Patient goals, motivations, and attitudes in a patient‐driven variant reclassification study

Abstract

Family studies to reclassify clinically ascertained variants of uncertain significance (VUS) can impact risk assessment, medical management, and psychological outcomes for patients and their families. There are limited avenues for patients and their families to actively participate in VUS reclassification, and access to family studies at most commercial laboratories is restricted by multiple factors. To explore patient attitudes about participation in family studies for VUS reclassification, we conducted semistructured pre‐ and post‐participation telephone interviews with 38 participants in a family‐based VUS reclassification study that utilized a patient‐driven approach for family ascertainment and recruitment. Participants had VUS from multigene panel testing performed at multiple clinical laboratories for cancer or other disease risk. Inductive thematic analysis of transcribed interviews highlighted four major themes: (a) Participants’ study goals were driven by the desire to resolve uncertainty related to the VUS, (b) Participants had mixed reactions to the VUS reclassification outcomes of the study, (c) Personal, public, and familial knowledge increased through study participation and (d) Participants used study participation to actively cope with the uncertainty of a VUS. As personalized genomic medicine becomes more prevalent, clinicians, clinical laboratories, and researchers could consider creating more opportunities for active partnership with patients and families, who are motivated to contribute data to familial VUS studies.

Exploring relatives’ perceptions of participation, ethics, and communication in a patient‐driven study for hereditary cancer variant reclassification

“…Our findings indicate that relatives had varied and nuanced experiences with patient‐driven familial VUS reclassification studies. Relatives share similar motivations with probands for participating in the VUS reclassification study, including a desire to increase knowledge about the variant and help their families and scientific researchers establish a link between the variant and their familial disease (Makhnoon et al, ; Tsai et al, ). Discussion of genetic information can open up health communications without impacting stress and anxiety levels, medical care, and behavior.…”

“…Eligible participants for the interviews were English‐speaking adults (18 years or older) who had enrolled as a relative of a family member in the FindMyVariant study (Makhnoon et al, ; Tsai et al, , ), a patient‐driven study for reclassification of VUS in hereditary cancer genes. Individuals were asked to participate in the FindMyVariant study by a family proband, defined as a family member found to have one or more VUS through clinical testing who had contacted the FindMyVariant study for further VUS reclassification efforts (Tsai et al, ).…”

“…In previous work, we found that actively involving patients as collaborators in charge of family communication for their own VUS reclassification studies led to reclassification of approximately 60% of variants, with an average time to classification of <1 year (Makhnoon, Garrett, Burke, Bowen, & Shirts, ; Tsai et al, , ). Unique aspects of this process included conveying uncertainty related to the clinical significance of the variant, patients’ and relatives’ involvement in aspects that might be considered research activities, and communication with relatives extending beyond the first and second degree of relationship.…”

“…Unique aspects of this process included conveying uncertainty related to the clinical significance of the variant, patients’ and relatives’ involvement in aspects that might be considered research activities, and communication with relatives extending beyond the first and second degree of relationship. Patients were motivated to engage in the patient‐driven process and appreciated the opportunity to proactively manage their uncertainty about their variant, connect with relatives during the study, and advance scientific research (Makhnoon et al, ; Tsai et al, ). This qualitative study describes the experiences of relatives who were asked to participate in the FindMyVariant study, a patient‐driven family variant study that aimed to reclassify a familial VUS in a hereditary cancer gene that was initially identified in another relative (Makhnoon et al, ; Tsai et al, , ).…”

“…Patients were motivated to engage in the patient‐driven process and appreciated the opportunity to proactively manage their uncertainty about their variant, connect with relatives during the study, and advance scientific research (Makhnoon et al, ; Tsai et al, ). This qualitative study describes the experiences of relatives who were asked to participate in the FindMyVariant study, a patient‐driven family variant study that aimed to reclassify a familial VUS in a hereditary cancer gene that was initially identified in another relative (Makhnoon et al, ; Tsai et al, , ). We interviewed relatives to explore motivators and deterrents to participation, the ethical implications of patient‐driven research, and the impact of participation on health care, family communications, and behavior.…”