ICF in Clinical Trials – A Comprehensive Guide

Making an informed decision: What is informed consent in research?

In order to join a clinical research study or clinical trial, volunteer participants must first be fully aware of the study’s objectives as well as the risks, requirements, and potential benefits of participating. Given all the required information, the prospective participant then makes an informed decision and either accepts and gives their permission (known as informed consent) and enrolls in the study, or decides not to participate. The process of providing this information to the prospective participant, which generally includes a conversation overviewing the written information, is known as the informed consent process.

A fundamental ethical tenet that underpins clinical research is that individuals must be able to make sound decisions regarding their involvement.[¹] The informed consent process must not involve any form of coercion; participants must consent willfully and voluntarily.

Informed consent form (ICF) meaning

The informed consent form, or ICF, refers to the form or document that is provided to prospective volunteers to inform them about the trial, and which is also used to obtain their formal consent.[²] By outlining key information about the study in a written format, the form acts as the source of information as well as the record of confirmation that the participant has given their informed consent. Signing the ICF signifies that the participant has understood the information provided and is willing to voluntarily participate in the trial.

ICF forms also serve as evidence (in the context of regulatory compliance) that researchers have fulfilled their obligation to inform the study participants and obtain their explicit permission. Throughout the clinical trial, the ICF further acts as a legally binding code of ethics to ensure the participant's welfare.

Who signs the ICF in clinical trials?

In clinical trials, the informed consent form (ICF) is signed by the participant and either a qualified member of their research team or the principal investigator[³].

For studies that involve children or adolescents, a parent or legal guardian signs the informed consent form on behalf of the minor. The age at which children can provide their own consent varies between different countries and jurisdictions around the world. It's possible for adolescents (typically defined as those under the age of 18) to provide assent - a term used to denote permission given by a minor. Assent from the minor still requires informed consent from the parent/legal guardian. However, different regions around the world have different laws and ethical codes governing the requirements for obtaining consent from minors. The involvement of parents or legal guardians in the informed consent process plays a critical role in protecting and promoting the welfare of minors during clinical trial studies.

ICF checklist: What must be included?

In order for patients and participants to be well-informed about the study, an informed consent form must contain certain details.[⁴] Even though the elements included in an ICF document can vary depending on applicable regulations and the nature of study, the following are a few fundamental aspects common to most ICFs:

• A clear explanation of the study's objectives and its relevance to the participant's condition or the broader population
• Description of the drug/treatment/device under study, including full disclosure that it is an experimental/investigational product and not an established treatment
• Description of all procedures involved, including any experimental interventions, tests, assessments, and data collection methods
• Disclosure of potential risks, discomforts, side effects, or adverse events associated with participation, including aspects of any travel required for study visits
• Description of the study timeline (procedures, interventions, visits, and expected overall duration)
• Any potential benefits or advantages of participating should be outlined, but must be stated realistically and without exaggeration or bias, and should not be emphasized relative to the rest of the text/information
• Explanation of alternative treatment options or study opportunities that may be available and how they differ from the proposed study
• Clear statement emphasizing that participation is voluntary, and the participants have the right to withdraw from the study at any time without consequences.
• Explanation of any compensation or reimbursement for participation, as well as any potential costs or financial obligations associated with the study.
• Assurance regarding the confidentiality and privacy of participant information, including how data will be used, stored, shared, and protected
• Contact details for the study team, principal investigator, or research coordinator, for the participants to ask questions, report concerns, or obtain additional information
• Mention of the ethical review and oversight body (IRB or IEC) responsible for ensuring participant protection, including relevant contact details

All language used in an ICF or informed consent document (ICD) should be as simple and straightforward as possible, tailored to the health literacy level of the general public and avoiding the use of complex technical jargon. While all of the information needs to be presented truthfully, it is important for the participant to accurately comprehend the details before signing the ICF document. This free resource can be extremely helpful for finding “layman terminology” for explaining common healthcare concepts. The consenting process will usually involve a dialogue with a study team member to confirm comprehension and to allow the participant to clarify any doubts they may have.

What cannot be stated in an ICF?

Just as ICFs must contain certain pieces of information, there are also things that are forbidden from being included in informed consent forms in order to adhere to ethical norms and legal requirements.[⁵] Sponsors are advised against mentioning or implying the following in the ICF:

• Guarantees of safety or effectiveness
• Excessively downplaying potential risks
• Promises of direct medical benefits
• Coercive language or undue influence
• Language that waives participant’s legal rights

Transparency and accuracy are essential elements of an ICF, and it's up to sponsors and researchers to avoid any coercive language or actions that could influence a prospective participant’s rational decision-making process. Regulatory bodies and ethics committees provide guidelines and oversight to help maintain ethical standards and the integrity of the informed consent process in research studies.

ICF development in clinical trials: How to design clear and effective informed consent forms

To ensure clarity and effectiveness in informed consent forms, sponsors can refer to the following suggestions[⁶]:

• Use plain language to make it comprehensible, even for those with low health literacy skills.
• A clear framework is essential for organizing information logically in an orderly manner. Smaller sections of information, organized with subheadings and bullet points, can help improve readability.
• Using special formatting such as bold and italics along with the underlined text is an effective way to accentuate vital pieces of information. Creating a separate dedicated section for said details is another option. This will assist participants in promptly recognizing and understanding the most essential aspects of the study.
• Include examples and visuals to enhance the understanding of complex concepts or procedures
• Don't leave anything out, and be truthful. Provide complete and accurate information to enable the participants to make confident and informed decisions.
• A readability assessment or preliminary testing can help determine how clearly written and understandable the ICF is and identify any areas that might require additional elucidation or supplementary clarification
• Incorporate discussion and question sessions to make it more interactive. Questions can be asked to confirm understanding, along the lines of “can you please summarize what this section explained?”

Incorporating these tips will help you produce ICFs that are transparent and easy-to-understand for research study participants, further minimizing time spent discussing and clarifying aspects of the study, and importantly, establishing a relationship built on clarity and transparency right from the first contact.

Patient centricity in informed consent

The concept of patient centricity can be embedded into the informed consent process and ICFs by considering the participants' needs and making it a top priority to provide them with a positive experience.[⁷] Patient-centric ICFs might incorporate some or all of the following features:

• Simplicity: Straightforward terminology, or even supplementary definitions for more complex concepts, can help ensure that the participants understand the ICF, which feels empowering.
• Conciseness: Refine the ICF to contain the necessary information while minimizing excessive or extraneous details.
• Highlight the participants' rights, including their right to choose not to participate or to leave the study at any time, with no negative repercussions for them.
• Provide a succinct outline of your approach to preserving client confidentiality and protecting sensitive information.
• Outline the steps that have been taken to ensure participant security and minimize risk.
• Predict and proactively address common concerns or queries that the participants are likely to raise in relation to the trial.
• Incorporate patient perspectives and feedback from past trials to optimize the consenting experience.
• Offer assistance/resources such as a helpline or dedicated web page, which might be useful for them to clarify doubts that arise later on, or for explaining the study to friends or family.
• Adapt the ICF to accommodate different populations, including children, individuals with disabilities, or those from marginalized communities, ensuring it is culturally sensitive and accessible to all. Examples might include adjustable font sizes, captioned videos, read-aloud text passages, and offering both paper alternatives to eConsent for those without access to the internet or who simply prefer to sign a paper document.
• Encourage the participants to ask questions, express their feelings and thoughts, and actively participate in the consent process to ensure they feel seen, valued, and comfortable.

E-consent: Electronic informed consent

The use of electronic informed consent (e-consent) is becoming increasingly prevalent in clinical research due to a variety of factors[⁸]:

• Digital tools like tablets or smartphones allow the participants to complete the informed consent process from anywhere at any time
• Videos, quizzes, animations, and other interactive content can be readily deployed within e-consent platforms to improve engagement and enhance (as well as confirm) understanding
• The integration of electronic signatures and timestamps provides a strong record of documents detailing participant approval
• Other electronic clinical trial (eClinical) systems such as EDC platforms and CTMS can be directly integrated with e-consent, enabling seamless data exchange that leads to improved accuracy and streamlines research workflows
• E-consent platforms typically employ robust security measures, including encryption, user authentication, and data access controls, to protect participant data
• Adopting eConsent can lead to cost savings in terms of printing, distributing, and storing paper consent forms

For further information, see our article dedicated to eConsent.

ICF review by the IRB

Informed consent forms must be reviewed by the institutional review board (IRB) as part of the ethical oversight process in research studies.[⁹] The IRB is an independent committee responsible for ensuring protection of the rights and welfare of research participants.

ICF templates and further guidance

Informed consent form (ICF) templates are available from numerous sources, like the websites of research institutions, regulatory authorities, and clinical trial registries. Some specific sources offering ICF templates include the FDA website [¹⁰] and ClinicalTrails.gov [¹¹].

These ICF templates should be taken as preliminary guidelines only, and should be customized to accurately reflect the specific clinical trial study protocol and regulatory requirements.

Conclusion

Various sources, including institutional websites and research ethics and regulatory authorities, offer templates for the informed consent form. It is important to consult with relevant authorities and adapt the template to accurately reflect the study procedures, risks, benefits, and other pertinent information. Researchers should ensure compliance with local regulations and seek guidance from institutional research ethics committees or legal advisors.