Chapitre II : Ddonnes de linnocuit pour la veille

pharmaceutique

Plan de chapitre II :
Introduction
I-Les donnes de la dtection de risque
II-Les donnes de lvaluation et de linvestigation des risques
III-Les donnes de la gestion et de la communication de risque

Chapitre II : Les donnes de linnocuit pour la veille des produits

pharmaceutiques

Plan de chapitre II :
I-Introduction
II-Les donnes de la surveillance de risque
III-Les donnes de lvaluation des risque
IV-Les donnes de la gestion et de la communication de risque

I-Introduction :

Tout au long de lvaluation prclinique et clinique et aprs lobtention de l'approbation et la

commercialisation, le mdicament doit montrer un profil bnfice-risque favorable Cela
ncessite une valuation continue de ce profil bnfice-risque durant le cycle de vie du
mdicament.

Le profil de bnfice est dtermin par :

-Lefficacit prouve du mdicament
- Les besoins non satisfaits du mdicament
- L'indication du mdicament (par exemple cancer par rapport flatulence) et quels sont les
traitements alternatifs le cas chant sont disponibles.

Le profil du risque est dtermin partir de l'analyse des informations de scurit obtenues
partir dtudes non cliniques (par ex. tudes sur les animaux), dessais cliniques du
mdicament, et des informations de scurit reues sur le mdicament commercialis.

Dans le cadre de la pr-commercialisation, la majorit des donnes sur linnocuit provenant

dessais cliniques comprennent : les vnements indsirables, les tests de laboratoire, les
Signes vitaux, les examens physiques, dautres tests selon les indications, par exemple, lEEG
dans lvaluation des troubles pileptiques .

Ds que le mdicament est commercialis, les informations de scurit sous forme de rapports
spontans (non sollicits ou volontaires) d'vnements indsirables (AE) proviennent
principalement des professionnels et des consommateurs. Les autorits rglementaires, les
vendeurs, et d'autres sources peuvent galement signaler volontairement les EIs au fabricant.
Dautres renseignements sur l'innocuit post-AMM viennent de la littrature et de
l'information sollicite par le fabricant sous forme d'tudes post-marketing, tudes pharmaco-
pidmiologiques, enqutes, registres, etc.

Pour sassurer quun risque nouveau et cliniquement important ne soit pas nglige ou
signal trop tard, les autorits de sant aux Etats-Unis, l'Union Europenne, le Japon, et
d'ailleurs exigent que les informations de scurit se rapporte la fois sur une base acclre
(dans un dlai de 7 ou 15 jour) et priodique (trimestrielle, semestrielle, annuelle, etc.

Les problmes de scurit de mdicament (par. Ex un vnement indsirable, rsultat

de laboratoire anormal, etc.) rpondant aux critres suivants : srieux. inattendue, relation au
traitement est suspecte (doivent tre signal aux autorits rapidement).

Les rsultats des tudes non cliniques qui indiquent un risque potentiel et cliniquement
importante pour les humains doivent galement tre signals rapidement.

Les autorits de sant exigent aussi la soumission priodique obligatoire des

informations sur linnocuit durant le dveloppement clinique et lorsque le mdicament est
commercialis
 I-les donnes de dtection de risque :
oluntary reporting of suspected unexpected
ADRs of new medicines by healthcare professionals (physicians,
pharmacists, nurses) or even patients and caregivers nowadays.
ICSR :
Definition
1cqs ou listing(series des cqs)
s/f pqpier ou elecroniaue(ICSR introduit dqns lq BD
des qgences
eudrqvigilqnce
FQRES

DAMM
Ces ICSR peuvent etre solicites ou non
Non solicites :
-cas du delcqlrqtion receuille pqr methode de notification spontanee
Individual Case Safety Reports
New types of individual case safety reports are now appearing, including Internet reports, solicited reports from
patient support
programs, surveys, epidemiologic studies, disease registries, regulatory and other databases, and licensor and
licensee interactions.
Consumer reports should be scrutinized and should receive appropriate attention and be included in PSURs.
Literature Reports
Literature reports should be sought in at least two internationally
recognized literature databases realizing, however, that publications may be a source of false information and
signals.
Broadcast and lay media should not ordinarily be monitored.
If the product source or brand is not specified, a company should
assume it was its product.
If there is a contractual agreement between two or more companies (e.g., for comarketing), the contract should
specify the responsibility for literature searches and reporting.
English should be the standard language for literature report
translations.
The clock starts when a case is recognized to have the four minimum criteria for reportability (reporter, patient,
drug, event).
Elements sous droits d'auteurCIOMS V Report 61
The Internet
A procedure should be in place to ensure daily screening of a company's or regulator's website(s) to identify
potential case reports,
but companies and regulators do not need to routinely monitor
the Internet beyond their own sites for AEs.
Solicited Reports
Solicited reports should be regarded as distinct from spontaneous unsolicited reports. They should be processed
separately and so identified in expedited and periodic reporting.
For regulatory reporting, solicited reports should be handled in
the same way as study reports. Causality assessments are needed.
Clinical Trials and Studies
Quality-of-life studies should be handled like clinical trial data.
Epidemiologic studies should have the same reporting rules for
suspected ADR cases as clinical trials.
For epidemiologic studies, unless there is specific attribution in
an individual case, expedited reporting is generally not appropriate.
If relevant, studies should be summarized in PSURs.
Expedited reports from comparator drug data should be forwarded to the relevant manufacturer(s) for their
regulatory
reporting.
Registries and Databases
A registry is not a study. Cases should be treated as solicited reports (causality assessment required). It is
unnecessary for a company to attempt to routinely collect ADRs from regulatory databases.
National and international
postmarketing safety databases
Once submitted to the national drug safety monitoring program, individual case safety reports
are
stored in computerized postmarketing safety databases. Many national drug regulatory
authorities
have databases that include suspected AE/ADR
reports derived from a postmarketing reporting
system, as well as suspected AE/ADR reports from
other sources, such as the published medical literature, and sometimes certain types of serious
adverse
events (SAEs; those considered related to study
drug) from clinical trials. Examples of national
reporting systems and databases include the Blue
Card system (Australia), Canada Vigilance
(Canada), the Canadian Adverse Events Following
Immunization Surveillance System (CAEFISS)
database (Canada), the French Pharmacovigilance
Spontaneous Reporting System database (France),
the Adverse Drug Reaction Information Management System of the Pharmaceutical and
Medication
Devices Agency, Ministry of Health, Labor, and
Welfare (Japan), the Lareb database (Netherlands),
the SWEDIS database (Sweden), the Sentinel database (United Kingdom), the Adverse Event
Reporting system (AERS) database (United States),
and the Vaccine Adverse Event Reporting System
(VAERS) database (United States). In addition,
there are two international reporting and database
systems: EudraVigilance23 in the European Union
(run by the European Medicines Agency, EMA)
and VigiBase24 pooling data from the approximately
100 member countries of the WHO International
Drug Monitoring Programme (run by the Uppsala
Monitoring Centre, UMC). VigiBase is also the
system used as the national database by 28 pharmacovigilance centers around the world;
reports
are stored directly in VigiBase, but entered,
managed, and analyzed remotely through an
internet-based data management tool, VigiFlow

he output from the CIOMS V Working Group of 2001. This is a

very large report covering a multitude of areas in drug safety. Some
of the highlights include:
Individual Case Safety Reports
New types of individual case safety reports are now appearing, including Internet reports,
solicited reports from patient support
programs, surveys, epidemiologic studies, disease registries, regulatory and other databases,
and licensor and licensee interactions.
Consumer reports should be scrutinized and should receive appropriate attention and be
included in PSURs.

CASE SERIES
M ultiple reports of the sam e or sim ilar AEs from different patients
used in signal identification and w ork up.
Individual case safety reports on patients (the cases) w ith a susp ected adverse drug reaction
reported spontaneously or during a
trial, a cohort, or a case-control study. No control group is involved.
Elements sous droits d'auteur46 Causality
After an initial postm arketing spon tan eo u s case report is found,
additional cases should be sought in the sp o n so rs database, the
FDA AERS database, the U ppsala database, published literature,
and other databases. Cases should be evaluated and followed up for
additional inform ation w here need ed and w here possible for signal evaluation.

Literature Reports
Literature reports should be sought in at least two internationally
recognized literature databases realizing, however, that publications may be a source of false
information and signals.
Broadcast and lay media should not ordinarily be monitored.
If the product source or brand is not specified, a company should
assume it was its product.
If there is a contractual agreement between two or more companies (e.g., for comarketing),
the contract should specify the responsibility for literature searches and reporting.
English should be the standard language for literature report
translations.
The clock starts when a case is recognized to have the four minimum criteria for reportability
(reporter, patient, drug, event).
Elements sous droits d'auteurCIOMS V Report 61
The Internet
A procedure should be in place to ensure daily screening of a company's or regulator's
website(s) to identify potential case reports,
but companies and regulators do not need to routinely monitor
the Internet beyond their own sites for AEs.
Solicited Reports
Solicited reports should be regarded as distinct from spontaneous
unsolicited reports. They should be processed separately and so
identified in expedited and periodic reporting.
For regulatory reporting, solicited reports should be handled in
the same way as study reports. Causality assessments are needed.
Clinical Trials and Studies
Quality-of-life studies should be handled like clinical trial data.
Epidemiologic studies should have the same reporting rules for
suspected ADR cases as clinical trials.
For epidemiologic studies, unless there is specific attribution in
an individual case, expedited reporting is generally not appropriate.
If relevant, studies should be summarized in PSURs.
Expedited reports from comparator drug data should be forwarded to the relevant
manufacturer(s) for their regulatory
reporting.
Registries and Databases
A registry is not a study. Cases should be treated as solicited reports
(causality assessment required).
It is unnecessary for a company to attempt to routinely collect
ADRs from regulatory databases.

MANAGEMENT OF ADR AND ADE DATA

In monitoring the safety of products, pharmaceutical companies need to
comply with worldwide regulations as well as the primary requirement of
helping doctors to prescribe safely. The intent in this chapter is not to provide
a comprehensive review but to provide an insight into the methods of managing
ADR data.