Diagnostic accuracy of the Point-of-Care Standard G6PD test™ (SD Biosensor) for Glucose-6-phosphate dehydrogenase deficiency: a systematic review of the literature

Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) is a common genetic enzymopathy that can induce hemolysis triggered by various factors, including some anti-malarial drugs. Although many Point-of-Care (PoC) tests, such as STANDARD G6PDTM manufactured by SD biosensor (StandG6PD-BS), are available to detect G6PDd, its pooled diagnostic test accuracy (DTA) remains unknown. To estimate the DTA of StandG6PD-BS at various thresholds of G6PDd, we conducted a systematic review with a DTA meta-analysis, searching EMBASE, MEDLINE, and SciELO databases up to June 30, 2023. We included studies measuring G6PD activity using StandG6PD-BS (reference test) and spectrophotometry (gold standard) in patients suspected of having G6PDd. We assessed the risk of bias (RoB) of the studies using the QUADAS-2 tool and the certainty of evidence (CoE) with the GRADE approach. Our approach included the estimation of within-study DTA, a random-effect bivariate meta-analysis to determine the pooled sensitivity and specificity for 30%, 70%, and 80% enzyme levels thresholds, and a graphical analysis of the heterogeneity using crosshair and Confidence Regions on receiver operating characteristic (ROC) space plots. After screening 2,407 reports, we included four studies with 7,864 participants covering all thresholds. Two studies had high RoB in QUADAS-2 domains 2 and 3, and the others had low RoB. We also found low, moderate, and high heterogeneity at the 30%, 70%, and 80% thresholds, respectively. The pooled sensitivity was 99.1% (95%CI 96.9-99.7%, CoE: high), 95.7% (92.0-97.0%, high), and 90% (78.0-96.5%, low) for 30%, 70%, and 80% thresholds, respectively. The pooled specificity was 97.4% (95%CI 95.0; 98.4%, high); 92.9% (85.0-96.4%, high); and 89.0% (76.0-96.0%, moderate) for 30%, 70%, and 80% thresholds, respectively. In conclusion, StandG6PD-BS is a PoC test with high sensitivity and specificity to detect G6PDd at different thresholds. Author summaryGlucose-6-Phosphate Dehydrogenase deficiency (G6PDd) is a common genetic disease that can induce the destruction of red blood cells leading to anemia triggered by various factors, including some drugs used for malaria treatment. After a literature search in different databases up to January 31, 2023, we pooled diagnostic test accuracy of the Point-of-Care (PoC) STANDARD G6PDTM test manufactured by SD biosensor (StandG6PD-BS) used to identify the G6PDd. Although two of the four studies included showed a high Risk of Bias related to the index test and the reference standard domains of the QUADAS-2 tool, the pooled sensitivity and specificity for 30%, 70%, and 80% enzyme levels thresholds were around 90%, with better sensitivity and specificity values for the 30% threshold (99.1% and 97.4%) compared with 70% (95.7% and 92.9%) and 80% (90% and 89%) threshold. We found low, moderate, and high heterogeneity at the 30%, 70%, and 80% thresholds. In conclusion, StandG6PD-BS is a PoC test with high sensitivity and specificity to detect G6PDd at different thresholds.