Diagnostic Sensitivity

Elevated D-dimer levels, as a result of fibrin formation, occur in various other conditions than venous thrombotic events (VTE). Therefore, the clinician needs to be aware of the fact, that although D-dimer determination is very sensitive, it does not represent a specific measurand for VTE management.

Diagnostic Accuracy: Sensitivity and Specificity

The diagnostic sensitivity of this parameter is of major importance, since it represents the rate of correctly classified positive cases. Any falsely negative classified result is critical and associated with high risks for the affected individual.

Thrombosisno Thrombosis
Tested positive with assaytrue positivefalse positive
Tested negative with assayfalse negativetrue negative

In the studies, sensitivity and specificity are defined against a reference, which divides the study population into the (disease-/condition-) positive group and the (healthy) control group. As a reference, an established method or guideline combining multiple methods is used. After defining the groups the agreement of the test result is evaluated.

With a sensitivity of 98% DiaSys D-Dimer FS fulfills and even exceeds international requirements for diagnostic sensitivity: ≥ 95% (FDA), ≥ 97% (CLSI).

Another important term in the context of D-dimer determination is specificity. This value is defined by the rate of correctly classified negative cases. Although this measurand is not as critical as sensitivity, due to fact that no individual with VTE is overseen, high specificity rates minimize the number of false positive cases and reduces additional costs for time-consuming confirmation procedures.

 

Cutoff
[µg FEU/mL]
Sensitivity
[%]
Specificity
[%]
DiaSys0.59880.5
Competitor A0.599.345.8
Competitor B0.59842.7
Competitor C0.510042.1
Competitor D0.597-
Competitor E0.5599.437.8
Competitor F0.510035
Competitor G0.29564

Diagnostic Value

The performance of a screening test is measured by its “predictive value” which reflects the diagnostic value of the test results.

In a retrospective view the positive or negative test result is checked against the reference to confirm the classification.

  

Thrombosis (confirmed)no Thrombosis (confirmed)
Tested positivetrue positivefalse positive
Tested negativefalse negativetrue negative

 

Positive predictive values (PPV) and negative predictive values (NPV) represent the probability of the presence of disease (PPV) in case of a positive test result resp. the probability of the absence of disease (NPV) if the test result is negative.

The PPV represents the correctness of a positive test result, given:

The prevalence has an important impact on NPV and PPV in D-Dimer as it influences the amount of false positives tremendously.

Considering the same patient group of 100.000 individuals, and a given prevalence for this group, the negative predictive value and the positive predictive value represent the correctness of a negative or positive test result.

Prevalance20%50%
NPVPPVNPVPPV
DiaSys99.4%55.7%97.6%83.4
Competitor A99.6%31.4%98.5%64.7%
Competitor B98.8%30.0%95.5%63.1%
Competitor C100.0%30.2%100.0%63.3%
Competitor D
Competitor E99.6%28.5%98.4%61.5%
Competitor F100.0%27.8%100.0%60.6%
Competitor G98.1%39.7%92.8%

72.5%

Due to the high sensitivity of most tests, a negative test result can be considered to be true negative in >98% with all tests for a prevalence given with 20%. – Low D-Dimer- levels can be used to rule out DVT.

On the contrary, only about 33% of all positive cases are true positives for most assays, whereas 55% true positives are found among the positive results with DiaSys. – increased D-Dimer- levels need further diagnosis and medical attention.

The figures on DiaSys and a prevalence of 20% represent that out of 11 positive test there are only 5 falsely positive tested patients, who have to undergo further examinations, whereas with other assays there are 8.