Balancing scientific interests and the rights of participants in designing a recall by genotype study

Abstract

Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants’ views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.

Participant perspective on the recall-by-genotype research approach: a mixed-method embedded study with participants of the CHRIS study

“…First, researchers should be attentive to what is important for participants and adequately address participant needs and views as partners. Second, as already highlighted in other empirical studies [19,20,[23][24][25], the context in RbG is essential, both in a sense previously identified [7] and at a societal level. Considering the specific disease under study and the meanings attached to it (e.g., possible stigma or discrimination) and the socio-economic conditions (including the access to health care) where the study is conducted would allow a deepened reflection on the societal implications of RbG studies and the extent to which specific research practices are transferrable to other contexts.…”

“…The mother tongue of most residents in Val Venosta/Vinschgau is German [11]. Participant recruitment and the broader empirical RbG study have been described elsewhere [7,8] and summarized in Table 1.…”

“…For this reason, exploring participant perspectives on the RbG approach is crucial to improve research practices and develop suitable policy. The Cooperative Health Research in South Tyrol (CHRIS) study, a longitudinal study with the general population of Val Venosta/ Vinschgau, South Tyrol in Italy, conducted its first RbG study in a sub-sample of the CHRIS cohort (pilot RbG study) as a joint project with the University of Lübeck, in the framework of the ProtectMove Research Unit project (FOR2488), in 2018 [7,8]. The ProtectMove project investigates movement disorders, including Parkinson's disease.…”

“…Our study, a mixed-method empirical study embedded within the pilot RbG study, aims to understand participant perspectives on RbG research approach and participant experience of invitation and participation in a specific RbG study. The present work was motivated by process of policy design for RbG studies within the CHRIS study [7]. A participant-centered approach, which considers participant views, is key in the CHRIS study, which uses dynamic consent as an informed consent model [9][10][11].…”

Ten years of dynamic consent in the CHRIS study: informed consent as a dynamic process

“…In 2018, the beginning of recall-by-genotype studies within the CHRIS study necessitated a change in the return of results policy. CHRIS participants were involved in this revision and empirical studies explored their views on the return of individual research results [ 17 ] and on the recall-by-genotype research approach [ 21 ]. The findings showed that participants want to make autonomous choices on the return of individual research result, and that a series of criteria affects their choice [ 17 ].…”