Read about and report a research project involving extensive mapping of an individual's genome, in which an exemption from the consent requirement is sought.

Comprehensive mapping of the genetic material

The research project must be submitted to NVK if an exemption is sought from obtaining a new consent to make extensive mapping of already sampled biological material, which has either been collected in a previously approved health science research project (research biobank) or from patients in connection with treatment (clinical biobank ).

Methods that fall under comprehensive mapping of the genetic material:

  • Whole genome sequencing - Whole Genome Sequencing (WGS)
  • Total exome sequencing - Whole Exome Sequencing (WES)
  • Total RNA sequencing, e.g. sequencing of RNA from benign human tumors
  • Genome Wide Associations Studies (GWAS) with mapping of rare variants where there is a risk of the emergence of secondary findings.
    • This applies, for example, to the use of the original version of the Infinium Global Screening Array
  • Epigenetic studies based on NGS methods with extensive DNA sequencing of a large number of areas in the genetic material

Methods that are not extensive mapping of the genetic material:

  • Targeted sequencing, where the sequencing targets a limited number of defined genes
  • RNA-sequencing with “TAG-based” methods (short sequences), where expression levels and not sequence variation are studied
  • Epigenetic studies where extensive sequence information is not generated. This applies, for example, to the use of methylation arrays which do not generate extensive DNA sequence information, e.g. Infinium MethylationEPIC array BeadChip
  • Genome Wide Association Studies (GWAS) with SNP arrays with frequent variant mapping

Dispensation access

Dispensation from the requirement for renewed consent can be granted if the experiment does not involve health risks and the project cannot otherwise be a burden for the subject, or if it is impossible/disproportionately difficult to obtain consent.

When deciding on exemption from the consent requirement, NVK places, among other things, weight on

  • That the purpose of the project is related to the previous project/clinical area where the material was sampled/collected
  • That the test subjects are initially informed about research into genetics (genes), if it is a previous research project
  • Whether a significant part of the subjects have died
  • Whether searching for highly penetrant variants of significance for serious diseases, with derived consequences for the risk of significant health-related secondary findings
  • That the reviewer follows the NVK's guidelines regarding significant health-related secondary findings, including the use of a committee of experts to assess them
  • The time when the consent was obtained. There is particular reason to be aware of the information and consent given several years ago
  • That the trial manager/biobank manager at clinical biobanks will check whether the subjects have opted out of research in the Tissue Use Register

Do you have to report a research project where you carry out extensive mapping of the genetic material?

Then you can find guidance here (also projects with children and projects with exemption from consent):

Document requirements

Requirements for protocol

Requirements for protocol summary

Requirements for participant information

Researcher checklist - Special requirements research in genomes

Standards for Consent Statements

 

How to report via the Report Database

 

Frequently Asked Questions About Projects Involving Extensive Mapping with Exemption from Consent

Currently, the use of Next Generation Sequencing (NGS) for total genomic sequencing (Whole Genome Sequencing, WGS), total exome sequencing (Whole Exome Sequencing, WES), or total RNA sequencing is considered as extensive mapping. This also applies to the aforementioned methods used on DNA/RNA from human tumors, as the results often reveal the genetic profile of the rest of the body.

However, gene sequencing of bacteria isolated from humans is not considered extensive mapping of an individual's genome.

Targeted sequencing, where the sequencing is directed at a limited number of defined genes, is also not covered by the term "extensive mapping of an individual's genome". This also applies to Genome Wide Association Studies (GWAS), performed using SNP-arrays, which examine common gene variants. GWAS that also map rare variants, which can have high predictive value and thus significant importance for the trial subjects, are considered extensive mapping (for example, Infinium Global Screening Array from Illumina).

Epigenetic studies are considered extensive mapping of an individual's genome if they can generate incidental findings of significant importance for the trial subject being examined. Analyses that do not provide extensive sequence information are not covered. This includes, for example, the use of methylation assays (which examine a limited part of CpG sites in the human genome). However, methods that involve DNA sequencing by NGS of a large number of areas in the genome are considered to be extensive mapping (for example, whole genome bisulfite sequencing, which can provide information on all CpG sites).

Even if extensive sequencing is not carried out, the committee system recommends following the principles in the genome guidance if there is a risk of making unexpected findings (for example, in targeted investigation of a very large number of genes).

Trials involving extensive mapping of an individual's genome, where informed consent is obtained from trial subjects, must be reported to the regional ethical committees.

Trials involving extensive mapping of an individual's genome, where an exemption from the requirement to obtain informed consent from the trial subject is sought, must be reported to the National Ethical Committee (NVK).

Trials that do not fall under the concept of "extensive mapping of an individual's genome," such as targeted sequencing, and where an exemption from obtaining informed consent is sought, must be reported to the Regional Ethical Committees (RVK).

In these cases, the committees particularly consider:

  • That the search is not for known variants significant for other serious diseases, thereby minimizing the risk of incidental findings.
  • That clear and appropriate guidelines are established for handling incidental findings in accordance with the NVK's guidelines. It is recommended to set up a committee of independent experts who, in the event of incidental findings, will assess whether feedback should be given according to the guidelines, including the process for this.
  • That the purpose and aim of the new project are not substantially different from the original project from which the biological material was extracted, or that the material was taken from patients within the same disease group (for material taken from previous trials) and that the trial subjects were informed that there would be investigations of genes, and that some of the participants had the opportunity to decide if they wanted feedback on significant health-related findings.
  • That a significant portion of the participants are presumed to have died.

Additionally, the material must have been legally extracted and stored up to the time of use.

Read more about the practice in exemption cases.

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

If a trial can only be conducted with children, it is required that the trial offers significant benefits for children with the studied disease. These requirements are in accordance with the rules of the committee law (§ 19).

In biobank research, where an exemption from the consent requirement is sought, children can participate in the research if the trial does not pose a new risk or burden to the child (committee law § 10).

It is considered a burden to children, especially healthy ones, if they, as a result of extensive mapping of their genome, could be confronted with incidental findings of a serious health nature, which might not manifest until adulthood.

Therefore, healthy children are normally not allowed in biobank trials involving genome sequencing.

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

Documents for Use in Application

If you are reporting a research project in already extracted biological material and seek an exemption from consent, you can find guidance here.

Document Requirements

Requirements for Protocol

Requirements for Protocol Summary

II. Special Requirements - Research in Biological Material with Exemption from Consent

If you are reporting a research project involving extensive mapping of the genome, you can find guidance here (including projects with children and projects with an exemption from consent).

Document Requirements

Requirements for Protocol

Requirements for Protocol Summary

IV. Special Requirements - Research in Genomes

Last updated 01-02-2024

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