Building a clear and compliant Participant Information Sheet / Informed Consent Form
1 – Introduction
ICH-GCP(R3) section 2.8 requires that all participants in a clinical study go through a consenting process with the investigator or a member of the investigational site staff delegated by the investigator prior to any study procedures. The information provided to support the consenting discussion should be as clear and concise as possible, use simple language and avoid unnecessary jargon, length and complexity. Participants (or their legally authorised representatives) must be able to understand the study’s purpose, alternatives, potential benefits and risks, expected burdens/procedures, their rights, and what participation involves, to make an informed decision.
Consent is documented on a Participant Information Sheet / Informed Consent Form (PIS/ICF), approved by the appropriate Ethics Committee(s)/Institutional Review Board(s) (EC/IRB) prior to use.
Contents
2 – PIS/ICF Requirements
- ICH-GCP(R3)
- EC/IRB recommendations and templates
- Data Protection/GDPR
- Other country/local legal requirements
- The age and/or capacity of the potential participants
3 – When should you write the PIS/ICF?
The content of the PIS/ICF is driven by the requirements above, but also by the Investigator Brochure (IB; safety information) and the Protocol (details of procedures). Therefore, we would suggest not to start writing the PIS/ICF until near final versions of these documents are available. Writing the PIS/ICF can pick up inconsistencies with the protocol that need to be corrected. Therefore, if your company SOPs allow, we suggest that you work to finalise the protocol and PIS/ICF at the same time, only doing so when all discrepancies have been corrected. This may also be the case for safety information transferred from the IB regarding adverse events, although this is much less likely to occur.
4 – PIS/ICF Content
PIS/ICF development starts with the “Master”. This is written in the language most appropriate for writing and review (usually English) and contains all text that is relevant to participants in all sites. Once this is complete, other PIS/ICFs will be developed from it as required (see section 5).
Many PIS/ICF SOPs contain a checklist of all required content. If you do not have one, perhaps it’s worth suggesting it to your Quality department, or even creating your own.
4.1 Formatting
- Headers and footers appear on every page
- Header/footer information should include:
- Protocol number
- EC/IRB Study Id (if applicable)
- Page x of y
- PIS/ICF master version number
- Sub version number, if site specific changes and/or translations are to be used
- Participant ID number
- Site specific information placeholders should be clearly identifiable (e.g., [Investigator name])
4.2 PIS Content
4.3 ICF Content
Once the potential participant has read the PIS and has had any questions answered by the consenter, they must sign and date the ICF. This will then be counter-signed by the consenter and a copy be given to the participant for their records.
Technically, all that is required for a compliant ICF is a statement that by signing the consent form, the investigator or delegated investigator site staff attests that the informed consent was freely given by the participant and the information was accurately explained and understood by the participant.
However, it is more common that the participant initials a number of boxes showing their acceptance of each point and then signs below.
For example:
| Item | Initial/Tick |
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Yes □ No □ |
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Yes □ No □ |
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Items marked with * are optional, depending on the nature of the study. Also, you may wish to include Yes/No boxes for portions which are not mandatory.
4.4 Templates
- EC/IRB(s)
- Sponsor or CRO SOPs
- Investigational site templates (e.g., from a Phase I unit)
- PIS/ICFs approved for earlier studies
4.5 Data Protection/GDPR
As the study will involve sharing of participant’s data with the Sponsor and other organisations, it is important that the PIS contains wording to cover data protection/GDPR. This wording is likely to be included in any templates that you use. Note that the Sponsor may require legal review of this wording, if so, you need to allow sufficient time for that to occur in the review process.
In the UK, the Health Research Authority (HRA) has implemented pre-approved GDPR wording since April 2025. This wording has undergone extensive discussions with patient groups. It is possible for alternative wording to be used, but you need to prove to the HRA that equivalent interactions with patient groups have occurred. In practice, the HRA approved wording should be used.
4.6 Country and Site Customisations
[UK sites: UK specific wording]
[German sites: Germany specific wording]</mark<
The appropriate blocks of text will then be included when the country-specific versions are created. A similar approach should be used for any site-specific changes. Note: the addition of information such as Investigator name, site contact details etc. will be entered by the sites when they create the site-specific version for use with their participants. Administrative details of this type do not need to be separately approved by the EC/IRB. Any country or site-specific changes which go beyond simply administrative will need to be submitted and approved in addition to the “master”.5 – Readability
The PIS/ICF should be written in simple, “lay” language, which can be easily understood by people without medical knowledge. It should also be as concise as possible. For example, instead of writing out the procedures that occur at each visit, it may be better to provide the participant with a list of all procedures and then refer them to a Schedule of Events later in the document which shows what occurs at each visit and provides the visit timings. Ideally, large chunks of text and long sentences should be avoided. The PIS/ICF should be formatted for ease of reading.
The HRA recommends splitting the PIS into 3 sections: introduction; what’s involved; supporting/further information. They also recommend using the active voice (e.g., “We invite you to participate” not “You are invited to participate”).
You can use a Readability tool to estimate how easy (or difficult) a document is to read. There are various options available, but MS Word will calculate the Flesch Reading Ease scale (FRE; 0-100; 0 = very difficult; 100 = very easy) and the Flesch-Kincaid Grade Level (FKGL; US school grades) of your document. These scales look at things like average sentence length and the average number of syllables per word.
Ideally, a PIS/ICF should have an FRE of 60+ (plain English) and an FKGL of 8 (reading age 14) or below. Depending on the complexity of the study and the procedures involved, it may be necessary to exceed these scores. For reference, this article has an FRE score of 46 and an FKGL of 11, so is considered to be fairly difficult to read and readable by someone aged 16.
6 – PIS/ICF Review and QC
- Medical review – to check the information regarding participant safety/adverse events
- Protocol review – to check for consistency between the protocol and the PIS/ICF
- Readability review – to check that the information provided is in appropriate language
- Legal review – if requested by the Sponsor
- QC – to be performed on the final draft; an independent, detailed check of the PIS/ICF content for consistency, and against the checklist and protocol
7 – Consenting Children and Adults without Capacity
The information above relates to PIS/ICF content where the potential participant is a legal adult and has the capacity to give informed consent. If this is not the case, the participant’s legally acceptable representative will consent of their behalf. However, where possible, a simplified version of the PIS/ICF should be created, written at a level that can be understood by the potential participant. They can then sign this to give their assent to enter the study.
In the case of children, novel approaches can be used, for example an increased use of images, comic strips etc. to explain what is going to happen to them.
ICH-GCP(R3) section 2.8.8 also provides information on consenting participants in emergency situations.
8 – EC/IRB Review
The document package should only be submitted to the EC/IRB when the Protocol, IB excerpts, and PIS/ICF are fully aligned. Documents to be submitted must include all versions relevant to the country of the submission, in both the language of the Master ICF and translation:
| Document | Comments |
| Master ICF | Main version, from which all other versions will be derived (if needed). This version may contain text that only applies to certain countries and/or sites and is marked as such e.g., [Poland only: text …..] |
| Country-specific ICF | Translated into applicable languages. Includes relevant sections from the master. |
| Site-specific ICF (major changes) | Submitted if site-specific changes go beyond simply administrative, e.g., if the site has different procedures for participant payments to the master ICF |
Site-specific ICF changes that are purely administrative (e.g., replacing placeholder text with the site and investigator details), do not need to be submitted.
9 – Amendments and Version Control
- Master version
- Sub-version (if applicable)
- Protocol version
- Territory(ies) where the document was submitted
- Submission/review status
- Amendments to the protocol
- Changes made at the request of the EC/IRB following their review
- Changes to the relevant safety information (e.g., adverse event profile)