Principles and Practice of Pharmaceutical Medicine

In clinical trials of IMPs without a MA, sponsors
must report all serious unexpected suspected
adverse drug reactions (SUSARs) within eight
calendar days if they were fatal or life threatening,
and within fifteen days for other serious cases. The
initial report has to be followed up within seven
days for fatal or life-threatening cases and within
fifteen days for other serious reports. These expe-
dited reporting requirements mean that the treat-
ment code in blinded trials must be broken, as it is
otherwise impossible to decidewhich treatment the
patient received and, therefore, impossible to
determine whether an event could possibly be a
reaction: if a patient received placebo, then there is
no suspicion of a possible adverse reaction to the
IMP and authorities do not require expedited

reporting (unless the AE could have been a reaction

related to an excipient present also in the placebo).

‘Expected’ adverse drug reactions in clinical

trials – even if serious – are not reported in an

expedited fashion. An‘Expected’ adverse drug reac-

tion isonethat is mentioned inthe SmPC(in thecase

of a licensed product) or in the investigator’s bro-

chure in the case of an IMP. It is important to under-

stand that expectedness is solely referring to

experiences made with a given individual product

• class reactions, if not observed with an individual
  medicinal product or reactions relating to the under-
  lying disease are not ‘expected’ for thegiven product
  and if considered possibly related to the medicinal
  product, must be reported in an expedited fashion, if
  fulfilling the criteria for expedited reporting.

No*

Determine treatment

(e.g. Unblind Rx code, if needed)

Placebo

Active

Comparator

No

Report

SUSAR

expeditedlyto:

1) Regulators in all

EEA States

where studies

with IMP are

underway

2) Lead ethics

committees in the

same countries

3) EMEA, when the

IMP has no

marketing

authorization in

the EEA.

No expedited

report

Case report

Serious and Rx

Related?

Expected

?

Yes

Yes

**With rareexceptions,for example No

excipient-induced

anaphylaxis are

SUSARs

Reassess:

Expected

?

Report to MAH (recommended)

*Unless

Company

Upgrades

Active

IMP

and

Yes

SUSAR:- Suspected unexpected serious adverse event

Rx:- Treatment EEA:-European economic area

MAH:- Marketing authorization holder

Figure 34.4 Flowcharts for reportability assessment: (a) assessment of expedited reportability (Europe): investiga-
tional medicinal products (IMPs); (b) assessment of reportability of individual case safety reports (ICSRs) in Europe:
post-marketing

478 CH34 MEDICINES REGULATION IN THE EUROPEAN UNION