There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probe-based real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis.
Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered.
Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.
PROSPERO—NIHR Prospective Register of Systematic Reviews (CRD42011001289).
To describe the plans of a systematic review aimed at determining the diagnostic accuracy of a new real-time PCR technology (LightCycler® SeptiFast), designed to detect bloodborne pathogens in the setting of life-threatening infection (sepsis).
To highlight the unmet need for accurate and rapid infection diagnostics in the setting of life-threatening infection (sepsis).
The study will provide the first independent systematic review of clinical validity studies of multiplex real-time PCR technology aimed at detecting circulating pathogen DNA straight from blood in the setting of suspected life-threatening infections (sepsis).
Based on the results of this study, independent recommendations will be made to the UK's Department of Health to help determine whether the real-time PCR technology has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
Strengths and limitations
The systematic review is focused on a single Conformité Européenne (CE)-marked real-time PCR technology designed for use in the setting of life-threatening infection (sepsis)
The systematic review is non-commercial and has been planned systematically by a multidisciplinary team of experts, working on behalf of the key stakeholders within a nationalised healthcare system.
Current clinical infection diagnostic reference standards may not have high diagnostic accuracy in all clinical settings and with all infections