Informed consent material

Elements of an informed consent material

The elements of an informed consent material are outlined in the Health Products (Clinical Trials) Regulations, Medicines (Clinical Trials) Regulations, and ICH E6 (R3) Good Clinical Practice (GCP) guideline.

Use of varied approaches for informed consent material and process

Varied approaches (e.g., text, images, videos, and other interactive methods like telephone or video conferencing) may be used in the provision of information to the participant.

• The characteristics of the potential population and the suitability of the method of obtaining consent should be taken into consideration when developing the informed consent materials and process. For example, electronic consent may not be suitable for elderly participants, due to potential challenges with digital literacy.
• When electronic consent is used to obtain informed consent, it would be recommended for participants to be given the option to use a paper-based approach as an alternative.

Refer to our Guidance on Electronic Consent for more details on electronic consent.

Important considerations

In order to enable potential participants to evaluate the benefits, risks and burden of participating in the trial and to make an informed decision on trial participation, the information should:

• be clear and concise as possible;
• use simple language;
• avoid unnecessary volume and complexity; and
• should not contain any language that causes the participant to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor or their service providers from liability for negligence.

Submission requirements

The English informed consent material must be approved by the relevant Institutional Review Board (IRB) and us prior to use. Translated informed consent materials need not be submitted to us.

All amendments to the informed consent material must be submitted to the relevant IRB prior to use. Additionally, substantial amendments to the informed consent material must be submitted to us for review and approval prior to use. Refer to our Clinical Trials Guidance on Determining Whether an Amendment to a Clinical Trial is a Substantial Amendment for more details.

Informed consent process

General considerations

The informed consent process should take into consideration relevant aspects of the trial, such as:

• the characteristics of the participants;
• the trial design;
• the anticipated benefits and risks of medical intervention(s);
• the setting and context in which the trial will be conducted (e.g., trials in emergency situations); and
• the potential use of technology to inform participants (or their legal representatives) and obtain informed consent.

Who should obtain informed consent?

The Principal Investigator (PI) or any other Sub-Investigator, who is delegated by the PI and adequately qualified to obtain informed consent, should conduct the informed consent discussion and obtain informed consent from the participant.

Other investigator site staff (e.g., Clinical Research Coordinators, Nurses etc.) may be delegated to assist with the informed consent discussion (e.g., explaining administrative aspects of the ICF), but should not obtain informed consent from the participant.

What should be used for the informed consent discussion?

The latest approved version of the informed consent material should be used for the informed consent discussion. The participant should understand the oral and written language of the informed consent material.

When should informed consent be obtained?

Informed consent should be obtained and documented from every participant prior to clinical trial participation.

Where should informed consent be obtained?

Informed consent may be obtained in-person or remotely, where appropriate. It should be done in a conducive environment without any coercion, duress or undue influence.

Regardless of the mode of informed consent, the investigator should assure himself / herself of the identity of the participant. For example, the verification may be performed based on the participant's photo identification.

How should informed consent be obtained?

The participant should be provided with ample time and opportunity to enquire about the clinical trial and decide on trial participation. Questions about the trial should be answered in a satisfactory manner.

The ICF should also be signed and dated by the investigator obtaining informed consent, the participant or the participant's legal representative, and the impartial witness (if the participant is unable to read, or sign or date the informed consent material).

• By signing the ICF, the investigator attests that the informed consent was freely given by the participant or the participant's legal representative, and the consent information was accurately explained to and apparently understood by the participant or the participant's legal representative.
• The ICF may be signed via physical or electronic signatures. Refer to our Guidance of Electronic Consent for further details on electronic signatures.
• No signature and date stamps are allowed as a means of signing and dating the ICF.
• The signature of the investigator obtaining informed consent should be consistent with the Signature Sheet.
• If there are checkboxes to be completed in the ICF, it would be recommended that the checkboxes are completed by the participant or the participant's legal representative.
• There is no regulatory provision regarding the number of copies of ICFs that should be signed and dated. The signed and dated ICF should be provided to the participant or the participant's legal representative and filed in the Investigator Site File.

Use of impartial witness

An impartial witness is required to participate in the informed consent discussion in any of the following scenarios:

• Participant or their legal representative is unable to read the informed consent material; and/or
• Participant or their legal representative is unable to sign or date the informed consent material

The role of an impartial witness is to attest that:

• where the participant or their legal representative is unable to read the informed consent material, the informed consent material has been accurately explained to and apparently understood by the participant or their legal representative; and
• the informed consent was freely given by the participant or their legal representative.

As such, the impartial witness must be able to read the informed consent material in order to fulfil this role.

The impartial witness should be independent of the clinical trial, and should not be influenced by people involved in the clinical trial. The possible choices for an impartial witness may include:

• a family member of the participant;
• a friend of the participant;
• a staff who is not a part of the investigator site team; or
• a layperson

The impartial witness may participate in the informed consent discussion in person or remotely.

Use of translator

A translator is required to be present during the informed consent discussion if the participant or the participant's legal representative is unable to converse with the investigator.

• The role of a translator is to facilitate the informed consent discussion between the participant or their legal representative and the investigator.
• The translator should be adequately qualified or certified in the local language.
• The translator may be part of the investigator site team, unlike an impartial witness.
• It is acceptable for an impartial witness to act as a translator if the impartial witness is able to fulfil that role as well.
• Information on the translator should be completed in the ICF or participant's medical records.

Scenarios for use of translator and/or impartial witness

The following table provides scenarios when an impartial witness or translator is required during an informed consent process.

Remote consent

The default mode for obtaining informed consent should be in person, as the investigator may not be familiar with the participant and should meet the participant in person to conduct screening assessments to determine eligibility.

Informed consent may be obtained remotely in exceptional situations if it is not possible to obtain informed consent in person. For example,

• Enrollment of potential participants in a pandemic where participants are in isolation or there are restrictions to visit the investigator site; or
• Re-consent of participants where the new information may impact the participant’s willingness to continue trial participation

In situations where remote consent will be implemented for enrolment of potential participants,

• The rationale, fitness for purpose and feasibility for remote consent should be described in the protocol or protocol-related document, and submitted to the IRB and us for review.
• An impartial witness should be present during the remote consent process as an additional safeguard, regardless of whether the participant is able to read or sign / date the ICF. The role of the impartial witness in this case would be to ensure that the identity of the potential participant had been verified and consent had been freely given.

The PI may want to consider the following for remote consent:

• Electronic consent may be considered, if the computerised system is available. Refer to our Guidance on Electronic Consent for more details on electronic consent.
• Consult the institution (e.g., IT department) on the acceptable telemedicine software to be used for remote consent.
• Ensure that the informed consent discussion is conducted in a secure manner, and adequate measures are in place to safeguard participant privacy and data integrity and confidentiality.
• Provide a copy of the informed consent material to the participant via snail mail / courier / email / messaging to read before conducting the informed consent discussion.
• Verify the identity of the participant during the remote consent discussion.
• Request the participant to sign and date on the ICF, and return a signed copy of the ICF to the trial site via snail mail / courier / email / messaging.
• Sign and date the ICF with the current date upon receipt. It is important to note that the ICF should not be back dated.
• Document details of the remote consent process in the participant’s source records. The discrepancy in the consent dates should be explained if all parties had signed and dated the ICF on different dates.
• Retain the signed copy of the ICF (signed by all parties) at the investigator site in a manner that has secure and limited access and prevents unauthorised editing. The participant should also be provided with a signed copy of the ICF in a similar manner.

New information

The participant must be informed in a timely manner if new information becomes available that may be relevant to the participant's decision to continue trial participation.

• The communication of this new information and confirmation of the willingness to continue trial participation should be documented.

New information that could impact a participant's willingness to continue trial participation should be assessed to determine if re-consent is needed.

• For example, depending on the stage of the clinical trial (e.g., on active treatment or survival follow up) one should consider whether the new information is relevant only to new participants or to existing participants.
• If reconsent is required (e.g., information on emerging safety information), the new information should be clearly identified in the revised informed consent materials, which must be submitted to the IRB and us for review and approval prior to use.

Clinical trials in vulnerable participants

There may be situations where participants have limited capacity to make voluntary and informed decisions about trial participation. Such participants are vulnerable, and require additional safeguards to protect their rights, safety and well-being. Examples of vulnerable participants may include minors and adults lacking capacity.

• The legal representatives of vulnerable participants should act in the participants' best interest, and provide consent prior to trial participation.
• These vulnerable participants should be informed about the trial in a manner that facilitates their understanding.

Clinical trials in minors

A minor is a legal person who is below 21 years of age, and is not and was never married. For clinical trials in minors, the legal representative must either be the:

• Deputy of the minor
• Adult parent of the minor
• Legal guardian of the minor

The investigator should determine if the minor has sufficient capacity or understanding and intelligence to give consent.

• If the minor has sufficient capacity or understanding and intelligence to give consent, the minor's legal representative and the minor must give consent for the minor to participate in the clinical trial.
• If the minor does not have sufficient capacity or understanding and intelligence to give consent, the minor's legal representative must give consent for the minor to participate in the clinical trial. Assent forms for clinical trials in minors do not need to be submitted to us. Please check with your IRB about the requirements for assent forms.
• If the minor is subsequently deemed by the investigator to have the capacity or understanding and intelligence to give consent during the clinical trial, the minor must be re-consented accordingly.

Refer to the Guidance on Safeguards and Consent Requirements in Vulnerable Participants for further details.

Clinical trials in adults lacking capacity

A person who lacks mental capacity in relation to a matter is someone who, at the material time, is unable to make a decision for himself or herself in relation to the matter due to an impairment of, or a disturbance in the functioning of, the mind or brain.

An individual is unable to make a decision for himself if he is unable to perform any one or more of the following functions:

• Understand the information relevant to the decision
• Retain that information
• Use or weigh that information as part of the decision-making process
• Communicate his decision, whether by talking, using sign language, or any other means

For clinical trials in adults lacking capacity (ALC), the participant's legal representative must be either one of the following:

• The donee or deputy appointed pursuant to, or under the Mental Capacity Act in relation to the giving or refusing of consent on behalf of the adult to be a participant
• Where there is no appointed donee or deputy, any one of the following persons can be the legal representative, in descending order of priority:
  
  • A spouse of the adult
  • An adult child of the adult
  • A parent or guardian of the adult
  • An adult sibling of the adult
  • Any other adult named by the adult (i.e. when the adult did not lack capacity) as someone to consult on the issue of the adult being a participant

Refer to our Guidance on Safeguards and Consent Requirements in Vulnerable Participants for more details.

Clinical trials in emergency situations

A clinical trial in emergency situation is a clinical trial to determine the safety or efficacy of an investigational product where:

• The participant is facing a life-threatening situation where intervention is necessary.
• The participant is unable to give consent for the clinical trial as a result of their medical condition.
• It is not feasible to request consent from their legal representative during the window period.

Refer to our Guidance on Safeguards and Consent Requirements in Vulnerable Participants for more details.

Documenting informed consent

Documenting informed consent

It is recommended that the investigator obtaining informed consent document the following in the participant's medical records or alternative source record:

• Protocol reference
• Date of informed consent
• Informed consent process (e.g. use of legal representative, impartial witness or translator)
• Signed copy provided to participant

Use of short form consent forms

Use of short form consent forms

There is no regulatory provision for the use of short form consent forms. The participant or their legal representative (if applicable) must sign the full ICF that has been approved by the IRB and us (except for changes of administrative nature). Please refer to the relevant IRB for further information on the use of short form consent forms.