The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Encephalitis is the most serious complication of herpes simplex virus (HSV) infection. 6 While rare, HSV is commonly included among causes of viral encephalitis. Since HSV infection can be treated effectively with acyclovir, it is critical to rapidly and accurately establish the diagnosis and initiate treatment to reduce morbidity and mortality. Culture of cerebrospinal fluid (CSF) is insensitive for the diagnosis of HSV encephalitis, so brain biopsy, a very invasive procedure with significant morbidity, was historically required to make a diagnosis, with results not available for days afterward. Several studies demonstrated that detection of viral DNA by polymerase chain reaction (PCR) using CSF samples performed equivalently to brain biopsy, including a landmark study in 1995. [7] [8] [9] Given the ease of collecting CSF samples, the lower risk of complication, the lower cost, and speed of results, PCR became the standard of care for diagnosing HSV CNS infections in the mid-1990s, with LDPs used for nearly 20 years. It was not until 2014 that the first FDA-cleared PCR test for the diagnosis of HSV encephalitis became available, with a second test cleared in 2015. Laboratory-developed testing procedures dramatically improved the quality of care for many patients and continue to be used successfully today, as the 2 cleared tests have limitations, requiring specific instrumentation not standard in many laboratories. Additionally, one of the tests is highly multiplexed, which may not be appropriate in all clinical situations.