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Informed Consent Form for research: ICF in clinical trials

Tessa Aminetzah

When you are looking for an Informed Consent Form example or an Informed Consent Form template for research, there is one major thing you need to understand. Informed consent in research is more than obtaining a participant’s signature on a form. Rather, it is a process that involves providing the participant (subject) with information to make a well-informed decision about participating in a clinical trial. The Informed Consent Form (ICF) is merely the documenting element of the complete consent process. In this blog, you will learn about the documents and process.

Download the Informed Consent Form from the CCMO

You need to use an Informed Consent Form template for research. Often the use of a specific template is obligatory. What template you need to use, is dependent on the Member State concerned and regulatory body.

Download the Informed Consent Form template for research in the Netherlands.

You need to understand that the content of the template may only be changed if needed. Follow the guidelines for ICF and keep the information factual and understandable.

In short: what is informed consent?

The definition of informed consent in research is:
“A process that ensures competent individuals voluntarily enter studies with all the research-related information about what it means for them to take part, and that they give consent before their participation begins.”

ICF clinical trial process explained in goals

Informed consent is both an ethical and legal requirement in research. The informed consent process, and therefore, the participant information letter (subject information sheet) and Informed Consent Form in clinical trials, has four essential goals:

  1. Provide necessary information to the potential participant (subject) to make an informed decision.
  2. Enhance the understanding of shared research-related details.
  3. Promote the voluntariness of the decision to participate in the research.
  4. Inform the participant to adhere to the clinical trial (by signing the clinical trial consent form the participant affirms to come to visits, fill out questionnaires, etc.)

Why do you need an Informed Consent form? And more specific: Why do you need an ICF in research?

Before the First in Human (FiH) trial, preclinical studies, and a tox study were conducted. However, it is always uncertain how a new drug or medical device will work in humans. The clinical trial exposes a participant to potential side effects and, in the case of radiopharmaceuticals or radiolabeled compounds, to radioactivity. In addition to this, there is the burden of visits to the research facility and the tests and procedures that are performed. It is important for potential participants to understand their role as a “subject of research” in a clinical trial. An Informed Consent Form is required for medical intervention and research.

When does the informed consent process begin?

Article 2 (25) of the EU CTR states that, unless differently defined in the study protocol, the recruitment of potential participants is the start of a clinical trial. To obtain approval from regulatory authorities for your clinical trial, you need to have approval on all documents and processes, including the ICF process.

What is the informed consent process?

What are the steps of the informed consent process? Before we explain the steps, it is important to understand the following. The whole process of obtaining informed consent for research from a potential participant should be documented. The process itself needs to be submitted to, and approved by the relevant regulatory body. This includes the subject information sheet, the ICF, and the recruitment material. During the clinical trial, for each participant, the complete process needs to be documented.

Initial contact

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.

Maximum response time

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.

Receiving informed consent before continuation

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.

IRB consent form requirements

The Institutional Review Board (IRB) needs to review your ICF. For the informed consent IRB requirements vary based on legal and ethical standards in different regions and fields. For a clinical trial, researchers should adhere to applicable regulations and seek ethical approval from relevant review boards. You can download the IRB consent form template, but keep in mind that the CCMO also offers its informed consent form template for research. If your IRB consent form requirements differ from those of the CCMO or other Medical Research Ethics Committee, you should seek guidance before you proceed.

For the USA, read more about the FDA informed consent guidance.

The elements of an Informed Consent Form

Even though the elements of an Informed Consent Form can vary based on the research and region, there are certain elements that are almost always included.

Keep in mind that the ICF form is a part of the subject information sheet. Usually, this form can be found at the end of that document. It includes statements that are an abstract of the subject information sheet that the participant and researcher agree upon.

Content of ICF form

Often the ICF is the last page of the subject information sheet. It is a form that states that the participant is well-informed, participates voluntarily, and agrees with the terms of the research. It also states the rights the participant and researcher have:

  • The participant has the right to exit the study at any time.
  • The researcher has the right to access medical information about the participant.
  • If applicable, it states that the participant is not allowed to conceive during the trial.
  • The participant may grant the researchers the right to use the collected data for other studies as well and to share and archive the data.

Subject information sheet

To sign the Informed Consent Form, the potential participant needs to be informed first. The ICF is therefore often the last page of the subject information sheet. We explain the different elements of the subject information sheet below. Use the subject information sheet template and follow the guidance provided by the regulatory authorities. Keep practical guidelines in mind, like maximum word count and language level (this is often B1).

1. General information of the clinical trial or research study

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.

2. Goal of the clinical study

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.

3. Background of the research study

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.

4. Course of the study and timeline

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.

5. Agreement of participation

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.

6. Risks and side effects

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.

7. Benefits of participating in clinical trial

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.

8 and 9. Study closure

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.

10. Data and privacy

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.

11. Compensation

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

12. Insurance

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.

13. Informing of GP and/or treating specialist and/or pharmacist

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.

14. Questions about the study

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.

15. Informed Consent Form

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.

Tone of voice and language use in an ICF

When writing an Informed Consent Form for research study there are several writing guidelines to follow:

  1. Write an ICF as if you are explaining the details in person with them. So, in the second person – “you”.
  2. Minimalize the use of passive voice.
  3. Language needs to be friendly, straightforward, and conversational.
  4. When writing for adults, write on level B1, between 6th and 8th grade reading level. This means a readability score of more than 50 (the higher the score, the easier your subject information sheet and ICF are to read).
  5. Try to avoid medical/scientific/technical language or include simple definitions/explanations for such terms if they must be used.

Other formatting decisions

  • Regulatory bodies recommend using a 12-point font. When including certain populations, such as children or visually impaired participants, larger font sizes can be appropriate.
  • Researchers may use flowcharts and tables to enhance reading comprehension.
  • A place for the subject and researcher signature and date must appear on the informed consent document. A witness signature is required in specific circumstances.
  • When using tick-boxes there must be an opt-in option. Tick-boxes may never be colored in advance, and they should allow for a “Yes” AND “No” option.

FAQ ICF

This article explained the informed consent process. A process that involves the recruitment of participants for the study and includes the subject information letter and the ICF in clinical research. Below we answer some of the frequently asked questions on this topic.

What is an Informed Consent Form?

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.

Is consent form and informed consent the same?

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.

Is informed consent in research and treatment similar?

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.

Who approves the Informed Consent Form for clinical research?

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.

What language should you write an informed consent?

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.

Why a consent form for research?

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.

How do you write an Inform Consent Form?

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.

Does the Netherlands have informed consent?

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.

What is Article 29 of the EU CTR?

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.

Discuss your clinical trial with TRACER, CRO in the Netherlands

TRACER is a CRO based in the Netherlands. Therefore, we refer in this article often to the CCMO, the Dutch Central Committee on Research Involving Human Subjects, and the EU CTR. The Netherlands is for drug developers around the globe an interesting country for conducting their clinical research. You can read more on this in our blog: Four reasons to conduct your clinical trial in The Netherlands. In case you want to know more about clinical trials in the Netherlands, another EU country, or multiregional studies, please contact us.

Contact us today

Abbreviations in this article:

CCMO

Dutch: Centrale Commissie Mensgebonden Onderzoek / English: Central Committee on Research Involving Human Subjects

CRO

Clinical Research Organization

CTR

Clinical Trial Regulations

FDA

Food and Drug Administration

ICF

Informed Consent Form

IRB

Institutional Review Board

PET

Positron Emission Tomography

SPECT

Single-Photon Emission Computed Tomography


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