BACKGROUND: According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. METHODS AND FINDINGS: Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (<10%), 19% (14%) at intermediate (≥10-<20%), and 11% (6%) at high (≥20%) 10-year CVD (CHD) risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02-0.19). The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01-0.03) with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38%) moved to low and 22% (30%) to high CVD (CHD) risk. Improvements with other novel risk markers were limited. CONCLUSIONS: Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies.

Background and objectives

Genomic sequencing (GS) is increasingly used for diagnostic evaluation, yet follow-up care is not well understood. We assessed clinicians' recommendations after GS, parent-reported follow-up, and actions parents initiated in response to learning their child's GS results.

Methods

We surveyed parents of children who received GS through the Clinical Sequencing Evidence Generating Research consortium ∼5 to 7 months after return of results. We compared the proportion of parents who reported discussing their child's result with a clinician, clinicians' recommendations, and parents' follow-up actions by GS result type using χ2 tests.

Results

A total of 1188 respondents completed survey measures on recommended medical actions (n = 1187) and/or parent-initiated actions (n = 913). Most parents who completed recommended medical actions questions (n = 833, 70.3%) reported having discussed their child's GS results with clinicians. Clinicians made recommendations to change current care for patients with positive GS results (n = 79, 39.1%) more frequently than for those with inconclusive (n = 31, 12.4%) or negative results (n = 44, 11.9%; P < .001). Many parents discussed (n = 152 completed, n = 135 planned) implications of GS results for future pregnancies with a clinician. Aside from clinical recommendations, 13.0% (n = 119) of parents initiated changes to their child's health or lifestyle.

Conclusions

In diverse pediatric clinical contexts, GS results can lead to recommendations for follow-up care, but they likely do not prompt large increases in the quantity of care received.

Purpose

There is limited payer coverage for genome sequencing (GS) relative to exome sequencing (ES) in the U.S. Our objective was to assess payers' considerations for coverage of GS versus coverage of ES and requirements payers have for coverage of GS. The study was conducted by the NIH-funded Clinical Sequencing Evidence-Generating Research Consortium (CSER).

Methods

We conducted semi-structured interviews with representatives of private payer organizations (payers, N = 12) on considerations and evidentiary and other needs for coverage of GS and ES. Data were analyzed using thematic analysis.

Results

We described four categories of findings and solutions: demonstrated merits of GS versus ES, enhanced methods for evidence generation, consistent laboratory processes/sequencing methods, and enhanced implementation/care delivery. Payers see advantages to GS vs. ES and are open to broader GS coverage but need more proof of these advantages to consider them in coverage decision-making. Next steps include establishing evidence of benefits in specific clinical scenarios, developing quality standards, ensuring transparency of laboratory methods, developing clinical centers of excellence, and incorporating the role of genetic professionals.

Conclusion

By comparing coverage considerations for GS and ES, we identified a path forward for coverage of GS. Future research should explicitly address payers' conditions for coverage.