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.
The NIH Collaboratory recently convened a workshop to explore embedded pragmatic clinical trials comparing two or more therapeutic medical interventions. These “A vs B” trials are meant to test existing, viable treatment alternatives where there is uncertainty about which treatment is best in which populations. There are unique barriers that make these types of pragmatic trials especially challenging to implement. For the workshop, a panel of experts gathered to discuss challenges and solutions regarding partnering with healthcare systems to conduct the trials, unique legal and ethical issues, and design and operational considerations. The summary of the workshop is now available: Workshop Summary: Embedded Pragmatic Clinical Trials of Therapeutic A vs. B Interventions
Embedded pragmatic clinical trials of therapeutic A vs. B interventions workshop videocast.
Khaled El Emam, PhD
Department of Pediatrics, University of Ottawa
Children’s Hospital of Eastern Ontario Research Institute
Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets
Clinical trials; Research ethics; Data security; Data sharing; Sensitive research data; De-identified data
The cycle of risk de-identification involves setting a risk threshold, measuring the risk, evaluating the risk, and applying transformations to reduce the risk.
The Safe Harbor method of de-identification (removal of 18 categories of data) is a legal minimum standard that does not take context into account, and may not be sufficient when sharing sensitive data publicly.
A higher standard for de-identification is the “Expert Determination” method, whereby an expert with contextual knowledge of the broader data ecosystem can determine whether the risk is “not greater than very small.”
With increasing concern about the risks of sensitive data sharing, it is important to be transparent with data participants and continue to build trust for data uses.
When is a dataset safe for sharing? What is the risk of re-identification, and how can we reduce the risk? Consider who you are releasing the data to and what other kinds of data might they have access to that could potentially lead to re-identification.
For more information on the de-identification of protected health information, visit the U.S. Department of Health and Human Services’s Guidance Regarding Methods for De-identification of Protected Health Information in Accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.
Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the new UG3 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.
Using patient-centered outcomes research (PCOR) data requires balancing the need for sufficient private health information to support meaningful research with the need to protect patient privacy and autonomy. In support of this dual goal, The Office of the National Coordinator for Health Information Technology (ONC) has just released a document that provides a collection of tools and resources aimed at helping a broad audience of stakeholders understand the ethical and regulatory requirements related to collecting, using, sharing, and disclosing PCOR data.
“An architecture is necessary to ensure patient privacy is protected and health information is appropriately secured during collection, access, use, and disclosure as required by law, regulation, and/or policy.” —Legal and Ethical Architecture for PCOR Data
PCOR data will help expand the evidence base for therapies and improve health outcomes for individual patients.
Chapter 1: Overview of Legal and Ethical Architecture for PCOR Data provides background for the project and an overview of key ethical and regulatory requirements.
Chapter 2: Legal and Ethical Significance of Data for PCOR describes fundamental concepts for organizing data into categories such that legal and ethical frameworks can be applied. The chapter includes key considerations and types of data relevant to PCOR, such as clinical, administrative, patient-generated, etc.
Chapter 3: Linking Legal and Ethical Requirements to PCOR Data organizes the relevant legal provisions according to the key data considerations outlined in Chapter 2: identifiability, subject, source, access and use/purpose, consent/authorization, security, and legal status.
Chapter 4: Framework for Navigating Legal and Ethical Requirements for PCOR is designed as a decision tool that builds on the key data considerations described in Chapters 2 and 3. The goal of this chapter is to help researchers determine whether laws apply to particular data and if so, what requirements to attach to their collection and use.
Chapter 5: Mapping Research Flows to Legal Requirements identifies 6 hypothetical use cases, identifies decision trigger points, and maps representative data flows to the relevant legal requirements.