Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record

Abstract

The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans. Thus, the HNP presents an opportunity to evaluate the efficiency of participant and provider responses to notification of important genetic findings, using electronic health records (EHRs) at Renown Health (a large regional hospital in northern Nevada). Out of 520 HNP participants with findings, we identified 250 participants who were notified of their findings and who had an EHR. 107 of these participants responded to a survey, with 76 (71%) indicating that they had shared their findings with their healthcare providers. However, a sufficiently specific genetic diagnosis appeared in the EHRs and problem lists of only 22 and 10%, respectively, of participants without prior knowledge. Furthermore, review of participant EHRs provided evidence of possible relevant changes in clinical care for only a handful of participants. Up to 19% of participants would have benefited from earlier screening due to prior presentation of their condition. These results suggest that continuous support for both participants and their providers is necessary to maximize the benefit of population-based genetic screening. We recommend that genetic screening projects require participants’ consent to directly document their genetic findings in their EHRs. Additionally, we recommend that they provide healthcare providers with ongoing training regarding documentation of findings and with clinical decision support regarding subsequent care.

From the patient to the population: Use of genomics for population screening

“…In the general population, there is less evidence on the uptake of preventive strategies or outcomes. Several studies indicate that many BRCA1 /2 carriers identified through population screening do undergo risk-reducing procedures such as surveillance or prophylactic surgery ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ). In some cases, HBOC-associated cancers were diagnosed because of the screening initiated based on the genomic screening results ( Buchanan et al, 2020 ).…”

“…Evidence on the outcomes of population genomic screening for LS beyond detection rate is limited. Several studies of population genomic screening for LS have found that a proportion of individuals with pathogenic LS variants underwent risk-reducing procedures, including colonoscopy and prophylactic surgery ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ). Several individuals were diagnosed with LS-associated cancers because of follow-up initiated based on their genomic screening results ( Buchanan et al, 2020 ).…”

“…Several individuals were diagnosed with LS-associated cancers because of follow-up initiated based on their genomic screening results ( Buchanan et al, 2020 ). However, there is some literature that suggests the uptake of risk-reducing strategies is very low (< 10%) when patients are responsible for communicating their results to their clinicians ( Elhanan et al, 2022 ).…”

“…Evidence of clinical outcomes of population genomic screening for FH is emerging, but limited to short-term outcomes. Several studies have found that population genomic screening identified individuals with clinical manifestations of FH who were previously unaware of their condition ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ). In these studies, a proportion of individuals with pathogenic FH variants initiated risk-reducing strategies such as LDL-lowering medications ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ).…”

“…Several studies have found that population genomic screening identified individuals with clinical manifestations of FH who were previously unaware of their condition ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ). In these studies, a proportion of individuals with pathogenic FH variants initiated risk-reducing strategies such as LDL-lowering medications ( Buchanan et al, 2020 ; Lee et al, 2021b ; Elhanan et al, 2022 ). In one study in which patients were tasked with informing their healthcare provider of their population genomic screening results, LDL-C levels improved in the short term for only 9% of patients with pathogenic FH-related variants, while the remainder exhibited no change in their clinical management ( Elhanan et al, 2022 ).…”