The NIPT/Cell Free DNA Screening Performance Calculator (“Calculator”), also known as "NIPT/cfDNA Performance Calculator", is provided solely for use by healthcare professionals with an understanding of positive predictive value (“PPV”) and negative predictive value (“NPV”). The Calculator is intended to aid such healthcare professionals in counseling their patients about PPV and NPV relative to certain non-invasive prenatal tests (“NIPT”) and the clinical meaning of the patient’s screening results. The Calculator should not be used to provide risk assessment independent of clinical correlation/context and is not intended to replace a health care professional’s best medical judgment based on the clinical circumstances.
The Calculator is provided for educational and informational purposes only, and neither the Genetic Support Foundation (“GSF”) nor the National Society of Genetic Counselors (“NSGC”) approves or endorses any specific values, methods, practices, or sources of information. Use of the Calculator does not create any provider-patient relationship with GSF, NSGC or their respective committee or board members.
The Calculator uses statistical calculations based on the information provided by the user to determine the predictive values of NIPT/Cell Free DNA Screening utilizing prevalence information based on mateage and population study. The values generated by the Calculator should not be construed as dictating an exclusive course of management, nor does the use of such predictive values guarantee a particular outcome. Proper use of the Calculator requires that the user (i) input accurate data; and (ii) have sufficient understanding of the methodology used and relevance of the results generated. Neither NSGC nor GSF guarantees, or take any responsibility whatsoever for, the accuracy of the results generated by the Calculator.
In consideration of your use of the Calculator, you covenant not to sue, and further waive, release and discharge, NSGC, GSF, and any person and/or organization associated with the Calculator from any and all claims to liability for death, personal injury, or property damage of any kind or nature, whatsoever arising out of, or in the course of, your use of the Calculator. Neither GSF, NSGC, or any other individual, organization or other party involved in the preparation or publication of the Calculator or this website shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any use of or reliance upon the Calculator, the results or values generated by the Calculator or other information or materials included on this website.
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This calculator will allow you to estimate the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of noninvasive prenatal tests (NIPT), also known as Cell Free DNA Screening (cfDNA), based on estimates of population prevalence or by entering your own prevalence numbers. The results of this calculator only apply to patients who have a result from NIPT/cfDNA.
Estimates of NIPT/cfDNA sensitivity and specificity based on a meta-analysis of available studies (Gil et al 2015) are included as default data for some conditions for which NIPT/cfDNA screens. The user may also input the sensitivity and specificity information based on test performance of a specific laboratory. For some conditions, such as microdeletions, there is insufficient data available in the medical literature to determine test performance. The user may wish to contact the specific NIPT/cfDNA lab for sensitivity and specificity information for specific conditions included on NIPT/cfDNA panels.
The calculator utilizes the incidence of trisomy chromosome conditions screened for by the age of the pregnant patient at 16 weeks gestational age. For some conditions, such as 45,X and the microdeletion conditions, the incidence does not vary significantly with the pregnant patient’s age. In some cases, prevalence at gestational ages prior to 16 weeks may be higher, and prevalence at greater than 16 weeks may be lower, given the possibility of spontaneous loss in pregnancies with some chromosome conditions. The prevalence defaults may not be the best estimates of an individual patient’s prior risk for a chromosome condition. Users should be aware that other factors such as ultrasound findings or the results of biochemical aneuploidy screening may affect the estimated prior risk for a chromosome condition for an individual patient and this should be considered when using this calculator. See the FAQs page for more information.
Sensitivity refers to the detection rate - the proportion of all individuals with a condition who are correctly identified as “positive” by a screening test. If 1,000 tested individuals have a given condition and 990 of them test “positive“ for that condition, the test’s sensitivity is 99%. Sensitivity = Detection Rate = 990/1,000 = 99%
Specificity refers to the proportion of all individuals without a condition who are correctly identified as “negative” by a screening test. If 99,000 out of 100,000 unaffected individuals do not have a condition and 98,000 test “negative”, the test’s specificity is 99%. Specificity = 98,000/99,000 = 99%
The Positive Predictive Value (PPV) represents the proportion of positive test results that are truly positive. It answers the question: “If my test is positive, what is the chance my baby is affected?” For example, a PPV of 50% indicates that half of the cases in a given population who have a positive test result are predicted to actually be affected with the condition. Although test sensitivity and specificity are expected to remain the same across a broad population, the PPV of a test varies based on the prevalence of the condition in a given population. The rarer the condition in a given population, the lower the PPV when sensitivity and specificity remain unchanged.
The Negative Predictive Value (NPV) represents the proportion of negative test results that are truly negative. It answers the question: “If my test is negative, what is the chance that my baby is unaffected?” For example, if the NPV is 99% in a given population, then approximately 99% of individuals who have a negative test result in that population would be expected to have an unaffected pregnancy. In this example, 1% of women receiving a negative result will have an affected pregnancy (false negative result).
The False Positive Rate (FPR) reflects the percentage of unaffected cases that test positive. If 1,000 of 99,000 unaffected individuals have a positive test result, the false positive rate is 1,000/99,000 = .01 or 1%.
The False Negative Rate (FNR) reflects the percentage of affected cases that test negative. If 100 of 1,000 affected individuals have a negative test result, the false negative rate is 100/1,000 = .01 or 1%.
Accuracy describes the proportion of all tests that are correctly called. For rare conditions, as is often the case for conditions screened with NIPT/cfDNA, the majority of individuals screened will be correctly called as “negative” and therefore NIPT/cfDNA is described as “highly accurate”. However, the chance that any positive result is a true positive result depends on the Positive Predictive Value (PPV) of the test (see above). It is important to note that although the prior probability of many chromosome conditions is influenced by the pregnant patient’s age, other factors such as biochemical screening results and ultrasound markers may also indicate the likelihood of a condition in an individual pregnancy. The table below illustrates components of accuracy:
|AFFECTED n = 1,000||UNAFFECTED n = 99,000||TOTAL TESTED n=100,000|
|Tested POSITIVE||True Positive = 990||False positive = 1,000||PPV - 990/1,990= 49.75%|
|Tested NEGATIVE||False negative = 10||True negative = 98,000||NPV - 98,000/98,010 = 98.99%|
|Sensitivity - 990/1000 = 99.00%||Specificity - 98,000/99,000 = 98.99%|
What prevalence information should I use when calculating predictive values?
Use the best estimate for the individual patient. Some factors that influence the likelihood of a chromosome condition in a pregnancy include biochemical screening results, ultrasound findings, or a personal or family history of a chromosome condition. Not sure what estimate to use? Consider referral to a genetic counselor for assessment and counseling. A genetic counselor can be located on the National Society of Genetic Counselors website.
Where do the prevalence estimates come from?
A taskforce including members of the National Society of Genetic Counselors and the Perinatal Quality Foundation reviewed the medical literature and came to consensus regarding the best estimates for prevalence for the conditions included in this calculator. Sources can be found under the Reference tab.
For the trisomy and sex chromosome conditions, the estimates are from review of the data and reflect best estimates for prevalence at 16 weeks gestational age. For some conditions, the prevalence varies by the pregnant patient’s age. In some cases, prevalence at gestational ages prior to 16 weeks may be higher, and prevalence at greater than 16 weeks may be lower, given the possibility of spontaneous loss in pregnancies with some chromosome conditions. The prevalence defaults may not be the best estimates of an individual patient’s prior risk for a chromosome condition.
There is limited information regarding the prevalence of microdeletion conditions during pregnancy. Most of the estimates of prevalence come from the pediatric population and therefore, it is possible that this may not represent the prenatal prevalence for these microdeletions. Underestimates of prevalence would result in a lower PPV. Furthermore, there may be specific ultrasound findings or family history that would suggest a higher baseline risk, and this should be taken into account when using this calculator.