PrenaTest Performance Qualification

 

Performance evaluation of the new PrenaTest® Option 1 for the detection of trisomy 21 (study of December 2016)

The performance of the PrenaTest® Option 1 has been validated in a clinical study. The study results of the maternal plasma samples (n=966) demonstrated a positive percentage agreement (PPA; equates to sensitivity) of 100 % (lower 1-sided 95% confidence interval of 91.8 %; n=35/35) and a negative percentage agreement (NPA; equates to specificity; n=931/931) of 100% compared to NGS-based PrenaTest®. The negative predictive value (NPV) was 100 % (lower 1-sided 95 % confidence interval of 99.68 %). The average fetal fraction of all examined blood samples was 8.1%. In 54 blood samples with a fetal fraction below 4% and as low as 2.4% a correct test result was achieved.

 

Based on the 100% positive as well as negative percentage agreement of the results of the validated qNIPT concept (the new PrenaTest® Option 1) compared to the PrenaTest® based on next generation sequencing (NGS), the test quality for the PrenaTest® remains unchanged. Please note that the new PrenaTest® Option 1 cannot be used in the case of a twin pregnancy. Please also read the limitations. Learn more about the method.

 

Performance evaluation of the new PrenaTest® Option 1 for the detection of trisomy 21 (study 2016):

 

Correctly classified samples:       966/966  (100%)

Trisomy 21 positive:                           35/35     (100%)

Trisomy 21 negative:                          931/931 (100%)

 

Sensitivity:                                         100% (91,8%)

(lower 1-sided 95% condidence interval)

Specificity:                                           100% (-)

(lower 1-sided 95% condidence interval)

NPV:                                                  100% (99,68%)

((lower 1-sided 95% condidence interval)

 

 

Significance of the PrenaTest® for the fetal aneuploidy of chromosomes 21, 18, 13, X and Y (test options 2 and 3)

Results of the clinical studies regarding the fetal aneuploidy of chromosomes 21, 18, 13, X and Y can be found here (page 27 ff).

 

 

Validity of the PrenaTest® to exclude or detect a 22q11.2 microdeletion, associated with DiGeorge syndrome and velo-cardio-facial syndrome (Shprintzen syndrome)

Validation of the test method:
Data from synthetic pooled DNA specimens as well as several specimens from pregnant women whose unborn child had a 22q11.2 microdeletion were investigated using next generation sequencing. In all cases, a 22q11.2 microdeletion was correctly detected. The validation process was performed in three phases:

 

Phase 1
Four synthesized specimens, each of which had a different cffDNA level (16%, 8%, 4% and 2%) and which had a 22q11.2 microdeletion, were analyzed several times. The 22q11.2 microdeletion of the two specimens with a cffDNA level of 8% and 16% was correctly determined, while the results of the specimens with a lower cffDNA level were not significant.

 

Phase 2
Four specimens from pregnant women whose unborn children had a 22q11.2 microdeletion were retrospectively tested and the 22q11.2 microdeletion was correctly detected in each case. In this phase, the 22q11.2 microdeletion was previously confirmed in three of the specimens using invasive diagnostic procedures. In the case of the fourth specimen, a cardiac defect (DORV; double outlet right ventricle) was confirmed by ultrasound. The DiGeorge syndrome was confirmed after birth.

 

Phase 3
In a final internal blinded study, specimens from phase 2 with a 22q11.2 microdeletion as well as euploidic specimens were investigated. All specimens were correctly classified. Due to the low number of cases, a concrete test sensitivity and specificity cannot currently be derived.

 

Correctly classified specimens       16/16
Total detection rate                          2/2
False-positive rate                          0/14

 

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