Dr. Kevin Weinfurt and colleagues in the Regulatory/Ethics Core of the NIH Collaboratory recently published an article in the American Journal of Bioethics regarding how acceptable different approaches to notification and authorization are to potential participants in pragmatic research. The authors conducted a series of interviews using 24 different hypothetical scenarios reflecting different types of studies and approaches to notification and authorization.
- People have significant difficulty understanding 1) randomization and 2) that all the data are collected during routine care, and no extra visits or tests are required.
- For some types of pragmatic research, many of the respondents viewed
- Active alternatives to written consent—such as oral consent—as acceptable.
- Less active approaches to notification—such as no notification ahead of time or broad notification—as unacceptable.
- When using written consent in cases where researchers are testing accepted medical interventions that have known clinical risks but with no incremental risks of participating in the research, it was acceptable to omit the clinical risks from the consent documents, thereby shortening the forms.
- A significant portion (28-49%) of respondents would decline to participate regardless of notification approach, which could lead to non-trivial consent bias (in other words, there could be significant differences in people who decline vs people who agree to participate).
Based on these findings, the authors suggest alternate approaches to notification and authorization should be further developed and tested.
Read the full article here.
The Department of Health and Human Services and 15 other agencies have announced revisions to the Federal Policy for the Protection of Human Subjects, otherwise known as the Common Rule. The final rule can be found here and will be officially published in the Federal Register on January 19, 2017.
The changes to the rule that will have a significant impact on the conduct of pragmatic clinical trials and embedded research include:
- New requirements regarding the information that must be given to patients as part of the informed consent process, including
- Key information that is most important to the subject and likely to help a patient (or legal representative) make a decision about participation
- An opportunity to discuss the information
- An approach that emphasizes the fostering of overall understanding (as opposed to specific length requirements)
- Allowing the use of broad consent for the use of identifiable information or identifiable biospecimens for other research studies (other than the proposed one) for
- Storage and maintenance for secondary research use
- Secondary research (including future uses)
- New exempt categories of research based on risk profile
- A requirement for U.S.-based institutions engaged in cooperative research to use a single Institution Review Board (IRB)
- A removal of the requirement for continuing review of ongoing research for studies that undergo expedited review.
The NIH has issued a final policy requiring the use of a single institutional review board (sIRB) for multi-site non-exempt human subjects research funded by the NIH. The policy will take effect May 25, 2017.
According to the policy announcement, “while the NIH anticipates that that there will be challenges associated with implementation, we expect these to be short-lived. Once the transition to the new way of operating is made, the benefits of widespread use of sIRBs will outweigh any costs and, ultimately, reduce burdens to the research process.”
In proposals submitted to the NIH, applicants will be expected to include a plan identifying the sIRB that will serve as the IRB of record for all study sites. It will be the applicants’ responsibility to assure that the sIRB is qualified to serve. NIH acceptance of the submitted plan will be incorporated as a term and condition in the award. Awardees will be responsible for ensuring that the authorization agreements between IRBs (“reliance agreements”) are in place.
According to the policy, “The additional costs associated with sIRB review may be charged to grants or contracts as direct costs, provided that such costs are well-justified and consistently treated as either direct or indirect costs according to applicable cost principles in the NIH Grants Policy Statement and the FAR 31.202 (Direct Costs) and FAR 31.203 (Indirect Costs).”
Before the policy takes effect, the NIH will be issuing guidance and resources to assist with implementation.
Read the full policy for additional details.
The FDA has released a Draft Guidance for Industry to facilitate the use of data from electronic health record (EHRs) in clinical investigations. The draft guidance provides recommendations on how to use EHRs as a source of data for research, ensure data quality and integrity, and satisfy the FDA’s inspection, recordkeeping, and record retention requirements. An additional goal of the draft guidance is to promote interoperability, or the ability to exchange and use information between EHR systems that capture information during patient care visits and electronic data capture (EDC) systems that support clinical investigations. Sponsors of clinical research must also consider whether there are any reasonably foreseeable risks involved in using the EHR for research—such as an increased risk of data breaches—that should be disclosed in the informed consent document.
Read the full draft guidance here.
On Tuesday, May 10, 2016, the NIH Collaboratory invites you to view a public webcast of the workshop, Ethical and Regulatory Issues of Pragmatic Clinical Trials.
This workshop will include several topics from a series of articles discussing regulatory and ethical issues related to the conduct of pragmatic clinical trials. Panelists from the NIH Collaboratory pragmatic trial Demonstration Projects, along with experts in the areas of informed consent, vulnerable populations, IRBs, data monitoring committees, and privacy issues, will participate in moderated discussion using case examples from the NIH Collaboratory.
A new article published in Circulation by a group of authors from the Duke Clinical Research Institute describes tensions between pragmatic clinical trial design and Good Clinical Practice (GCP) guidelines, which were established in 1996 to help ensure the safety of participants in clinical trials and the validity of trial findings. Pragmatic clinical trials (PCTs) are designed to test interventions in real-world settings and populations rather than under highly controlled conditions, and thus rely on simplified procedures, such as those used for screening, informed consent, and participant follow-up.
The authors concede that many PCT features appear to be at odds with GCP guidance, which has arguably led to improvements in the consistency and quality of trial conduct. However, they also note data suggesting that the intensive approach to monitoring and documentation fostered by GCP may ultimately increase trial cost and complexity by emphasizing minutia that “may direct focus away from critical aspects of trial conduct.”
The authors go on to suggest that GCP guidance should be updated to account for a growing proportion of research that incorporates aspects of pragmatic trial design and is conducted with data gathered from electronic health records and registries. They also offer a path forward for pragmatic research under current GCP guidelines by outlining strategies for areas that include participant enrollment, monitoring, study visits, participant follow-up, and documentation.
The authors conclude that collaborative efforts from trial sponsors, regulators, clinical trialists, and patients will be necessary to realign the guidance with contemporary trial conduct while preserving its central goal of protecting trial participants.
For further information:
For additional reading:
Introduction to PCTs
eBook on PCTs (University of Colorado Denver)
Ethics and regulatory issues in PCTs articles
NIH Collaboratory PCT: Time to Reduce Mortality in End-Stage Renal Disease (TiME)
NIH Collaboratory PCT: Blood Pressure Medication Timing Study (BPMedTime)
PCORnet PCT: ADAPTABLE, the aspirin study
Clinical Trials Transformation Initiative Quality by Design Project
Clinical Trials Transformation Initiative GCP Training Project
The NIH Collaboratory’s Health Care Systems Interactions Core has published a document entitled Lessons Learned from the NIH Health Care Systems Research Collaboratory Demonstration Projects. The Principal Investigators of each of the Demonstration Projects shared their trial-specific experience with the Core to develop the document, which presents problems and solutions for initiation and implementation of pragmatic clinical trials (PCTs). Lessons learned are divided into the following categories: build partnerships, define clinically important questions, assess feasibility, involve stakeholders in study design, consider institutional review board and regulatory issues, and assess potential issues with biostatistics and the analytic plan.
Other tools available from the Health Care Systems Interactions Core include a guidance document entitled Considerations for Training Front-Line Staff and Clinicians on Pragmatic Clinical Trial Procedures and an introduction to PCTs slide set.
The Clinical Trials Transformation Initiative’s Informed Consent Project will unveil recommendations and associated resources for informed consent on Thursday, November 19.
Presenters include Jennifer Lentz, Global Informed Consent Process Owner in Global Clinical Operations at Eli Lilly and Company, and Michele Kennett, Assistant Vice Chancellor for Research and Director of the Institutional Review Board at the University of Missouri.
• Topic: Informed Consent Project Recommendations
• Date: Thursday, November 19, 2015
• Time: 12 – 1 pm EST
To join the public webinar:
Meeting Link: Join WebEx Meeting
Meeting Number: 732 884 847
Meeting Password: ctti
After you connect to the website, please follow step-by-step instructions for connecting to the audio. If you prefer to connect to audio only, you can join by phone at:
1-855-244-8681 Call-in toll-free number (US/Canada)
1-650-479-3207 Call-in toll number (US/Canada)
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
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.
- 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.