Research ethics

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.

October 28, 2019: Latest Ethics and Regulatory Updates from NIH Collaboratory Trials Available

Posted on by Gina Uhlenbrauck

Six NIH Collaboratory Trials—ACP PEACE, EMBED, GGC4H, HiLo, Nudge, and PRIM-ER—have recently transitioned from the planning to implementation phase of their embedded pragmatic clinical trial (ePCT). During the transition, study teams reviewed and updated their ethics and regulatory meeting minutes from discussions with the Ethics and Regulatory Core. The minutes describe ethics and regulatory issues the trials have encountered, along with approaches the trials are using for informed consent, HIPAA, and monitoring and oversight:

Ethics and regulatory issues can pose challenges to embedded pragmatic trials because of the unique nature of clinical research conducted in the setting of routine clinical care. The Ethics and Regulatory Core provides assistance to study teams as they navigate the ethics and regulatory landscape of ePCTs.

October 15, 2019: Postdoctoral Fellowship in the Ethics and Regulatory Aspects of Pragmatic Clinical Trials at Johns Hopkins

Posted on by Gina Uhlenbrauck

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.

How to apply: For details on how to apply see: https://bioethics.jhu.edu/education-training/fellowships/#fellowship-pragmatic. Applications must be submitted by December 16, 2019.

September 28, 2018: Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets (Greg Simon, MD, MPH, Deven McGraw, JD, MPH, Khaled El Emam, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Gregory Simon MD, MPH
Investigator, Kaiser Permanente Washington Health Research Institute

Deven McGraw, JD, MPH, LLM
General Counsel & Chief Regulatory Officer, Ciitizen

Khaled El Emam, PhD
Department of Pediatrics, University of Ottawa
Children’s Hospital of Eastern Ontario Research Institute

Topic

Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets

Keywords

Clinical trials; Research ethics; Data security; Data sharing; Sensitive research data; De-identified data

Key Points

  • 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.

Discussion Themes

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.

The Health Information Trust Alliance de-identification framework identifies 12 criteria for a successful de-identification program and methodology.

Tags

#pctGR, #PragmaticTrials, #HealthData, @HealthPrivacy @Collaboratory1, @PCTGrandRounds

Recent Collaboratory Publications on Research Ethics

Posted on by Gina Uhlenbrauck

The American Journal of Bioethics has recently published three articles authored by members of the Regulatory/Ethics core group describing various questions related to research on medical practices:

  • Is shared decision making an appropriate analytic frame for research on medical practices (Sugarman 2015) discusses the role of shared decision making (SDM) in research on medical practices. The author cautions that “while SDM is in many ways similar to informed consent, there are some important differences, especially in the research setting.” This publication is freely accessible through PubMed Central.
  • Patients’ views concerning research on medical practices: implications for consent (Weinfurt et al. 2015) describes the results of focus group sessions that elicited a range of patients’ views and opinions about different types of research on usual medical practices. The authors state that “our data suggest that effective policy and guidance will involve balancing different patients’ interests and potentially different sets of interests for different types of research studies on usual medical practices.”
  • Ethics of research in usual care settings: data on point (Sugarman 2016) introduces a special five-article supplement in the American Journal of Bioethics, stating that the “growing empirical ethics literature regarding research in usual care settings provides data to inform conceptual and policy debates regarding this research and suggests areas that require further study.”

These publications were supported by a bioethics supplement awarded to the Regulatory/Ethics Core group by the NIH’s Office of the Director.

Modernizing the Common Rule for the 21st Century

Posted on by Gina Uhlenbrauck

The New England Journal of Medicine today published a perspective by NIH Deputy Directory Kathy L. Hudson, PhD, and NIH Director Francis S. Collins, MD, PhD, in which they outline the major reforms proposed for regulations governing the ethical conduct of research involving humans, known as the Common Rule (45 CFR 46, Subpart A).

The proposed changes are meant to enhance respect for research participants, calibrate oversight to level of risk, simplify consent documents, streamline IRB review, increase privacy and security safeguards, and facilitate broad participation in research.

“These long-overdue reforms will bring the Common Rule into the 21st century. They should help the scientific community take a giant leap forward in showing respect for research participants, without whom the biomedical research enterprise would cease to exist.”

The NIH is encouraging all stakeholders—the public, researchers, and patients—to closely review the proposed changes and participate in the comment process by the December 7, 2015, deadline.

For more information on the proposed revisions:

Grand Rounds Presentation, Kathy Hudson (video)

Department of Health and Human Services' website on the NPRM 

OHRP Webinars on the NPRM

Living Textbook Chapter: Informed Consent: Emerging Issues and Controversies

OHRP Town Hall Meeting to Discuss NPRM

Posted on by Gina Uhlenbrauck

The Office for Human Research Protections (OHRP) has announced a public Town Hall Meeting to be held October 20, 2015, to respond to questions related to the Federal Policy for the Protection of Human Subjects Notice of Proposed Rulemaking (NPRM) published on September 8, 2015.

The goal of the NPRM is to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991. The NPRM seeks comments on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.

The purpose of the Town Hall Meeting (agenda) is for OHRP, HHS agencies, and other Common Rule departments and agencies to provide responses to questions from the public about the NPRM in order to clarify the NPRM proposals and better inform public comment on the NPRM. The public will be able to ask questions during the Town Hall Meeting, and to submit questions before the meeting. Watch via webinar.

Public Town Hall Meeting 
October 20, 2015, 9 am to 5 pm
Hubert H. Humphrey Building, Great Hall
200 Independence Ave SW
Washington, DC 20201

This PDF document (#2015-25564) contains details about the format of the public Town Hall Meeting and how to register or submit questions prior to the meeting.

Important deadlines:

  • While there is no registration fee, individuals planning to attend the Town Hall in person must register by 5:00 pm October 13, 2015. Registration will be accepted on a first-come, first-served basis and may be completed by sending an email to OHRP@hhs.gov, with the subject line “Registration for OHRP Town Hall Meeting.”
  • The deadline for submission of questions about the NPRM prior to the Town Hall Meeting must be received no later than 5:00 pm October 13, 2015.
  • Details on the NPRM are at the OHRP website. To be assured consideration, comments on the NPRM must be received no later than the extended deadline of January 6, 2016.

 

Report from NIH Collaboratory Workshop Examines Ethical and Regulatory Challenges for Pragmatic Cluster Randomized Trials

Posted on by Gina Uhlenbrauck

A new article by researchers from the NIH Collaboratory, published online this week in the journal Clinical Trials, explores some of the challenges facing physicians, scientists, and patient groups who are working to develop innovative methods for performing clinical trials. In the article, authors Monique Anderson, MD, Robert Califf, MD, and Jeremy Sugarman, MD, MPH, MA, describe and summarize discussions from a Collaboratory workshop on ethical and regulatory issues relating to pragmatic cluster-randomized trials.

Pragmatic Cluster-Randomized Trials

Many of the clinical trials that evaluate the safety and effectiveness of new therapies do so by assigning individual volunteers to receive either an experimental treatment or a comparator, such as an existing alternative treatment, or a placebo. However, this process can be complex, expensive, and slow to yield results. Further, because these studies often take place in specialized research settings and involve patients who have been carefully screened, there are  concerns that the results gathered from such trials may not be fully applicable to “real-world” patient populations.

For these reasons, some researchers, patients, and patient advocacy groups are interested in exploring different methods for conducting clinical trials, including designs known as pragmatic cluster-randomized trials, or CRTs. In a pragmatic CRT, groups of individuals (such as a clinic, hospital, or even an entire health system) are randomly assigned to receive one of two or more interventions being compared, with a focus on answering questions about therapies in the setting of actual clinical practice—the “pragmatic” part of “pragmatic CRT.”

Pragmatic CRTs have the potential to answer important questions quickly and less expensively, especially in an era in which patient data can be accessed directly from electronic health records. Just as importantly, that knowledge can then be fed back to support a “learning healthcare system” that is constantly improving in its approach to patient care.  However, while cluster-randomized trials are not themselves new, their widespread use in patient-care settings raises a number of potential challenges.

For example: in a typical individually randomized clinical trial, patients are enrolled in a study only after first providing written informed consent. However, in a CRT, the entire hospital may be assigned to provide a given therapy. In such a situation, how should informed consent be handled? How should patients be notified that research is taking place, and that they may be part of it? Will they be able to “opt out” of the research? What will happen to the data collected during their treatment? And what do federal regulations governing clinical trials have to say about this? These are just a few of the questions raised by the use of pragmatic CRTs in patient-care settings.

The NIH Collaboratory Workshop on Pragmatic Cluster-Randomized Trials

The NIH Collaboratory Workshop of Pragmatic CRTs, held in Bethesda, Maryland in July of 2103, convened a panel of experts in clinical trials, research ethics, and regulatory issues to outline the challenges associated with conducting  pragmatic CRTs and to explore ways for better understanding and overcoming them. Over the course of the intensive 1-day workshop, conference participants identified key areas for focused attention. These included issues relating to informed consent, patient privacy, oversight of research activities, insuring the integrity of data gathered during pragmatic CRTs, and special protections for vulnerable patient populations. The article by Anderson and colleagues provides a distillation of discussions that took place at the workshop, as well as noting possible directions for further work.

In the coming months and years, the NIH Collaboratory and its partners, including the National Patient-Centered Clinical Research Network (PCORnet), plan to build on this workshop experience. Together, they hope to explore these issues in greater detail and propose practical steps for moving forward with innovative clinical research methods, while at the same time maintaining robust protections for patients’ rights and well-being.

Jonathan McCall, MS, and Karen Staman, MS, contributed to this post.

Read the full text of the article here:

Anderson ML, Califf RM, Sugarman J. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems. Clin Trials 2015 [e-Pub ahead of press].
doi:10.1177/1740774515571140 
For further reading:

Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: Increasing the value of clinical research decision making in clinical and health policy. JAMA 2003;290(12):1624-32. PMID:14506122; doi:10.1001/jama.290.12.1624.

The Ottawa Hospital Research Institute Ethical Issues in Cluster Randomized Trials Wiki.

Special Report: Ethical Oversight of Learning Health Systems. Hastings Center Report 2013;43(s1):S2–S44, Si–Sii.

Sugarman J, Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA 2014;311(23):2381-2. PMID: 24810723; doi: 10.1001/jama.2014.4164.

PCORI Executive Director Dr. Joe Selby to Speak on Regulatory Issues Concerning Big Data

Posted on by Gina Uhlenbrauck

The meeting of the Secretary’s Advisory Committee for Human Research Protections (SACHRP) scheduled for July 21-22, 2014, will include a session on “Regulatory Issues Concerning Big Data.” Joe Selby, MD, MPH, executive director of the Patient-Centered Outcomes Research Institute (PCORI), will speak, along with leaders from the NIH and FDA. The session is scheduled for 1:30-3:45 pm on Monday, July 21.

SACHRP provides recommendations on human subjects protection to the Secretary of the U.S. Department of Health and Human Services and reviews activities of the Office for Human Research Protections (OHRP). Other topics to be covered during the two-day meeting include informed consent comprehension, the return of research results to human subjects, and ethical/regulatory issues in interventional social media research.

The meeting is available to the public and will be videocast live.

View the meeting agenda
View the live webcast (available July 21-22, 2014)

A link to materials from the meeting will be provided in an update to this post when available.