CT SOP version no 1.0.

Main changes from LM SOP No. 3.1. Adapted to the wording of the clinical trial regulation no 536/2014.

The sponsor has overall responsibility for ensuring that this SOP is followed.

The sponsor’s responsibilities shall be described in the quality system of the sponsor institution. Tasks are delegated according to SOP Roles and Responsibilities in clinical trials implemented in the institution.

The sponsor may transfer any or all of the sponsor's trial-related duties and functions to a third-party vendor such as a Contract Research Organisation (CRO), but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf. Transfer of duties shall be specified in a written agreement.

Principal investigators (PIs) have responsibility for ensuring that written informed consent is obtained prior to subject participation in a clinical drug trial.

Requirements for informed consent

The subject information and consent form should be prepared using a template covering all required elements, e.g a template provided by the ethics committee that will review the study (for example REK in Norway) and with reference to the SOP Preparing Written Information and Consent Form - SOP. The subject information and consent form shall be approved by the ethics committee prior to use. The latest approved version should always be used.

Informed consent is required from all subjects participating in clinical drug trials.

The informed consent must be given voluntarily, explicitly and must be documented.

The person obtaining consent shall ensure that the consent is given freely and voluntarily, without unreasonable influence or any form of coercion. Subjects need to know that they can withdraw at any time during the trial, without giving a reason and without any negative consequences or disadvantages for them.

Requirements for subjects under 18 years

When carrying out drug trials in subjects who are under 18 years old the requirements for consent from the age groups 0 to 18 years should be followed, including local regulations.

As a general rule, both parents/guardians should sign the consent form on behalf of the child, if both have parental responsibility.

All children should have information that is appropriate for their age and ability to understand and designed for them, see Regulation (EU) No 536/2014 Article 32. In Norway there are specific regulations including separate information for children from 12 years old and the child should be given the opportunity to assent.

Care should be taken when asking children between 12 and 16 years of age to sign an assent form since they are not legally able to consent. However it can be done in trials when ethical approval has been given for that process.

If the child does not want to participate, the child’s wishes must be respected, as long as it does not have serious consequences for the child's health.

Requirements for subjects not able to give consent

There are specific requirements for subjects who are unable to consent or who are incapable of giving consent due to illness or mental incapacity, see Regulation (EU) No 536/2014 Article 31.

In this case the written information should be given to the subject's legally acceptable representative (e.g. next of kin) so that they can give written consent on behalf of the trial subject after they have been informed.

If the person is not able to give a written consent, oral consent can be obtained after the information is given. Oral consent must be confirmed in writing by an independent witness.

If the trial subject later becomes able to give consent, he/she should be given the written information and asked to sign the consent form to confirm that he/she is willing to continue participating in the trial. If trial subjects in such cases refuses study participation/written consent, data collected for the subject must be removed from the study database.

Responsibility for obtaining consent

PI, investigator, or other qualified person who has been assigned this task by the PI, can provide information and obtain consent on the PI’s behalf. The task can be delegated to, for example, a trial nurse or medical doctor.

The delegation of the task of providing information and obtaining consent should be documented in writing in the trial Delegation Log - Template.

If a trial subject is in a dependent relationship to the person requesting consent and could feel that they are obliged to give consent, informed consent must be obtained by a different person without such relationship.

Persons who have been delegated the task of providing information and obtaining consent should have the necessary knowledge about the clinical trial and the therapeutic area, to be able to perform the task in a satisfactory manner. If this person is not a doctor the subject must always be given the opportunity to speak with a doctor before they sign the consent form.

Timing of informed consent

Consent must be obtained before any trial related procedures or assessments are performed.

Exceptions to this rule are only possible for research in medical emergencies, see Regulation (EU) No 536/2014 Article 35. In emergency medical situations, written consent will be requested as soon as trial subject is able to give it.

Required information

Subjects will be given oral and written information. The subject will be fully informed of all pertinent aspects of the trial. When the trial is done in subjects who are incapable of giving consent, consent should be obtained from the legally designated representatives (as defined in local laws) of incapacitated persons and minors.

The information should be clear and understandable and unnecessary technical or medical terminology should not be used.

The information should be adapted to the age and ability to of the person to understand.

The subject should be given sufficient time to ask questions about the trial and the questions should be answered to the satisfaction of the subject.

Subjects shall have the opportunity to consult with relatives, family doctor or others, before they decide whether or not to participation in the trial.

Procedures for persons giving consent

The consent form should be signed and dated in real timeby the trial subject or the subject’s legally designated representatives, if the subject cannot give consent.

The person who conducted the informed consent discussion and obtained consent must confirm that the information was provided by signing and dating the consent form.

The trial subject should be given a copy of the information and the signed and dated consent form to keep.

Procedures for persons not consenting

The subject should be thanked for taking the time to consider participation in the trial. It should be emphasised that the subject’s refusal to participate will not have any consequences regarding further treatment.

Trial personnel or the PI should make sure that the subject is referred to the appropriate persons for follow-up according to current medical practice. No data should be entered into the CRF.

Information to subjects during the trial

If important new information becomes available during the course of the trial that may be relevant to the subject’s willingness to continue participation in the trial the PI will inform the subject in a timely manner.

The PI shall promptly inform the trial subject if any injury is caused by the trial procedures, or complications which occur as a result of the trial.

At the same time the subject should be told how to get compensation. For example in Norway: from Norsk Pasientskadeerstatning (NPE) and any injury should be reported to the Norsk pasientskadeerstatning.

The information mentioned in the previous points, must be documented in the patient's medical records.

If there are significant changes in a clinical trial, written consent must be re-obtained when the changes are believed to be relevant to the subject’s willingness to continue participation in the trial.

The written information and consent form must be revised to include the new information in addition to that which was provided when consent was originally given.

When consent has to be renewed the trial subject should receive prior oral and written information before signing and dating the revised consent form, according to the procedure for obtaining the original consent.

Documentation

The process for obtaining consent should be documented in the patient's medical records. The following should recorded:

• That the trial subject received oral and written information about the trial and agreed to participate.
• The date on which the subject signed the consented form.
• That the trial subject was given a copy of the written information and signed consent form.

If the trial subject is under 18 years old, it must be noted that both parents/guardians signed the consent form.

All original signed consent forms should be kept in investigator’s site file (ISF), or other specified place. If consent forms are not kept in the ISF, there should be a note in the ISF that gives the location of the consent forms. Refer also to the Location of Document if not in ISF - Template.

All consent forms, both those signed by subjects who completed the trial and those who withdrew from the trial, should be filed.

Signed consent forms will be archived after end of the trial. Refer to the archiving requirements in SOP Completion, Reporting and Archiving – SOP 1.6.b.

All subjects who consented and were screened will be logged in the trial screening log. Refer to the Screening Log - Template.

Subjects that consent and are treated will be logged on the list of trial subjects. Refer to the Identification & Enrollment Log - Template.

• Prescreening Log - Template
• Screening Log - Template
• Identification & Enrollment Log - Template
• Delegation Log - Template
• Location of Document if not in ISF - Template