Some ethical considerations

Most studies in iPSYCH are based on the identification of cases and a population control cohort through registers, and retrieval of blood samples for these individuals in The Danish Neonatal Screening Biobank (DNSB).  Under Danish law this process is, after obtaining the necessary ethical approvals, possible without obtaining specific informed consent from each included person, if the Committee on Health Research Ethics decides to waive the need for informed consent.

This possibility is key to iPSYCH, because it allows us to include epidemiologically sampled cases and controls from a delineated total population cohort without the selection biases inherent to most studies.  However, since this possibility is not common outside of Denmark, and since this raises a number of ethical issues we describe these below in more detail:

In connection with the routine sampling of the blood of the neonate for screening purposes, the parents are informed that the remains of the samples can be used for future unspecified research, pending approval from relevant authorities. They have thus given a broad consent, delegated to a third party (= the Committee on Health Research Ethics in Denmark, the DNSB Steering Committee and the Danish Data Protection Agency). The parents are also informed how to opt out from inclusion in research studies.

According to Danish legislation, research data from the national biobanked samples are considered to be register-based data from which feedback never is given to the individual citizen. This general rule, however, needs special consideration with respect to incidental findings (IF).

The iPSYCH initiative was approved by the Committee on Health Research Ethics in Denmark Central Region in August 2012 including exemption from the individual informed specific consent. In November 2015 the Committee approved an extension of the study. In February 2017 the Committee on Health Research Ethics approved our current guidelines regarding incidental findings:

First of all, in iPSYCH whole exome and whole genome sequencing data obtained from the DNSB samples can be analyzed only in projects that study mental disorders and their somatic comorbidities. In projects performing agnostic (hypothesis-free) analyses of mental disorders as single or cross-disorder outcomes, the risk of IFs is considered negligible. However, in projects studying somatic comorbidities with mental disorders, or performing hypothesis-driven analysis (e.g. analysis of candidate genes or candidate gene sets), the risk of IF is increased. Therefore, in such projects the bioinformatic analysts will only be given access to analyze sequencing data where the data concerning genes considered to harbor clinically significant variants have been removed. The selected genes are in accordance with the current recommendations of the American College of Medical Genetics and Genomics (ACMG). Subsequent updates will be implemented as published by ACMG. The rule is a protection of the analyst against the ethical dilemma of non-disclosure of medically actionable genomic information from an anonymous research participant.

Genomic research evolves fast and in the future some of the genetic variants that we study now may turn out to be medically actionable variant of a severe disorder. In this case, iPSYCH will consult the Committee on Health Research Ethics in Denmark Central Region to discuss the case and plan for nondisclosure vs disclosure and genetic counseling.

Our set-up thus minimizes the likelihood of disclosure of incidental findings to the researchers and secures back-up if such disclosure should occur in the future.

Description of The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.