Principles and Practice of Pharmaceutical Medicine

Figure 34.4 illustrates the evaluation of a
reported case for reportability.
Clinical trial sponsors also have the obligation to
report safety information to investigators and
ethics committees in a timely fashion. Ethics com-
mittees can be informed in an unblinded fashion
within the same timeframe as the regulatory autho-
rities, or in reasonable, regular intervals (com-
monly quarterly). The investigators can be
updated periodically in a blinded fashion, provided
that no compelling safety reason to unblind have
emerged.
Annual update reports for all clinical trials are
required to be sent to regulators and ethics com-
mittees. For short trials (up to six months), or trials
involving less than 50 subjects, this can be com-
bined with the notification of end of trial.
Clinical trials constitute well-monitored envir-
onments, in which most events (whether related to

the IMP or not) can be collected and added to a

database which will gradually outline the safety

profile of the drug, allowing for a risk–benefit

assessment that will form the cornerstone of any

marketing application. After MA has been granted,

the population exposed to the drug usually

increases exponentially, while the conditions of

product use become suddenly less well controlled.

Thus, new safety issues often surface immediately

after MA.

The MAH is, therefore, required to provide with

the application for MA a pharmacovigilance plan,

outlining the intentions and systems in place to

further evaluate and strengthen the risk–benefit

analysis of the medicinal product under review.

During the early phases of drug development,

safety assessments in clinical trials are generally

viewed as ‘hypothesis forming’ – broadly applied

systems to collect as much useful data that might

--------------Alternative sources of ICSRs ------------

Is

case valid

?*

Yes Serious

and Rx related

?

No

expedited

report

No

Determine treatment

(e.g. break Rx code for clinical trials

cases, if needed)

Yes

Has

case arisen

In EEA

?

Expedited SUSAR Report

Event Yes to RA in country of origin

Expected

?

Yes No

Expedited SUSAR report to RA in each

EEA country and to EMEA

No

Consumer

Healthcare professionals

or scientific literature Clinical study

No

*Requires real patient,

identified reporter, drug

name, and adverse event

type.

Rx:- treatment

EEA:- European Economic Area

Placebo

**With rare exceptions, for example

excipient-induced anaphylaxis

Sponsor’s

Licensed

Product

SUSAR:- Suspected unexpected serious adverse event

RA:- Regulatoryauthority(ies)

Other Active Comparator(s):

proceed as for active comparators

in Investigational Medicinal Products algorithm

**

Figure 34.4 (Continued)

34.14 SAFETY REPORTING AND PHARMACOVIGILANCE 479