Immunological biomarker discovery in cure regimens for chronic hepatitis B virus infection.

There have been unprecedented advances in the identification of new treatment targets for chronic hepatitis B that are being developed with the goal of achieving functional cure in patients who would otherwise require lifelong nucleoside analogue treatment. Many of the new investigational therapies either directly target the immune system or are anticipated to impact immunity indirectly through modulation of the viral lifecycle and antigen production. While new viral biomarkers (HBV RNA, HBcAg, small, middle, large HBs isoforms) are proceeding through validation steps in clinical studies, immunological biomarkers are non-existent outside of clinical assays for antibodies to HBs, HBc and HBe. To develop clinically applicable immunological biomarkers to measure mechanisms of action, inform logical combination strategies, and guide clinical management for use and discontinuation of immune-targeting drugs, immune assays must be incorporated into phase I/II clinical trials. This paper will discuss the importance of sample collection, the assays available for immunological analyses, their advantages/disadvantages and suggestions for their implementation in clinical trials. Careful consideration must be given to ensure appropriate immunological studies are included as a primary component of the trial with deeper immunological analysis provided by ancillary studies. Standardising immunological assays and data obtained from clinical trials will identify biomarkers that can be deployed in the clinic, independently of specialised immunology laboratories.

FDA perspectives on diagnostic device clinical studies for respiratory infections.

Two pathways are described for submission to FDA for clearance of a diagnostic device: a Premarket Application (PMA), which can lead to approval of a diagnostic device, and a Premarket Notification, which can lead to clearance. The latter is often called a 510(k), named for the statute providing for this path. Recent FDA clearance of molecular-based multiplex panels represents the beginning of a new era for the diagnosis of respiratory infections. The ability to test for multiple pathogens simultaneously, accompanied by the increasing availability of molecular-based assays for newly recognized respiratory pathogens will likely have a major impact on patient care, drug development, and public health epidemiology. We provide a general overview of how FDA evaluates new diagnostics for respiratory tract infections and the agency's expectations for sponsors developing new tests in this area.