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.

Cytomegalovirus (CMV) can cause a wide range of complications among both solid organ transplant and hematopoietic stem cell transplant recipients, as well as in other immunocompromised patients. Cytomegalovirus has a high seroprevalence, and large numbers of transplant patients experience reactivation or primary infection, with probability increasing based on pre-transplant serostatus, severity of pretransplant conditioning, and allograft relatedness. 14, 15 Although infection can be subclinical, high or increasing viral load signals increased the risk of symptomatic disease, which can range from relatively mild constitutional symptoms to severe end-organ infection or potentially fatal disseminated disease. Preemptive therapy of high-risk patients based on the detection of increasing CMV load in peripheral blood was shown to be effective in the 1990s 16, 17 ; however, the first FDA-approved IVD test did not appear on the market until 2012. 18 In the intervening years, laboratory-developed assays played a critical role in bridging the gap. The presence of such methods and their adoption across the country enabled the routine use of CMV screening for asymptomatic patients in transplant centers soon after data supported its utility. The availability of such methods has likely saved many lives over the years, supporting early diagnosis, preemptive treatment strategies, and the assessment of therapeutic treatment efficacy. 14, [18] [19] [20] The widespread use of LDP CMV quantitative methods produced a generation of transplant physicians comfortable with the use of such methods and changed the epidemiology of posttransplant CMV disease, markedly reducing the incidence of early disease in such patients. Over the years of LDP use, numerous studies focused on continuous improvement and optimization of methods, 21 including the development of international quantitative standards in 2010. 22 The ability to rapidly incorporate advances in technology (including the advent of real-time quantitative methods) has been demonstrated by the improvement in sensitivity and other performance characteristics of such tests over time. The data accumulated throughout these experiences informed the development of the first commercially available CMV IVD assays. In fact, the absence of LDPs and the vast clinical and laboratory experience that they provided likely would have delayed the availability of commercial methods, and their performance characteristics taken longer to optimize to today's levels.