Module 5

Lesson 2

Hi!

I would like to start by showing you a picture, and then asking you a question: Is two cows a great
number of cows?

Well, if we look at those two cows they have large fields, plenty of space around them and we know
by experience that there could be many more cows in this situation. So, in this context two cows
does not seem to be a great number of cows. But now, imagine a totally different context: Two cows
on the highway. I ask you again the same question, is two cows a great number of cows? Well, it is
for a place you would not expect two, not even one but no cows at all.

Let's bring back the example to pharmacovigilance. Imagine that in your database of individual case
reports you observe three reports for a specific drug and a specific adverse event. Here comes the
question, is three reports a great number of reports? Like in the cow example, we can only answer
this question if we know the expectation. Depending on the context, being in a field or being on a
highway, our expectation will change.

In the case of pharmacovigilance, the expectation depends mainly on three things:

First: how many people get the adverse event in general? Is the event common or very rare? We
would expect more reports for common events than rare events.

Second: how many people take the drug? Are we talking a few thousands or a few millions? This will
also obviously affect the number of reports you would expect to see.

Third: what is the reporting rate? In other words, are people likely to report their adverse event?

In reality, getting those numbers is difficult. We might get some statistics about some drugs or some
events, but in general those numbers are hard to get. So, what to do?

The idea behind disproportionality is to use the database of spontaneous reports itself to compute
the number you would expect if the drug and the event are co-occurring by chance. Once we have
the expectation, we can evaluate the observation in the lights of that expectation. This comparison
between observation and expectation is called disproportionality analysis.

The word disproportionality comes from “proportional” and the negative prefix “dis”. It basically
means “out of proportion”. This happens when the observed is far from the expectation, either by
seeing too few or too many. When there is no association between the drug and the adverse event
we expect the observed number to be proportional to the frequencies of the drug and the event
respectively.

So, in our case, if we have observed three case reports in our database mentioning a specific drug
and a specific adverse event while we computed an expected number of one report, we might have
disproportional reporting and should perhaps submit the combination to the scrutiny of expert
reviewers.