EU Clinical Trial Regulation (536/2014)
- Informed Consent -
CTR training EMA – HMA - COM
March 9-10, 2021
Monique Al
Teamcoordinator National Clinial Trial Office
CCMO, The Netherlands
1. General rules (art. 28,29)
2. Cluster trials – simplified means (art. 30)
3. Incapacitated persons and minors (art 31, 32)
4. Deferred consent (art 35)
Overview – Informed consent
1. General rules (art. 28,29)
2. Cluster trials – simplified means (art. 30)
3. Incapacitated persons and minors (art 31, 32)
4. Deferred consent (art. 35)
Overview – Informed consent
General rules – informed consent (IC)
subject information sheet (minimum requirements: art 29)
interview by qualified member study team (qualified person: up
to national law)
adequate time for subject to consider participation
verification that subject has understood information
written, dated and signed by subject and qualified person
performing the interview (IC by electronic means – according
to national law)
subject unable to write: alternative means (e.g. oral) in the
presence of at least one impartial witness. Impartial witness
has to sign and date the ICF
subject unable to give consent: IC by legal representative
(legal representative: according to national law)
1. General rules (art. 28,29)
2. Cluster trials – simplified means (art. 30)
3. Incapacitated persons and minors (art 31, 32)
4. Deferred consent (art. 35)
Overview – Informed consent
Cluster trials
CTR,
considerans 30
........ clinical trials where the methodology of the trial requires that
groups of subjects rather than individual subjects are allocated to
receive different investigational medicinal products. In those clinical
trials the investigational medicinal products are used in accordance
with the marketing authorisations, and the individual subject receives
a standard treatment regardless of whether he or she accepts or
refuses to participate in the clinical trial, or withdraws from it, ........
Such clinical trials, which serve to compare established treatments,
should always be conducted within a single Member State.
Cluster trials – IC by simplified means
Conditions all to be fullfilled:
clinical trial to be conducted in one single MS
the simplified means for obtaining IC are according to national
law in the Member State concerned
the methodology of the clinical trial requires that groups of
subjects rather than individual subjects are allocated to receive
different investigational medicinal products in a clinical trial
the clinical trial is a low-intervention clinical trial and the
investigational medicinal products are used in accordance with
the terms of the marketing authorisation
there are no interventions other than the standard treatment of
the subjects concerned
the protocol justifies IC with simplified means and describes
the informed consent process
General rules – informed consent (IC) in
cluster trials not mandatory
interview by qualified member study team (qualified person: up
to national law)
adequate time for subject to consider participation
verification subject has understood information
written, dated and signed by subject and qualified person
performing the interview (IC by electronic means – according
to national law)
subject unable to write: alternative means (e.g. oral) in the
presence of at least one impartial witness. Impartial witness
has to sign and date the ICF
subject unable to give consent: IC by legal representative
(legal representative: according to national law)
Cluster trials – IC by simplified means
How?
Information to be provided on
the nature, objectives, benefits, implications, risks and
inconveniences of the clinical trial
the subject's rights, e.g. to refuse to participate or to
withdrawn at any time without any resulting detriment and
without having to provide any justification;
the conduct of the trial
follow-up measures if participations is discontinued
applicable damage compensation
EU trial number and summary of results in EU database
information should be comprehensive, concise, clear, relevant,
and understandable to a layperson
no objection to participate (instead off written IC)
1. General rules (art. 28,29)
2. Cluster trials – simplified means (art. 30)
3. Incapacitated persons and minors (art 31, 32)
4. Deferred consent (art. 35)
Overview – Informed consent
Incapacitated persons,
additional conditions IC:
incapacitated subject has not refused to give, informed consent
before the onset of their incapacity
informed consent from their legally designated representative
legally designated representative: according to national law
incapacitated subjects will receive information about their rights
and the clinical trial in a way that is adequate in view of their
capacity to understand it
explicit wish of an incapacitated subject who is capable of forming
an opinion and assessing the information to refuse participation in,
or to withdraw from, the clinical trial at any time, is respected by
the investigator
the subject shall as far as possible take part in the IC procedure
both signatures on ICF: of legally designated representative(s)
and the incapacitated person (assent) – according to
national law
Minors,
additional conditions IC (1):
informed consent from their legally designated representative
legally designated representative: according to national law
the minors will receive the information on their rights and clinical
trial (taken into account age and mental maturity)
information given by qualified member study team trained or
experienced in working with children;
explicit wish of minor who is capable of forming an opinion and
assessing the information to refuse participation in, or to withdraw
from, the clinical trial at any time, is respected by the investigator
the minor shall as far as possible take part in the IC procedure
(taken into account age and mental maturity)
both signatures on ICF: of legally designated representative(s)
and the minor (assent) – according to national law
Minors,
additional conditions IC (2):
during a clinical trial the minor reaches the age of legal
competence to give informed consent as defined in the law of the
Member State concerned:
informed consent shall be obtained before that subject can
continue to participate in the clinical trial
1. General rules (art. 28,29)
2. Cluster trials – simplified means (art. 30)
3. Incapacitated persons and minors (art 31, 32)
4. Deferred consent (art. 35)
Overview – Informed consent
Deferred consent – clinical trials in an
emergency situation
considerans 36
...... emergency situations ...... relate to cases where for example a
patient has suffered a sudden life-threatening medical condition
due to multiple traumas, strokes or heart attacks, necessitating
immediate medical intervention ........ in certain emergency
situations, it is not possible to obtain informed consent prior to the
intervention ....... such patients may be enrolled in the clinical trial
under very strict conditions ..........
Clinical trials in an emergency situation
and deferred informed consent (art 35)
Conditions all to be fullfilled:
subject is unable to provide prior informed consent and to receive
prior information on the clinical trial due to urgency of the situation
the clinical trial will have the potential to produce a direct clinically
relevant benefit for the subject
therapeutic window too short to obtain prior IC from legally
designated representative
the clinical trial relates directly to the subject's medical condition
the clinical trial is of such a nature that it may be conducted
exclusively in emergency situations
minimal risk and burden in comparison to standard treatment
Deferred informed consent (art 35)
no objections to participate in the clinical trial previously expressed
by the subject;
following CT intervention – IC shall be sought from legally
designated representative(s) and/or subject without undue delay
In case subject is not a minor or subject is capacitated to form an
opinion: informed consent to continue the participation in the
clinical trial shall be obtained from the subject as soon as he or
she is capable of giving informed consent.
no informed consent from subject or legally designated
representative (if applicable) : subject shall be informed of the right
to object to the use of data obtained from the clinical trial
subject dies before informed consent from legally designated
representative: data collected during the study may be used. No
IC is needed.
Clinical trials in an emergency situations
Flow charts deferred consent and obtaining informed consent afterwards
https://english.ccmo.nl/investigators/publications/publications/2020/04/07/ccm
o-memorandum-flowcharts-deferred-consent-for-medical-research-in-
emergency-situations
Clinical trials in an emergency situations
Flow charts deferred consent and obtaining informed consent afterwards
https://english.ccmo.nl/investigators/publications/publications/2020/04/07/ccm
o-memorandum-flowcharts-deferred-consent-for-medical-research-in-
emergency-situations
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