Reference Samples to Compare Next-Generation Sequencing Test Performance for Oncology Therapeutics and Diagnostics.

OBJECTIVES: Diversity of laboratory-developed tests (LDTs) using next-generation sequencing (NGS) raises concerns about their accuracy for selection of targeted therapies. A working group developed a pilot study of traceable reference samples to measure NGS LDT performance among a cohort of clinical laboratories. METHODS: Human cell lines were engineered via CRISPR/Cas9 and prepared as formalin-fixed, paraffin-embedded cell pellets ("wet" samples) to assess the entire NGS test cycle. In silico mutagenized NGS sequence files ("dry" samples) were used to assess the bioinformatics component of the NGS test cycle. Single and multinucleotide variants (n = 36) of KRAS and NRAS were tested at 5% or 15% variant allele fraction to determine eligibility for therapy with the EGFR inhibitor panitumumab in the setting of metastatic colorectal cancer. RESULTS: Twenty-one (21/21) laboratories tested wet samples; 19 of 21 analyzed dry samples. Of the laboratories that tested both the wet and dry samples, 7 (37%) of 19 laboratories correctly reported all variants, 3 (16%) of 19 had fewer than five errors, and 9 (47%) of 19 had five or more errors. Most errors were false negatives. CONCLUSIONS: Genetically engineered cell lines and mutagenized sequence files are complementary reference samples for evaluating NGS test performance among clinical laboratories using LDTs. Variable accuracy in detection of genetic variants among some LDTs may identify different patient populations for targeted therapy.

Molecular Diagnosis of Coronavirus Disease 2019.

OBJECTIVES: To review molecular diagnostics for coronavirus disease 2019. The world is in the midst of a coronavirus disease 2019 pandemic. Containing the spread of the severe acute respiratory distress coronavirus is critical. Instrumental to the future success is the ability to reliably and reproducibly detect this inciting pathogen to inform public health containment policies and treatment decisions. DATA SOURCES: Molecular diagnostics focusing on molecular detection methodologies for detection of the virus and the presence of the disease. STUDY SELECTION: Narrative review. DATA EXTRACTION: Literature, PubMed, Scopus, and official government documents. DATA SYNTHESIS: Diagnosing severe acute respiratory syndrome coronavirus is done through real-time reverse transcriptase-polymerase chain reaction tests, cell culture, and serology. For patients, diagnostics are an integral part of a full medical history, physical examinations, blood tests, and diagnostic imaging. CONCLUSIONS: Here, we review current approaches to the molecular diagnosis of coronavirus disease 2019.

Economics of Coding, Coverage, and Reimbursement for Molecular Diagnostics.

This editorial highlights the article from the Association for Molecular Pathology's Economic Affairs Committee that appears in this issue.

Renewed Commitments to Key Partners.

This Editorial highlights the updates to the publication frequency, member benefits, and societal oversight of The Journal of Molecular Diagnostics beginning in January 2020.

The Journal of Molecular Diagnostics: 20 Years Defining Professional Practice.

This editorial highlights 20 years of JMD defining professional practice.

Integration Standardization and Diagnostics Oversight of Laboratory Testing.

This editorial highlights the article by Schreier et al that emphasizes on reforming the process for regulating laboratory developed testing.

Expanding the Scope of The Journal of Molecular Diagnostics to the Informatics Subdivision of the Association for Molecular Pathology.

This editorial describes the expanded scope of The Journal of Molecular Diagnostics, to include informatics-based articles.

Translating Risk of Consumer-Initiated Genetic Testing.

This editorial highlights the article by Bick and colleagues that proposes a framework for evaluating elective genomic testing.

Keeping Practice Recommendations in Step with Advancing Knowledge.

This editorial comments on the updated molecular testing guideline for lung cancer patients.

Navigating the Peer Review Process.

This editorial provides insights and guidelines for publishing in The Journal of Molecular Diagnostics.

Guidelines for Colorectal Cancer Testing: Evidence-Based Practice Recommendations.

This Editorial provides readers additional insight on the colorectal guideline appearing in this issue.

Diagnostic Quality Assurance Pilot: A Model to Demonstrate Comparative Laboratory Test Performance with an Oncology Companion Diagnostic Assay.

This Editorial highlights a model demonstrating laboratory test performance with a companion diagnostic assay.

Evaluation of Diverse Health Professionals' Learning Experience in a Continuing Education Activity for Quality Practices in Molecular Genetic Testing.

OBJECTIVE: This study was conducted to evaluate the responses of 3,265 health professionals who took a continuing education (CE) activity during June 2009 - April 2012 for a comprehensive set of good laboratory practice recommendations for molecular genetic testing. DESIGN: Participants completed an evaluation questionnaire as part of the CE activity. Responses were summarized to assess the participants' learning outcomes and commitment to applying the knowledge gained. PARTICIPANTS: Participants included nurses (47%), laboratory professionals (18%), physicians (14%), health educators (4%), public health professionals (2%), office staff (1%), and other health professionals (10%). RESULTS: Only 32% of all participants correctly answered all 12 open-book knowledge-check questions, ranging from 4 to 42% among the different professional groups (P<0.0001). However, over 80% of all participants expressed confidence in describing the practice recommendations, and 75% indicated the recommendations would improve the quality of their practice. Developing health education materials and local practice guidelines represented the common areas in which participants planned to use the knowledge gained (49% and 18% of all participants, respectively). CONCLUSION: Despite perceived self-efficacy in most participants, as high as 68% did not fully use the learning materials provided to answer the knowledge-check questions. These findings suggest the need for improved CE activities that motivate effective learning and address the specific needs of different health professions.

Anticoagulation manager: development of a clinical decision support mobile application for management of anticoagulants.

Patients with certain clotting disorders or conditions have a greater risk of developing arterial or venous clots and downstream embolisms, strokes, and arterial insufficiency. These patients need prescription anticoagulant drugs to reduce the possibility of clot formation. However, historically, the clinical decision making workflow in determining the correct type and dosage of anticoagulant(s) is part science and part art. To address this problem, we developed Anticoagulation Manager, an intelligent clinical decision workflow management system on iOS-based mobile devices to help clinicians effectively choose the most appropriate and helpful follow-up clotting tests for patients with a common clotting profile. The app can provide physicians guidance to prescribe the most appropriate medication for patients in need of anticoagulant drugs. This intelligent app was jointly designed and developed by medical professionals in CDC and engineers at Georgia Tech, and will be evaluated by physicians for ease-of-use, robustness, flexibility, and scalability. Eventually, it will be deployed and shared in both physician community and developer community.