Informed Consent Form for research: ICF in clinical trials

Healthy volunteers can be recruited through general advertising. Patient recruitment often starts with their treating physician informing them about the clinical trial and inquiring if the patient is willing to participate. After a patient confirms, the treating physician can share contact details with the researcher.

When a potential participant is approached but does not respond, also not to a reminder, it should be assumed that the person has no interest. Approaching participants should preferably be done via written communication and after one unanswered reminder, the researcher should cease attempts. The ethics committee provides guidelines for the maximum response time.

The participant information sheet is the information about the clinical trial that can be shared with the potential participant. The researcher can discuss the clinical trial with the participant, but before an ICF is signed, it is not allowed to move forward or start the inclusion process.

The first part of the subject information sheet provides general information. It makes clear that this is a medical scientific research study. It provides the study title and parties concerned. If the participant is selected based on indication, it needs to state that. This part should also emphasize that participating is voluntary, that the participant will be given the time to consider, is encouraged to ask questions and share considerations.

The second element of the subject information sheet outlines the goal of the research and procedure. This part corresponds with the phases of clinical trials for drug development; safety assessment, Phase I, dose-finding, or efficacy.

This part will give background to the study. The template does not provide guidance for this. You can find a background of a study example online. However, before you get lost in Informed Consent Form examples, writing the study background is very simple: Write down the main objectives of the study, the hypothesis, the area of interest, the procedure, and the context of the study.

First state how long the clinical trial will take for the participant. Explain the selection process for the participants to be included; physical tests, medical history, and questionnaires. After this, you provide information on the course and contents of the study. This part is a complete and detailed list of all procedures and timelines.

The participant must understand very clearly what will be expected and what commitment will be agreed upon. For clinical trials for drug development, this includes the administration of the drug, attending visits, undergoing examinations, and contacting the researchers on specified events.

A description of any reasonable risks to the participant needs to be included. It should state the expected side effects and events where the participant should immediately contact the researchers. This part is not limited to the administered compound but also includes side effects from the used methods of examination. Examples: blood sampling, imaging methods like PET, SPECT etc.

If there are no benefits for the participant, state this. You can almost always state how participating helps the researchers and can increase knowledge in the area of interest. If the participant can experience benefits on indication or positive side effects, state those. Also mention the investment required of the participant, e.g.: time and inconvenience. If applicable, inform the participant about the possibility of discovering underlying conditions relevant for the participant and/or family members. Emphasize in this paragraph that participating in clinical trials is voluntary.

Explain when the study is over for the participant. Of course, the study is over after completion. However, you need to list events when the study ends for an individual participant. For instance, when the participant becomes pregnant, when the researcher assesses that it is better to stop, when the study sponsor or a regulatory authority decides upon early closure of a study, or when the participant expresses the wish to leave the study. It also provides information on the procedure of early ending the study. Paragraph 9 explains the options participants have after study closure.

The subject information sheet / Informed Consent Form also includes a statement regarding the confidentiality of personal information. In case of any exceptions, they should be explained in this section. In relation to data archiving, the information should state:

• what data is gathered;
• how long it will be stored;
• what the purpose is;
• who can access the data;
• if data can be used in other research;
• how you can withdraw your permission;
• participant’s rights over their data and privacy.

In this paragraph, the procedure should be explained for an unexpected discovery of an underlying condition.

If applicable, provide specific details regarding compensation or reimbursement for participants, along with associated terms. If no compensation is given, state that.

The Informed Consent Form template can provide standard text about the insurance. The subject information sheet should indicate if and how the insurance of the participant is covered.

State what medical professionals are contacted by the researcher and what information is provided to them. State that this is regarding the participant’s own safety.

It is important for informed consent that the participant has had the opportunity to ask questions or raise concerns. This paragraph explains this and encourages the participant to do so. It can also provide the list of independent professionals the participant can contact and whom to contact in the case of a dispute or complaint.

The final, but most important element of an Informed Consent Form is the assessment that the participant understands all the above elements. This is a section where participants acknowledge that they have read, understood, and agreed to the terms outlined in the subject information sheet. It is followed by a signature and date field for the participant to indicate their informed and voluntary consent. The investigator should also sign and date the form, affirming their commitment to providing information and obtaining informed consent. For underaged, and physically or mentally limited or incapable participants, a legally designated representative should sign the ICF.

An Informed Consent Form for research purposes is a legal document that provides in an understandable manner information about the research to individuals before participating in the clinical trial. In other words, the ICF is a written, signed, and dated document that represents the participant’s informed consent.

The terms consent form and informed consent are related but are not the same. Informed consent refers to the entire consent process of informing a potential participant and obtaining consent. The consent form is part of the process as a documentation of the informed consent. Sometimes the ICF combines the subject information sheet and consent form, but they can also be separate documents.

The consent form for research is very different than informed consent for treatment. The name already explains the difference in goals. Some of the major differences are:

• Participation in research is always voluntary and the participants are given the time to consider.
• For treatment immediate action can be necessary, meaning in an emergency simplified or implied consent is sufficient. A clinical trial can (almost) never be an emergency or necessity (flowchart).
• ICF in research informs the participant of the compensation to participate.
• ICF for treatment informs the patient about costs and insurance.
• ICF can inform the patient of other treatments and the probability of success while ICF for research only provides information on the specific study.

Under the EU CTR the ICF for clinical research is submitted at Phase II of the application process. This means it is assessed by each concerned Member State individually.

An Informed Consent Form should always be in a language that is understood by the participant (or authorized representative). In general, this means the ICF is written in the language where the trial is conducted. For example, Dutch in The Netherlands or Spanish in Spain. In the case of multinational clinical trials, an ICF needs to be created for every country. As a result, one trial can have multiple translations of the Informed Consent Form. If legislation between countries differs, or additional information is requested, the content of the ICF may deviate.

When study subjects are not fluent enough in the national language, but they add value to the study, a document in a different language should be created. Read more about consenting subjects who do not read, speak or understand English or who are differently abled.

Without a signed ICF participation in a clinical trial is not possible. But what happens before informed consent for participation in a clinical trial is given by the potential participant? An informed consent process that is approved by regulatory bodies needs to be in place. The process should make clear that participants voluntarily choose to participate based on all research-related information. For research in particular it should inform about the risks participants accept and their rights.

Generally speaking, you first read the requirements of the regulatory body or bodies of the country or countries you are going to conduct the clinical trial. If they provide a template or an example, you adhere to it. You fill in the requested data. In doing so, you make sure that the subject/participant information letter and the ICF ensure that the participant can make an informed decision. If you’re not sure where to start or if you have a question, contact TRACER via the contact form.

Yes, you can download the informed consent template from the CCMO. You can read the English version. However, you need to submit your Informed Consent Form in Dutch to the CCMO.

Article 29 of the EU CTR covers the informed consent process and form. It explains who needs to sign the ICF and what information should be provided in order to pass the consent as informed. EU CTR Article 29 (2) explains in detail the nature of the document; how it should be written, what aspects of the clinical trial should be mentioned, and the informed consent signature requirements. It is important to read Article 29 of the EU CTR thoroughly and not only download an Informed Consent Form pdf and fill it out.