Frequently Asked Questions - RVK

An emergency trial must be reported to the relevant Regional Research Ethics Committees

It is a requirement in connection with the conduct of emergency trials that the person responsible for the trial subsequently tries to obtain the consent as soon as possible, which due to the urgency of the situation was not possible to obtain before the inclusion of the trial subject. (In drug trials, consent must also be obtained beforehand from a trial guardian.)

Should the trial subject regain their capacity to act during the trial, and if a substitute consent has already been obtained at this point, informed consent must also be obtained from the trial subject before the research project can continue. This is stipulated by the Information Regulation..

Yes. If a trial participant is legally included in an emergency trial, one can subsequently use data collected up to the point where it is determined that a subsequent substitute consent cannot be obtained, e.g. because relatives do not return and sign the consent form.

It should be noted that it is a requirement to always try to obtain the substitute consent as soon as possible after inclusion.

Once it has been determined that subsequent consent cannot be obtained, no further (new) data about the patient may be collected, and the trial subject may no longer be followed (in the patient's medical record). Access to medical record information after this point requires authorization in other legislation, such as the health law.

If you want to learn more about the topic, read the letter dated February 28, 2014, from the Ministry of Health and Prevention regarding the use of data in emergency trials (PDF).

An emergency trial is defined by the situation where the trial can only be conducted immediately, which is why there isn't time to obtain proxy consent. If it's possible to obtain prior representative consent, then it isn't considered an emergency situation that justifies conducting an emergency research project.

In a specific case, NVK determined that since the research intervention was required to be initiated within 12-24 hours, the project couldn't be described as urgent. The start of the treatment/method should therefore occur shortly after the onset of the illness/trauma for it to be considered an emergency situation.

Difficulties in contacting next of kin, the person with parental authority, or the guardian don't justify using the rules on emergency trials.

Yes. The provisions on emergency research projects in the committee law generally also apply to children as well as adults who are permanently incapacitated, who meet the criteria. The relevant factor is that it is an emergency trial.

When including children or adults who are permanently incapacitated in emergency trials, the trial – in addition to meeting the requirements for an emergency trial – must also comply with the current rules on risk assessment when involving children and incapacitated adults in trials (committee law § 19). You can read more about this in the Guidelines on Informed and Substitute Consent in Health Science Research Projects

In special cases, yes. NVK, in connection with a specific case, was presented with the question of whether a control group could be established in an emergency research project with trial subjects who had not lost their capacity to act. The trial consisted of an intervention group where emergency surgical procedures had to be performed on patients with acute aortic dissection (tear in the main artery) upon arrival at the hospital. Upon arrival, the patients were in hemodynamic shock or unconscious and intubated. This part of the trial was assessed by NVK to meet the requirements for an emergency trial.

NVK also approved the inclusion of a control group with trial subjects who had not lost their capacity to act. These trial subjects had a different underlying disease and treatment need, as they did not have the same lesion in the aorta, or the lesion had a different location in the aorta, which meant that the situation was not as acute as in the intervention group. Thus, the trial subjects in the control group were able to give informed consent. It was assessed that it was a genuine control group, where the data was solely to provide necessary baseline data for comparison with data from the intervention group. The control group consisting of patients who had not lost their capacity to act was therefore permitted.

Human biological material, where the tissue donor or donor cannot be identified, including via a code or similar to data, and which is thus not attributable to an individual, and where the material can neither directly nor indirectly be traced back to a person.

Pseudonymized material, where the biological material can be traced back to the tissue donor or donor via, for example, a name or numerical code, is not considered anonymous in the sense of the committee law. If there is just one person who has the "key", then the material is not anonymous, but personally identifiable.

Without a personally identifiable name or code, the information tied to the biological material might be traceable to individuals if it concerns a very small group of people with a rare diagnosis, for instance, carried by 5-10 individuals. In this case, it would be difficult to label the material as completely anonymous.

It should also not be possible to indirectly link personal information to the material. If the biological material is taken by the researcher themselves in connection with or for use in the project, the material typically cannot be considered anonymous, as the researcher knows who the procedure was performed on and can identify the tissue donor or donor.

Whether such material can be considered anonymous depends on whether it's possible to directly or indirectly identify the individuals from whom the material originates (see question 1). In typical cases, gender and age alone will not lead to identification.

However, one should always consider whether the material might lead to indirect identification, for instance, if it concerns biological material taken from individuals with very rare diseases (e.g., carried by fewer than 5-10 people). In such cases, it would probably be difficult to consider the material as completely anonymous.

Research projects should be reported to the regional committee located in the same area as the responsible researcher's workplace/research site. Find contact information for the regional scientific ethics committees here.

Research projects concerning particularly complex areas should be reported to NVK. See here which areas are considered particularly complex.

Only research projects that involve personally identifiable humans or human material such as eggs, cells, or tissue, need to be reported to a scientific ethics committee.

Projects that only involve data and numbers, called register research projects, do not need to be reported to a scientific ethics committee.

Anonymous human biological material does not need to be reported to a scientific ethics committee unless it concerns a research project related to fertilized human eggs and reproductive cells intended for fertilization. It's a requirement that the material is completely anonymous (there must not be an identification code to data), and that the material is collected in accordance with the legislation at the collection site.

Yes. The principle is that all clinical trials of medical equipment should be reported - not only trials that are part of a biomedical research project, as a clinical trial of medical equipment in itself is a biomedical research project.

A clinical trial of medical equipment on humans is any experiment on humans that aims to discover or verify the safety or performance of medical equipment.

The obligation to report to the committee system applies to all clinical trials, regardless of whether the equipment is CE-marked or not. The equipment being examined can be new medical equipment or well-known medical equipment that is already on the market in Denmark. The obligation to report to the scientific ethics committee system is thus broader than the reporting obligation to the Danish Medicines Agency..

No, such trials, which typically aim to investigate how intense a toxicological impact humans can be exposed to before they get sick, do not need to be approved by the scientific ethics committee system. This is because such trials do not meet the conditions of the committee law to be considered a biomedical trial and thus fall outside the committee system's jurisdiction.

Biomedical trials on humans, in simple terms, aim to investigate processes or develop medications, etc., which in the long run contribute to health and healing.

According to the chemical law, the approval of pesticides falls under the Ministry of the Environment. The Environmental Protection Agency has stated that if a human trial is submitted in connection with an application for the approval of, for example, a pesticide, the trial will not be used to expedite the approval procedure.

Yes, the protocol can be in English. However, a Danish protocol summary must be attached, and the rest of the project material should be in Danish. Nordic languages are accepted though.

A protocol addendum is an addition to the protocol, ensuring the protocol meets Danish requirements, e.g., guidelines for oral participant information, etc. It's often used in sponsor-initiated drug trials.

Just like the protocol, a "Danish" protocol addendum can be submitted in English. The addendum is considered part of the protocol.

The protocol addendum must not be confused with the protocol summary. The protocol summary must always be in Danish.

It depends on the specific project. For example, drug trials and clinical trials involving medical equipment must be reported to the Danish Medicines Agency (Lægemiddelstyrelsen).

Public research projects where personal data is processed also need to be reported to the Danish Data Protection Agency (Datatilsynet).

As of May 15, 2012, private research projects that need to be reported to the committee system are exempted from the obligation to report to the Danish Data Protection Agency (Datatilsynet). However, the Personal Data Act (Persondataloven) must still be complied with.

It is the responsibility of the trial manager to ensure that the required notifications, as stipulated by Danish law, are made.

According to Article 32 of the Helsinki Declaration, a new method can be tested against the best current prophylactic, diagnostic, and therapeutic methods. However, according to the notes on the committee law, this should be understood to mean that trials cannot be conducted where some trial subjects receive a treatment that's inferior to the best current prophylactic, diagnostic, and therapeutic method - for instance, a trial subject gets a placebo instead of the medication that actually works.

However, this does not exclude the use of placebo or non-treatment, provided there is no effective treatment or documented method available, and the trial subjects are not exposed to the risk of serious or irreversible harm.

The person responsible for the trial must explain the use of placebo and the choice of control group in their application, and there must be a detailed description of the duration of placebo use and safety procedures.

Emergency drug trials can be carried out by obtaining consent from a trial guardian. However, emergency drug trials can only be conducted where the nature of the trial means it can only be carried out in emergency situations. This is a necessary precondition for the execution of the research project. Therefore, if the trial can also be conducted with a regular proxy consent from the nearest relatives, parents, etc., then it does not meet the conditions to be considered an emergency trial.

Difficulties in contacting the nearest relatives, the general practitioner, the holder of parental authority, or the guardian do not justify using the trial guardian's consent instead of the rules for regular proxy consent. The trial guardian's consent is therefore only an alternative if it's absolutely impossible to obtain regular proxy consent under any circumstances.

Yes, you may. Unless the committee specifically states in its decision that a document may not be used, the missing listing is merely an expression that, according to the law, the committee does not have the competence to assess the document.

This will typically be the case for patient cards, actual instructions on how, for example, a drug should be taken, most questionnaires and patient diaries, participant information for young people under 15 years, etc.

See the List of documents approved by the committee.

All substantial modifications to a research project must be reported to the scientific ethics committee that approved the project.

Modifications to a trial protocol may only be initiated once the scientific ethics committee has approved them.

In the committee system's advisory list of Modifications to approved projects, you can see which changes typically require reporting.

See more about modifications to approved projects here

When defining “trial medication,” the crucial factor is the design of the trial.

There are fundamentally two types of trials to consider:

1. In add-on trials, the new medication is added to the medication that participants are already receiving as part of their “standard” treatment. In this type of trial, only the new medication is considered “trial medication.” Therefore, it cannot be demanded that the already existing medical treatment be made free as part of the trial, as this medication is not “trial medication.”

2. In trials where the new medication is given directly in comparison to the existing medication, there are, for example, 2 “arms” in the trial, with one being the new product and the other the existing product. Participants receive either one product or the other, and the results are compared. In this case, both products are considered “trial medication,” and thus should be free of charge for the trial participants.

The determining factor for whether something is considered trial medication is whether the medication is part of the trial, or if it is just a part of the patients' “basic treatment.”

Compensation for lost earnings and for pain and inconvenience (inconvenience compensation) in a health science research project is taxable. However, the part of the compensation that covers documented expenses associated with participation, such as transportation costs, is not taxable.

It is the responsibility of the trial leader to report the entire compensation to the tax authorities. The trial participant must themselves declare the income in their tax return. The amount to be declared is the part of the compensation that exceeds the trial participant's documented expenses for participation. The trial participant can contact the trial leader or the tax authorities if they are unsure about what is taxable.

See the guideline's Appendix 1: Guidelines for compensation or other benefits to voluntary trial participants (PDF). There is no fixed limit for the size of the compensation, but it should be appropriate in relation to the intervention or the inconvenience the trial participant is subjected to.

The compensation is taxable and must be reported to the tax authorities by the trial leader. The trial participant must declare the income in their tax return.

This is a standard description that should be attached to the written participant information. It must be used by the researcher, who must provide the information to the trial participant, unless the information from here is reproduced in the written participant information.

See Trial Participants' Rights in a Health Science Research Project.

The brochure is a general information for trial participants who want to know more about what it means to participate in a trial.

Before you decide (PDF)

A consent to participate in a health research project will, as a starting point, also include consent for the dissemination and processing of information about the trial participant's health conditions, other strictly private matters, and other confidential information as part of self-control of the research project, including quality control and monitoring, which the sponsor or monitor is obliged to carry out. Therefore, under the committee law, the sponsor and monitor have access to relevant information in the trial participants' patient records within the framework of the sponsor and monitor's duties under the GCP rules, and a separate power of attorney is not required to document this.

The Health Authority can, as part of its control of clinical drug trials, access information about trial participants' health and personal matters without separate consent or power of attorney from the trial participant themselves, their closest relatives, or guardian. However, if there is to be an inspection by representatives from foreign authorities to control the trial, a power of attorney is required. The committee system can also review the power of attorney statement.

See the Health Authority's: Guidance for applying for permission for clinical drug trials on humans.

See Guidelines on Side Effects

NVK has discussed whether the monitor can be present during actual patient contacts, including when the trial participant is deciding whether or not to participate in the trial.

The monitor is the representative of the pharmaceutical company and ensures that all data is correctly reported to the pharmaceutical company. The argument in some trials has been that — by being present when the researcher asks questions to the trial participant — the monitor can observe if there is correct data entry into the Case Report Form (CRF). The CRF is the document that reports information to the company about each individual trial participant.

NVK found that there is a risk that the presence of the monitor might unduly influence the confidentiality between the doctor and the patient. The integrity of the trial participant must also be protected, which is why the monitor should not be present.

In register research projects where consent has been waived, the trial participant has not had the opportunity to decide whether they wish to be informed about new health information that emerges during the project. In such cases, the same rules apply as in the treatment area, where doctors may disclose health information to family members under certain conditions.

The comments on the Health Act state the following: "A condition for disclosure (of health information) under § 41, subsection 2, no. 4, in cases where the disclosure concerns serious, genetically conditioned diseases, is that there is a reasonable degree of probability that family members also have the genetic predisposition. In addition, it is a condition that there is a secure documented connection between the genetic predisposition and the development of the disease, and that the tests used to determine the genetic predisposition are reliable. Finally, it is a condition that the disease can be substantially prevented or treated."

In register research projects where there has been an exemption from obtaining consent from the trial participants, this means that the researcher must contact the trial participant about a serious genetically conditioned disease when:

• There is a reasonable degree of probability that a genetic predisposition is present.
• There is a secure documented connection between the genetic predisposition and the development of the disease.
• The tests used to determine the genetic predisposition are reliable.
• The disease can be substantially prevented or treated.

As a starting point, the deputy assumes the subject's right to refuse to be informed if significant information about the subject's state of health comes out during the experiment. The representative should — in order to be able to look after the subject's interests as best as possible — involve the subject in the decision-making process before the trial begins. The involvement must be adapted to the subject's maturity and the situation in general.

If the subject/representative has not indicated any special wishes regarding the right not to know, and new significant health information about the subject subsequently emerges, it will depend on a concrete assessment whether the information must be withheld from the subject or his representative. The assessment depends on, among other things of the nature of the health information obtained, including whether there are findings of infectious or life-threatening diseases.

Children can normally only participate in intervention research if research with adults does not provide the same benefit, and participation in the trial gives the child a direct health benefit.

If an experiment can only be carried out with children, it is a requirement that the experiment provides very large benefits for children with the disease under investigation. These requirements follow from the rules of the Committees Act (Section 19).

In the case of biobank research, where an exemption from the consent requirement is applied for, children can be included in the research if the experiment does not pose a new risk or burden on the child (Section 10 of the Committee Act).

It is considered a burden on children, especially healthy ones, if in their childhood or adolescence, as a result of extensive mapping of their genome, they risk being confronted with chance findings of a serious health nature, which may only had to break through in adulthood.

Healthy children are therefore not normally allowed in biobank experiments with genome sequencing.

You can read more about the committees' practice regarding children in Guidance on Genomics and Research in Sensitive Bioinformatics Data.

You can find general information about reporting side effects here. This applies to both drug trials and other trials.

Reporting of both suspected serious unexpected adverse reactions (SUSARs) and annual reporting of suspected serious adverse reactions must be done to the regional committee that approved the project. The National Scientific Ethics Committee shall not receive side effect reports.

The annual list of all suspected serious (expected and unexpected) side effects must be accompanied by a report assessing the safety of the subjects. This is the same report (and list) that is reported to the Danish Medicines Agency. Reference is made to the guidelines for reporting side effects arising from clinical trials (CT3) , section 8. The annual report and list of serious suspected side effects can be replaced by the Development Safety Report (DSUR). Read more about the DSUR below in question and answer no. 5.

No, the annual report applies to all suspected serious side effects seen in the trial in all countries.

Both reporting to SUSARS and the annual reporting can be done in English. The report must therefore no longer be accompanied by a Danish covering letter or an independent Danish assessment of the subjects' safety.

DSUR stands for: Development Safety Update Report, which is the common standard for annual reporting of adverse reactions developed by ICH for use in the USA, Europe and Japan. Read more about ICH . The annual report and list of suspected adverse reactions may be replaced by the Development Safety Update Report. Read more about DSUR in ICH's guidelines (ICH E2F).

Incidents must not be reported in the annual reporting of side effects, but must be included in the final report on the results of the trial, which must be submitted no later than 1 year after the end of the trial to the Danish Medicines Agency. The final report or summary/synopsis thereof can also be used for reporting the final publication/report to the regional scientific ethics committee. Read about reporting to The Regional Research Ethics Committees.

The annual reporting obligation applies as long as the treatment of experimental subjects is ongoing in Denmark (see CT3 section 8). The treatment is considered to end at the "last visit of the last patient" (in Denmark).

The reporting obligation ends when the trial ends in Denmark. This means "last visit of the last patient" (in Denmark).

It is the rules in the Personal Data Act that basically apply to the storage of personal data in all research projects.

The Personal Data Act requires:

• Deletion or anonymisation of all personal data when the research project has been completed (however, see below about drug trials)
• Alternatively, the information can be transferred to an archive in accordance with the Archives Act.

Both private and publicly employed researchers can hand over research material, including personally sensitive data, to public archives (at the Danish Data Archive, research data can be preserved in electronic form), and in this way meet the requirements of the Personal Data Act. You can contact  the Danish Data Protection Authority  or  the Danish Data Archive if you want to know more.

If it is a clinical trial with medicinal products, the Danish Medicines Agency requires that the material in the trial's Trial Master File be available in min. 5 years after the end of the trial, so that they are available at a possible control. Contact  the Danish Medicines Agency if you want more information.

Yes, provided there is no doubt about the competence of the person concerned, the signature could be a cross on the declaration of consent or a fingerprint with printing ink.

If, for special reasons, there is a need for extra security in relation to documentation of the participant's identity and authority, general contract law principles can be applied in connection with giving consent. You can therefore use witnesses to document the authority and identity of the signatory. Witnesses can only testify and certify the time of signature, the identity of the signatory and that the signatory is in full use of his senses at the time of signature.

It is the rules in the Personal Data Act that basically apply to the storage of personal data in all research projects.

The Personal Data Act requires:

• Deletion or anonymisation of all personal data when the research project has been completed (however, see below about drug trials)
• Alternatively, the information can be transferred to an archive in accordance with the Archives Act.

Both private and publicly employed researchers can hand over research material, including personally sensitive data, to public archives (at the Danish Data Archive, research data can be preserved in electronic form), and in this way meet the requirements of the Personal Data Act. You can contact  the Danish Data Protection Authority  or  the Danish Data Archive if you want to know more.

If it is a clinical trial with medicinal products, the Danish Medicines Agency requires that the material in the trial's Trial Master File be available in min. 5 years after the end of the trial, so that they are available at a possible control. Contact  the Danish Medicines Agency if you want more information.

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 the preservation provisions in the executive order on the preservation and disposal of archives in the regions.

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

In general, the researcher must inform the regional scientific ethics committee and with this agreement the further procedure. In drug trials, the sponsor should also inform the Danish Medicines Agency about the situation.

If there is a question of obtaining renewed consent, this should be done in accordance with an additional protocol that partly provides a justification for the situation and partly contains the information that will be given to the subjects. This ensures that the process is documented for reasons of possible later control or document access request.

The background for the Danish Medicines Agency's involvement in drug trials is that, in accordance with the order on good clinical practice in connection with clinical trials of medicinal products on humans (BEK no. 695 of 12/06/2013) § 5, letter 8, the sponsor must ensure that, in the event of a deviation, steps are taken to ensure the quality of the trial, and that in the event of serious or repeated deviations, the Danish Medicines Agency is also immediately notified. In addition, the agency is the supervisory authority.

If a declaration of consent/copy of such is not available, and it is not possible to get in touch with the subject, data cannot basically be included in the project. If it appears from the patient record and the GCP monitoring that consent has been obtained, the regional committee or the Danish Medicines Agency may, after a concrete assessment, allow data to enter.

Information is given and consent is received by the person responsible for the experiment or a person authorized to do so, who has the professional qualifications to be able to convey the content of the research project, and is directly connected to it.

The person in charge of the trial or the authorized person must then sign the declaration of consent (certify) in the period from when information is provided to as soon as possible after the subject has agreed to participate in the trial.

If it is a multi-centre trial with a main trial manager and a number of trial managers who are responsible for the practical implementation of the trial at various other trial sites, it is the trial manager or an authorized person at the given trial site who must sign the declaration of consent.

When authorizing a person, cf. above, there must be a written agreement to this effect. The responsibility for whether adequate information has been provided always rests with the experimenter.

NVK has prepared pre-printed standard declarations of consent that you can use.

No, a written power of attorney is required.

In the case of children's participation in experiments, as a rule, proxy consent must be obtained from both parents when there is joint custody. According to the committee act, the substitute consent from the parents must be in writing, dated and signed (possibly by digital signature).

On the basis of the committee act's requirement that consent be given in writing, it is required that there must be a  written power of attorney  from one parent so that the other parent can make a decision about the child's participation in a specific trial within a given period, if both parents cannot be present when the declaration of consent must be signed. The committee system's standard parental power of attorney can be used.

This question can only be answered by the committee to which the notification was sent. The law, however, sets a deadline of no more than 60 days to make a decision on the project's approval.

The deadline only starts to run when a properly drawn up application is available. If the researcher is asked by the committee to submit additional information, the time limit is suspended until this information is received.

Complaints about a regional committee's decision must be submitted to NVK no later than 30 days after the decision from the regional committee has been received by the person in charge of the trial.

The complaint must be submitted directly to NVK and must be accompanied by a copy of the regional committee's decision as well as the case files that formed the basis of the regional committee's decision.

When calculating the appeal deadline, the starting point is that the decision was received the day after it was sent. The 30 days therefore run from this day. If the deadline expires on a Saturday, Sunday or public holiday, it is extended to the following weekday. The deadline expires at the end of office hours.