How to communicate and what to disclose to participants in a recall-by-genotype research approach: a multistep empirical study

Journal of Community Genetics https://doi.org/10.1007/s12687-024-00733-8 RESEARCH How to communicate and what to disclose to participants in a recallby-genotype research approach: a multistep empirical study Katharina Tschigg1,2 · Luca Consoli3 · Norbert Brüggemann4,5 Deborah Mascalzoni2,7 · Roberta Biasiotto2,8 · Andrew A. Hicks2 · Ciara Staunton2,6 · Received: 30 April 2024 / Accepted: 4 September 2024 © The Author(s) 2024 Abstract Recall-by-genotype (RbG) is a bottom-up approach using existing genetic data to design follow-up stratified studies. Genetic information may be partially disclosed at invitation, thus raising ethical issues which call for defined best practices for disclosure and communication in RbG approaches. Within the context of the ProtectMove sub-project of the Cooperative Health Research in South Tyrol (CHRIS) study, we investigated research participant perspectives on RbG communication strategies (Step 1 and 4, questionnaire with a subsample of CHRIS participants with and without previous experience of RbG, respectively). Additionally, we explored researchers’ and study personnel’s experience with RbG (Step 2 and 3, focus group discussion). In step 1 (N = 95), participants were generally satisfied with the study process. Most (71.6%) wanted to know their carrier status for personal and collective benefit. Tailored disclosure strategies and transparent, effective, and well-thought-out communication approaches were advocated by study personnel (Step 2, N = 6) and researchers (Step 3, N = 7). Challenges in dealing with uncertainty, concerns caused by RbG invitations, and the possibility of misunderstanding were also raised. In step 4 (N = 369), participants valued being informed of study details at the first invitation stage, and generally felt comfortable towards RbG study invitations (58.5%) and to receiving genetic information after the study (58.5–81.6%). Comfort and perceived impact of disclosure of genetic information varied according to the type of variant being potentially disclosed. This study suggested designing communication strategies, based on clear and understandable explanations, sensitive to participant expectations and preferences, developing case-by-case solutions for disclosure. Keywords Recall-by-genotype · Disclosure of genetic information · Communication · Research participants · Policy · Informed consent Deborah Mascalzoni 1 Department of Cellular, Computational, and Integrative Biology, University of Trento, Trento, Italy Katharina Tschigg 2 Institute for Biomedicine, Eurac Research, Bolzano, Italy 3 Luca Consoli Institute for Science in Society, Radboud University, Nijmegen, Netherlands 4 Norbert Brüggemann Department of Neurology, University Hospital SchleswigHolstein, Campus Lübeck, Lübeck, Germany 5 Andrew A. Hicks Institute of Neurogenetics, University Hospital SchleswigHolstein, Campus Lübeck, Lübeck, Germany 6 Ciara Staunton School of Law, University of KwaZulu-Natal, Durban, South Africa 7 Center for Research Ethics and Bioethics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden 8 Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy Roberta Biasiotto 13 Journal of Community Genetics Abbreviations CHRIS Cooperative Health Research in South Tyrol ELSI Ethical, legal, and social/societal implications FGD Focus group discussion GDR Genotype driven research/recall/recruitment RbG Recall by genotype RoRR Return of research results PD Parkinson’s disease PRKN Parkin gene Background The availability of genetic, genomic, and other types of health data in biobanks has rapidly increased research opportunities with translational potential, while causing interest to proliferate in the ethical, legal, and social/societal implications (ELSI) of this type of research (Bledsoe 2012; Boyer et al. 2012; Cadigan et al. 2013). While the traditional approach to human genetics research relied on a phenotypefirst approach, recent discoveries have been made using a ‘genotype-first’ approach (Mefford 2009; Wilczewski et al. 2023). In recent years, this advancement has led to targeted bottom-up approaches to participant selection, such as recall-by-genotype (RbG). The RbG or genotype-driven research (GDR) recruitment design (i.e., recruitment based on defined genetic characteristics of interest) has proven to be a powerful tool compared with traditional random sampling strategies. This is particularly so in cases where specific genetic characteristics are rare, and the phenotyping of large sample frames would be too costly (Atabaki-Pasdar et al. 2016; Franks and Timpson 2018; Minion et al. 2018; Corbin et al. 2018; Finer et al. 2020; Momozawa and Mizukami 2021). RbG studies reuse biobank material and data, thus decreasing possible public concerns about the underutilisation of biobank resources, which may undermine public trust (Cadigan et al. 2013, 2014; Klingler et al. 2022). However, RbG approaches raise issues concerning the involvement of participants (Minion et al. 2018; Corbin et al. 2018; Mascalzoni et al. 2021). Disclosure concerns have been explicitly highlighted because the disclosure of genetic information may be moved to the invitation phase (Beskow and Burke 2010; Beskow et al. 2012a, b). Thus, by inviting prospective study participants to an RbG study, they may incur partial or potential disclosure of their genetic information, possibly without being aware of its implications or without providing their personal decision to participate in these types of studies, especially if the possibility of participating in future RbG studies was not clarified nor asked during the original consenting process. The challenges of ethically managing recall and consent require careful assessment in various contexts, such as patient cohorts and 13 healthy population cohorts, where participants’ expectations can differ significantly (Heinzel et al. 2022). While patients might anticipate and even welcome being re-contacted to gain deeper insights into their condition, the same assumption might not hold for healthy individuals. Due to these ELSI challenges, policies for guiding the research are required. As part of this policy development, empirical research can contribute to identifying both issues and their solutions (Bergner et al. 2014; McGowan et al. 2018; Rutakumwa et al. 2019; Mwaka et al. 2021). While policies that govern participant data and novel study designs, such as RbG in biobanks, need more uniformity, there is no one-size-fits-all solution for such policies (Henderson et al. 2013; Lemke and Harris-Wai 2015). Stakeholder involvement and engagement have been used to provide ‘contextual evidence’ and inform specific practices and research (Krahn and Naglie 2008; Hoffman et al. 2010; O’Haire et al. 2011; Barry and Edgman-Levitan 2012; Carman et al. 2013; Fleurence et al. 2013; Lemke and Harris-Wai (...truncated)