Comparison of Triage PlGF Test and Elecsys sFlt-1/PlGF Ratio
The two PlGF-based tests recommended by the National Institute for Health and Care Excellence have been subject to direct comparison.23-25 McCarthy and colleagues (2019) compared the Triage PlGF test, Elecsys sFlt-1/PlGF ratio and the DELFIA Xpress PlGF 1-2-3 tests in 305 women, of whom 62 developed early-onset pre-eclampsia.23 They found that the AUC were nearly identical for the Elecsys sFlt-1/PlGF ratio and the Triage PlGF test, with that for the DELFIA Xpress PlGF 1-2-3 test very similar. This suggests that the tests are similarly effective, and trade-off between sensitivity and specificity is dependent on the thresholds, which currently are slightly different. As more clinical data becomes available, appropriate and equivalent thresholds for clinical utility can be derived. It has been suggested that high sensitivity is a more useful attribute in early detection of pre-eclampsia than specificity because consideration of benefits, harms and costs indicates a much greater preference for minimizing false negatives than false positives, although the ideal would be to avoid both.26
In the COMPARE study,23 equivalent clinical thresholds for PlGF rule-out differed by 50% and the DELFIA Xpress PlGF 1-2-3 has a rule-out threshold of 150 pg/ml, whereas the rule-out threshold for the Triage PlGF test is 100 pg/ml. This illustrates that they are not identical assays, nor are they interchangeable clinically. The differing thresholds are likely due to variable PlGF recovery and isomer cross-reactivity. PlGF is a homo-dimeric glycoprotein which exists in four isomers, derived from different splicing of primary gene transcripts.27 PlGF-1 and PlGF-2 are the most abundant forms, and they are secreted in a strongly correlated manner. Isomer cross-reactivity is variable; one study found 12 to 19% cross-reactivity with PlGF-2 and 16 to 23% cross-reactivity with PlGF-3 for the Roche Elecsys PlGF assay.28 This contrasts with the manufacturer reports; Roche Diagnostics quote less than 8% cross-reactivity and Triage quote 9.6% cross-reactivity with PlGF-2.28
There have been other interassay comparison studies.24, 25, 28 Stepan and colleagues (2016) performed a prospective multi-centre case-control study of 569 women (178 with confirmed pre-eclampsia).24 They found the Elecsys immunoassay had a higher specificity and lower sensitivity compared to the Triage assay at the thresholds selected, but used a cut off of ≤33 for the Elecsys sFlt-1/PlGF ratio. As the sensitivity and specificity are highly dependent on the thresholds selected, it is difficult to draw any conclusions from these comparative predictive statistics.
A smaller retrospective case-control study in 128 women (44 with confirmed preeclampsia) found that the Triage assay had a higher sensitivity than the Elecsys ratio at only a small reduction of specificity (sensitivity 100% (95% CI 86-100) compared to 64% (95% CI 43-82), and specificity 96% (95% CI 85-99) compared to 100% (95% CI 93-100)).24 This study also clearly demonstrated that PlGF concentrations were lower when measured on the Triage assay compared the Elecsys assay. They defined a positive test as PlGF <5th centile for a gestational-age dependent range, and >85 for the Elecsys sFlt-1/PlGF ratio.
In summary, both tests recommended by the National Institute for Health and Care Excellence have strong test performance with AUC outperforming currently used tests for diagnosing pre-eclampsia (see Table 1). The Triage PlGF test has a higher sensitivity when used with the current rule-out threshold of 100pg/ml, compared to the Elecsys sFlt-1/PlGF ratio threshold of 38, which has a higher specificity. These and other tests available on the market appear to be clinically similar in prediction, and other factors such as cost, and ease of use will dictate clinical uptake.