Challenges and questions remain as the one year anniversary of the implementation of the Revised Common Rule approaches
One year has passed since the implementation of the Revised Common Rule, and many challenges and questions remain. While IRBs wait for promised guidance to materialize, we are left to interpret various aspects of the rule ourselves. This has resulted in variability across IRBs in how the new requirements are interpreted and operationalized.
Variability in the Key Information Summary
A significant area of confusion and variability relates to informed consent. The Revised Rule requires that “informed consent must begin with a concise and focused presentation of key information that is most likely to assist a prospective subject or legally authorized representative (LAR) in understanding the reasons why one might or might not want to participate in the research.”
Overall the response to the requirement for the Key Information section has been positive among IRB members since it provides an opportunity to highlight the most important information. However, significant challenges remain. IRBs have come up with a wide variety of approaches to meet this new requirement, ranging from brief paragraphs to lengthier, organized tables of information.
In our experience, industry sponsors have also not uniformly grasped the intent of this section, which is meant to be concise. Sponsor representatives often cut and paste long, complicated sections of risk language from the main body of the consent document (often multiple pages worth). This creates complex key information sections, resulting in more work for those who prepare consent documents, and more back and forth with sponsors.
Broad Consent Poses More Questions
Some additional informed consent issues that have been problematic relate to the provision of “clinically relevant research results” and under what circumstances they should be provided back to subjects, the statement regarding future use of research specimens, and the required element regarding whole genome sequencing.
Although the broad consent option was intended to give researchers better options for obtaining consent to use information and specimens for research, the fatal flaw seems to be the requirement to track refusals. Given the final rule’s definition of what was identifiable, and the removal of the concept that all biospecimens are identifiable, the need for a mechanism such as broad consent was diminished. As a result it seems that institutions are not utilizing the new broad consent option.
Institutions, particularly large medical centers with multiple facilities, still need guidance on how to operationalize the mechanism of broad consent. How far does the refusal to broad consent have to be tracked? What if an individual visited multiple facilities and gave conflicting answers to the request for broad consent? What if an individual changes their mind? Broad consent does not appear to be a great option for most research institutions at this point.
Navigating the Transition
For IRBs that have not transitioned studies that were approved prior to January 21, 2019 to the Revised Rule, another challenge is having two sets of rules to follow, as some studies fall under the pre-2018 requirements, and others under the 2018 requirements. An additional complicating factor is the lack of harmonization with FDA regulations. For many, their systems had to be customized to allow for labelling of studies so it is clear which regulations are applicable to a particular study. IRB reviewers also need to be particularly cognizant as they review multiple studies for one meeting, as there is no one set of rules to follow.
The transition to the revised Common Rule has been challenging to a community that worked under rules that remained largely unchanged for several decades. While the changes were definitely needed, and welcomed by most, there will be growing pains. As exemplified by some of the scenarios above, some areas will need to be refined as we gain experience in applying the new rules. While we patiently wait for guidance and harmonization, IRBs continue to do a magnificent job of sharing best practices among each other. At the end of the day IRBs seek to protect the rights and welfare of research participants, despite any hurdles that come along.
New CITI Program Courses and Webinar Help Researchers and Institutions Meet Regulatory Requirements
(Miami, FL) — The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, has announced new online courses and webinars designed to help research professionals understand and comply with regulatory requirements for clinical trials.
The three courses and webinars address critical regulatory requirements:
- Transitioning research to the Revised Common Rule
- Protocol registration and disclosure on ClinicalTrials.gov
- The role of principal investigators in meeting regulatory requirements
Transitioning Research to the Revised Common Rule: The What, How, and Why, a webinar that outlines considerations and challenges for transitioning pre-existing research to the revised Common Rule, as well as required documentation and tips for IRB review, is offered to both institutions and individual learners.
Designed for research professionals, including investigators, institutional review boards and research staff, the webinar reviews pre-2018 and 2018 versions of the Common Rule, including factors an organization may want to consider when deciding whether to transition a pre-existing study (or studies) to comply with the revised Common Rule, and strategies for the management and communication of transition decisions.
The webinar is presented by Karen Christianson, RN, BSN, a principal with HRP Consulting Group.
Recently published research demonstrates that many research institutions are not prepared to meet current requirements for registering and reporting clinical trials. A new course addresses this gap.
Protocol Registration and Results Summary Disclosure in ClinicalTrials.gov, an innovative video-enhanced course, guides learners through critical parts of the regulations and provides a step-by-step guide to data entry. This course can help organizations/investigators clearly understand protocol registration requirements to avoid the risk of significant civil monetary penalties or loss of NIH grant funding due to non-compliance with protocol registration and results reporting.
Biomedical PI focuses on key topics essential to the biomedical investigator’s role and responsibilities in conducting a clinical investigation of a product regulated by the U.S. Food and Drug Administration (FDA). This role-based course covers supervision, delegation, management, reports, and communication for investigators.
These courses, along with dozens of others available at CITIprogram.org, train investigators and research professionals to understand and meet research ethics standards and compliance requirements.
About CITI Program
The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, is dedicated to promoting the public’s trust in the research enterprise by providing high quality, peer-reviewed, web-based educational courses in research, ethics, regulatory oversight, responsible conduct of research, research administration, and other topics pertinent to the interests of member organizations and individual learners.
The Revised Common Rule and Informed Consent: Public Posting
An important provision in the Revised Common Rule is the requirement to post, to a publicly-available federal Web site, a copy of an IRB-approved version of the consent form that was used for enrollment purposes for each clinical trial conducted or supported by a federal department or agency. The Office for Human Research Protections (OHRP) has identified two publicly available federal websites that will satisfy the consent form posting requirement in the revised Common Rule: http://ClinicalTrials.gov and a docket folder on http://Regulations.gov. It is possible that additional sites may be identified in the future.
The consent form will need to have an up-front concise and focused presentation of the key information as required by 46.116(a)(5).
The specific requirement is that an IRB-approved consent form that was used for enrollment purposes be posted. There is no requirement to post multiple forms for multicenter studies, or for a study that has separate consent forms for different subject groups (e.g., adults versus pediatric participants). Also, for consent forms that underwent revision over the course of the study, the final rule does not stipulate that the posted document be the most recently approved version.
The posting can take place any time after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol. Information that should not be made available on a federal website, as determined by the federal department or agency supporting or conducting the clinical trial, can be redacted.
The purpose of the new provision is to increase transparency, which some feel will lead to improved consent form quality. The commentary to the Final Rule, describes how having an easily accessible repository of such forms freely available for analysis and public discussion will foster public discussion and create multiple opportunities for improving these forms, and thereby improve one of the most important aspects of our human subjects protections system.
For More On The Revised Common Rule and Informed Consent, see our previous article on Consent Waivers
The Revised Common Rule and Informed Consent: Consent Waivers
The Revised Common Rule has a few important changes regarding consent waivers.
Under the revised Common Rule, broad consent is provided as an alternative to the informed consent requirements for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. If an individual was asked and refused to provide broad consent, the IRB is prohibited from waiving informed consent at a later date for the use of the subject’s identifiable private information or identifiable biospecimens in a secondary study. This means that this information must be tracked. This may be complicated, particularly for larger health care institutions and systems, and therefore the broad consent mechanism may not be widely utilized.
Of note is that the use of the individual’s materials in a nonidentifiable manner in secondary research continues to be permissible, even if there was a refusal to broad consent, since this particular use would not otherwise require a waiver of informed consent since the activity does not constitute research with human subjects.
The Revised Common Rule also adds a new waiver criterion. In order to waiver or alter consent, the IRB must find and document the following:
- The research involves no more than minimal risk to subjects;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects;
- The research could not practicably be carried out without the requested waiver or alteration;
- (New as of January 21, 2019) If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format; and
- Whenever appropriate, the subjects or legally authorized representative will be provided with additional pertinent information after participation
The term “practicably” has not been clarified in the revised rule.
In the case of recruitment and screening of research subjects, the pre-2018 rule required an IRB to determine that informed consent can be waived under the .116(d) criteria before investigators could record identifiable private information for the purpose of identifying and contacting prospective subjects for a research study. Although not considered a “waiver,” under the new rule, an IRB can approve an investigator’s proposal to obtain information directly from a prospective subject, or to obtain already collected identifiable information or identifiable biospecimens by accessing records or stored biospecimens, for purposes of screening, recruiting, or eligibility assessment, without the informed consent of the prospective subjects.
The Revised Common Rule’s section on waivers or alterations of consent can be complicated, so it is important for research professionals, researchers and IRBs to review the changes and the exceptions.
For More On The Revised Common Rule and Informed Consent, see our previous article on Broad Consent
The Revised Common Rule and Informed Consent: Broad Consent
While the industry waits for additional guidance on the Revised Common Rule, there are some aspects that are worth taking note now. This is a series of blog posts that address various important changes for research professionals to keep in mind as they implement the Revised Common Rule.
BLOG POST #2 — Broad Consent
One of the significant changes in the Revised Common Rule is the introduction of Broad Consent., a new type of consent intended to serve as a substitute for traditional informed consent in certain circumstances. “Broad Consent” is a very specific term in the revised regulations used to describe a regulatory pathway, and is different from the concept of obtaining consent for future use of information or specimens under the prior regulations.
The new regulations also provide two new exempt categories for the storage, maintenance and research use involving identifiable private information or identifiable biospecimens when broad consent has been obtained.
Broad consent may prove to be problematic, particularly for large medical centers or health care systems, due to the documentation requirements. The regulations stipulate that an IRB cannot waive consent for storage, maintenance, or secondary research use of the identifiable information or identifiable biospecimens if an individual was previously asked to provide broad consent and refused. Such tracking requirements may make broad consent very difficult to implement, and may limit its usefulness.
A Broad Consent Form must contain certain elements in order to be valid. The following elements are unique to broad consent, and must be included:
- A general description of the types of research that may be conducted with the information or biospecimens that a reasonable person would need to make a determination
- A description of the identifiable information or biospecimens that might be used in research, whether sharing might occur, and the types of institutions or investigators that might conduct such research
- A description of the period of time allowed that the information or biospecimen would be stored and maintained or used for research purposes (may be indefinite)
- Statement that the subject or LAR will not be provided details about specific research studies that might be conducted using the information or biospecimens including the purposes of the research and that they might have chosen not to consent to some of those specific research studies
- Results may not be disclosed to subjects
- Contact information for questions about rights and storage and use of the information and specimens, and whom to contact if the event of a research-related harm
These elements are required in every broad consent document, and cannot be waived.
For More On The Revised Common Rule and Informed Consent, see our previous article on Concise Summary
The Revised Common Rule and Informed Consent: Concise Summary
While the industry waits for additional guidance on the Revised Common Rule, there are some aspects that are worth taking note now. This is a series of posts that address various important changes for research professionals to keep in mind as they implement the Revised Common Rule.
Consent forms must facilitate comprehension by providing information that a “reasonable person” would understand in order to make an informed decision about whether or not to participate in a clinical research protocol. This includes a brief summary that is concise, focused and includes the key information about the research.
So far there has been very little guidance on the length or specific required content of the summary. It likely depends on the study itself, as well as the patient population that is being asked to participate. This will allow for flexibility in what is included in the summary.
The summary can refer to information included later in the consent, which provides the full context of a study, including its risks and benefits. Generally speaking, these five factors will most likely assist a “reasonable person” in making a decision about study participation:
- The fact that consent is being sought for research and that participation is voluntary
- The purposes of the research, the time commitment that will be expected, and the main procedures
- The most common risks or discomforts to the prospective subject
- Benefits to subject or others that are reasonably expected
- Alternative procedures or courses of treatment, if any, that might be advantageous
- Any significant costs that will be incurred
These new guidelines apply to all federally supported studies, and may also apply to other studies depending on how each institution applies the requirements of 45 CFR 46 across the board to all studies.
It will be important to note in the summary that the key information that is presented up front does not include all of the information related to the study. Potential subjects will need to be advised that in order to have all the details about the study and their participation in it, they will need to refer to the full consent form and also discuss any questions or concerns with the study doctor during the consent process.