Version 1.0 - February 2017

Guidelines on Informed and Substitute Consent in Health Science Research Projects

1. Introduction

The guidance describes the general rules regarding consent that are common for all types of trials and the special rules when the trial participant is a minor or an adult without the capacity to act. It also covers situations where the trial participant may be under pressure to give consent. Consent must be obtained before the trial is initiated.

Subsequently, the rules are outlined for the very exceptional cases where consent can, under specific circumstances, be obtained afterwards, i.e., in research involving acute situations as well as scenarios where exemptions can be sought to obtain consent for research on biological material already extracted from individuals.

In conclusion, the requirements for updating the consent and for storing documentation that informed or proxy consent has been given are detailed.

1.1 General Information on Consent in Medical Research Projects

Medical research projects may involve trial participants if they have given a voluntary informed consent prior to participation (as per the Committee Act § 3).

If biological material is extracted and stored for the trial, i.e., in a research biobank, a voluntary informed consent for this must also be obtained (Committee Act § 6).

If the trial participant is under 18 years of age or is an adult without the capacity to act, the consent must be received from a proxy (Committee Act § 4).

Consent is a decision to participate in the trial, made by the trial participant or the proxy of their own free will (Committee Act § 2, items 10 and 11).

Consent can be withdrawn at any given time. In such cases, the personal data and information already collected for the trial can still be used (Committee Act § 3, subsection 4).

Consent implies that the person responsible for the trial and any potential sponsor have the right to obtain information from the patient's medical records that is relevant and necessary for quality control of the trial (Committee Act § 3, subsection 3).

1.2 Consent Must Be in Writing

Consent must be in writing, dated, and signed by the trial participant or possible proxies, and the person providing the information (Committee Act § 2, item 10). As a general rule, it should be obtained beforehand, meaning it must be available before the trial begins. It can be in paper form or in digital format with a digital signature and a security level equivalent to the OCES standard, for example, NemID. Signatures can also be obtained using tablets.

Standard consent forms p. 1 - p. 2 can be used if no biological material is extracted and stored. When biological material is extracted for storage in a research biobank, p. 3 - p. 4 can be used. If the trial participant has the capacity to act but physical disabilities prevent signing, power of attorney can be given for someone else to sign the consent form (see questions and answers).

If a personalized consent form is created, it must contain the same points as indicated in the standard consent form relevant to the trial.

The person providing the information must sign to confirm that written information has been given to the trial participant, and that verbal information has been provided.

On the consent form, options can be given to:

Opt-out of being contacted about significant health findings.
Express a desire to know the project's results or implications for the trial participant.

The original consent forms must be stored by the person responsible for the trial. If the trial participant requests it, a copy of the signed consent form must be provided (Information Regulation § 13, subsection 2).

1.3 Consent Must Be Informed

The trial participant and the proxy must receive comprehensive information about the nature, significance, scope, and risks of the trial, both verbally and in writing (Information Regulation §§ 6-9). The content requirements for the information are detailed in Information for Researchers

The person responsible for the trial can directly inform the trial participant or the proxies, or this task can be delegated to another individual. The responsibility to ensure that the information is comprehensive always lies with the person responsible for the trial (Information Regulation § 12, subsection 3).

The individual or individuals to whom the information task is delegated must be directly associated with the trial and have the professional qualifications to inform about the trial. It is the responsibility of the person in charge of the trial to ensure this.

1.3.1 If new information arises about the trial participant during the trial

If significant new health-related information about an individual trial participant emerges during the trial, the trial participant must be informed about this and its practical implications. This might relate to the purpose of the trial or could be information unrelated to the trial's purpose, i.e., incidental findings.

The trial participant may have previously opted out of being informed about data that emerges during the trial. This is especially relevant for individuals who might be carriers of a genetic disorder, where the trial aims to identify predispositions for serious genetic diseases that might manifest after a prolonged period. Before involving the person in the trial, there should be a clear written agreement wherein the trial participant waives receiving information of the mentioned nature.

1.4 The Agreement to Provide Information and Obtain Consent Must Be in Writing

If someone other than the person responsible for the trial informs the trial participant or the proxy, there must be a written agreement at the trial location between the person in charge of the trial and the person providing the information.

The agreement describes:

who provides the information and obtains consent, and
who signs to confirm that verbal information has been given and written information has been provided to the trial participant.

1.4.1 Duties of the Informing Person

The informing individual or the person responsible for the trial must attest on the consent form that written information has been provided to the trial participant or proxy, and that verbal information has been given (Information Regulation § 13, subsection 2).

Consent should be obtained as soon as possible after the information has been given. However, it should be emphasized that participants must always be offered a reflection period. Participants, who after being offered this reflection period wish to do so, can give consent during the information meeting. The length of the reflection period depends on the specific trial. As a general rule, the reflection time should be at least 24 hours. However, the committee can approve a shorter reflection period based on a specific assessment. In such cases, the reason for the shortened reflection period should be detailed in the protocol.

If the trial participant or the proxy requests it, the informing person or the person responsible for the trial must provide a copy of the signed and attested consent form.

2. Consent in Trials with Children and Adolescents

This section describes who can provide the proxy consent on behalf of the child, including situations where an adolescent can independently give consent.

2.1 Consent from Holders of Parental Authority

Medical research projects may involve children/adolescents under the age of 18 if the holders of parental authority have provided consent. Both parents must sign the consent form when there is joint parental authority. p. 5 and p. 6 are standard consent forms that can be used for parents' consent.

However, a written parental power of attorney can be made from one parent to the other to give consent for the trial. The power of attorney should specify its purpose (e.g., the child's participation in "title of the trial") and the duration for which it is valid. The standard declaration can be used.

For certain less invasive trials, such as swabbing trials, it is sufficient for just one holder of parental authority to provide consent for the child's participation in the trial.

2.2 If Only One Parent Has Parental Authority

If only one parent holds the parental authority over the child, only that parent needs to sign the consent form. In such cases, the person responsible for the trial must ensure the necessary documentation for parental authority, for example, by asking the parent to present an extract from the CPR register (Civil Personal Registration) or a copy of the custody decree.

For children born before 2004, there is no available information in the CPR register; therefore, a declaration of truth and honesty can be accepted.

2.3 Involvement of Children and Adolescents

The person informing the child or adolescent should be familiar with the area of the trial and possess the pedagogical prerequisites to inform a child of the respective age group. However, this doesn't necessarily mean the person needs to have an educational background in pedagogy.

Furthermore, the child or adolescent should be informed and involved in discussions with the parents about the medical research project to the extent that they can understand the trial situation. Therefore, the information should be tailored to the child's comprehension level. This doesn't apply if it could harm the child.

The child or adolescent's own will should be considered when it is pertinent and relevant. Resistance is understood not only as verbal opposition but also as indicated by the child's attitude, body language, or resistance to physical interventions. This also applies during the trial's execution. Parental consent never implies that a trial can proceed against the child's will.

If the 15-17-year-old trial participant desires, and the information can elucidate the trial, its risks, and benefits for the adolescent, then the adolescent should receive written information about the project. Both the verbal and written information should be age-appropriate. The information should be based on the parental information and should be attached to the trial protocol. See, if necessary, the committee system's manual for Participant Information for 15-17-year-olds.

2.4 When the Adolescent Attains Legal Majority

Should a participant attain the age of legal majority during the course of the trial, it is imperative to secure a written informed consent from the individual, now recognized as a legal adult, as stipulated in Information Regulation § 14, subsection 2.

2.5 Trials Where the Adolescent Independently Provides Consent – Exemption from Parental Consent

In trials that are non-intrusive in nature, an exemption can be sought from obtaining consent from the holders of parental authority, allowing the 15-17-year-old adolescent to independently provide consent. In such cases, the adolescent must receive both written and verbal information.

The committee will assess the appropriateness of granting such an exemption based on an evaluation of the trial's nature, risks, and burdens. For instance, a diagnostic intervention (e.g., a swab test) might be offered to the 15-17-year-old without the need for parental consent (Committee Act § 9, subsection 1).

Adolescents under 18 years of age who have entered into marriage are deemed legally adult unless the state authority, upon granting permission for the marriage, has stipulated conditions of them being minors (Guardianship Act § 1, subsection 1).

2.5.1 Parents Must Be Involved When the Adolescent Provides Consent

Holders of parental authority must receive the same information as the adolescent and be involved in the adolescent's decision-making. Emphasis is placed on striking an appropriate balance between the adolescent's right to self-determination and the parents' duty of care. This ensures that parents are informed and can support the adolescent in any considerations and issues that might arise for them.

3. Consent in Trials with Adults Lacking Capacity to Act (Incapable)

Medical research projects may involve adult individuals lacking the capacity to act when there is consent from the proxy as specified in the Committee Act. An individual without the capacity to act is someone who cannot manage their own affairs. This term is synonymous with the expression "incapable."

3.1 Guardianship for Individuals

Guardianship is established for those who, due to mental illness, including severe dementia, inhibited mental development, or another form of severely compromised health, are incapable of managing their own affairs. This is in accordance with the Guardianship Act § 5, subsection 1.

The guardian can provide proxy consent if the guardianship includes the authority to give consent for trials. Refer to the consent forms p. 7 and p. 8 .

3.2 Other Trial Participants Lacking Capacity to Act

For other trial participants lacking the capacity to act, it is the closest relative and the trial guardian who have the authority to provide consent for the participant's involvement in the trial (Committee Act § 4, subsection 3). Refer to the consent forms p. 7 and p. 8.

3.3 Definition of "Closest Relative"

The term "closest relative" can refer to a cohabiting spouse, direct-line relatives, and siblings. Foster children are often considered as closest relatives. In cases where a trial participant does not have a relative in the form of a family member, or they cannot be contacted, other family members, friends, and similar individuals who have regular contact with the trial participant can also be considered as relatives. A specific assessment will determine who among these is deemed the closest relative.

3.4 Definition of a "Trial Guardian"

A trial guardian is a doctor who looks after the interests of the trial participant and is independent of the interests of the person responsible for the trial and of interests in trial projects in general (Committee Act § 2, item 11).

Based on knowledge of the trial's content and their professional expertise, the trial guardian must assess whether it is safe for the trial participant in their current condition to participate in the specific trial.

The trial materials must detail how the trial guardian is appointed. The appointment will depend on the nature and extent of the trial. For example, a trial guardian could be the on-duty doctor at the trial location.

3.5 Involvement of Trial Participants Lacking Capacity to Act

The consent must be in the best interest of the trial participant. The trial participant should be involved in the discussions, and their expressed preferences should be given significance to the extent that they are pertinent and relevant (Committee Act § 4, subsection 4). The trial participant should be informed in a manner tailored to their level of comprehension. Resistance is understood not only as verbal opposition but also as indicated by the participant's attitude, body language, or resistance to physical interventions. This also applies during the trial's execution. Consent from the proxy never implies that a trial can proceed against the will of the trial participant.

The individual providing consent might rely on tools such as a living will, a future power of attorney, or other previous indications from the potential trial participant regarding their stance on participating in clinical trials.

3.6 If the Trial Participant Regains Their Capacity to Act

Should a trial participant regain their capacity to act during the course of the trial, it is imperative to obtain a written informed consent directly from the individual in question.

4. Situations Where the Voluntariness May Be Questioned

Even if the trial participant has the capacity to act and can provide informed consent, doubts about the voluntariness of the consent can arise in specific situations.

There might be instances where the trial participant, due to institutional placement, deprivation of liberty, employment conditions, or similar, might feel pressured to participate. For example, if the trial participant is employed at the same place as the person responsible for the trial or the sponsor.

The committee conducts a specific assessment to determine if there might be pressure to participate and can decide that the trial participant's consent should be given in front of a person whom the committee has approved.

The committee can also decide that, in such cases, the provided information should be supplemented with a note stating that the trial is monitored by an independent expert (Information Regulation § 10).

4.1 Psychiatry

Patients who are deprived of their liberty under the Psychiatry Act may not participate in medical research projects. Furthermore, coercion within psychiatry cannot be used on voluntarily admitted patients for the purpose of participation in medical research projects (Psychiatry Act § 23, subsections 1 and 2).

5. Subsequent Consent – Trials in Acute Situations

The general rule is that consent for a trial must be provided before the trial commences. However, in specific projects conducted in acute situations, consent can be obtained subsequently, provided that the strict requirements of the law are met.

5.1 Acute Situations Outside of Drug Trials

If the nature of the trial dictates that it can only be conducted in acute situations, where the trial participant suddenly loses their capacity to act, such as in cases of blood clot, brain hemorrhage, unconsciousness, cardiac arrest, or severe injuries or traumas, the committee can allow the trial to be conducted without prior consent.

However, the person responsible for the trial must promptly obtain consent from the trial participant or their proxy, which can be the holder of parental custody, the guardian, the closest relative, or the trial guardian (Committee Act § 11). Refer to the section on adults lacking capacity to act for details on what constitutes a trial guardian.

Please refer to the Guidelines on Research in Acute Situations for additional requirements related to these trials.

5.2 Acute Situations in Drug Trials

If a drug trial can only be conducted in acute situations, where the trial participant suddenly loses their capacity to act, such as in cases of blood clot, brain hemorrhage, unconsciousness, cardiac arrest, or severe injuries or traumas, the committee can allow the consent to be obtained from a trial guardian (Committee Act § 12).

However, the person responsible for the trial must promptly obtain consent from the trial participant or from the proxies mentioned in Committee Act § 4.

Please refer to the Guidelines on Research in Acute Situations for further details.

6. Exemption from Consent

The committee can waive the requirement for consent in trials involving biological material that has already been taken from trial participants or patients.

Exemption can be sought if the project does not entail health risks and the research project otherwise does not pose a burden to the trial participant.

The same applies if it would be impossible or disproportionately difficult to obtain consent from the trial participant or their proxies.

Please refer to the Guidelines on Biobanks for further details.

7. Updating the Consent

If significant new information arises during the trial concerning the trial's effects, risks, side effects, complications, or disadvantages, the trial participant or their proxies must be requested to provide a new consent.

This also applies if the trial design needs to be significantly changed for safety reasons.

Please refer to Addendums to an Ongoing Research Project for further details.

8. Storage of Consent Forms

Consent forms, like other trial documentation, must be stored during the trial. Consent forms contain personal data and must be stored in accordance with the regulations of the Data Protection Act. Please refer to the Questions and Answers section on this topic.

9. Abbreviations for Reference to Legislation

Komitéloven: Act no. 593 of June 14, 2011 on the Ethical Review of Health Research Projects
Informationsbekendtgørelsen: Decree on Information and Consent to Participation in Health Research Projects and on Reporting Supervision of Health Research Projects
Psykiatriloven: Decree no. 1160 of September 29, 2015 on the Use of Coercion in Psychiatry
Værgemålsloven: Decree no. 1015 of August 20, 2007 on Guardianship.

10. Rules and Guidelines

Decree on Information and Consent to Participation in Health Research Projects and on Reporting Supervision of Health Research Projects. DEC no. 498 of 13/05/2018.. BEK nr. 498 af 13/05/2018.
Act on Clinical Trials with Medicinal Products
§ 37 deals with amendments to the komitéloven outside of drug trials: § 37 no. 7-8 and no. 13,14 (consent of the trial guardian)
§ 37 no. 10 (the consent gives the sponsor direct access to the patient's medical record when necessary for quality control, etc.)
Decree of law no. 1160 of September 29, 2015 on the Use of Coercion in Psychiatry (psykiatriloven)
Act no. 593 of June 14, 2011 on the Ethical Review of Health Research Projects (§§ 3-6, §§9-12)
Act no. 604 of June 18, 2012 amending the Act on Ethical Review of Health Research Projects (§ 1)(Consequences of revoking consent and the ethical committees' handling of personal data)

Consent Declarations

Discover the committee system's preprinted consent declarations and the requirements that apply if you do not use the standard.

1. Can participants who cannot sign a consent declaration participate in experiments?

Yes, provided that there is no doubt about their capacity, the signature can be a cross on the consent declaration or a fingerprint with ink.

If, for special reasons, there is a need for extra security regarding documentation of the participant's identity and authority, ordinary contractual principles can be used in connection with giving consent. Thus, witnesses can be used to document the signer's authority and identity. Witnesses can only testify and attest to the time of signing, the identity of the signer, and that the signer is of sound mind at the time of signing.

2. Rules for Storing Consent Declarations (Project Material)

The rules of the Data Protection Act generally apply to the storage of personal data in all research projects.

The Data Protection Act requires:

Deletion or Anonymization: All personal data must be deleted or anonymized when the research project is completed (however, see below regarding drug trials).
Archival Transfer: Alternatively, the data can be transferred to an archive in accordance with the Archival Law.

Both privately and publicly employed researchers can submit research material, including sensitive personal data, to public archives (research data can be stored electronically in the Danish Data Archive), thereby meeting the requirements of the Data Protection Act.

For further information, you can contact the Danish Data Protection Agency or the Danish Data Archive.

For clinical drug trials, the Danish Medicines Agency requires that the material in the trial's Trial Master File is available for at least 10-15 years after the end of the trial, so it is available for any checks. For more details, contact the Danish Medicines Agency.

If you, as a researcher, are employed at a public hospital, you should also be aware of whether the material from the research project is covered by preservation provisions in the regulation on the preservation and disposal of archives in the regions.

3. How should one act if signed consent declarations are lost?

If you already have a copy of the consent declaration, this can be accepted as sufficient documentation of consent. If this is not the case, you must either obtain a copy from the participant's copy or obtain renewed consent.

Generally, the researcher should notify the regional scientific ethics committee and agree on the further procedure with them. In drug trials, the sponsor should also inform the Danish Medicines Agency about the situation.

If it becomes necessary to obtain renewed consent, this should be done according to a supplementary protocol that both provides a reason for the situation and contains the information that will be given to the participants. This ensures that the process is documented for the sake of possible later control or requests for access to documents.

The reason for involving the Danish Medicines Agency in drug trials is that, according to the regulation on good clinical practice in connection with clinical drug trials in humans (BEK no. 695 of 12/06/2013) § 5, item 8, the sponsor must ensure that in case of deviation, steps are taken to ensure the quality of the trial, and in case of serious or repeated deviations, there should also be immediate notification to the Danish Medicines Agency. In addition, the agency is the control authority.

4. Can data from a participant be included in the final analysis if consent declarations are lost, and it is not possible in any way to obtain consent again?

If there is no consent declaration/copy of such, and it is not possible to contact the participant, the data cannot be included in the project as a starting point. If the patient record and GCP monitoring indicate that consent has been obtained, the regional committee or the Danish Medicines Agency may, after a specific assessment, possibly allow the data to be included.

5. Signature on the Consent Declaration

Information is provided and consent is received by the person responsible for the study or a duly authorized person who has the professional qualifications to convey the content of the research project and is directly associated with it.

The person responsible for the study or the authorized person must then sign the consent declaration (attest) in the period from when the information is given to as soon as possible after the participant has consented to participate in the study.

In the case of a multi-center study with a principal investigator and several researchers responsible for the practical implementation of the study at various other study sites, it is the researcher responsible or an authorized person at the given study site who must sign the consent declaration.

When authorizing a person, as mentioned above, there must be a written agreement on this. The responsibility for providing comprehensive information always rests with the person responsible for the study.

NVK has prepared pre-printed Consent Declarations and Forms that one can use.

6. Can a verbal power of attorney from one custodial parent to the other be accepted in connection with a child's participation in a study if both parents cannot be present when the consent form is to be signed?

No, a written power of attorney is required.

When children participate in studies, a substitute consent must, as a starting point, be obtained from both parents when there is joint custody. The substitute consent from the parents must, according to the committee law, be in writing, dated, and signed (possibly by a digital signature).

Based on the committee law's requirement for written consent, there is a requirement for a written power of attorney from one parent to allow the other parent to make a decision about the child's participation in a specific study within a given period if both parents cannot be present when the consent form is to be signed. The committee system's standard parent power of attorney can be used.

7. When do updates/changes in participant information mean that the subject must be informed about this and sign a new consent form?

If the research project's design is significantly changed regarding the subject's safety, the subject must be informed, and renewed consent must be obtained from the subject. The same applies if new information emerges about the effect, risks, side effects, complications, or disadvantages of the study. The committee must approve the updated/changed participant information before obtaining renewed consent.

If the changes to participant information are not considered significant, it is not necessary to obtain renewed consent. However, in some cases, it would be appropriate to inform the subject by an information letter. It is also not necessary to get approval for a non-significant change to participant information, as it will be sufficient to send a notification about this to the committee.

The above follows from the information regulation § 16, para. 1.

Last updated 01-02-2024

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