Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing

Abstract

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

Keywords: actionable genetic findings; clinical outcomes; electronic health records; healthcare costs; healthcare utilization; monogenic sequencing; return of results; translational.

Figure 1

eMERGE cohort inclusion criteria There were 16,218 adults in the eMERGE III cohort that had return of result data, of which 970 had pathogenic or likely pathogenic (P/LP) findings. After removing participants that had been enrolled for specific conditions, had P/LP finding in other conditions, did not have adequate code data (at least 1 CPT or ICD code), or were missing return age, the individuals were 1:1 matched on age, sex, and enrollment site to individuals receiving negative reports. The final analysis cohort consisted of 477 adults in the P/LP and negative report category each.

Figure 2

Number of individuals receiving at least one healthcare service differs based on actionable genetic finding More individuals received at least one qualifying health care service in the P/LP (dark blue) group after RoR compared with those with negative reports (black) in four of the five conditions examined. Number of unique individuals shown in the pre-RoR period (P/LP) are shown in light blue and (negative) gray. P/LP, pathogenic or likely pathogenic, RoR, return of results; FH, familial hypercholesterolemia; ^∗p < 0.05 when post-RoR P/LP and post-RoR negative reports are compared.

Figure 3

Cost differences are observed after the return of arrhythmia, breast cancer, and cardiomyopathy genomic results Difference in spending after return of results minus before return for individuals receiving P/LP findings (blue) and negative (black) findings. There were significantly higher costs in three conditions (arrhythmia, p < 0.0001; breast cancer, p = 0.0013; and cardiomyopathy, p = 0.001), and a marginally significant difference in colorectal cancer (p = 0.059). No significant difference was observed in FH (p > 0.05). Box represents interquartile range (IQR), with whiskers representing variability outside the quartiles, and outliers represented as dots. Data shown are limited to 5 to 95 percentiles of costs. IQR for colorectal cancer and FH are 0. FH, familial hypercholesterolemia; ^∗p < 0.05.