From the Editor

Friday, December 23, 2016 Published in On-Demand Winter 2012 Written by David Persing M.D., Ph.D., Chief Medical and Technology Officer, Cepheid

During the production of this issue of On Demand, the CDC declared the official start to the flu season, the latest start in 25 years. Drs. Ellen Jo Baron and Fred Tenover have written an up-to-date review of molecular diagnostic methods for respiratory infections, including the Xpert Flu test which provides on-demand results for FluA/B and H1N1 novel 2009, all of which are circulating this flu season. As the science and practice of Precision Medicine evolves toward the ultimate goal — providing the right patients with the right doses of the right medication at the right time — the impact of molecular diagnostics has never been greater. In the article by Donna Wolk and Daniel Olsen, you will find an excellent overview of the Verification and Validation processes that underpin the basic credibility and reliability of the diagnostic results we furnish on a daily basis. We hope you will benefit from reading both articles in this issue.

Verification of Qualitative Real-time PCR Methods

Friday, December 23, 2016 Published in On-Demand Winter 2012 Written by Donna M. Wolk, MHA, Ph.D., D(ABMM) and Daniel Olson, MPH*

Clinical laboratories rely on the FDA clearance/approval process to ensure that commercially available molecular tests have been evaluated and found to be accurate and medically useful. However, the FDA-approval process is only the first step towards ensuring diagnostic accuracy in your laboratory. The process of in-house verification is governed by the Clinical Laboratory Improvement Amendments (CLIA) regulations5, and begins with the laboratory undertaking studies to reproduce the manufacturer's claimed performance characteristics4,5,9. Verification of an FDA-cleared assay by a laboratory performing the test exactly as described in the product insert is less stringent than the validation process needed for a modified test. If a test is not performed according to the published manufacturer guidelines, for instance, if the sample transport matrix is different from that in the package insert, then a more extensive method validation (not simply a verification) must occur and the test is then considered "off-label use" or a laboratory developed test (LDT), depending on the extent of deviation from approved protocols. This makes the user legally responsible for complete validation of the assay5. This article focuses on the process for implementing an FDA-cleared assay in your laboratory. The parameters of a commercial test that a laboratory must document in their own performance of the test are accuracy (analytical sensitivity and specificity), precision (reproducibility), reference range (for qualitative assays), and reportable range (for quantitative assays).

Flu Season 2011-2012

Friday, December 23, 2016 Published in On-Demand Winter 2012 Written by Ellen Jo Baron, Ph.D., D(ABMM), Prof. Emerita, Stanford University Director of Medical Affairs, Cepheid

Laboratories performing tests for respiratory viruses can attest to the changing epidemiology of this formerly reliable season. For many years, like clockwork, new influenza strains, having mixed and matched up genetic material from pigs, birds, and humans, originated in Southeast Asia. In the past, the first influenza cases of the year appeared in Australia in June, peaked in late July, and petered out around December.1