Legally, adults must be assumed to be capable of taking decisions unless the opposite has been demonstrated for a particular decision.

Where doubt exists, the chief investigator (CI), principal investigator (PI) or another experienced and independent clinician should formally assess the capacity of the individual to make an informed decision about participation in a research project adhering to North Bristol NHS Trust Mental Capacity Act 2005 decision making flowchart. This assessment and the conclusions should be recorded in the medical records. A participant is deemed to lack legal capacity to consent or refuse only when they cannot be helped to reach their own decisions with memory aids or sign language for example.

The term used in the regulations is “an adult unable to virtue a physical or mental incapacity to informed consent”.

A hierarchy prescribed in the regulations for determining what type of legal representative should be approached to give informed consent on behalf of an incapacitated adult prior to inclusion of the participant in the study. The provisions in England, Wales and Northern Ireland differ from those in Scotland.

The Medicines for Human Use (clinical trials) (Amendment no.2) Regulations 2006 made additional provision relating to trials involving incapacitated adults in emergency situation. Where the treatment to be given to an incapacitated adult as part of the trial needs to be given urgently, time may not allow for the written consent of a legal representative to be obtained first. The amendment allows incapacitated adults to be entered into a trial prior to consent being obtained from a legal representative provided that:

• Having regard to the nature of the trial and the particular circumstances of the case, it is necessary to take action for the purpose of the trial as a matter of urgency.
• It is not reasonably practicable to obtain informed consent prior to entering the participant.
• The action to be taken is carried out in accordance with a procedure approved by the ethics committee.

Where an incapacitated adult is recruited in an emergency situation without prior informed consent, steps must be taken to seek informed consent either from the participant (if capacity has been recovered) or from a legal representative as soon as practicable after the initial emergency has passed.

Where consent is withheld, the participant must be withdrawn from the trial.

Conditions

The legal representative:

• Has had an interview with the investigator, or another member of the investigating team, in which opportunity has been given to understand the objects, risks, and inconveniences of the trial and the conditions under which it is to be conducted.
• Has been provided with a contact point where further information about the trial may be obtained.
• Has been informed of the right to withdraw the participant from the trial at any time.
• Has given informed consent to the subject taking part in the trial.
• May, without the patient being subject to any resulting detriment, withdraw the participant from the trial at any time by revoking the informed consent.
• The participant has received information, according to his or her capacity of understanding, about the trial and its risks and benefits.

In the event of an emergency the above points do not apply

• The investigator must consider the explicit wish of a patient capable of forming an opinion and assessing the information provided. This applies both to the wish of a participant to refuse to take part or to withdraw from the trial at any time.
• No incentives or financial inducements are given to either the participant or to the legal representative, except the provision of compensation for injury or loss.
• There are grounds for expecting that administering the medicinal product to be tested in the trial will produce a benefit.
• The trial is essential to validate data obtained (a) in other clinical trials involving persons able to give informed consent, or (b) by other research methods.
• The clinical trial relates directly to a life-threatening or debilitating clinical condition from which the subject suffers.

Principles

• Informed consent given by a legal representative shall present the presumed will of an incapacitated adult.
• The trial has been designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and the cognitive abilities of the participant.
• The risk threshold and the degree of distress have to be specially defined and constantly monitored.
• The interests of the participant always prevail over those of science and society.