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.
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 Clinical Trials Transformation Initiative (CTTI) has released its Annual Reportfor 2015. The report describes major achievements from the previous year, including new recommendations and related tools and checklists for improving the safety, efficiency, and overall quality of clinical research.
Highlights of the 2015 Annual Report include recommendations on topics including:
Ethics review processes
Good Clinical Practice training for trial investigators
Research protocol design
Engagement of patient groups as equal partners in clinical research
Informed consent processes
Safety reporting systems for research participants
A public-private partnership whose many stakeholders include government agencies, advocacy groups, professional societies, academic research organizations, and representatives from the medical products industry, CTTI’s mission is to “identify and promote practices that will increase the quality and efficiency of clinical trials.”
A PDF version of the report is available here. Previous Annual Reports are also available on the CTTI website.
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.
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 MeetingMeeting 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.
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 pmHubert H. Humphrey Building, Great Hall200 Independence Ave SWWashington, 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.
A new series of 12 articlespublished in a special issue of the journal Clinical Trials addresses ethical and regulatory challenges particular to pragmatic clinical research. Pragmatic clinical trials are designed to efficiently provide answers to important clinical questions, yet they present special challenges in conforming to the ethical and regulatory guidelines that were developed for more traditional clinical research. The special issue describes these challenges and begins to outline possible solutions that will protect the rights and welfare of research participants while allowing pragmatic clinical trials to gather much-needed evidence for informing healthcare decisions. An introductory article is followed by 11 articles addressing individual topics, such as alteration of informed consent, privacy, gatekeepers, and defining minimal risk research. The effort was funded by the NIH Health Care Systems Research Collaboratory, with additional support from the Patient-Centered Outcomes Research Institute (PCORI), and involved diverse groups of stakeholders, including researchers, patient advocates, bioethicists, and regulatory experts. Robert M. Califf, MD, and Jeremy Sugarman, MD, MPH, were editors of the special issue.
The U.S. Department of Health and Human Services(HHS) and 15 other federal departments and agencies have announced proposed revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule (45 CFR 46, Subpart A) in 1991. A Notice of Proposed Rulemaking (NPRM) was published in the Federal Register on September 8, 2015 (see the press release).
The NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. Comments must be received no later than the extended deadline of 5 pm on January 6, 2016. Visit the HHS page for a summary of the proposed changes and instructions on submitting or browsing comments.
Webinars are availableexplaining the changes proposed in the NPRM, and a town hall meeting is planned to be held in Washington, DC, in October.
Among the major changes being proposed in order to better protect research subjects and help build public trust are modifications to rules affecting patient informed consent. With regard to informed consent in general (such as consent to participate in a clinical trial), the rules would be significantly tightened to ensure that the process becomes more meaningful. Consent forms in particular would be affected. A common complaint about informed consent forms is that they are often unduly lengthy and cumbersome, with important information often buried and hard to find. Under the proposed changes, such documents would need to be streamlined in ways that provide appropriate details about the research that is most relevant to a person’s decision to participate in the study, such as information a reasonable person would want to know, and present that information in a way that highlights the key information.
The proposed modifications are designed to continue to uphold the ethical principlesupon which the Common Rule is based, as applied to the current social, cultural, and technological environment. In brief, the most significant changes proposed in the NPRM include:
Improve informed consent by increasing transparency and by imposing stricter new requirements regarding the information that must be given to prospective subjects.
Generally require informed consent for the use of stored biospecimens in secondary research.
Exclude from coverage under the Common Rule certain categories of activities that should be deemed not to be research, are inherently low risk, or where protections similar to those usually provided by IRB review are separately mandated.
Add additional categories of exempt research to accommodate changes in the scientific landscape and to better calibrate the level of review to the level of risk involved in the research.
Change the conditions and requirements for waiver or alteration of consent such that waiver of consent for research involving biospecimens (regardless of identifiability) will occur only in very rare circumstances.
Mandate that U.S. institutions engaged in cooperative research rely on a single IRB for that portion of the research that takes place within the United States, with certain exceptions.
Eliminate the continuing review requirement for studies that undergo expedited review and for studies that have completed study interventions and are merely analyzing data or involve only observational follow-up in conjunction with standard clinical care.
Extend the scope of the policy to cover all clinical trials, regardless of funding source, conducted at a U.S. institution that receives federal funding for non-exempt human subjects research.