Disclosure of onset-predictive biomarker results to research participants at risk of genetic frontotemporal dementia: a European perspective

Abstract Background As understanding of biomarkers for genetic frontotemporal dementia (FTD) advances, there is a need to develop onset-predictive biomarker tests (OPBTs) to detect changes before the onset of symptoms. OPBTs can be used to recruit carriers or individuals at 50% risk of carriership into clinical trials of investigational therapies targeting the preclinical and prodromal phases of FTD. OPBT results should be disclosed as part of the informed consent process, with positive results indicating that symptom onset is likely in the next few years. This information can be psychologically burdensome, especially in individuals at 50% risk, for whom a positive OPBT result would reveal their genetic status. There is a need for ethical guidance for disclosure processes to help researchers implement disclosure of OPBT results responsibly at their study sites. Methods Existing literature on disclosure of genetic and biomarker results in neurodegenerative conditions informed the design of this disclosure process for OPBT in FTD. Drafts were discussed with the multidisciplinary research team, scientific and clinical FTD experts across European countries, and other stakeholders and revised accordingly. Results The suggested disclosure process provides guidance for first-time or repeated disclosure of OPBT results to carriers or individuals at 50% risk of genetic FTD in research settings. Conclusions Researchers involved in clinical trials using OPBTs can adopt this disclosure process as a framework for responsible communication of OPBT results at their study site. The process was designed for international applicability and facilitates the alignment of disclosure processes for clinical trial recruitment across European countries.