Informed consent can be defined as providing a potential participant with enough information about a study to allow for an informed decision about their participation in a clinical trial. The process is a vital one revolving around participant education and communication, and one that is highly controlled through local, country-specific, and global regulations.
While informed consent form (ICF) signatures traditionally have been collected on paper at a physical site, today’s digital approach — electronic consent (eConsent) — offers more than high-tech signature collection. It provides an upgrade to patient education and communication as well, empowering participants in new ways. Moreover, eConsent can democratize clinical trial access, allowing researchers to recruit broader and more diverse participant groups through entirely remote consenting processes. This broader and less burdensome access also can increase the speed of recruitment and reduce drop-out rates.
In addition, when the eConsent solution is part of a larger platform for decentralized clinical trials (DCTs), it can facilitate automated workflows to further reduce both trial site and patient burden. Plus, as part of an interactive multimedia experience, eConsent offers the opportunity to present information in new and interesting ways to aid in reaching participants with various learning styles.
While the eConsent experience offers a number of opportunities for enhanced communication, it’s important to recognize that it is not a replacement for discussions between clinical trial site staff and trial participants. This discussion, facilitated by the consent documents, will always remain the bedrock of the informed consent process.
Informed consent forms (ICFs) can be difficult for some clinical trial participants to understand. For starters, today’s ICFs are far longer than those of decades ago. In one review, ICFs averaged between 10 and 20 pages in length and were frequently written at higher-than-eighth-grade level. Clinical trial designs are increasingly complex, and the language often used on ICFs is often too technical for those with average or below-average literacy levels.
In a recent review of four COVID-19 vaccine trial ICFs, all ICFs were written above a ninth-grade reading level and required approximately 35 minutes to read. Further adding to the complexity of the informed consent documents is the environment in which they are presented. The experience of being presented with a complex 20-page document that often has a very legal appearance in a surgical center, hospital or doctor’s waiting room was often described as intimidating during a discussion with the Medable Patient Advisory Council.
For trial sponsors that are committed to a better ICF experience, finding a way to communicate clearly with participants, and in a setting that is better suited to comprehension, is paramount. That can be accomplished by simplifying ICFs — that is, reducing the amount of pages to wade through and writing in plain language for readability. Another tool to improve comprehension is eConsent. The objectives of an eConsent process are:
Consistency. A well-designed eConsent provides an opportunity for study designers to thoroughly and consistently explain the study to participants using a broader range of tools, including multimedia, interactive knowledge checks, tiered information, and links to websites.
Patient empowerment. With clear explanations presented in an easier-to-understand format, eConsent empowers patients to make more knowledgeable, informed decisions and feel confident moving forward in the study. Plus, participants can digest information at their own pace in a comfortable setting of their choice.
Patient engagement. The dynamic interface engages participants, which enhances patient recruitment and retention.
Less burden. eConsent reduces the burden on clinical trial site staff by enabling a remote patient screening and paperless consent process.
Improved data management. The digital process eases the retrieval of source documents for inspections, audits, and monitoring and enhances oversight with real-time data reporting to both sites and sponsors.
More efficient workflows. Utilizing eConsent enables improved quality and efficiency for clinical trials through the automation of workflows, integrations, and reducing the administrative burden.
eConsent’s Impact on Patient Enrollment, Recruitment, and Retention
Adopting a remote consenting and screening process allows researchers to cast a wider net in recruiting participants. Minimizing the need for participants to travel also allows for a more diverse participant pool. Recent research has demonstrated the high travel burden experienced by clinical trial participants. This travel burden reduces the likelihood of participation, shining light on reasons why only an estimated 4% of patients participate in a trial. Using remote consent to reduce the initial burden can greatly enhance access to clinical research trials.
The average number of patient dropouts for clinical trials is roughly 30%, and participant dropout is costly — making the work of retention as critical as recruitment. The consent process is a major driver of keeping participants enrolled. Traditional informed consent forms can be confusing, and when patients don’t understand what’s required of them, they are more inclined to drop out of the study. In fact, one research review indicated that 35% of patients who dropped out of a study early said the ICF was hard to understand compared with 16% who completed the trial.
Patients are more likely to stay in a study if their informed consent process appropriately sets expectations, including what study participation will entail, what is required of the participant, and where to turn should questions arise — all of which can be better supported through eConsent than traditional paper.
Using eConsent to communicate with patients in an engaging way can help boost recruitment and retention, as potential participants feel informed, empowered, and confident in their choices.
Reducing Quality Risks with eConsent
A paper consent process also carries a number of quality risks. Since 2018, over a third of all 483 FDA Warning Letters related to issues with the informed consent process, including when the consent process took place, who conducted the consent process, and who signed the consent form. Similar findings can be observed with EMA[AM1], and European Regulator Inspections, where issues with the informed consent process represent one of the most common reasons for critical issues as well as spontaneous notifications for GCP breaches. An eConsent aids in the accurate, real-time capture of these data points and makes it easy for trial staff to easily access participant consent forms should the need arise.
FDA Warning Letters also called out trial sponsors for using old and out-of-date versions of the consent form and a lack of documentation. With eConsent, the risk of sending old or outdated forms is mitigated, as once an ICF is updated on the platform, sponsors are assured that all future participants will receive the latest version. Plus, the eConsent process is clearly defined in the platform, and documents are easy to pull for IRBs, regulators or others.
Electronic consent offers numerous benefits to everyone involved in the clinical trial process, specifically:
For patients. Electronic consent offers patients a more engaging experience. Videos, images, audio, charts, and diagrams help guide patients through the informed consent process, helping them understand the study’s design and research objectives as well as what is expected of them as a study participant. Patients can review materials in the comfort of their over home in a low-stress environment. It’s no wonder, then, that research shows patients prefer eConsent to traditional paper ICF.
For sites. For trial sites, an eConsent process reduces the burden on staff — eliminating paper burden and making documentation easier to find. While interaction and conversations with patients will always be important and necessary, stronger communication via eConsent reduces the number of questions patients have. Plus, eConsent allows for the automation of workflows and reduces administrative burden. Sites also benefit from broader recruitment and retention. When up to 50% of trials are not completed because of insufficient enrollment, a larger potential participant pool can be an important differentiator for sites. Such is the interest in eConsent that a recent survey published in Nature [AM2] showed that 59% of investigators expect the use of eConsent to increase and 40% rating it in the top 3 most valuable technologies.
For ethics committees/regulatory authorities. The digital process makes it easier to retrieve the source data for inspections, audits, and monitoring. eConsent can document patient comprehension, while capturing investigator and patient agreements to proceed. Having access to digital records helps set the foundation for ongoing digital engagement between sites and patients.
For sponsors. Study sponsors benefit from the ability to recruit and enroll a more diverse patient population, which enhances their research. Plus, they experience streamlined workflows and enhanced data quality and compliance, and they see increased transparency with real-time reporting and insight into study progress. eConsent also eliminates many of the quality issues noted in regulatory inspections, with the system controlling when and who conducts the process, automatically archiving the obsolete consent forms, and providing automated documentation of the consenting process.
There are a handful of misconceptions around eConsent, but they can be effectively overcome.
Initial investment. Although the implementation of an eConsent process requires an initial investment of both time and money, neither should be a significant concern. When properly managed, the implementation of an eConsent system can be completed alongside the set-up of the trial, and the initial investment will be minimal compared with the return on investment gained through decreased recruitment time, reduced patient drop-out, and fewer issues with quality. With a risk-adjusted financial model[AM3] , sponsors can more effectively assess how patient engagement activities impact enrollment, adherence, and retention.
Stakeholder discomfort. Moving to a digital consent process can be effectively managed with change management strategies. Clear communications with sites, patients, ethics committees or IRBs and health authorities can ensure all stakeholders understand the benefits of eConsent and support its use.
Technical requirements. eConsent platforms can often require a specific device, such as a tablet, for both patient and site. But Medable’s eConsent solution is offered across all web-enabled devices, such as smartphones, tablets, laptops, and desktop computers, and across all four major browsers. This flexibility significantly broadens access and minimizes the obstacles to this enhanced consenting process, especially with the increasing level of personal technology around the globe.
Regulatory Considerations and Adoption
As you consider whether eConsent makes sense for your study, it’s wise to review the guidance from the U.S. Food & Drug Administration (FDA). According to the FDA’s guidance, researchers can use eConsent to aid in the following:
- Protecting patients’ rights and safety
- Facilitating patients’ understanding of the information presented in the ICF
- Obtaining appropriate documentation of consent
- Ensuring data quality
The FDA’s guidance provides information on how to present information in the eConsent, how to conduct the eConsent process, how to answer participants’ questions and provide additional information, how to use eSignatures, and more.
ICH E6(R3) Good Clinical Practice
The International Council for Harmonisation (ICH) E6 Good Clinical Practice Guideline is a common reference for researchers. The ICH E6(R3) Expert Working Group released an initial draft [AM4] of their updated Good Clinical Practice guidelines in April 2021, which include guidance on informed consent. This guidance includes direction to sponsors to give consideration to the potential use of technology to inform participants and obtain informed consent, highlighting the acknowledgement of the benefits of eConsent and the expectation of its growing use.
International digital signature considerations
Another regulatory consideration is the acceptance of eSignatures around the world. Countries fall into a few categories:
eConsent is explicitly permitted. These countries, which include the U.S. and the United Kingdom, have what is known as minimalist laws, allowing eSignatures to be enforceable in almost all situations and give the same weight to an eSignature as a handwritten signature.
eConsent is explicitly denied. In a handful of countries, such as Austria, eConsent is not allowed.
eConsent guidance is vague. In these countries, such as Spain and Italy, eSignatures might be accepted if compliant with eIDAS [AM5] requirements, but there isn’t specific guidance on whether eConsent and eSignature can be used for clinical trials.
With Medable’s extensive experience working in eConsent’s mixed regulatory landscape, we can help trial sponsors navigate the international regulatory challenges that arise. Plus, the flexibility of the Medable platform enables the accommodation of multiple countries in a single deployment — allowing for a range of signature-collection methods based on each country’s regulatory requirements.
Regulatory considerations also center around local Institutional Review Boards (IRB) or Ethics Committees (EC). The IRB or EC is responsible for reviewing the informed consent form and process to ensure compliance and patient safety, and it’s important to understand what the IRB needs in order to grant its approval. The required elements of informed consent, for example, are essential regardless of whether you’re using a traditional paper ICF or eConsent.
An IRB will often require review of the informed consent process as well as the informed consent content. IRBs tend to view eConsent systems quite favorably, acknowledging their benefits around participant comprehension and quality. Reviewing the platform from the perspective of a participant to assess the user experience before granting study is critical.
Through experience in deploying the eConsent platform across multiple global studies, Medable has developed both an experiential and regulatory insight knowledge set to help navigate the complex global landscape. Each study team implementing the Medable platform is provided access to our IRB/Regulatory Submission Pack designed to guide teams through the process.