RESUMEN
CONTEXT.: Existing targeted cystic fibrosis screening assays miss important pathogenic CFTR variants in the ethnically diverse US population. OBJECTIVE.: To evaluate the analytic performance of a multiplex polymerase chain reaction (PCR)/capillary electrophoresis (CE) CFTR assay panel that simultaneously interrogates primary pathogenic variants of different ethnic/ancestral groups. DESIGN.: Performance characteristic assessment and variant coverage comparison of the panel with a focus on ethnicity-specific CFTR variants were performed. Sample DNA was primarily from whole blood or cell lines. Detection of CFTR carriers was compared across several commercially available CFTR kits and recommended variant sets based on panel content. RESULTS.: The panel interrogated 65 pathogenic CFTR variants representing 92% coverage from a recent genomic sequencing survey of the US population, including 4 variants with top 5 frequency in African or Asian populations not reflected in other targeted panels. In simulation studies, the panel represented 95% of carriers across the global population, resulting in 6.9% to 19.0% higher carrier detection rate compared with 10 targeted panels or variant sets. Precision and sensitivity/specificity were 100% concordant. Multisite sample-level genotyping accuracy was 99.2%. Across PCR and CE instruments, sample-level genotyping accuracy was 97.1%, with greater than 99% agreement for all variant-level metrics. CONCLUSIONS.: The CFTR assay achieves 92% or higher coverage of CFTR variants in diverse populations and provides improved pan-ethnic coverage of minority subgroups of the US populace. The assay can be completed within 5 hours from DNA sample to genotype, and performance data exceed acceptance criteria for analytic metrics. This assay panel content may help address gaps in ancestry-specific CFTR genotypes while providing a streamlined procedure with rapidly generated results.
RESUMEN
BACKGROUND: Patient outcomes were assessed based on a pre-biopsy ExoDx Prostate (EPI) score at 2.5 years of the 5-year follow-up of ongoing prostate biopsy Decision Impact Trial of the ExoDx Prostate (IntelliScore). METHODS: Prospective, blinded, randomized, multisite clinical utility study was conducted from June 2017 to May 2018 (NCT03235687). Urine samples were collected from 1049 men (≥50 years old) with a PSA 2-10 ng/mL being considered for a prostate biopsy. Patients were randomized to EPI vs. standard of care (SOC). All had an EPI test, but only EPI arm received results during biopsy decision process. Clinical outcomes, time to biopsy and pathology were assessed among low (<15.6) or high (≥15.6) EPI scores. RESULTS: At 2.5 years, 833 patients had follow-up data. In the EPI arm, biopsy rates remained lower for low-risk EPI scores than high-risk EPI scores (44.6% vs 79.0%, p < 0.001), whereas biopsy rates were identical in SOC arm regardless of EPI score (59.6% vs 58.8%, p = 0.99). Also in the EPI arm, the average time from EPI testing to first biopsy was longer for low-risk EPI scores compared to high-risk EPI scores (216 vs. 69 days; p < 0.001). Similarly, the time to first biopsy was longer with EPI low-risk scores in EPI arm compared to EPI low-risk scores in SOC arm (216 vs 80 days; p < 0.001). At 2.5 years, patients with low-risk EPI scores from both arms had less HGPC than high-risk EPI score patients (7.9% vs 26.8%, p < 0.001) and the EPI arm found 21.8% more HGPC than the SOC arm. CONCLUSIONS: This follow-up analysis captures subsequent biopsy outcomes and demonstrates that men receiving EPI low-risk scores (<15.6) significantly defer the time to first biopsy and remain at a very low pathologic risk by 2.5-years after the initial study. The EPI test risk stratification identified low-risk patients that were not found with the SOC.
