Swissmedic Vigilance News

Regulatory
The masking effect in pharmacovigilance: A signal detection challenge
amidst the COVID-19 vaccine rollout
Irene Scholz, Thomas Stammschulte
Safety of Medicines Division, Swissmedic, Bern, Switzerland
The COVID-19 pandemic has been a global health
crisis necessitating rapid development and deployment
of vaccines to curb its spread. The broad use
of COVID-19 vaccines and the considerable attention
to potential safety issues in the media and
among the public led to an unprecedented large
number of reports of suspected adverse events. All
these reports are evaluated and stored in databases
on a national and international level in order to
identify previously unknown adverse effects. In this
context, a known phenomenon called the "masking
effect" has presented a challenge as regards
statistical signal detection in databases of adverse
event reports. This “masking effect” is caused by
the large number of COVID-19 vaccines but applies
to signal detection for other medicines or the vaccines
amongst each other in the database.
In order to detect potential safety issues in databases
containing adverse event reports, a statistical
and a scientific analysis are combined. A statistical
disproportionality analysis enables screening of a
database of reported adverse events for patterns
that may indicate a larger number of certain adverse
events than expected for certain medicinal
products. An identified “disproportionality” will
then be substantiated by a clinical review of cases
and screening of the scientific literature and studies.
There are different statistical methods for the
disproportionality analysis. One of the most common
of these is the reporting odds ratio (ROR),
which is based on a 2x2 contingency table. The ROR
corresponds to the ratio between the odds of an
adverse event of interest with a certain medication
or vaccine to the odds of the same adverse event
with all other medicinal products and vaccines in
the database (Table 1).
Table 1: Calculation of the reporting odds ratio (ROR)
Medication or
vaccine of interest
All other medications
and vaccines
Adverse event
of interest
a
All other
adverse events
When the lower limit of the 95% confidence interval
is greater than 1, the chosen adverse event
of interest could be a signal. A prerequisite for the
ROR to work is that there is a randomly scattered
background rate.
Since the COVID-19 pandemic, the large amount
of adverse event reports has impacted databases
worldwide and affected signal detection for other
medicines based on disproportionality analysis
by significantly changing the background rates
of reports in the databases. This phenomenon is
called the “masking effect”: The signal detection
ratio for a specific drug event of interest, identified
through quantitative methods, is reduced or inhibited
due to the presence of another product (e.g.
COVID-19 vaccines) in the database, with overrepresented
reporting of the event in question. Masking
effects may complicate the interpretation of
adverse event data by potentially obscuring safety
issues and thus delay timely intervention.
c
b
d
Swissmedic Vigilance News | Edition 31 – November 2023
32