Informed Consent

The International Conference on Harmonisation Good Clinical Practice provides us with a definition of informed consent. ‘A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form’:’ ICH tripartite guideline for good clinical practice E6 (R1). 1996.

Seeking robust valid informed consent is not a mere tick box exercise; it is a central ethical and legal component to the conduct of all health research. This includes Randomised Controlled Trials, but in addition applies to all other types of research involving human participants. This article will make specific reference to the requirements for informed consent in the UK, and whilst the guiding ethical principles of consent on which this article are based can be applied to all research involving human participants, you should check for any specific legislation and guidance in the country in which you are conducting your research.

For consent to be informed, consideration must be given to the key elements involved: disclosure; comprehension; voluntary choice and authorisation.

Disclosure – the person providing informed consent should be adequately informed. A written Patient Information Sheet (PIS) is a valuable tool and can be used to open the exchange of information between a patient, their family and the clinical research teams. This is a document which explains what taking part will involve and will include details about why the research is being done, how long it will last, what methods are being used and the possible risks and benefits. The PIS can also be important should the patient wish to share this with someone independent of the trial.

Comprehension – does the person have capacity to understand what they are making a decision about? Are they ‘competent’ to make these decisions? For example, young children are not considered competent to give consent on their own, but as they grow up they will develop a capacity to understand their decisions.

Voluntary Choice – the decision to take part in a clinical trial should be voluntary with no undue influence.

Authorisation – who can obtain informed consent? Has the investigator, who is responsible for the trial participants at their site, authorised the person taking consent to do so?

Informed consent is an ongoing communication process between the investigator - that is the individual responsible for the conduct of the trial where participants are being recruited; or a member of their team to whom they have delegated this duty and the trial participant. At the heart of informed consent is the person’s voluntary choice to take part in a clinical trial, documented in a written, signed and dated informed consent form. Informed consent is a continual process that begins before any trial related procedures are conducted and is continually sought throughout the study by checking with participants on a regular basis that they are happy to continue in the trial, and through the provision of any information that may become available during the course of the trial, which may affect an individual’s decision to continue.

When developing information for patients and their families about a clinical trial it is important to consider what they will want to know – the ‘what’ ‘why’ ‘how’ ‘when’ ‘who’ ‘where’.

What – what are you asking them to do?

Why – why have they been asked to take part?

How – how will this affect them – are there different ways of taking medication, will there be long clinical visit days, will it be more frequent hospital visits, will I have to take time off work?

When – when will it take place? How long will they be in the study?

Who – will it be with their clinical team or an un-known research team, will a partner, carer or friend be able to come with them?

Where – where will they have to go? Will it be at a different hospital/department?

There are some essential pieces of information that must be provided to potential trial participants and patient information sheet templates will commonly contain sections that ensure this information is communicated.

Involves Research	Purpose of the trials	Trial treatment (s) and probability for random allocation to each treatment procedures to be followed (Including invasive)
Subjects responsibilities	Experimental aspects of trial	Reasonability foreseeable risks or inconveniences
Any expected benefits	Any alternative treatments/procedures	Participation is voluntary, may withdraw at any time
Direct access to medical records for monitors, auditors, regulatory authorities	Confidentiality of records, anonymity if results published	Informed of any new info relevant to willingness to continue
Who to contact in the event of trial related injury	Foreseeable circumstances under which h subjects participation may be terminated	Expected duration of participation
Expected numbers participating	Expected numbers participating	Expected numbers participating

Developing the Patient Information Sheet

Patient information sheets are a tool to aid the process of communication and are invaluable in referring back to conversations between the clinical research team and the participant and their family. In the UK, the Medical Research Council and the NHS Health Research Authority have a comprehensive online tool giving guidance on ‘Informing participants and seeking consent.’ Whilst there may be varying requirements between different countries, the recommendations and guidance provided in these online tools will be useful for all research. These tools also provide useful guidance on how to write a patient information sheet for different populations who may have varying levels of understanding and reading ability. For example, a 6-year-old will have a very different level of understanding on perceived risk than a 16 year old and therefore it would be important that different information sheets are produced for children in different age groups. Where adults who lack capacity are included in research, information must be provided to the person who will consent on their behalf, and this must be taken into consideration when designing the information sheet and consent form. The depth of information provided in the PIS may also vary according to the complexity of the trial, its potential risks and the commitment for the participant.

It is also important to consult with a patient and public involvement group (PPI) who can advise on whether the format, language and information covered is of relevance to the population who will receive the information sheet. In particular this can be vital when ensuring you are able to provide clarity on expected risks and benefits of taking part in the trial.

Methods of presenting information

Patient Information Sheets are used to convey ever complex clinical trials with an ever growing list of ‘regulatory’ requirements. Increasing the size of the information sheet does not necessarily increase the person’s understanding and different individuals have differing information level requirements.

Patient Information Sheets are used to convey ever complex clinical trials with an ever growing list of ‘regulatory’ requirements.

It is unclear what information is critical to inform understanding in an individual and some patients want wide-ranging information whilst others prefer selected details.

Common Messages that get missed or are inadequately explained:

What is the purpose of randomisation?
What is a placebo group?
Should they still be seeing their own GP?
What they should do if they felt unwell after discharge from the clinic?
What are the common side effects of trial drugs?
Are there any pre-trial dietary restrictions?
What is the number of return clinic visits?

There is a growing move towards a ‘layered’ approach to information giving, which involves providing potential participants initially with a short summary with enough brief information to decide whether or not to take part in the research. This can then be backed up with user-friendly methods of access to further, more detailed information presented in one or more layers. This way, potential participants control the amount of information they access.

Text based information is also not always the best format through which to provide information. Non text based approaches include:

Videos
Cartoons
Animations
Infographic cards
Flipcharts
Brochures
Audio

Think about how you would like to be told about a clinical trial, what would grab your attention?

Would the use of pictures, smart design/graphics, video, tabloid style or on-line resources aid your decision making?

When clinical teams approach a patient to take part in a trial their priority is to protect the subject’s rights and well-being and to provide them with the information required, in a variety of formats to enable them to make an informed decision as to whether or not to take part. The patient must have the ability to make this decision without coercion (or undue influence) from the investigator or the clinical team. Informed Consent is a core element of clinical research and an area we should all aim to excel in. Informed consent is a process of providing information to aid the decision making process, allowing patients and their families to make effective, informed and enlightened decisions on whether the trial is the right thing for them at that point and time.

The process of informed consent requires that alongside the written information that is provided in the form of a Patient Information Sheet, the process should also include a verbal exchange between the potential participant and the investigator or a member of their team to whom they have delegated this duty. The person receiving consent must have enough knowledge and experience to discuss not only the trial and the information required to ensure the participant is making an informed choice, but also the disease under study, the risks and benefits and any alternative treatments to what are being offered on the trial.

The potential participant must be provided with the opportunity to ask questions, and be given adequate time to digest the information, and perhaps discuss their potential involvement with family members or significant others, before making their decision. The time required may differ between individuals and may also depend on the complexity of the trial. In certain situations it may not be possible to gain consent prior to receiving an intervention in a trial. In the UK, the law allows for participants to be recruited into clinical trials without prior consent in emergency situations if the treatment needs to be given urgently. These trials will have received prior approval and consent should be sought from a legal representative as soon as possible and if the participant regains capacity they should be consented.

There are many ethical and legal issues to consider when involving children and young people in research. The requirements for consent, where participants are children and/or young people depend on the type of trial and in what country the research is taking place. The Medicines for Human Use (Clinical Trials) Regulations (UK regulations) prohibit children under the age of 16 from giving consent to take part in a Clinical Trial of an Investigational Medicinal Product (CTIMP). Consent must be given on behalf of the child by a parent or someone with parental responsibility or a personal legal representative.

That is, a person not connected with the conduct of the trial who is suitable to act as the legal representative by virtue of their relationship with the child or young person, and is available and willing to do so. A legal representative should only ever be approached if someone with parental responsibility cannot be contacted prior to the proposed inclusion of the child or young person, by reason of the urgent nature of the treatment provided as part of the trial. If a personal legal representative is not available, then a professional legal representative such as a doctor responsible for the medical treatment of the child or young person, so long as they are independent of the study, or a person nominated by the healthcare provider, can give consent on behalf of the child/young person.

There is no statute in England, Wales or Northern Ireland governing a child’s right to consent to take part in research other than a Clinical Trial of an Investigational Medicinal Product (CTIMP), that is, consent for non-CTIMPs. Case law suggests that if a young person has sufficient understanding and intelligence to understand fully what is proposed, and can use and weigh this information in reaching a decision he or she can give consent to research. A child or young person’s right to give consent is dependent upon their capacity to understand the specific circumstances and details of the research being proposed, which in turn will relate to the complexity of the research itself.

The Mental Capacity Act 2005 provides a comprehensive framework for decision making on behalf of adults aged 16 and over who are unable to make decisions for themselves, that is, they lack capacity. The core principles of this act are:

A person must be assumed to have capacity unless established otherwise
Individuals should be helped to make their own decisions as far as practicable
A person is not to be treated as unable to make a decision merely because he makes an unwise decision
All decisions and actions must be in the best interests of the person lacking capacity
All decisions and actions must be the least restrictive of the person’s rights and freedom of action.

A person lacks capacity if he or she is unable to make or communicate a decision about a particular matter because of an impairment of, or a disturbance in, the mind or the brain. The act contains a two-stage test of capacity, which must be assessed at each opportunity when a decision is made as loss of capacity may be temporary and capacity may fluctuate. It is the responsibility of the researcher, consulting as appropriate with other care professionals to decide whether a potential participant has the capacity to consent for themselves to take part in research.

Where the person giving consent is unable to sign or mark the consent form to indicate consent, they may give their consent orally in the presence of at least one witness who must sign the consent form to attest that accurate explanation was given and understood by the subject and that consent was freely given.

Informed consent must be evidenced and in general this will be in writing; by inviting the person giving consent (or their representative) to sign and date the consent form, and for CTIMPs this is a legal requirement. A subject has the right to withdraw from the trial at any time without being subject to resulting detriment.

For Canvas related technical support please see the 24/7. The 'Help' icon on the left-hand navigation

Informed Consent

Developing the Patient Information Sheet

Methods of presenting information

Receiving Informed Consent

Informed Consent with Vulnerable Subjects

When must consent be witnessed?

Documentation of Consent