The informed consent process is fundamental to every clinical trial. Study participants must be provided with sufficient information to understand the study, its procedures and commitments, the possible treatments they may receive, and any possible risks involved. Conveying this quantity of information in a way that is easily consumed and understood remains a challenge, with current paper informed consent forms (ICFs) often spanning 15 to 20 pages of densely typed material. Perhaps it is not surprising that early drop-out due to not fully understanding study requirements remains in the top three reasons for early withdrawals from clinical trials.
Electronic informed consent (eConsent) solutions promise to improve the comprehension of study information through the use of multimedia (e.g., video and audio) and interactivity, which can make consuming complicated information more engaging and help limit potential functional literacy concerns. The use of interactive quizzes, for example, can provide engaging components and help to test understanding, which can be reinforced during investigator-participant discussion.
Moreover, eConsent offers solutions to current issues with the paper process. First, by ensuring clear signature and time/date stamping and that the correct versions of each consenting document are used at all times, eConsent solutions remove possible ambiguity in the signature process – a common reason for inspection findings. Second, eConsent solutions simplify the consent and re-consent process throughout the study with effective document and workflow management.
Leveraging these advantages, this article considers six factors important in implementing eConsent at scale across drug development portfolios.
Factor 1. One size does not fit all
Clinical trials vary considerably – from phase I healthy volunteer studies, to prophylactic vaccine trials, to new targeted oncology treatments in patients. The information needed to enable informed consent for each also varies enormously. In some studies, a simple static document may suffice. In others, the use of interactivity and multimedia may be a real benefit in conveying complicated treatment or study information in an effective and engaging manner. That’s why, for certain studies, a simple signature and document management solution – directly leveraging existing PDF versions of the approved ICF – may provide an efficient, cost effective and rapid solution to implement eConsent (Figure 1). The PDF-based model is often the easiest and most cost-efficient method to use for scaling up since it doesn’t require the IRB-approved documents to be recreated in a proprietary system. Despite its simplicity, this solution contains all the advantages of traceability, document version control, and workflow management expected amongst the more sophisticated methods.Figure 1. PDF-Signature Management solution for eConsent using pre-approved PDF ICFs
Contrast this with a fully featured eConsent solution where ICF content is developed within the solution’s inbuilt pages and forms; video, audio and interactive elements can be embedded to aid comprehension; and participants can interact with the content, for example flagging sections to indicate question areas. Perhaps most valuable where complex information needs to be communicated, or where functional literacy is a concern for some participants, this provides a more feature rich approach for other types of studies.
This level of solution flexibility allows study teams to match functionality and implementation models more precisely to their protocols and participant populations. It also affords sponsors the opportunity to implement across low budget and higher budget studies alike, enabling scale up across the development portfolio from Phase I to post-marketing trials.
Factor 2. Re-usability – an essential property to scale up
Elements of eConsent solutions are designed for efficient scale up by enabling re-use of content across trials and programs. Some solutions, for example, have Word/PDF import capabilities that enable electronic solutions to be auto-populated from an existing Word or PDF document, accounting for appropriate sections and structure defined by these versions. This provides a rapid starting point for solution content development using a draft or final document version created outside the design tool. This same import tool can also provide the same rapid import and assembly for different language versions as needed.
Not needing to start from a blank page for each new trial, but leveraging the investment in previous studies, is essential for organisations wishing to implement efficiently across their study portfolio. Library elements of pre-approved content, and re-usable study templates provide a means to enable easy re-use and efficient study content development. Pre-approved content elements should also be associated with pre-approved translated versions as they become available, as discussed below.
Careful consideration of the re-usability of multimedia library assets can facilitate speed and scale up. For example, creating video resources that describe general concepts (e.g., a clinical trials overview, or descriptions of specific treatments and procedures) that may also be needed in future studies in a way that they are sensitive to being culturally appropriate for use in many countries enhances the ability to leverage asset libraries through re-use of material.
Factor 3. The importance of solution flexibility
Scalable solutions require flexibility to enable good application across a range of scenarios.
Fundamental solution properties define certain elements of flexibility that affect scalability. Accommodating right-to-left languages appropriately, for example, provides solution utility in global, multinational studies.
We discuss signature options below as we consider regulatory thinking, but in addition to facilitating “print-to-sign” options for territories requiring wet ink signatures, solutions with broad applicability need to enable the consenting of adults with reduced capacity to consent for themselves, and children. In these situations, the ICF signature process may include the capture of the signature of a legally authorized representative, and (where appropriate) the assent of the participant themselves. This facilitates leveraging the solution in populations such as paediatrics and those with reduced mental capacity, such as Alzheimer’s disease.
Increasingly important as the industry considers greater decentralization of clinical trial components, the ability for solutions to support workflows associated with different administration settings is vital. Scalability to adapt to different usage options, often including within-study flexibility, is an important property. Typical use cases include:
- The study information delivery and consenting process is conducted entirely in-clinic.
- Study information access is provided remotely, ahead of a clinic visit, with the consenting discussion and signature process conducted at site.
- A fully remotely conducted workflow, including telemedicine to enable site-participant discussion ahead of signature decision making.
Fully remote trials, where patient recruitment is conducted beyond the site pool of known patients, may also require additional processes to ensure identity verification, such as qualification through documentation review over telemedicine.
Factor 4. Streamlining translations management
Simple processes for managing the translation and cultural adaptation of master consent documentation in a base language to the individual language versions required by the trial’s participating territories is an essential feature of eConsent solutions. Scalable products enable full visibility of the translation and approval process; simplify the import and export of approved translations provided by translation partners; and facilitate the associated pre-approved library content in multiple language versions for rapid implementation.
Factor 5. Self-service and full-service solutions
Sponsors and CROs seeking to scale up will need to consider how to leverage their existing in-house resources used in the development and management of consent documentation development. In some cases, adapting to a self-service model where internal teams work directly with the eConsent solution design tools to create and manage their own consenting documentation and forms may be an optimal longer-term solution. Selecting a solution provider with both self-service and full-service options is often a key enabler of operating efficiently at scale. In a full-service model, the vendor builds the consent forms and solution to manage the trial, often based on information provided by the sponsor. Self-service can lead to better use of internal resources, and can cut direct costs, while full-service options enable the implementation of more complex requirements or managing peaks in demand to be accomplished seamlessly.
Factor 6. Navigating regulatory thinking
Elements of the consenting process bring additional challenges that are navigable but need careful consideration. Data privacy, for example, raises unique considerations for eConsent compared to other clinical trial technologies. Most clinical trial solutions use pseudonymization to minimize privacy concerns associated with the sensitive health data and information collected. Electronic consent, by its very nature, does not have this option. This raises important requirements around data encryption, data storage and data access controls. Enabling the investigator to authorise a CRA to have access to personal identifiable information (PII) for the purposes of source data verification through system permissions is a necessary feature, but vital this is fully under the control of the investigator. While some may assume that eConsent brings data security and privacy risks, in fact encrypted eConsent systems safeguard the study and participant information through limited access and combining identification codes with passwords. In addition, as discussed above, enhanced traceability and version control in fact leads to fewer deviations and compliance ambiguities, protecting the integrity of the trial.
Processing sensitive personal data is heavily restricted in most jurisdictions. Some countries require wet ink signatures on the consent form, as opposed to electronic or digitized approaches. However, even when a wet ink signature is required, the benefits of a digital process to information delivery and document management still provides significant advantages for those using an electronic solution. Most solutions include a “print-to-sign” option to allow for the administration of the wet ink signature process in territories where this is required.
The FDA’s 2016 guidance on use of electronic informed consent provides a useful perspective on how to address common regulatory questions .
The benefits of eConsent are well understood, and regulatory questions very addressable by good solutions with flexible features. Greater benefits can be observed by scaling the use of eConsent from select studies to use across the portfolio. In addition to associated operational adjustments, sponsors and CROs can benefit from scaled up application by considering solutions that offer the good scalability properties discussed in this article.
Mika Lindroos, Ryan Bowe, Sammar Mekki and Bill Byrom
References: Food and Drug Administration (2016). Use of Electronic Informed Consent: Questions and Answers. Guidance for Institutional Review Boards, Investigators, and Sponsors. https://www.fda.gov/media/116850/download