Projected Cost-Effectiveness for 2 Gene-Drug Pairs Using a Multigene Panel for Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: For patients undergoing percutaneous coronary intervention, gene-drug associations exist relevant to first-line treatment options-antiplatelet agent, clopidogrel, and pain medication, tramadol. Knowledge of genotype information may allow for avoidance of adverse drug events during critical clinical windows. OBJECTIVE: This evaluation estimated cost-effectiveness associated with a multi-gene panel pre-emptively testing two genes providing CYP2C19 genotype-guided strategy for antiplatelet therapy, with CYP2D6 genotype-guided pain management, compared to single gene test for CYP2C19 with random assignment for pain treatment, and to no testing (empiric clopidogrel with random assignment for pain treatment). METHODS: Decision analysis modeling was used to project costs from a payer perspective and patient quality-adjusted life years (QALYs) from the three strategies. The model captured composite risks of major adverse cardiovascular events and pain therapy-related adverse drug events and associated utility estimates. We conducted sensitivity analyses to assess influential input parameters. RESULTS: Over 15 months, multi-gene testing was least costly and yielded more QALYs compared to both single gene and no testing; total incremental costs were $1646 lower with incremental gains of 0.04 QALYs for multi-gene compared with single gene and $11 368 lower with 0.17 QALY gains compared to no test. Base case analyses revealed multi gene was dominant compared to both single gene and no test, as it demonstrated cost savings with increased QALYs. CONCLUSIONS: For these patients, a multi-gene-guided strategy yields a favorable incremental cost-effectiveness ratio compared to the other two treatment strategies. Pre-emptively ascertaining additional gene-drug pair information can inform clinical and economic decision-making at the point of care.

Insurance coverage does not predict outcomes of genetic testing: The search for meaning in payer decisions for germline cancer tests.

In this work, we explore the results of germline cancer genetic tests in individuals whose insurance would not cover this testing. We enrolled 31 patients with a personal history of cancer whose health insurer denied coverage for a clinical germline cancer panel genetic test recommended by a medical genetics provider into a study providing exome sequencing and return of cancer-related results. Five participants (16%) had a pathogenic variant identified related to increased cancer risk. Three participants (10%) had a variant of uncertain significance (VUS) in a gene related to their cancer history. These rates are not significantly different than the 12% rate of pathogenic or likely pathogenic (P/LP) variants and VUS in 1,462 patients approved by insurance to have a similar clinical germline cancer test (p = .59 for P/LP variants; p = .87 for VUS; Shirts et al., Genet Med, 18:974, 2016). Health insurance guidelines may not meaningfully differentiate between patients with cancer who are likely to benefit from germline cancer genetic testing and those who will not. Failure to identify pathogenic variants in this research cohort would have led to suboptimal care. Strategic evaluation of current germline cancer genetic testing coverage policies is needed to appropriately deliver precision medicine.

Consideration for Employer-Based and Geographic Attributes Included in Value Assessment Methods of Next-Generation Sequencing Tests.

There is a need for formal cost-effectiveness evidence to better model the real-world payer decision context in which general economic models are currently being used, specifically regarding clinical genomics health services (for next-generation sequencing (NGS) tests). We reviewed literature focused on cost-effectiveness studies after completion of the Human Genome Project within the Tufts Cost-Effectiveness Analysis (CEA) Registry and found that only 33% of eligible studies were conducted from the U.S. payer perspective. Additional interpretation challenges include economic models that do not account for true payer-negotiated costs, limits in internal expertise for quality-adjusted life-year inferences, and limited internal policies to use CEA research in decision making. This Viewpoints article highlights numerous opportunities to increase the translational effect of economic modeling work. Specifically, geographically relevant cost and outcomes data should be considered for integration within best practices for economic evaluations of NGS tests. Such data integration may provide more informed decision making regarding the allocation of constrained resources for health care services and technology. DISCLOSURES: No outside funding supported the writing of this article. Hart is supported by an unrestricted gift from Pfizer, which played no role in the study referred to in this article. The authors have no conflicts of interest to report.

Psychological outcomes related to exome and genome sequencing result disclosure: a meta-analysis of seven Clinical Sequencing Exploratory Research (CSER) Consortium studies.

PURPOSE: As exome and genome sequencing (ES/GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) Consortium collaboration, we evaluated participants' psychological outcomes across multiple clinical settings. METHODS: We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale [HADS]/Generalized Anxiety Disorder 7-item), depressive symptoms (HADS/Personal Health Questionnaire 9-item), and multidimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/Feelings About Genomic Testing Results scale). RESULTS: Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to postdisclosure revealed an overall trend for a decrease in participants' anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses. CONCLUSION: Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.

Correction: Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study.

The originally published version of this Article contained errors in Fig. 2. The numbers below the black arrowheads were incorrect; please see incorrect Figure in associated Correction. These errors have now been corrected in the PDF and HTML versions of the Article.

Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study.

PURPOSE: Clinical sequencing emerging in health care may result in secondary findings (SFs). METHODS: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions. RESULTS: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care. CONCLUSION: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.