Anderson, Katherine C

Abstract The 21st Century Cures Act Final Rule (Final Rule) increases patient access to their health records but raises concerns about distress and misunderstanding of automatically released results and documentation. Little is known about genetic counselors' (GCs') experiences with the Final Rule. In Fall 2023, we conducted a cross‐sectional survey of US GCs about the Final Rule's perceived impact on practice and assessed if being the ordering versus non‐ordering provider for genetic testing affected perceptions of Final Rule‐related changes. GCs ( n = 102) reported demographic and workplace characteristics, institutional policy changes, workflow changes, and perceived patient harms and benefits due to the Final Rule. To compare ordering and non‐ordering providers, we conducted Fisher's exact tests for categorical variables and trend tests for ordinal variables. Open‐response questions elicited examples of positive and negative patient impacts, the effects of patient characteristics, and practice changes in response to the Final Rule. Twenty‐seven GCs were ordering providers and 66 were non‐ordering providers. Relative to ordering providers, non‐ordering providers expressed stronger agreement with statements indicating concern about the emotional impact on patients reviewing results or notes without support ( p = 0.002, 33% vs. 51% strongly agree), patients misunderstanding or misinterpreting results ( p = 0.025, 44% vs. 70% strongly agree), and patients contacting the inappropriate party to discuss results ( p = 0.023, 19% vs. 48% strongly agree). Agreement with the statement “patients have more knowledge/context/questions at our disclosure session due to previous results review” also differed by ordering provider status ( p = 0.007). In open responses, GCs expressed concerns about patients' strong emotional reactions, patients misinterpreting results, workflow disruptions, and widening health disparities. Benefits included patients' ability to be reassured, informed, or empowered earlier; ease of sharing health information; more efficient workflow due to the automatic release of results. These results emphasize the importance of clear communication within health systems and between patients and providers.

Background: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart disease (CHD), and 1-year outcomes following return of results in phase III of the electronic medical records and genomics network. Methods: Adult participants (n=18 544) at 7 sites were enrolled in a prospective cohort study to assess the clinical impact of returning results from targeted sequencing of 68 actionable genes, including LDLR , APOB , and PCSK9 . FH variant prevalence and penetrance (defined as low-density lipoprotein cholesterol >155 mg/dL) were estimated after excluding participants enrolled on the basis of hypercholesterolemia. Multivariable logistic regression was used to estimate the odds of CHD compared to age- and sex-matched controls without FH-associated variants. Process (eg, referral to a specialist or ordering new tests), intermediate (eg, new diagnosis of FH), and clinical (eg, treatment modification) outcomes within 1 year after return of results were ascertained by electronic health record review. Results: The prevalence of FH-associated pathogenic variants was 1 in 188 (69 of 13,019 unselected participants). Penetrance was 87.5%. The presence of an FH variant was associated with CHD (odds ratio, 3.02 [2.00–4.53]) and premature CHD (odds ratio, 3.68 [2.34–5.78]). At least 1 outcome occurred in 92% of participants; 44% received a new diagnosis of FH and 26% had treatment modified following return of results. Conclusions: In a multisite cohort of electronic health record–linked biobanks, monogenic FH was prevalent, penetrant, and associated with presence of CHD. Nearly half of participants with an FH-associated variant received a new diagnosis of FH and a quarter had treatment modified after return of results. These results highlight the potential utility of sequencing electronic health record–linked biobanks to detect FH.