Clinical Researcher—April 2018 (Volume 32, Issue 4)
Julie Blasingim, MBA, CIP; Sandra “SAM” Sather, MS, BSN, RN, CCRC, CCRA
The informed consent process is essential to the ethical conduct of research on new medicinal products, therapies, and approaches to improving healthcare. The investigator can use various tools to optimize this process, but the most important feature of informed consent is the investigator’s commitment to high standards in its conduct. This article looks at the institutional review board’s (IRB’s) perspective on the informed consent process, and how electronic informed consent is propelling human research forward.
Technology continues to transform how society receives and retains information. With more people using electronic devices to read and retain information, it is the logical step to do the same for obtaining informed consent in clinical research. Electronic consent (eConsent) solutions can serve as a tool for investigators for obtaining and documenting informed consent, and can help address many of the challenges associated with the traditional, paper-based consent process. Solutions can come in the context of a variety of media, including text, audio, and video features woven together to create a multi-dynamic approach to enhancing subject comprehension. The introduction of eConsent represents a major advancement in comprehension, experiences, and overall clinical research program improvement.
A credit to its many benefits, the interest in eConsent continues to grow, and it is increasingly being adopted by sponsor and contract research organization (CRO) study teams and research institutions. A recent survey capturing the opinions of 146 respondents from 100 biotech, pharmaceutical, CRO, and IRB organizations revealed that the major factors driving eConsent adoption today are the opportunities brought by enhancing understanding and improving overall participant satisfaction.1 Indeed, the momentum of adoption is likely to continue, with 55% of respondents saying that their organizations will adopt eConsent over the next 12 months, rising to 82% by 2020.1
There are many stakeholders involved in implementing an eConsent solution, and this article will provide thoughts from an IRB perspective, including traditional consent vs. eConsent, benefits and opportunities, challenges and barriers, preparation and best practices, and the importance of collaboration among stakeholders.
The Current Consent Process
Informed consent is a requirement set forth by a number of U.S. regulatory authorities, such as the Food and Drug Administration (FDA) through the Federal Policy for the Protection of Human Subjects in Research (the Common Rule), and it is incorporated in international guidelines for conducting human research, including those from the International Council for Harmonization (ICH).
FDA mandates in 21 CFR Part 50.20 of the Code of Federal Regulations, “No investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.”
Often people mistakenly view the term “informed consent” to mean simply obtaining a handwritten signature on a lengthy consent document. The process of informed consent starts when the study begins recruiting participants, and it continues providing the potential participant with adequate information so that he or she can make an informed decision on whether to participate in the research. Potential participants must be allowed ample time to read the consent form, discuss the study with the site study personnel and their friends and family, and ask the study team questions. In addition, the process is an ongoing decision for participants, and they need to decide not only in the beginning, but also throughout their time in the study, if they want to continue their participation when new information arises.
FDA regulations require that an IRB/ethics committee review and have the authority to approve, require revision or modification, or disapprove a study. Sponsors and investigators considering an eConsent solution must obtain IRB/ethics committee approval of the consent document text, technology platform, and embedded media.
Traditional, paper-based informed consent has evolved to be a lengthy document that often includes complex and confusing information for participants, incorporating legal jargon that is of little value to someone trying to make an informed decision as to whether to participate in the research. From an IRB review perspective, a document this complex could be overwhelming for potential participants. As a result, the IRB must evaluate the process in which paper-based informed consent is used, to ensure that there is ample time for the participant to comprehend the information. Further, IRBs often query what measures are in place to assess comprehension, how researchers will answer participant questions, and whether the participant has the option to take the paper-based informed consent home to discuss with others.
A paper-based informed consent is limited to static text, pictures, and diagrams (unlike eConsent, which can include multiple forms of media that may not only provide information in a dynamic way, but include additional resources and information by using links to Internet material [e.g., dictionary]). Version control can also be challenging with traditional informed consent, with sponsor and IRB versions as well as subsequent, site-specific versions.
Changes to a paper informed consent can be slow to disseminate. These changes need to be made across hundreds of sites for a single study, and with a paper-based system, this can take a significant amount of time and logistics, thereby introducing an element of risk. Compliance issues could potentially arise if a site is using an outdated version of the consent because site staff have not yet received the updated approved documents or unintentionally used an outdated or draft version.
Traditional Consent and eConsent: The Differences
No matter the format for the informed consent process—paper, eConsent, or a combination—the responsibilities set forth in the regulations related to the IRB and investigator have not changed; how they are accomplished changes, and some of those in an eConsent environment are performed by the eSystem. The traditional, paper-based process is recognized as having limitations in effectively supporting the IRB and investigator. With so many eConsent options available, it is important to think about each study individually, and how eConsent will impact the informed consent process on a case by case basis.
There are certain elements of consent, from an IRB review and a regulatory perspective, that must be included in any consent, regardless of the format. The following elements are particularly crucial when discussing eConsent:
- A signature is required from either the subject or his/her legally authorized representative, unless a waiver of documentation has been approved by the IRB.
- The process must facilitate comprehension, including the investigator or designee answering the subject’s questions prior to signing.
- Language must be understandable and not include exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights.
An IRB’s review of eConsent is essentially focused on protecting the human subject and ensuring that each participant is offered a comprehensive and informative consent process. This includes assessing how eConsent can contribute to better protection for individuals participating in research.
What is different?
- The Interface. eConsent is more interactive, and can include text, graphics, audiovisual, animation, website links, and more, which can also result in more information being available to participants.
- Subject Comprehension. eConsent has the potential to help improve subject comprehension by providing hyperlinks to more detailed information about a particular subject area.
- Timely Adjustments. Depending on the vendor, eConsent allows for version control by only providing the latest approved version to the site to use, and for more timely amendments to implementation/subject notification.
- Improved Oversight. Greater sponsor and CRO oversight of the study, resulting from greater access to timely data collected during the informed consent process.
- Subject Familiarity. Many people prefer to view information electronically because they use similar devices in their everyday lives.
Opportunities with eConsent
Most IRBs are aware of the issues with paper-based informed consent and embrace eConsent for its significant enhancements to the consent process. eConsent offers many opportunities to improve subject enrollment and retention and the ability for researchers to oversee these. There is also the opportunity to present information better, with better assessment of an individual’s comprehension that can be built right into the system. For example, in eConsent, the flow of information can be adapted so that it is not a linear page of words.
Having the ability for someone to take a break, track their progress, and/or ask questions as they go along results in better-informed participants who are making an informed decision when they commit to being in the study (and they understand what their compliance requirements are). Better-informed participants are more likely to stay on a trial and be more committed.
However, 44% of people asked in recent research said that concerns over gaining IRB approval of eConsent was a barrier to implementation.2 In the U.S., there is a lot of acceptance of eConsent, especially when working closely with an IRB upfront, before study review. From an IRB perspective, benefits include:
- Better Subject Comprehension. Having an interactive interface, such as the audio/visual effects and hyperlinks that are typically included within eConsent, may help facilitate not only the subject’s understanding of the information presented, but also his/her ability to retain the information.
- Transparency, Auditability, and Control. eConsent solutions can track how long individuals are on any given page, if participants skipped a page or skipped something that may be of value, and pages where they flagged questions. Many systems include a way for subjects to highlight text that they may not understand in order to discuss it with the investigator, and many have a way to “test” the subjects’ understanding of the information, whether it be at the end of the consent process or anytime throughout.
- eConsent can be integrated or tracked into other eSystems.
- Informed Consent Form (ICF) Version Control. Version control is tightly tracked and managed by most platforms, and there is a much quicker way to close past versions of the consent and disseminate new updated consents to participating sites.
- From an IRB perspective, there is also the ability to quickly stop individual sites from accessing ICFs if there are any noncompliance issues or unanticipated problems, or to verify that a site is using the correct version for more critical and timely reconsenting needs.
- Faster Processes. Integration and dissemination of new information (e.g., risks, additional procedures, etc.) can be handled much faster in an eConsent solution.
- Working with an IRB upfront promotes timely entry of eConsent data into the study databases and allows for more timely collection of the subjects’ informed consent from remote locations.
However, the adoption of an eSystem to support consent brings some risk and the need for sites, sponsors, and IRBs to determine the impact on their consent processes. The challenges and barriers to adopting eConsent at many sites come from the lack of experience with eConsent to support the better understanding of the following:
- Cost/return on investment
- Change management for the site, sponsor, and IRB study team adoption into current quality systems
- For consent development, the ability for ICF content contributors to easily edit and communicate changes needed
- Participant adoption/comfort
- Perceived IRB acceptance of the multimedia format
- IRB oversight (will IRBs have access to the system tracking?)
- Impact on compliance
- Variability in regulatory requirements for eSystems
- Consistency in approach from vendors related to what part of the consent process is documented by the system, within the system, or outside the system (e.g., site discussion with the participant about his or her study questions)
Sponsors, CROs, sites, and eConsent vendors typically describe the above as barriers or typical management challenges associated with implementing a new technology in an area that is highly regulated and has a high personal touch to it. The above challenges can be grouped into four areas: 1) the impact to the study team’s informed consent quality systems, 2) the cost or return on investment, 3) adoption—will the people participating in the studies be comfortable with it, and 4) the regulatory/IRB considerations—will the solution meet all the requirements.
For the IRB, reviewing an eConsent is quite different from reviewing a paper-based consent. Unlike with electronic participant-reported outcome (ePRO) systems, where the IRB only approves the content, the IRB reviews both the eConsent content and the eConsent platform. This means reviewing just a Word document of eConsent content or screenshots is not sufficient—the IRB needs to also review the content in the same context as a participant will review it, so reviewers need to see the complete eConsent system, including any hyperlinked or interactive portions.
Beyond the elements of consent, the IRB looks for aspects such as ease of navigation, identity verification, remote consenting as an option, system security, and additional comprehension measures or features that are only available because the consent is electronic. To gain approval, the following must be considered:
- All elements of consent must be included
- Adequate study information
- Process—place, method, acceptable time of Q&A
- That process facilitates a subject’s or potential subject’s comprehension
- Documentation of informed consent
- Language understandable to participants
- Security of data collected and shared
The format is also different. Because every eConsent platform is different, IRBs need to have flexible review processes to accommodate the variety of review methods available. Developing a review process around one platform can create unnecessary submission requirements and may distract the IRB from important review elements. Different elements include paper, storyboards, graphics, hyperlinks, videos, and final formatted layouts.
The following should be completed upfront to facilitate speedy IRB approval:
- Encourage the IRB and eConsent vendor to collaborate. Collaboration is key with all stakeholders, including sponsors, ethics committees, vendors, research sites, etc.
- Try to work with representatives from an IRB and vendor who are willing to collaborate—this is critical as early in the process as possible.
- Choose an IRB that supports and has experience in e-collaboration.
- In advance, the IRB receives information regarding:
- Security features
- Security access
- Signature requirements
- Change management
- Principal investigator/site training
- IRB pre-approves system for study and any future study with the vendor.
- Vendor provides IRB with access to the eConsent system so that study-specific eConsents can be reviewed in the native environment.
Best Practices at Protocol and Site Levels
There have been many changes over the last few years regarding acceptance of eConsent and a greater shift toward its use. Ultimately, better-informed research participants are better research participants: they understand more, so they are more likely to stay on for the duration of the study. eConsent will likely continue to integrate into other subject notification systems for ongoing information about the study, including study results (i.e., lay summaries) and critical new information that needs to be immediately communicated to the participants.
It is easy to see the benefits of eConsent and support its usage—when implemented properly, eConsent makes some real improvements to the informed consent process, which is in everyone’s best interest. The logistics of using eConsent—and collaboration and communication between IRBs, study sponsors, researchers, and eConsent vendors—are critical concerns as stakeholders work toward an efficient and thorough review process. eConsent may take more time than the traditional, paper-based consent process, but it’s worthwhile.
- Sather S. 2017. Surveying the state of eConsent: are there still barriers to be broken down? Appl Clin Trials. appliedclinicaltrialsonline.com/surveying-state-econsent-are-there-still-barriers-be-broken-down
- CRF Health. 2017. Webinar recording presented by Sandra “SAM” Sather. Visibility and oversight: what paper informed consent isn’t offering you. http://resources.crfhealth.com/webinars/visibility-and-oversight-what-paper-informed-consent-isnt-offering-you
|Julie Blasingim, MBA, CIP, (Julie.Blasingim@Advarra.com) is Director of IRB Reviews at Advarra IRB.|
|Sandra “SAM” Sather, MS, BSN, RN, CCRC, CCRA, (firstname.lastname@example.org) is Vice President at Clinical Pathways, LLC and a Regulatory and Quality Consultant for TrialConsent at CRF Health.|