-out. There was also a statement that said they would receive the best care from their provider. For NUDGE, there was the initial letter where patients could opt-out by sending a postcard and they could also opt-out in response to the text messages. Opt-outs were different across health systems.

 

Tags

#pctGR, @Collaboratory1

March 31, 2022: GRACE Trial Has New Study Snapshot, Updated Ethics and Regulatory Documentation

Posted on by Damon Seils

GRACE Trial logoA downloadable study snapshot and updated ethics and regulatory documentation are now available for the GRACE trial, an NIH Pragmatic Trials Collaboratory Trial.

GRACE transitioned from the planning phase to the implementation phase in September. As part of the transition, the study team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core. The study is a hybrid effectiveness–implementation trial of guided relaxation and acupuncture for pain associated with chronic sickle cell disease in 3 large healthcare systems.

  • Read the updated ethics and regulatory documentation, including information about the study team’s approach to inclusion and exclusion criteria, informed consent, and collection of patient-reported outcome data.
  • Also available is a new study snapshot for GRACE. This downloadable handout summarizes the study’s aims, lessons from the planning phase, and links to other resources from this innovative pragmatic clinical trial.

GRACE is supported by the NIH through the NIH Heal Initiative under an award from the National Center for Complementary and Integrative Health. Learn more about the GRACE trial.

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.