“From Paper to Screen: Regulatory and Operational Considerations for Modernizing the Informed Consent Process”
Electronic platforms hold potential to improve the informed consent (IC) process by incorporating graphics, self-pacing, meaningful engagement, and access to additional information on demand. These elements have been shown to increase research participant understanding and satisfaction. This paper examines the experience of two Alzheimer’s Disease Research Center (ADRC) study teams who transitioned from a paper-based IC process to an electronic informed consent (eIC) process. These experiences will highlight some of the operational and regulatory challenges of eIC and explore how study teams and institutional review boards (IRBs) can navigate them. Key regulations and operational considerations will be emphasized.
The Belmont Report and key U.S. regulations governing human subjects research (e.g., the Common Rule [45 CFR 46.116]; Food and Drug Administration (FDA) regulations [21 CFR 50.20]), mandate that individuals be given the opportunity, to the degree they are capable, to choose whether to participate in research.
The U.S. Department of Health and Human Services (HHS) noted that IC documents are:
a) Excessively lengthy
b) Written in highly technical language
c) Perceived as legal documents meant to protect institutions rather than decision-making resources for potential research participants
The revised 2018 Common Rule thus included expectations that explicitly require the IC process to be organized and presented to facilitate participant comprehension. Web-based technologies can present the IC process as most individuals would regularly access information. Electronic IC platforms can thereby address comprehension challenges, reach a wider range of participants, and engage those who might be excluded from research participation.
ADRC study teams at Emory University and University of Wisconsin–Madison collaborated with Sage Bionetworks to transition from a paper-based to an eIC approach that considered the needs of (a) individuals with potential memory disorders and decreased decision-making capacity and (b) healthy controls.
eIC Regulations Considerations
The Common Rule communicates that consent forms may be signed electronically (45 CFR 46.117). In comparison, FDA regulations (21 CFR 11 aka “Part 11”) include requirements for any system capturing an electronic signature to be secure with restricted access, includes a method for validation, and produces an audit trail. Study teams must consider whether the HIPAA Privacy Rule applies and, if so, whether a separate authorization to use protected health information will be required.
eIC Tool Features
The ADRC team’s eIC tool began with a concise summary of the study followed by study details grouped into a table of contents presented as modules in a grid. The team created a participant-centered IC experience by:
a) Simplifying the language and presenting information in modules
b) Representing themes with iconography and graphics
c) Allowing participants to choose the order they view the modules
d) Providing optional (tiered) information about specific concepts
One major feature of the researchers’ eIC tool to aid enrolled individuals with memory deficits/mild cognitive impairments was that multiple-choice questions were listed following each module rather than at the end of the IC interaction. This tool can identify misunderstandings, lead to conversations that address knowledge gaps, and help potential research participants stay focused on the IC session.
eIC Regulatory Oversight and Logistical Challenges
IRBs and study teams should work together to develop a plan that addresses each of the following areas:
(1) Presenting the eIC experience to the IRB and tracking changes
(2) Retaining records
(3) Documenting the IC
(4) Providing a copy of the IC
Research teams are recommended to provide participants with a summary that highlights key information about the research study and which participants can either print either in tangible form or save electronically for easy reference. IRBs often require written representation of IC information to be stamped to assist study teams with tracking approved document versions. IRBs and study teams need to be flexible and develop procedures to identify these documents, such as using REDCap to generate PDFs that may be stamped.
Core Versus Optional Information
An interactive eIC tool can better meet some of the expectations outlined in the Common Rule for IC compared with a paper-based or eIC approach alone because the interactive features give participants more agency in determining the level of detail and order in which to consume the information. This tailored information approach is facilitated through hyperlinks and pop ups.
The Common Rule obligates IRBs to ensure the IC process includes information that a reasonable person would want to have to make an informed decision about whether to participate. The Common Rule does not define “reasonable person,” making it challenging to operationalize this standard.
The ADRC eIC incorporated the following to be responsive to the reasonable person standard:
a) A tiered-information approach that ensured individuals received core research information and allowed them to access supplemental information as desired.
b) A modular approach with iconography, simplified language (at the middle-school reading level), definitions, and glossary of terms
One of the key decisions the ADRC team made in collaboration with the local IRBs was determining what information could be tiered, resulting in:
a) Core information: presented to all and considered essential to decision making
b) Optional information: accessible on-demand via a popup window if the reader clicked the hyperlink
Several additional factors can affect the development of eIC, such as:
a) State laws: i.e. restrictions on what platforms may be used to capture electronic signatures or specific requirements for IC language and font size
b) Single IRB: any local context requirements and site-specific language related to eIC will need to be communicated to the reviewing IRB
c) Posting Clinical Trial Consent Forms: to a publicly available federal website
d) Non-English Speakers: Translation and interpretation needs should be factored into the development of any IC process
e) Assent: the development of age-appropriate materials if an assent process is required for studies involving children
Research teams developing eIC processes should consult with their IRB early on to ensure the team addresses applicable regulations, understands IRB review requirements, and factors in tracking, versioning, and maintaining materials involved in an eIC process.
IRBs must ensure eIC approaches improve the IC process. Wider adoption of interactive eIC experiences can enhance participant engagement and understanding and reduce potential selection bias. Increased use of eIC likely will become a mainstay of research and provides an opportunity to better meet the expectations for IC outlined in the revised Common Rule.