Clinical genome and exome sequencing (CGES) may identify variants leading to targeted management of existing conditions. Yet, CGES often fails to identify pathogenic diagnostic variants and introduces uncertainties by detecting variants of uncertain significance (VUS) and secondary findings. This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3-month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions evolved within disclosure sessions and at 3-month interviews toward acceptance and satisfaction. Families erroneously expected, and prepared extensively, to learn about risk for common conditions. During disclosure sessions, parents and adolescents varied in how they monitored and responded to each others reactions. Several misinterpreted, or overestimated, the utility of findings to attribute meaning and achieve closure for the CGES experience. Participants perceived testing as an opportunity to improve disease management despite results that did not introduce new treatments or diagnoses. Future research may examine whether families experience cognitive dissonance regarding discrepancies between expectations and findings, and how protective buffering minimizes the burden of disappointment on loved ones. As CGES is increasingly integrated into clinical care providers must contend with tempering family expectations and interpretations of findings while managing complex medical care.

Li-Fraumeni Syndrome (LFS) is a hereditary disorder that confers an approximately 90% lifetime risk of cancer and requires comprehensive lifetime cancer screening. We explored healthcare roles for managing LFS-related cancer risks and treatments that were assumed by parents, adolescents, and adult children. Semi-structured interviews were conducted with 23 families. Family groupings were comprised of 2-5 members, with the younger generation in each family ranging in age from 7 to 40 years. Using grounded theory methods, we conducted open and focused coding of interview transcript content. Family members described how the role of health leader was implemented in their family, as well as factors such as maturation of a child or death of a member that determined who assumed particular roles and how these roles shifted over time. They often expressed collective responsibility for helping relatives understand LFS and implement appropriate cancer risk management. Members demonstrated their health role by attending others' medical appointments for support or information gathering. The health leader role was intergenerational and provided the family necessary support in navigating complicated healthcare decisions. Our findings provide insight into healthcare providers regarding how LFS patients and their relatives develop unique medical decision-making and caring roles influenced by the hereditary nature of LFS, and how these roles change over time. Providers who are attuned to family role dynamics may be better able to meet relatives' psychosocial and medical needs by understanding how living with LFS influences the family system's functioning and facilitating members' support for each other.

We developed a novel approach to narrative Big Qual research that combines Carol Gilligan and Lyn Mikel Brown’s Listening Guide with Irwin Epstein’s clinical data mining. We adapted the voice-based research methodology of the Listening Guide for use with a corpus of clinical case notes drawn from an integrated data system (IDS) of a social service intervention serving families in an immigrant enclave. This methodological innovation was inspired by the insight that the Listening Guide can be used to trace and name the layering of meaning within any narrative, whether that narrative reflects the experience of an individual person or, as in this case, the community and everyday life of a social service intervention. Critically, this approach pivots on theorizing the subject as the collective of the intervention itself, as narrated by case managers, who can be understood as narrating subjects within the cultural, figured world of the intervention. In the context of a larger process and outcome evaluation, marrying these two approaches provided context, texture, and depth to supplement existing data sources like self-report survey data and participant observation, and offered a glimpse inside the “black box” of the intervention. We adapted the Guide through three readings of the clinical case notes: once for stanza structure, once inspired by the I-Poem technique but modified for these third-person narratives, and once with an eye to the contrapuntal voices of the inner and outer worlds of the intervention. As a methodological innovation this approach represents an advance in Big Qual and a promising approach to conducting narrative research on large qualitative data sets within mixed methods studies.