Returning negative results to individuals in a genomic screening program: lessons learned

Abstract

Purpose In genomics, the return of negative screening results for rare, medically actionable conditions in large unselected populations with low prior risk of disease is novel and may involve important and nuanced concerns for communicating their meaning. Recruitment may result in self-selection because of participants’ personal or family history, changing the characteristics of the screened population and interpretation of both positive and negative findings; prior motivations may also affect responses to results. Methods Using data from GeneScreen, an exploratory adult screening project that targets 17 genes related to 11 medically actionable conditions, we address four questions: 1) Do participants self-select based on actual or perceived risk for one of the conditions? 2) Do participants understand negative results? 3) What are their psychosocial responses? 4) Are negative results related to changes in reported health-related behaviors? Results We found disproportionate enrollment of individuals at elevated prior risk for conditions being screened, and a need to improve communication about the nature of screening and meaning of negative screening results. Participants expressed no decision regret and did not report intention to change health-related behaviors. Conclusion This study illuminates critical challenges to overcome if genomic screening is to benefit the general population.

Development and validation of a measure of comprehension of genomic screening—negative results (CoG-NR)

“…Although screening unselected populations will identify individuals with important positive results, most screened individuals will have normal/negative genomic screening results; that is, no genetic variants associated with these conditions will be identified. Based on recent studies [ 7 – 10 ] and our own prior research [ 11 ], we argue that there may be critical challenges and potential harms in the return of normal/negative population screening results, and addressing them is critical for realizing the promise of population genomic screening. As a first step to assess understanding among those who receive normal/negative screening results, we developed the measure described in this article.…”

“…In 2019, we reported lessons learned from returning negative results to individuals in a pilot genomic screening program, “GeneScreen” [ 11 ]. This study recruited 262 adults from a hospital-based general medicine clinic at the University of North Carolina, Chapel Hill (UNC) and the Kaiser Permanente Northwest research biobank.…”

“…First, contrary to expectations that the participants were “healthy” adults, we found disproportionate enrollment of individuals with an elevated prior risk for one of the conditions being screened. Before receiving results, nearly three-quarters of participants reported a personal or family history of at least one condition included on the panel [ 11 ]. Having an elevated prior risk increases the likelihood of a falsely reassuring negative screen, particularly when only a subset of relevant genes for a given disease phenotype is being evaluated and the results are limited to pathogenic or likely pathogenic variants.…”

“…Given the potential for a false negative result, this response indicates a misunderstanding of a negative result, particularly in participants with a prior increased risk of one of the conditions. Over half (51.9%) indicated it was “extremely unlikely” they had a pathogenic variant in a GeneScreen gene, a more accurate response [ 11 ]. We conclude that return of normal/negative results in this context may raise nuanced concerns for communicating their meaning [ 11 ].…”

“…Over half (51.9%) indicated it was “extremely unlikely” they had a pathogenic variant in a GeneScreen gene, a more accurate response [ 11 ]. We conclude that return of normal/negative results in this context may raise nuanced concerns for communicating their meaning [ 11 ].…”