The Vital and Ongoing Process of Modernizing Informed Consent

Clinical Researcher—July 2021 (Volume 35, Issue 5)


Gary W. Cramer with Alison Holland and Pamela Tenaerts, MD, MBA


In this special interview with thought leaders on clinical research processes from Medable, we concentrate on how clinical trials team members and technology trends are catching up to each other in the pursuit of increased efficiencies in the conduct of informed consent.

Q: Consenting participants across multiple study sites, potentially in multiple countries, is no easy process if sites are using different technology tools or some have electronic informed consent (eConsent) and others are still using paper-based processes. Are major sponsors and sites anywhere near the day when a common, high-tech eConsent tool will be in use in most cases?

A: As voices on inclusivity in clinical trials have become louder, it has never been more important to provide effective support for the informed consent process consistently across multiple locations. Certainly, the pandemic made eConsent a necessity, but even as onsite consenting resumes, technology adoption continues to grow as it helps reduce travel requirements and aids in comprehension and knowledge-sharing to augment the direct physician-to-patient meeting.

Utilizing a flexible eConsent module on a platform that offers other trial technologies, such as televisit and electronic clinical outcome assessment capabilities, reduces site burden when considering the overall trial requirements. Further, an eConsent tool that supports a country- and site-specific approach with workflows for multiple signatories, remote and onsite processes, and digital and print-to-sign capabilities, will ensure that an advanced tool can be applied across a study, or portfolio of studies, offering consistency, standardization, and technology familiarity at the site level.

Alison Holland, Executive General Manager of Decentralized Trials for Medable


Q: Reconsenting of participants due to changes in the study protocol is seen as a necessary, but tedious, practice. How can a more high-tech version of informed consent help?

A: Consent is an ongoing process, often further necessitated by protocol amendments and/or study data updates. With advanced eConsent technology, trial teams have access to consent templates, can create new versions, archive old versions, and change consent language on demand while following the necessary approval steps. It’s critical to ensure participants are always consenting on the right version, and a digital format makes this much easier as electronic workflows are continuously able to be updated. Most eConsent systems also incorporate active version management and are trackable, which dramatically reduces the burden on sites. They offer real-time monitoring of consenting and reconsenting updates, with notifications and reminders plus archiving and audit trail features, ensuring that re-consenting is streamlined for both participants and sites.


Q: What about cases in which the same consent details need to be presented in multiple languages depending on the site locations? Is eConsent technology making the language barrier any easier to handle for research teams?

A: Effective and compliant consenting is underpinned by the need for participant comprehension and knowledge transfer. This remains a critical part of the eConsenting process, making it crucial for solutions to support the local language options approved for use with the anticipated participants. Part of the consenting process can involve direct communication with the participant by the clinical study team, but it can also be done remotely. In addition, eConsent solutions should follow human-centered design principles to provide patients with an intuitive experience and increased modality flexibility. This may include the opportunity to deploy local language multimedia options such as videos. All information, documents, and multimedia must be available for review at any time by participants in their local language.

Multi-language capability in eConsent solutions helps overcome language barriers, as does data localization. Specifically, local cloud data residency supports this on the back end using a poly-nimbus cloud structure to comply with local regulations while making data available to those who need it in their language. Modern eConsent technology incorporates country- and site-specific configurations in local languages and reflects local cultures. Solutions should also provide 24×7 local language support and consider concierge services to enhance the participant experience.

Dr. Pamela Tenaerts, Chief Scientific Officer for Medable

Q: What do we know from experience about how the ease or difficulty of an informed consent’s terminology and the process itself affects potential participants’ likelihood of signing on for a study?

A: Advarra’s recent “Retention in Clinical Trials” survey found that there may be an opportunity to improve patient retention if the consenting process is improved. The study found that 35% of patients who dropped out early cited difficulties understanding the informed consent form. However, eConsent systems that offer the opportunity to use alternative methods to communicate information to the patient, such as videos, audio, or interactive “knowledge checks,” increase comprehension during the consenting process.

At Medable, we are currently deploying more than 45 studies globally that use our eConsent module, generating new evidence around uptake. We are already seeing a dramatic increase in engagement with patients who say they are excited to have more options that allow them to explore entry into a clinical trial from a non-hospital or clinic setting. Being able to dig through all that content in the consent form at their own pace and wherever convenient sets patients up for a much better experience and enhances their engagement with their clinicians/study team. It makes clinical trials more interesting and accessible to patients around the world.


Q: How does one go about scientifically proving or disproving the effectiveness of one way of conducting informed consent vs. another?

A: This is a great question, and something that came up multiple times by viewers of a recent Medable webinar. The truth is, the technology has not been in use long enough across enough different types of studies for there to be a simple answer. To level set, we do not have data on how well the current informed consent process works in a paper environment either, so there is no baseline for comparison. According to a McKinsey study, 62% of clinical trial investigators in the U.S. and 76% in investigators in the U.K. expect e-consent adoption to increase post-pandemic—one potential indicator that consenting through digital mechanisms is beneficial. It is intended to improve the process, increase comprehension, impart greater consistency across trials, remove many time-consuming manual processes, and improve the patient experience.

One of my areas of focus at Medable is to generate evidence on eConsent using specific performance metrics to prove its value. For example, time and date stamps allow us to measure speed and efficiency. Comprehension checks allow us to capture patient feedback around understanding throughout. Further, videos can aid comprehension. We can also use workflow management tools to prevent people from bypassing certain parts or fast-tracking through the informed consent form without reading and understanding everything they are consenting to in the document—another measurement. Again, there is no baseline to measure against, so we need to start on a macro level—for example, are the studies that successfully use eConsent more efficient? Are more patients participating in these trials for the duration?

We will get there. Fortunately, digital technologies finally enable us to develop reliable measuring sticks and a barometer that can grow more granular and reliable over time.

Dr. Tenaerts


Q: What about regulatory concerns over the use of these technologies?

A: There are many regulatory guidelines and rules globally around consenting for trial participation. One to highlight is the current ICH E6(R3) Draft Principles for Good Clinical Practice from the International Council for Harmonization: the third principle in the draft document states, “consent is integrally important for the ethical conduct of a trial.” It now mentions technology as part of this process, showing that regulatory bodies are evolving to support the deployment of eConsent, where applicable. Switching from paper to digital can improve the level of understanding—the “informedness” of this critical process.

When navigating differing regulatory standards, the key is flexibility. A one-size-fits-all system won’t work. For example, in the Code of Federal Regulations the U.S. allows for digital signature capture under the regulation called 21 CFR Part 11 for compliant digital signatures, but there are other countries that require wet signatures only (although this is changing). Direct print-to-sign functionality is helpful in the U.S., but an eConsent system must also incorporate a wet ink document upload feature to allow for real-time review and recall of the patient’s digital consenting form. There will also be personal information identifiers included in the system, so you need a system that can handle these data in accordance with each country’s privacy laws and standards.