Tag Archives: post-test probability

“The uncertainty of certainty”

There is one thing certain in the microbiology laboratory, that the results will be uncertain. This has nothing to do of course with laboratory systems or the competency of staff members. Just an acceptance that there is no such thing as a certain result…

The other thing to note is that the degree of certainty of results will vary between different tests, not only for separate tests but even for multiple tests contained in the one assay, e.g. any multiplex PCR.

Take for example a multiplex respiratory PCR, containing 24 or so different targets. (Most labs will “demand manage” such expensive assays, allowing them only for immunocompromised patients or the seriously ill. Nevertheless, such assays are becoming increasingly popular.)

In a multiplex respiratory assay, a positive result for rhinovirus is almost certainly going to have a greater chance of being “the genuine article” than a positive result for bocavirus.

This is because each individual target pathogen has a different positive predictive value (PPV), based on both its specificity and its relative prevalence in the tested population. As a result, positive predictive values for individual pathogens within a multiplex can, and do, vary greatly.

But how do we relate such information to the clinicians? Quoting the calculated PPV for each target in a multiplex would make for a long and complex laboratory report. I would not go there… It is probably best to use an appropriate comment for certain results. I.e. “Bocavirus is uncommonly seen in population x, therefore the positive predictive value of this result may be sub-optimal. Close clinical correlation is required.”

Of course, clinicians can increase the degree of certainty by clarifying the “pre-test probability”. I.e. A positive bocavirus result in a 6 month old during the winter season is much more likely to represent a true result than a positive bocavirus result in an adult during the summer season.

With multiplex PCRs, sometimes you are “forced” to perform a test, when it would be better not to know…

Clinicians, in general,  tend to believe that all laboratory results are certain, until we produce one that is very clearly wrong! After that, they will believe all results are uncertain until that trust is rebuilt over time.

To understand certainty of testing, you first of all need to understand the laws of probability. All a laboratory result ever does is convert pre-test probability of disease X into post-test probability. 

It neither confirms nor excludes…



“Measuring the odds….”

“Medicine is a science of uncertainty and an art of probability.” William Osler

This article is an extension of a previous article on sensitivity, specificity, and positive predictive value, this time looking at pre- and post-test probability.

Take the following hypothetical scenario:

A 15 yr old teenager and an 85 yr old Rest Home resident both present to their doctor with a sore throat and cervical lymphadenopathy.

An Epstein Barr Virus (EBV) screening test (with sensitivity and specificity both at 97%) is positive in both patients.

Without knowing any other information, what is the likelihood of each person having Infectious Mononucleosis/Glandular Fever due to EBV?

Let’s look at it before the EBV test is performed. The prevalence of glandular fever in 15 year olds with sore throats is many times greater than in 85 year olds. Thus the chance of the 15 yr old having glandular fever is much, much higher than the 85 yr old. (This is called pre-test probability).

After the test result is known, the post-test probability of glandular fever is extremely high in the teenager, but still relatively low in the 85 yr old, as the very low prevalence in this age cohort will lower the positive predictive value of the test. Therefore the chances of the EBV result being a false positive in the 85 year old is relatively high.

In conclusion, exactly the same result in different patients needs to be interpreted differently.

So what is the lesson from this?

I suspect that a lot of laboratory users don’t really think enough about pre and post-test probability when they see the laboratory result. They may well take the result at face value and diagnose the patient on the basis of it. (I have seen this happen many many times…)

It is our job in the laboratory to convince the requestors that on the basis of the factors described above, the results are not always perfect, however much we would like them to be……


p.s. I have added a quick powerpoint on the basics of Norovirus Infection to the website.