Performance & Technology

Most broadly studied NIPT

The Harmony® test has been studied in more scientific publications than any other cell-free DNA-based prenatal test and has been demonstrated in studies involving >268,000 women in >72 peer reviewed publications1.  Performance of the Harmony test has been extensively demonstrated in singleton and twin pregnancies, in women ≥ 18years and women of any risk category* 2,3,4,5. Other peer-reviewed studies have evaluated clinical implementation 6 and the accuracy and reproducibility of the Harmony fetal fraction assessment 7.

*Any risk refers to the average risk population (age < 35) and high risk population (age > 35).

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Performance of the Harmony test

The Harmony test delivers consistent, industry-leading performance for trisomy 21, trisomy 18 and trisomy 13 across clinical studies 2, as well as a higher detection rate and lower false-positive rate for trisomy 21 compared to first trimester screening 2.

 

Superior performance in the general population

The Harmony test outperformed traditional first-trimester screening (FTS) in a landmark study (NEXT) published in the New England Journal of Medicine 2. In this prospective blinded study, the Harmony test was found to be superior to FTS in terms of detection rate, false-positive rate and positive predictive value for trisomy 21.

References:

  1. Demonstrated by 72 peer-reviewed published studies using the Harmony prenatal test as of Jan 2021.
  2. Norton et al. N Engl J Med. 2015 Apr 23; 372 (17): 1589-97.
  3. Stokowski et al. Prenat Diagn. 2015 Dec;35(12):1243-1246.
  4. Nicolaides et al. Am J Obstet Gynecol.2012 Nov;207(5):374.e1-6.
  5. Gil et al. Fetal Diagn Ther.2014;35:204-211.
  6. Kagan et al. Ultrasound Obstet Gynecol.Sep 19. doi:10.1002/uog.18905.
  7. Schmid et al. Ultrasound Obstet Gynecol. 2018; doi:10.1002/uog.19036.
  8. Benn et al. Prenat Diagn 2015; 35: 725–734.
  9. Gregg et al. Genetics in Medicine 2016 Oct; 18(10):1056-65.
  10. Committee Opinion No. 640: Obstet Gynecol 2015; 126: e31-37.
  11. Takoudes and Hamar.Ultrasound ObstetGynecol 2015;14:112-116.

Technology

During pregnancy, cfDNA fragments of the mother and the fetus circulate in the mother’s blood. Harmony targets fetal DNA with its proprietary technology, DANSR® and FORTE®. This targeted approach yields a deeper analysis of the chromosomes of interest (e.g. 21, 18, 13) versus massively parallel shotgun sequencing 1-3.

Our unique method of targeted DNA analysis achieves a combined accuracy greater than 99% and a combined false-positive rate less than 0.1% for trisomy 21 4. We infuse the best of single nucelotide polymorphism (SNP) technology with a microarray platform, so clinicians get an analysis deeper than random sequencing. Our SNP analysis distinguishes maternal from fetal DNA and quantifies the fetal fraction. This is coupled with DANSR®, a unique and targeted approach focusing only on cfDNA from the chromosomes of interest. Harmony incorporates the fetal DNA measurement into its probability assessment using FORTE™, a proprietary algorithm, to more clearly distinguish high and low-probability results 1-3.

Fetal DNA measurements are incorporated into the FORTE algorithm, which also incorporates maternal risk factors and precise fetal fraction allowing Harmony to provide individual probability scores for each patient 2-3.

cell free DNA in blood

References:

  1. Sparks et al. Prenat Diagn. 2012 Jan;32(1):3-9.
  2. Sparks et al. Am J Obstet Gynecol. 2012 Apr;206(4):319.e1-9.
  3. Juneau et al. Fetal Diagn Ther. 2014;36(4):282-6.
  4. Stokowski et al. Prenat Diagn. 2015 Oct; DOI: 10.1002/pd.4686.
study design

The NEJM study

In the first and only blinded prospective study of its kind, the Harmony prenatal test proved superior to traditional first trimester screening for the detection of trisomy 21 (Down syndrome) 1. Nearly 19,000 women, regardless of age or risk, were enrolled in this unique study that compared the performance of two prenatal tests. The results, published in the New England Journal of Medicine 1, show Harmony prenatal test significantly outperforms the current screening standard for trisomy 21.

study results

The results found that Harmony testing for trisomy 21 had a higher detection rate, a lower false-positive rate, and a higher positive predictive value. Harmony had a 100% trisomy 21 detection rate compared to a 79% detection rate with FTS** 1.

Please view this information resource below to find out more about the NEJM study.

download NEJM STUDY FLYER

Twin pregnancies

Performance of the Harmony test has been published in peer-reviewed studies including over 1,300 twin pregnancies and has been used in over 16,000 twin pregnancies across the world 1-7.

References:

  1. del Mar Gil M, et al. Fetal Diagn Ther. 2014;35(3):204-211.
  2. Struble C et al. Fetal Diagn Ther. 2013;35(3):199-203.
  3. Bevilacqua E, et al. Ultrasound Obstet Gynecol. 2015;45(1):61-66.
  4. Stokowski et al. Prenat Diagn. 2015 Dec;35(12):1243-6.
  5. Sarno L, et al. Ultrasound Obstet Gynecol. 2016;47(6):705-711.
  6. Jones KJ, et al. Obstet Gynecol. 2018 51:274-277.
  7. Data on file.
download TWIN STUDies FLYER

Clinical scenarios included in published Harmony twin studies:

  • Monochorionic twins
  • Dichorionic twins
  • Twins conceived with in vitro fertilisation (IVF)
  • Twins conceived naturally
  • Pregnancies where both twins have aneuploidy
  • Pregnancies where only one twin has aneuploidy
  • First trimester testing
  • Second trimester testing

If further information regarding testing is required, or you need to discuss a patient, please contact:
Assoc. Prof. Mirette Saad on P: (03) 9538 6777 or E: Mirette.Saad@clinicallabs.com.au.