Table 1. Review of the appropriateness of Council for International Organizations of Medical Sciences (CIOMS) guidelines checklist (G): additional concerns that apply to family-based studies in isolated populations.

CIOMS G

Key issues and additional informational requirements for family-based studies in genetically isolated populations.

Selection of population (G1)

Defining a population as an isolate could be stigmatising if not defined clearly.

There may be a mismatch between the way in which a population is described in participant information leaflets and the way it is subsequently described in scientific publications.

The reasons that the population is considered suitable for the research should be made explicit and this information should be consistent between the participant information sheet and any future publications.

Withdrawal of consent (G2)

There may be technical problems in withdrawing all data on a single individual.

Withdrawal of single individuals may have consequences for collected family data.

Participants may feel under additional pressure from family members to participate or not participate in the study.

The right to withdraw from the study can only be meaningful if people are updated about major changes in the direction of the project.

Researchers should make clear what will happen to the data relating to withdrawn participants, including genealogical data.

Information leaflets should state clearly that participation is an individual decision but also that this may have implications for the rest of the biological family.

Major changes in project direction should be communicated to participants so that they are able to re-evaluate their decision to participate.

Research purpose (G3)

Participants may not be aware that researchers routinely verify pedigree relationships using genetic information. Crucially, this could potentially provide researchers with information, which may contradict that provided directly by the participants – for example, on paternity.

It should be made clear that the research is on extended families. The implications of this should be clearly explained: this means that family trees will be reconstructed and that pedigree relationships will be verified using genetic information.

Benefit sharing (6)

There is greater potential to direct benefits to the study population and to involve the population in decisions about benefit sharing because the study populations are small and well defined, in contrast to large, dispersed, population-based studies.

Researchers should engage with the community regarding the types of benefits that might accrue and those that would be welcomed.

Potential risks of (G9) participation

There are potential informational risks to participants' family members and to the wider community, whether or not they are themselves participants.

The potential risks to participants, their families and the wider community should be clearly explained, including learning about family illnesses, increased insurance premiums, disclosure of non-paternity, community anxiety about specific disease risk, and the use of data for criminal investigations.

Expected benefits of research (G11)

Research projects in small, isolated communities typically have a high profile, which may easily lead to unrealistic expectations as to what the study might find and what benefits might flow from this.

Care must be taken not to make unrealistic claims about the benefits likely to accrue to the community from the study.

Privacy concerns (G14)

Standard safeguards are insufficient to guarantee privacy, not just for the single individual but for the whole biological family. Through combined data (genealogies, health data, genotypes), families and individuals in the family may be identifiable.

There is a need to be open about the difficulties of guaranteeing complete privacy and to ensure that if a publication might potentially identify individuals and families, fully informed consent is obtained from those individuals and families before publication.

Disclosure of genetic data (G16)

Linked genetic, genealogical and health data can provide information about all members of the biological group, including non-participants.

There may be legal requirements to disclose data to the police, courts or other third parties in certain circumstances.

Families and individuals are more easily identifiable in small, close-knit communities than in more anonymous populations.

Researchers must state under what circumstances genetic information will be shared with external agencies (research partners, official agencies).

Information sheets should clearly state the policy according to the current law, for example, that data will not be disclosed to police/court unless there is a court order.

In publishing study findings, researchers must take great care not inadvertently to identify families through indirect information (‘the family in the study village with three affected children…').