This presentation provides a detailed description of various literature searches performed in pharmacovigilance including search criteria, different search engines etc

3. Country/ Region Frequency
EU Weekly
USA Not specified
India Monthly
Australia Weekly

6. Well recognized scientific and
medical journals
Medical Databases like Medline,
Pubmed, Embase, Quosa, Biosis
Previews, Ovid, Cochrane Library
and Google Scholar etc.

7. Considerations when choosing relevant Databases
Focus
Costs: Not all free;
costs can be high
Is the user interface
easy to navigate or
complex?
How dependable and
reliable are the
outputs?
Can the search engine
return de-duplicated
results?
Can the user make
selections for the most
relevant articles and
store your selected
citations?
Can the user be
notified when certain
articles of interest are
available?

8. Focus
Costs: Not all free; costs can be high
Is the user interface easy to navigate or complex?
How dependable and reliable are the outputs?
Can the search engine return de-duplicated results?
Can the user make selections for the most relevant articles and store your selected citations?
Can the user be notified when certain articles of interest are available?

12. 1. Periodic reports
Development safety
update report
Periodic safety
update report (PSUR)
These reports have a section that is specific to any safety findings that have been reported and identified in
the worldwide literature. These sections should include any new safety signals and emerging safety issues
that have been identified (or publications that the MAH/sponsor has become aware of) during the
reporting period. Any relevant pre-clinical data should also be discussed. Other sections of periodic reports,
for example, data included in summary tabulations, may include ICSRs that have originated from literature,
including non-serious case reports.

13. 2. Individual Case Safety Reports (ICSRs)
These searches are constructed
to identify the four essential
elements required for a valid
ICSR (identifiable patient,
identifiable reporter, adverse
event, suspect medicinal
product). These reports may or
may not qualify for expedited
reporting.
01
In addition to the four essential
elements, there must be a
reasonable suspected causal
relationship between the event
and suspected medicinal
product, as stated or implied by
the author. This should not be
confused with the concept of
“implied causality” for
spontaneous reports.
02
The MAH should apply medical
judgment when determining the
causal relationship if it is not
clear from the article. Special
situations (for example
overdose, drug abuse/misuse,
medication errors) and
pregnancy reports are relevant
for inclusion in a search
designed to identify ICSRs.
These reports may or may not
qualify for expedited reporting.
03
For regulatory reporting
purposes day 0 is the date the
MAH becomes aware of a
publication that contains the
minimum information for a valid
ICSR.
04

15. What does literature search include?
Published abstracts
Articles in medical/scientific
journals
Unpublished manuscripts
involving case reports
Important safety findings or
clinical studies including
posters, letters to the editors,
and associated communication
from scientific meetings.

16. Search Criteria for Medicinal Products
As a general rule, searches should be performed using the active
substance. For combination products, all active substances need to be
included in the search strategy. Searches should not be routinely
conducted that exclude unbranded products. It is common for authors
of literature articles to refer to a generic medicinal product and the
MAH should assume ownership of the product if it can not, with
absolute certainty, confirm that the product is not its own. In addition,
where the formulation is not specified, ownership of the product
should be assumed. For some regulators, reports should not be
excluded based on the formulation. Articles referring to a class of drugs
that describe a class effect, whilst not appropriate for ICSRs may be
relevant for inclusion in periodic reports.

18. Safety signals
that were
detected in
literatures

19. Example #1
Thalidomide-induced
Phocomelia (1961)
Obstetrician William G. Mc Bride published
a letter in the Lancet linking the rare birth
defect with the use of thalidomide by
pregnant women
NOTE: At that time, there was no structure
for reporting of ADRs to Regulatory
Reference: McBride WG. Thalidomide and
congenital abnormalities. Lancet. 1961;278:
1358

20. Example # 2
Granulocyte Macrophage Colony- Stimulating Factor and
Increased Risk of Viral Replication (1998)
• Literature search performed to assess safety of use of GM-CSF in the treatment
neutropenia in HIV patients (off label use in US)
• In vitro data suggested HIV up- regulation by GM-CSF Literature meta analysis
showed increased risk of viral replication by the use of GM-CSF in patients with
HIV not currently taking antiretrovirals.
• This type of safety concern would have never been detected by spontaneous
reporting.

21. Example # 3
Nifedipine and Fatal Aplastic Anemia (1998)
• Article described a case-control study linking six cases of fatal
anemia with nifedipine
• Report identified a Type B ADR (bizarre or idiosyncratic, dose
independent and unpredictable reaction)
• Reference: Laporte JR, Ibanez L, Ballarin E, Perez E, Vidal X. Fatal
Aplastic anemia associated with nifedipine. Lancet. 1998;352: 619-20

24. Adverse pregnancy outcomes for ICSR reporting are not covered in the search
strategy.
Event outcome terms are not routinely searched for (e.g. death).
Searches are not constructed to pick up special situation case reports that are
required for inclusion in periodic reports (e.g. overdose with no AE,
medication errors, off-label use, misuse and abuse, occupational exposure,
normal pregnancy outcomes).

25. The MAH does not include in the search (or excludes from processing as a valid
ICSR or inclusion in periodic reports), articles that refer only to the generic
medicinal product i.e. the article is excluded because it does not refer to the brand
name of the medicinal product.
Exclusion of non-serious expected terms.
The search is constructed to identify ICSRs only and is not broad enough to
identify articles that may be relevant for periodic reports.

27. Translations
 Published articles reported to the Competent
Authority must be provided in English. Abstracts
in English may be reported, followed by the
translated article.

28. Full text articles
 It is not considered sufficient to submit only the abstract to
the regulatory authorities.
 Initially case can be created and reported from a abstract.
 On the receipt of full text article, the information from the
full text article can be included in the case as a follow up
information and reported to the authorities.

29. Reporting
Articles citing multiple
individual identifiable patients
should be reported as
separate ICSRs if they meet
the requirements for
expedited reporting.
Full citation should be
included, in the style of the
Vancouver Convention. Initial
reports made from published
abstracts should be followed
up with a report from the full
article, if the article is not
available to allow initial
reporting within the 15-day
reporting deadline.