Enhancing Informed Consent Communications

The Declaration of Helsinki outlines fundamental ethical principles for human-participant medical research. Its succinct description of informed consent is the basis for any clinical trial’s essential requirement: obtaining participants’ free and informed consent for trial participation. These many groups have provided ample guidance and perspectives regarding the legal, regulatory, ethical, moral, institutional, and social aspects of the informed consent process:

• Legislative and regulatory bodies
• Researchers
• Research ethics organizations
• Industry associations
• Commercial companies
• Patient organizations
• Patient advocacy groups

Despite all these resources, successfully achieving informed consent is notably challenging. The success depends on various factors, including:

• Compliance with regulatory controls
• Availability of adequate information
• Patients’ comprehension of information
• Patients’ capacity for independent decision-making
• Trusting, respectful communication and relationships between researchers and patients

The complexity of each factor highlights the challenges of the informed consent process. There are also more practical questions, including:

• How can you meet the requirement for preparation of “comprehensive” yet “concise” trial information for prospective trial participants?
• How does one ensure informed consent communications meet the patient’s individual information needs?
• How can the informed consent process continuity be supported throughout the trial?

Considering all these factors, trial sponsors and researchers must achieve informed consent by considering and balancing these five key factors.

#1 Regulatory Requirements

Complex legislative and regulatory frameworks underpin the research environment of clinical trials. Understanding and complying with the full scope of requirements for obtaining informed consent (as applicable to a specific country) is essential.

For instance, consider clinical trials conducted in the European Union and European Economic Area (EU/EEA). In these locations, overall provisions for protecting trial participants and informed consent are outlined at the supranational level in the European Clinical Trials Regulation (CTR). The CTR covers:

• General rules for informed consent (art. 28 and art. 29)
• Informed consent by simplified means in cluster trials (in which groups or “clusters” of individuals rather than individuals themselves are randomly allocated to different investigational interventions) (art. 30)
• Informed consent in trials on incapacitated participants (art. 31), minors (art. 32), pregnant or breastfeeding women (art. 33), and other vulnerable populations (art. 34)
• Trials in emergencies (art. 35)

The CTR also clearly defines informed consent as having “an intrinsically national nature,” thus including respective national provisions in requirements. The national requirements are based on laws of the respective EU/EEA country where the recruitment takes place and may include (non-exhaustive list):

• Qualification requirements for research staff who can conduct informed consent discussions.
• The definition of “legally designated representative,” where such representative acts on behalf of the person unable to give informed consent.
• The requirement for signatures. For example, signatures of both the legally designated representative (informed consent) and a minor (assent) may be required if the minor can form an opinion and assess information provided.
• Applicability of simplified means for obtaining informed consent.

At the trial level, informed consent is a critical process. For industry stakeholders, compliance with informed consent requirements would be included in compliance and risk management at a system level (standard operating procedures, computerized systems, personnel), as established by the Good Clinical Practice (GCP).

#2 Adequate and Suitable Trial Information

The informed consent process isn’t limited to information provided in the patient information sheet or leaflet (PIS/PIL), informed consent form (ICF), or assent form. However, people often criticize these documents for their length and difficulty for patients to comprehend. Reducing word count may work if the underlying problem is verbose writing. Of course, this tactic may not help in all cases. A required level of essential information must be included in these documents for regulatory compliance. The design of a clinical trial, or the nature of its investigational medicinal product or investigational procedure, may also necessitate a more explanatory and lengthier description to ensure the information’s comprehensiveness.

More extensive explanatory descriptions emphasize the potential of patient involvement to help researchers. Patients may be able to assist in finding balance between comprehensive and concise information, ensuring patient communications are clear to a layperson. The European Patients’ Academy on Therapeutic Innovation (EUPATI)’s toolbox contains examples of collaboration between researchers, patients, and pharmaceutical organizations in co-developing ICFs and assent forms. Patient involvement may lead to innovative approaches to the format, content, and quality of writing. These examples also highlight some additional benefits: shortened review timelines from research ethics review bodies and fewer comments from them. Learnings and insights into patient involvement challenges are also helpful. These include trade-offs between what’s desired and realistically feasible, as well as considerations around planning, time, and costs of facilitating involvement.

#3 Meeting Patient’s Individual Information Needs

Patients’ difficulty in understanding trial information often happens when it’s inadequate. However, it’s also challenging for participants to understand trial information when they receive too much at once. The European Patients Forum (EPF)’s position paper on informed consent argues that information overload may impede a patient’s understanding of potential risks and benefits in trial participation. Thus, a flexible and tailored approach to information delivery (as advocated by the EPF) is as critical to meeting the patient’s individual needs as receiving high-quality information.

The connection between meeting a patient’s individual information needs and achieving a successful informed consent interview is also highlighted in the Clinical Trials Transformation Initiative (CTTI)’s recommendations on informed consent. A discussion aid tool, developed by industry, academia, and patient advocacy representatives, identifies specific individual characteristics that must be considered. Among these are patients’:

• Learning style
• Language facility
• Education level
• Health literacy
• Interest in learning as much as possible
• Comfort with numbers/probabilities
• Disabilities that may hinder the informed consent process.

Personalization and customization of communication will likely add significant time pressure at the operational level. The study by O’Sullivan and colleagues examined views on the informed consent process from research participants and staff. One finding is that insufficient time is a notable limiting factor to researchers’ ability to facilitate an optimal informed consent process. Ensuring adequate time for researchers to provide the information and confirm patients’ understanding of that information will significantly help advance patient-centricity.

#4 Informed Consent Enablers

Three key technological, methodological, and communication enablers could help trial sponsors and researchers meet patients’ individual information needs.

1. Using digital tools may improve patients’ understanding of the provided trial information, as well as enhance their overall informed consent experience. These tools may include:

• Videos
• Interactive and non-interactive multimedia aids
• Dedicated electronic systems for consent (eConsent), where trial information is provided, and consent is captured via an electronic device such as a smartphone or a tablet.

Digital tools should be chosen with the target patient population in mind. For example, findings of the systematic review of digital tools in the informed consent process by Gesualdo and colleagues suggest combining different multimedia formats (slides, audio, video, graphics) and engaging the patient through interaction with the digital technology (such as to verify understanding). This was found to be more effective in improving both understanding and satisfaction when compared with only using videos.

The considerations for the set-up and implementation of eConsent are outside the scope of this blog post due to their broad, complex nature. As with the paper-based method, digital tools to support patient communication and informed consent are subject to prior approval by respective research ethics review bodies. It’s vital to remember not every patient may be able or willing to use digital tools. When this is the case, trial sponsors or researchers should make available alternative methods for providing information and/or documentation of consent.

2. Both prospective trial participants and research teams may benefit from receiving training and education on informed consent. For example, training research staff on plain language and health literacy can offer guidance and demonstrate the importance of clear and simple language when communicating with patients, caregivers, or other involved persons. This training can also show how plain language communication helps patients make an informed choice about participating in a trial.

Prospective trial participants may benefit from being educated on the informed consent process itself. Having a better understanding of its concept, components, their rights, and the obligations and responsibilities of the research team may encourage them to become more active and engaged participants in the process. More active patient engagement will enable a more meaningful interaction and trusting connection between the research staff and the patient, thus attaining the prerequisites for the successful informed consent process.

3. The trial information provided to a (prospective) trial participant should be in a language they easily understand. Enrolling a diverse patient population ensures the research teams will encounter eligible participants with little or no command of the language of the trial. Advance planning of language support is essential in this case, especially because of varying requirements for how language support is organized, documented, and reported. For example, research ethics review bodies may have specific requirements concerning usage of approved document templates, content of the certificate of translation, provision of back-translations, or the timeframe for the submission of updated translations.

Through professional language service providers, trial sponsors or researchers may arrange language support (interpreting and/or translation) globally. When appropriate, language support may also be organized on an ad-hoc basis through research staff who are fluent in the language. Naturally, when a prospective participant provides informed consent for participation, requirements for adequate language support extend to the whole trial duration. Language support may also facilitate post-trial communication, such as sharing lay summaries of trial results.

#5 Ongoing Informed Consent

Obtaining informed consent in a clinical trial is an ongoing process. As the trial progresses, new significant information (for example, about new medical procedures in the trial) may become available. The GCP requires such information to be communicated to the trial participant or their legally designated representative in a timely manner. This is because this new information may impact the patient’s decision to participate. In these circumstances, the process of “re-consent” is initiated (and will trigger the update of the ICF/assent form and written information already provided). Another case when re-consent is necessary is when a minor participant reaches the age of legal competence (as defined in national law). In this situation, such as the case for clinical trials under the CTR, their participation would be terminated unless they confirm consent to continued participation by signing an ICF after being properly informed.

The above cases show examples of the “required” informed consent communication that must happen after obtaining initial consent. However, the spirit of informed consent necessitates an ethical requirement for ongoing and transparent communication throughout a trial. The CTTI’s recommendations on informed consent propose frequent follow-up conversations, study reminders, and updates about study progress. Indeed, by keeping communication open and accessible, researchers ensure trial participants always have the information they need to make informed decisions.

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Learn more about how Lionbridge’s Life Sciences translation services can help your team create better, more effective communications for prospective and current trial participants. Our clinical trial translation services facilitate informed consent throughout the entire clinical trial process. With our clinical research translation, you can reach a more diverse, multilingual patient population and ensure they have the information they need to make an informed choice about trial participation. Reach out to us today to learn more about our clinical translation services.