2.4 Rapid Influenza Diagnostic Testing

The U.S. Centers for Disease Control (CDC) has a web page intended to provide guidance to clinical laboratory directors about rapid influenza diagnostic tests (RIDT).  (http://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm, accessed on 7/13/18)  It includes a table with calculations of positive predictive value as a function of specificity and pretest probability.  A portion of the table is reprinted below.

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Positive Predictive Value (PPV) of a Rapid Antigen Test for Influenza

 

If Influenza Prevalence is…

And Specificity is…

Then PPV is…

False Pos. rate is…

VERY LOW (2.5%)

HIGH  (98%)

LOW  (39-56%)

HIGH (44-61%)

MODERATE (20%)

HIGH  (98%)

HIGH (86-93%)

LOW (7-14%)

 

 

(We deleted calculations assuming a “moderate” specificity of 80%, because specificity is generally much higher than that. Although the table uses the term “prevalence,” the web page says, “The interpretation of positive results should take into account the clinical characteristics of the case.”  So by “prevalence” they actually mean pre-test probability.)

 

a)      What definition of False Positive Rate did the CDC use in this table?

 

 

b)      In the first row of the table, the pre-test probability is 2.5% and the PPV ranges from 39% to 56%.  What sensitivity for the RIDT did they use for the 39% PPV estimate?

 

 

c)      The “GOOD” specificity of 98% may be too low.  The Quidel (QuickVue) rapid antigen test has a specificity of at least 99%.{Faix, 2009 #1065}  How would using 99% instead of 98% specificity, change the LR(+)?

 

 

d)      Repeat the calculation of the PPV in the first row of the table using 99% instead of 98% specificity.

 

 

The CDC website says that when the pre-test probability of influenza is relatively low and the RIDT is positive,

 

"If an important clinical decision is affected by the test result, the RIDT result should be confirmed by a molecular assay, such as reverse transcription polymerase chain reaction (RT-PCR)."

 

e)      Assume that the “important clinical decision” is whether or not to treat with oseltamivir (Tamiflu®) and the patient is a pregnant woman at high-risk for complications.  Further assume that the RT-PCR will not further identify the strain or sensitivities of the flu virus,[1] and it will take 3 days to get the results back.  Do you agree with the CDC about confirming a positive result?  Why or why not?

 

Show answer

a)      What definition of False Positive Rate did the CDC use in this table?

 

You can see that in each row the "False Positive Rate" is 1 – PPV = P(D–|Test+) = FP/(FP+TP))  This is different from the more commonly used definition, which is (1-specificity) = P(Test+|D-) = FP/(FP+TN).

 

b)      In the first row of the table, the pre-test probability is 2.5% and the PPV ranges from 39% to 56%.  What sensitivity for the RIDT did they use for the 39% PPV estimate?

 

You need to start with the formula for post-test odds given pretest odds and work backwards from there: 

Pre-test Odds × LR(+) = Post-test Odds.  So LR(+) = Post-test Odds / Pre-test Odds.  So let’s start with finding the LR(+):

Pre-test prob = 2.5% è Pre-test Odds = 2.5/(100 – 2.5) = .0256

Post-test prob = 39% è Post-test Odds = 39/(100-39) = .639

LR(+) = Post-test Odds / Pre-test Odds = 0.639/.0256 = 25

Now LR(+) = Sensitivity/(1 – Specificity), so Sensitivity = LR(+) × (1 – Specificity)

Sensitivity = 25 × 2% = 50%

 

c)      The “GOOD” specificity of 98% may be too low.  The Quidel (QuickVue) rapid antigen test has a specificity of at least 99%.{Faix, 2009 #1065}  How would using 99% instead of 98% specificity, change the LR(+)?

 

LR(+) = Sensitivity/(1 – Specificity), so changing specificity from 98% to 99% would change (1-specificity) from 2% to 1% and double the LR(+) from 25 to 50.

 

d)      Repeat the calculation of the PPV in the first row of the table using 99% instead of 98% specificity.

 

Doubling the LR would double the post-test odds calculated in part b: 2 ×  0.639 = 1.28.  So the post test probability would be 1.28/(1+1.28) = 1.28/2.28 = 56%

 

The CDC website says that when the pre-test probability of influenza is relatively low and the RIDT is positive,

 

"If an important clinical decision is affected by the test result, the RIDT result should be confirmed by a molecular assay, such as reverse transcription polymerase chain reaction (RT-PCR)."

 

e)      Assume that the “important clinical decision” is whether or not to treat with oseltamivir (Tamiflu®) and the patient is a pregnant woman at high-risk for complications.  Further assume that the RT-PCR will not further identify the strain or sensitivities of the flu virus,[1] and it will take 3 days to get the results back.  Do you agree with the CDC about confirming a positive result?  Why or why not?

 

The cost of failing to treat if she has the flu is higher than the cost of treating unnecessarily if she doesn’t, so a post test flu probability of 56% would prompt us to prescribe oseltamivir without further testing.

 

However, if the clinical decision were something (e.g., quarantining a village and setting off widespread panic) where doing it unnecessarily is worse than failing to do it when indicated, we would want to confirm a positive result.

 



[1] At this writing, the CDC’s assay for the novel swine-origin influenza A (H1N1) virus (S-OIV) known as swine flu is not widely available.  RT-PCR is the gold standard for identifying an influenza A virus infection but cannot further identify the strain or subtype.  This can only be done at special labs, primarily county health departments and the CDC.

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