Clinicians and researchers at Seattle’s Harborview Medical Center documented their experiences in the early weeks of the COVID-19 outbreak in King County, Washington. Their report offers lessons from clinical and research personnel, patients, and peer interventionists during the evolving pandemic response in an early US COVID-19 epicenter.
The article, published online in Psychiatry, presents a case series of experiences of frontline clinical and research teams in incorporating COVID-19 prevention strategies in the context of an ongoing comparative effectiveness trial of multidisciplinary, peer-integrated care coordination for patients with severe injury. The report also describes key themes from qualitative data collected during daily team meetings for the Trauma Survivors Outcomes and Support (TSOS) study, a pragmatic clinical trial also underway at Harborview. TSOS, an NIH Collaboratory Demonstration Project, is a stepped-wedge, cluster randomized pragmatic trial testing the delivery of screening and intervention strategies for patients with posttraumatic stress disorder and comorbid conditions at 24 level I trauma centers in the United States.
The case series offers evidence that primary and secondary prevention strategies can be integrated into ongoing clinical and research interventions during pandemic response. Procedures can also be developed to support team members who are adapting to rapidly changing individual, organizational, and societal demands.
This work was supported in part by the Patient-Centered Outcomes Research Institute (PCORI). TSOS is supported within the NIH Collaboratory by a cooperative agreement from the National Institute of Mental Health and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.
Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the UG3 PRISM Demonstration Projects. These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.
Shivan Mehta, MD, MBA
Assistant Professor of Medicine and Health Policy
University of Pennsylvania
Pragmatic Trials of Behavioral Economic Interventions to Increase Colorectal Cancer Screening
Behavioral economics; Colorectal cancer; Pragmatic clinical trials; Health technology; Communication modality; Informed consent
Colorectal cancer is the second leading cause of cancer deaths in the United States. Increased rates of screening can reduce mortality from colorectal cancer by 30% to 70%.
Use of behavioral economics can help us understand human motivation and behavior related to participating in clinical studies. How the message to patients is framed—and how choices are offered—can alter the response.
In the example pragmatic trial, the “choice architecture” for the colorectal cancer screening was designed by the study team in collaboration with health system stakeholders and clinical operations. Changing the framing from opt in to opt out had the effect of increasing participation in screening.
In some settings, choice overload can have a negative effect on participation.
When designing embedded pragmatic trials, researchers must be mindful not to increase burden on clinicians’ workflow.
While behavioral economics offers suggestions for how to increase colorectal cancer screening rates, its effectiveness in different contexts needs to be evaluated.
The Johns Hopkins Berman Institute of Bioethics invites applications for a Postdoctoral Fellowship in the Ethics and Regulatory Aspects of Pragmatic Clinical Trials. This position includes pursuing independent research, working alongside faculty members involved with the ethics and regulatory aspects of large-scale pragmatic clinical trials (PCTs), and participating in the Hecht-Levi Postdoctoral Fellowship in Bioethics. The postdoctoral fellow is expected to pursue one or more projects addressing the ethics and regulatory aspects of PCTs in collaboration with Berman Institute faculty members. The Fellow will actively engage with the Ethics and Regulatory Core of the NIH Health Care Systems Research Collaboratory and the Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Resource Coordinating Center.
Qualifications: Applications are welcome from candidates who will have an MD, PhD, or JD or their equivalent by the start date of the fellowship. Applicants should not have completed their terminal degree more than 3 years before the start date of the appointment. Physicians should not have completed a formal residency training program more than 3 years by the start date of the appointment.
Start date: September 1, 2020.
Terms of Appointment: The fellowship is guaranteed for 1 year with the expectation of a second year of funding, contingent on review. Applicants may not be employed by another institution and are expected to be in residence for the duration of the appointment.
Michelle N. Meyer, PhD, JD
Assistant Professor & Associate Director, Research Ethics
Center for Translational Bioethics & Health Care Policy
Faculty Co-Director, Behavioral Insights Team
Steele Institute for Health Innovation, Geisinger
Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials
A vs B trials; Comparative effectiveness research; Clinical equipoise; Randomization; Learning health system
Healthcare delivery systems often have an ethical obligation to experiment in order to determine the effects of their policies and treatments on stakeholders. A/B experiments conducted within health systems are intended to increase quality and safety, decrease waste or lower costs, and reduce inequity and injustice.
The “A/B effect” is the approval of untested policies or treatments (A or B) being universally implemented but disapproval of randomized experiments (A/B tests) to determine which of those policies or treatments is superior.
Experimentation aversion may be an important barrier to evidence-based practice.
Do you think the objection to random assignment is related to a sense that it is not “random?”
A potential solution to the “A/B effect” is to let patients be partners in improving healthcare by explaining that “we don’t know if A or B is better. Would you be willing to help us find out?”
CEO, Elektra Labs
Fellow, Harvard-MIT Center for Regulatory Science
Co-founder, Digital Medicine Society (DiMe)
Jen Goldsack, MS, MBA
Interim Executive Director, DiMe
Portfolio, Strategy & Ops, HealthMode
Introducing the Digital Medicine Society
Digital medicine; Mobile health; Digital technologies; Wearable health devices; Connected devices; Cybersecurity
Digital medicine is a rapidly evolving field that is by nature multidisciplinary and introduces new considerations for the healthcare community.
The Digital Medicine Society (DiMe) sits at the intersection of two communities: healthcare and technology. The Society is helping to move the field of digital medicine forward by developing a common language for diverse stakeholders from engineers and ethicists to payers and providers.
The U.S. healthcare system has strong protections for patients’ biospecimens like blood or genomic data, but what about digital specimens?
Are digital medical technologies worthy of the trust we place in them?
Should there be a Hippocratic Oath for manufacturers, organizations, and individuals delivering care through connected medical devices?
At the May 2019 meeting of the NIH Collaboratory Steering Committee, we talked with Judith Carrithers, coleader of the Ethics and Regulatory Core. The task of the Core is to develop a framework for conducting embedded pragmatic clinical trials (ePCTs) in an ethical manner and in compliance with federal and state regulations. Ms. Carrithers joined the Core last year prior to the start of the yearlong planning phase for 6 new UG3 Demonstration Projects. We asked her to reflect on the Core’s progress and challenges during the past year.
Please tell us about the Core’s recent accomplishments.
The Ethics and Regulatory Core is learning how to frame ethical and regulatory issues around ePCTs while talking with each study team to learn how their trial is going to work, what informed consent considerations they may have, and, for their population, what makes the most sense within the regulatory framework. By the time I joined, the Core had already gone through the first round of UH3 Demonstration Projects, and I was able to piggyback on the learning from that experience, which informed our interviews and discussions with the new UG3 studies last summer. The regulatory framework we’re working in is a little black, a little white—and a lot of gray. For ePCTs, and clinical trials in general, within that framework there are things it’s clear you can do and cannot do, and a lot of things where you’re using your best judgment in the context of a study.
“The regulatory framework we’re working in is a little black, a little white—and a lot of gray.”
What we see with pragmatic trials across those conducted in the Collaboratory is that many are clearly minimal-risk studies, so there is the possibility of managing informed consent in a different way. A written consent form is generally required under the federal regulations for studies that present more than minimal risk to participants. But if a trial is minimal risk, we can consider a waiver of consent or alteration of the consent process if traditional written consent affects the practicability of the trial. One focus of the Core’s work has been to study when a waiver or alteration of consent is appropriate in the various types of ePCTs. In addition, we explore what other methods could be used to advise patients that they’ve been enrolled in a research study, such as broadcast notification of the research placed in prominent locations, with contact information for questions.
From the inception of the Collaboratory, both the NIH and the Office for Human Research Protections (OHRP) have been involved in helping work through how to manage these issues in a way that respects individuals enrolled in a trial while also making it possible to conduct the trial without a lengthy informed consent process when it is not required under the regulations. We will continue to look at these issues with the new Demonstration Projects to get a better feel for emerging patterns. The Core has developed several publications addressing ethics and regulatory considerations for ePCTs, and we will continue to contribute to this growing body of knowledge to share with the larger research community.
What challenges lie ahead?
A big challenge is staying aware of how the regulatory framework may change during the course of the trial, and how those changes affect the conduct of a study. For example, the revised Common Rule impacted the way IRBs review research and investigators conduct their research. It’s also important to remember what we’ve learned as a research community—for example, we’re developing better ways of giving notice to patients that they’re enrolled in a trial. And the challenge in part is that studies have used different methods of notification with varying success, and so we need a way to compile that information into an accessible format to help future study teams decide how to apply those learnings to their study.
Our challenge is to build the grammar, the framework, and the thinking process for ethics and regulatory issues in pragmatic trials. Having resources like the Living Textbook available is helpful for researchers, providing insight into how others are framing these issues and conducting their trials.
Any words of advice for new ePCT investigators?
Sort out what part of the trial is research and what part is clinical care. This is essential for study teams to define so that they know what parts of the trial are subject to the federal regulations. It’s important to segment out and treat the clinical part of the study as clinical care. Within the research part, evaluate how the regulations apply. Think carefully about your trial and work through all the pragmatic pieces, for example:
What access to the electronic health record will you need?
How will you recruit participants?
If consent is required, how will you consent participants?
One of the strengths of the Core is that we’re able to work with study teams while they’re still finalizing the design of the trial, and together build on each others’ experiences, focus on specific issues, and in some cases, change their approach in order to make the study work better in the healthcare setting or with potentially large numbers of enrollees. I think the best resource for new investigators is meeting other researchers who have done this work and hear how they addressed and overcame challenges.
The Coordinating Center of the National Institutes of Health (NIH) Health Care Systems Research Collaboratory is supported by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Read more about the Ethics and Regulatory Core in the Living Textbook, and learn more about the NIH Collaboratory's other Core Working Groups.
Findings from a new article suggest that the majority of patients do not feel a personal responsibility to participate in clinical research. In the article, Kevin Weinfurt, Li Lin, and Jeremy Sugarman report the results of a national survey of nearly 3000 people regarding their attitudes towards research responsibilities as well as their trust in doctors, healthcare systems, and medical research. Ethical frameworks for learning health systems have suggested that patients have a responsibility to contribute to learning activities, including research. The findings from this survey suggest that most patients in the U.S. do not currently endorse such a responsibility.
“These data provide a useful snapshot of the public’s views toward the obligation to participate in research. It is unclear how, if at all, these views will shift with increased efforts to create mature learning health systems. And if such views do not shift, it is uncertain what that would mean for the success of learning health systems.” —Kevin Weinfurt, PhD
Consuelo H. Wilkins, MD, MSCI
Vice President for Health Equity, Vanderbilt University Medical Center
Executive Director, Meharry-Vanderbilt Alliance
Moving Beyond Return of Research Results to Return of Value
Health outcomes; Research results; Patient preferences; Value of information
In returning value to research participants, results are shared with added context, are prioritized by each participant, include specific suggestions for relevant actions, and incorporate participant recommendations and preferences.
Data captured for research purposes, including EHR data, vital signs, and genetic data, can be repurposed and reoriented for study participants.
Participants are more likely to trust research if results are returned—and they are more likely to participate again.
We need to return study results that are informed by participants, and we need to design approaches for accessing and understanding results that participants will want to use.
We should think carefully about risk mitigation when returning research results for which there is a clear next step or action for the participant.
Read more about understanding what information is valued by research participants in a recent article by Dr. Wilkins and colleagues in Health Affairs.
The NIH Collaboratory is pleased to announce the availability of a new self-paced, 10-module introductory course on how to design, conduct, and disseminate embedded PCTs (ePCTs). This course presents condensed material from the inaugural ePCT Training Workshop held in 2018 and provides users with important things to know and do when designing an ePCT, along with helpful links to additional learning resources within the Living Textbook.