Assessment of the current status of real-world pharmacogenomic testing: informed consent, patient education, and related practices.

Introduction: The practice of informed consent (IC) for pharmacogenomic testing in clinical settings varies, and there is currently no consensus on which elements of IC to provide to patients. This study aims to assess current IC practices for pharmacogenomic testing. Methods: An online survey was developed and sent to health providers at institutions that offer clinical germline pharmacogenomic testing to assess current IC practices. Results: Forty-six completed surveys representing 43 clinical institutions offering pharmacogenomic testing were received. Thirty-two (74%) respondents obtain IC from patients with variability in elements incorporated. Results revealed that twenty-nine (67%) institutions discuss the benefits, description, and purpose of pharmacogenomic testing with patients. Less commonly discussed elements included methodology and accuracy of testing, and laboratory storage of samples. Discussion: IC practices varied widely among survey respondents. Most respondents desire the establishment of consensus IC recommendations from a trusted pharmacogenomics organization to help address these disparities.

Identification of CYP2D6 Haplotypes that Interfere with Commonly Used Assays for Copy Number Variation Characterization.

Cytochrome P450 2D6 (CYP2D6) copy number (CN) variation affects the metabolism of numerous prescribed drugs. Sequence variation within primer or probe target regions of hydrolysis probe CN assays can generate false-positive calls for CN loss. Furthermore, CYP2D6-CYP2D7 hybrids and gene conversions can cause difficult to interpret discordant CN calls. The identification of haplotypes with CN variations and structural arrangements is important to predict phenotype accurately. During clinical testing with hydrolysis probe assays targeting three CYP2D6 regions (intron 2, intron 6, and exon 9), samples with haplotypes causing inconsistent CN calls were identified. To resolve these cases, next-generation sequencing and allele-specific Sanger sequencing was performed. Sequence analysis of 16 samples, all but one from subjects of African descent, identified six novel suballeles containing single-nucleotide polymorphisms, which cause false-positive calls for CN loss in introns 2 and 6. Five samples with an exon 9 CN loss contained CYP2D6/CYP2D7 hybrids (∗13 or ∗36) and one sample was found to have a novel haplotype, CYP2D6∗141. Interestingly, CYP2D6∗141 contains a CYP2D7-derived exon 9 conversion and core single-nucleotide polymorphisms that are otherwise found in CYP2D6∗17 and ∗27. Although these variants are rare, they can cause inconsistent CN calls that typically are reported as no calls or indeterminant, and thus may deprive patients, particularly those of African descent, from taking full benefit of pharmacogenetic testing.

Activities of Memphis-area hospitals to meet National Patient Safety Goals for warfarin therapy.

PURPOSE: The activities of Memphis hospitals to meet National Patient Safety Goals (NPSGs) for warfarin therapy are described. SUMMARY: In March 2008, leadership from the Mid-South College of Clinical Pharmacy (MSCCP), a local chapter of the American College of Clinical Pharmacy, commissioned a task force on anticoagulation, comprising pharmacy administrators, clinical pharmacy practitioners, and pharmacy faculty from local hospitals within the greater Memphis area. The charge of the task force was to (1) identify practice variations in regard to NPSG.03.05.01, (2) develop professional collaboration among both academic and nonacademic institutions to share policy and protocol development, and (3) facilitate all institutions in meeting the deadlines set forth by the Joint Commission. The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners in the Memphis area. There was no one-size-fits-all approach; however, meetings and discussions were beneficial and led to idea generation. Having input from multiple institutions in different clinical settings with varying levels of experience created a rich environment from which all institutions benefited. For example, smaller institutions felt that they drew support for physician acceptance with protocol approval based on the knowledge of the policies approved or lessons learned at larger institutions. In addition, the larger institutions felt that the working group was helpful in validating their interpretation of the NPSG elements. CONCLUSION: The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners to offer solutions to meet NPSG.03.05.01 as it related to the needs of each institution.