Stats, CRP and Sick Kids

So I have been having a particularly nerdy week.

After the recent review of the point-of-care CRP paper I got to thinking.  We all seem to have an opinion about CRP based on what we think we know – but I think most of us have a pretty shady understanding of the true diagnostic characteristics of the ubiquitous CRP.

So I have taken the raw data from the POC-CRP paper and boiled it down to the numbers.  Recall this is about using a Point-of-care CRP assay in children with an acute illness presenting to the GP (in Belgium). The baseline prevalence of serious bacterial infection in the population studied was 0.35 % or about 1 in 285…  which is about one truly sick kid a year if you see roughly one kid a day with acute illness!

To explain.

The “proportion of patients” indicates what percentage of the children tested with POC CRP had a result above the various cutoffs.  That is, in how many of your patients would the result be over this cutoff?

The rest are as per biostats school.

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So what can we do with these numbers?  If we think about the test in terms of “yield” when you are dealing with a single patient sitting before you – how does it stack up?

First observation is that less than half of the patients had a CRP under the “magic 5”.  Sure it was 100 sensitive at this cutoff… but 54% will fall into the next bracket where the test performed very poorly.

Low – mid range CRPs were basically useless.  Insensitive and poorly predictive.  A + CRP around 20 in a patient from a low-prevalence (GP) population moved the risk of SBI from 0.35 to 0.7%.

Using a cutoff of 80 did improve the diagnostic performance.  I think this is the cut-off that makes the most sense to use.  The likelihood ratios are reasonably potent in both directions.  Unfortunately only about 1 in 20 kids will have a CRP over this level.

EDIT:  A few tweets pointed out that the CRP cutoff of 80 had more sensitivity than 20, which makes no sense when we think about how tests should work.  I have rechecked the numbers and it seems this is the result of the relatively low numbers of true positives.  If you can find another error or explanation please comment below.

A CRP over 200 is two things – suggestive of a serious bacterial infection and quite rare.

So here is how I teach when it comes to the question: ” should I do a CRP?”

  1. Estimate the risk based on the clinical picture – use your history and careful examination.
  2. Next imagine that the CRP comes back as 42.
  3. Now decide what you would do with that information
    • Are you still worried about the patient?
    • Are you reassured?
  4. If you are wanting to “exclude a serious infection – you may get lucky and get a low… but you are more likely to return an annoyingly mildly positive result – in which case you are back at point 3.

At the end of the day we are “probabilisticians” – we are not trying to diagnose sepsis right now – we are trying to decide which kids get the empirical treatment or transfer into ED.  I would imagine it is worthwhile to treat a good number of children empirically in order to try and catch all cases of true infection.

The CRP as shown in this data set does very little to sort the deck.  It is a crude filter for the majority of patients to whom it may be applied.  I personally do not find it to be particularly useful in making these decisions.  I may be wrong.

I would love to see a trial comparing “clinical acumen”to “acumen + CRP” as strategies with the goal of testing if or how much the CRP adds to our accuracy and ability to define a smaller sub-group who may be at higher risk.  As of today though I am not convinced it adds enough to make it worthwhile – particularly in a low prevalence population e.g.. usually healthy kids attending the GP clinic.

Thoughts?

Casey

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