Abstract
Recall-by-genotype (RbG) strategies are bottom-up approaches to conducting targeted follow-up studies or substudies with eligible participants. They use specific genetic information derived from previous genome-wide association studies or whole-genome sequencing enabled by next-generation sequencing.
Genetic information may be partially disclosed when certain participants are recalled for RbG studies, and information on the study design and eligibility criteria is provided. These distinguishing peculiarities of RbG approaches have ethical, legal, and social/societal implications (ELSI).
In this thesis, we present and discuss the results of research on the ELSI aspects of RbG approaches and within the Cooperative Health Research in South Tyrol (CHRIS) studies (RbG1, RbG2) on genetic risk factors of Parkinson's disease (PD).
We used various qualitative and quantitative methods, including interviews, surveys and focus group discussions (FGD). Thereby, we sought to address the need for qualitative data from diverse stakeholders, including critical voices in the CHRIS research ecosystem, such as participants, researchers, ethics board members, and study assistants, to develop effective recall and communication strategies through a collaborative approach refining the CHRIS RbG policy.
The exploration began with a literature review revealing the explicit and implicit ELSI of RbG study designs. It uncovered a consensus on the significant ethical challenges RbG poses while highlighting the diversity in consent models and Return of Research Results (RoRR) policies employed in different research and biobanking contexts.
Then, a secondary analysis of interviews and surveys from a mixed-methods study with CHRIS RbG participants from the RbG pilot study (RbG1) followed. Alongside the second follow-up RbG study (RbG2) study, we then designed a survey, informed by the results of RbG1, to gather further perspectives on their experience of an RbG study, and other fundamental considerations pertinent to engagement and communication in RbG studies. Then, to explore the operational and practical aspects of RbG studies, we identified the relevant stakeholders who shape and decide on RbG study designs. Consequently, we designed and conducted FGD to examine stakeholder perspectives on the RbG study design, communication, and disclosure strategies. Further, we collected feedback and perspectives from CHRIS study personnel and coordinators who accompanied the RbG1 and 2 study process. Finally, we conducted a large-scale survey with CHRIS participants to strengthen the conclusions of previous empirical research. This collaborative approach aims to refine the CHRIS RbG policy, develop effective recruitment and communication strategies, and promote transparency.
The study's findings underscore the value of personalised engagement and sensitive communication through tailored disclosure and communication strategies. Stakeholder views on ELSI in RbG studies reveal diversity, highlighting the need for adaptable approaches aligned with study contexts. Overall, the results suggest that participants are highly interested in receiving information on carrier status on the genetic variations investigated by the RbG study, but views and motivations were heterogeneous. This adds to the complexity of the challenges in integrating these insights into communication strategies and disclosure policies. More research is necessary to investigate the effects of various disclosure strategies, the impact of disclosure on awareness, and how framing affects participants' reception of study-specific information.