Cell-free DNA (cfDNA), also going by the monikers of Noninvasive Prenatal Testing (NIPT) and Noninvasive Prenatal Screening (NIPS), screens for a handful of genetic conditions. The detection rate of cfDNA is high for many of these conditions, especially for Down syndrome. Many labs boast that their cfDNA is “greater than 99% accurate”. So what does “>99% accurate” really mean? Let’s start first with what it does not mean.
A positive cfDNA result rarely ever means that there is a greater than 99% chance that the baby has a genetic condition!
In fact, if your cfDNA result is positive, the chance your baby actually has the condition is often far less than 99%. So how do we answer the question: what is the chance my positive result is a true positive result? For this we need to know the Positive Predictive Value (PPV). Learn more about PPV here.
Are the claims of 99% accuracy false advertising?
They are not false. However, it is important to keep the magnitude of these claims in perspective. Accuracy refers to the proportion of ALL test results that are correct, both positive and negative results. Since cfDNA screens for relatively rare conditions, most results will be negative indicating a low chance for the conditions screened, and indeed they will be true negatives. The rarity of the conditions screened makes achieving 99% accuracy quite attainable! But also not very meaningful.
Statistically, if every pregnant woman were to be told that their baby will not have a chromosome condition, it would be 99% accurate because less than 1 out of 100 babies are born with a chromosome condition.
Of course, unlike cfDNA which has a high detection rate, a method that assigns a “negative” result to every patient across the board is not at all precise and the detection rate of such a screen is a big fat zero. This example is used merely to illustrate the point that claims of >99% accuracy aren’t necessarily anything to be impressed by.
What is more important is the sensitivity (detection rate) and specificity (false positive rate) so that personalized predictive values can be calculated for each individual. These are the numbers that will allow an individual to determine the chances that their negative result is a true negative (negative predictive value) or that their positive result is a true positive (positive predictive value).
Because most women start off with a very small chance to have a baby with any of the conditions cfDNA screens for, the negative predictive value for cfDNA is high, usually >99%. Most women will have negative results indicating that the chance of a having a baby with any of the screened for conditions is low and most of these women will have true negative results since the conditions are generally rare. On the other hand, the likelihood that a positive cfDNA result is a true positive result (positive predictive value) is often to be far less than the coveted 99%. For more information about cfDNA and what it can and can’t do, click here.