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Adverse Event Monitoring

using Embase

New ways to identify relationships

between drugs and associated

events

Dr. Ivan Krstić Product Development Manager Embase

September 23, 2015

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Webinar control panel:

• ‘Ask a question’ for

questions and comments

• Option for full screen view

• Q&A at the end

Need to know

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How Does Information in Literature Support Drug Safety?

• Identify/monitor adverse drug reactions

• Monitor and anticipate safety risks = better risk management

• Detect rare signals — identify possible new, undiscovered or

un(der)investigated adverse drug reactions

Articles are indexed for drug, disease, medical device and essential life

science concepts

Terms such as 'adverse drug reaction' and 'drug therapy', when indexed

with a drug term, give a precise idea of what the article covers

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Agenda

How to get Drug Profiles in Embase

• adverse drug reaction (safety profiles)

• drug-drug combination

• drug-drug comparison

• drug-drug interaction

• drug therapy

How to create a Pharmacovigilance search

using Emtree, mapping and subheadings

Indexing in

Embase

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Pharmacovigilance is defined as the science and activities concerned

with the

• detection (Embase),

• assessment,

• understanding and

• prevention of adverse reactions to medicines (i.e. adverse drug

reactions or ADRs).

The ultimate goal of Pharmacovigilance is to improve the safe and

rational use of medicines, thereby

• improving patient care and

• improving public health.

Pharmacovigilance

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EMA PV guideline recommends that

the marketing authorization holders:

• are expected to monitor international scientific and medical literature in

order to detect new safety signals or emerging safety issues reported for

medicinal products through a systematic literature review of widely used

reference databases (e.g. Medline, Embase) no less frequently than once a

week.

• Reports of suspected adverse reactions from the scientific and medical

literature, including relevant published abstracts from meetings and draft

manuscripts, should be reviewed and assessed by marketing authorisation

holders to identify and record ICSRs originating from spontaneous reports or

non-interventional post-authorisation studies.

Pharmacovigilance

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Embase is the most comprehensive biomedical database and it currently

covers 8,600 journals

We cover in-press articles from 2,200 journals and

conference proceedings from 5,600 conferences (since 2009)

Embase for Medical Literature Monitoring

Embase provides:

one stop source for PV searches,

compliance with EMA PV guideline for literature monitoring

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Indexing for Embase is a manual process performed by trained

indexers with a biomedical background

Indexing principles

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Indexers read and analyze the full text

of articles in order to identify relevant

concepts, and index them with the

most specific Emtree terms

Indexing principles

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Index terms are controlled by the

Emtree thesaurus,

resulting in

consistent coverage of concepts

that may be expressed in many

different ways in the literature.

Indexing controlled by Emtree

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Embase indexing

‘furadantine‘

136 results

‘furadantin’

614 results

‘ivadantin’

3 results

Article 1 Article 2 Article 3 Article 2

furadantine ivadantin

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Embase indexing – Emtree search

Query Results

'nitrofurantoin'/de 13,395

'furadantin'/de 13,395

'ivadantin'/de 13,395

Indexing facilitates consistent and comprehensive retrieval of information

from Embase, significantly enhancing search options – power of mapping.

Emtree

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How to Get Drug Profiles in Embase

Embase contains information on:

• adverse drug reaction

• drug combination

• drug comparison

• drug interaction

• drug therapy

that is easily accessible and searchable.

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Subheadings

Subheadings are Emtree terms that are also used as concept

qualifiers for drugs, diseases and devices, providing a very precise

idea of what an article covers.

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Subheadings

Term Key Subheading

drug 'adverse drug reaction'

drug 'drug combination'

drug 'drug comparison'

drug 'drug interaction'

drug 'drug therapy'

device 'adverse device effect'

device 'device comparison'

disease 'drug therapy'

disease 'side effect'

Subheadings = concept qualifiers for drugs (17), diseases (14) and

devices (4)

Nine subheadings are denoted as key subheadings.

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Triple linking

Term Key Subheading Linked term Triple indexing example

drug 'adverse drug reaction' 'disease' 'vioxx'/'adverse drug reaction'/'hypertension'

drug 'drug combination' 'drug' 'vioxx'/'drug combination'/'ibuprofen'

drug 'drug comparison' 'drug' 'vioxx'/'drug comparison'/'naproxen'

drug 'drug interaction' 'drug' 'vioxx'/'drug interaction'/'calcitriol'

drug 'drug therapy' 'disease' 'vioxx'/'drug therapy'/'osteoarthritis'

device 'adverse device effect' 'disease' 'stent'/'adverse device effect'/'stenosis'

device 'device comparison' 'device' 'stent'/'device comparison'/'balloon'

disease 'drug therapy' 'drug' 'osteoarthritis'/'drug therapy'/‘vioxx'

disease 'side effect' 'drug' 'hypertension'/'side effect'/‘vioxx'

Since 2007, key subheadings have included triple linking — three

level indexing — which includes information on a term, key

subheading and linked term.

Triple indexing has started in 2007 for the drug triples (drug therapy

from 2009). Devices began in 2014.

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How is the Information in Triple Links Shown?

Triple links — relationships between drugs, diseases or devices and

their associated events — can be seen in individual results and can be

used to search or get an overview of all linked terms (for example all

adverse events) reported for a specific drug (since July 2015)

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Triple linking Information

For each drug, device and

disease key subheadings

and linked terms can be

visualized and filtered

1. New filter options

2. New search query language

• 'vioxx'/'adverse drug reaction'/'hypertension','stroke','nausea','vomiting'

• 'vioxx'/dd_ae/'hypertension','stroke''nausea','vomiting'

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How to use New Filter Options

1. Expand a filter. Note the new Details option

Drugs, Diseases and Device results filters are labelled Beta to signify that this

will be assessed as a Beta feature for 6-9 months. It is hyperlinked to help.

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How to use New Filter Options

2. Note the Key subheadings information that appears

• Check the box beside a key subheading to select all (e.g.) adverse

drug reactions for a drug

• Click on a key subheading text to display specific linked terms

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How to use New Filter Options

3. Check the box beside or click on linked term(s) to select them

When one or more linked terms are selected the key subheading (e.g.

adverse drug reaction) gets semi-checked and ‘Details’ button gets

highlighted

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Users can select multiple linked-terms (adverse drug reactions) for one key

subheading.

Application interprets this as:

'rofecoxib'/'adverse drug reaction'/'hypertension','stroke','thrombosis'

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Application interprets that as combination of two searches connected with OR

operator:

'rofecoxib'/'adverse drug reaction'/'hypertension','stroke' OR 'rofecoxib'/'drug

therapy'/'colorectal cancer','osteoarthritis'

Users can select multiple key subheading and multiple linked-terms (adverse

drug reactions, therapies) for one drug.

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Application interprets this as combination of multiple searches connected with

OR operator:

'rofecoxib'/'adverse drug reaction'/'hypertension','stroke' OR 'naproxen'/'adverse

drug reaction'/'heart infarction','hepatitis'

Users can select multiple drugs and multiple key subheading and multiple

linked-terms (adverse drug reactions, therapies).

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Apply Multiple Filters at Once

• All selected filter options

will be applied when

is clicked

• indicates all linked terms

are selected

• indicates one or more

linked terms are selected

• Linked terms can be

exported to identify (e.g.)

all ADRs for a specific drug

• Multiple options within a

filter cluster are searched

using ‘OR’. Between

different filters clusters,

‘AND’ is applied

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Linked terms are

displayed and

sortable by

# records:

descending and

ascending.

Allows to:

Detect rare signals —

identify possible new,

undiscovered or

un(der)investigated

adverse drug reactions

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Drug Profiles

Drug details can be exported provided

the information on:

• adverse drug reaction

• drug combination

• drug comparison

• drug interaction

• drug therapy

Such drug profiles can be easily

filtered by publication year.

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New Search Query Language

With a single search string, users will be able to specify multiple search

parameters:

• Drug term (or device or disease)

• Key Subheading(s) (e.g., adverse drug reaction, drug therapy)

• Linked terms (e.g., hypertension, stroke, nausea, vomiting, etc.)

Multiple subheadings or multiple linked terms can be listed in a single

search string separated by a comma (no space after the comma).

e.g. 'vioxx'/’adverse drug reaction’/'hypertension','stroke''nausea','vomiting'

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New Search Query Language

Newly-introduced search syntax (e.g., ‘adverse drug reaction’) can be

used, in addition to the existing query codes (e.g., dd_ae).

• Autocomplete enables users to quickly identify the correct search

syntax to use.

• The same principal works for drugs, diseases and devices

Some examples:

• Drug/Subheading/Linked term(s). 'vioxx'/'adverse drug reaction'/'hypertension','stroke','nausea','vomiting'

• Drug/Subheading (as code)/Linked term(s). 'vioxx'/dd_ae/'hypertension','stroke''nausea','vomiting'

• Drug/Multiple subheadings. 'vioxx'/'adverse drug reaction','drug therapy'

More info: http://help.elsevier.com/app/answers/detail/a_id/6197/p/9754/c/9863,10681

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Drug subheadings

'ivadantin'/de/'drug toxicity','adverse drug reaction'

Pharmacovigilance search using Emtree (mapping & subheadings)

mapping

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Drug subheadings and generic terms for adverse effects

'ivadantin'/de/'drug toxicity','adverse drug reaction‘ OR

(‘ivadantin'/de AND ('adverse drug reaction'/exp OR 'side effect'/exp OR 'drug

safety'/exp OR 'drug toxicity'/exp OR safety OR complication* OR toxicity OR adrs

OR (adverse OR side OR undesirable) NEXT/2 (effect* OR reaction* OR event* OR

outcome*) OR 'toxicity and intoxication'/exp OR 'fertility'/exp OR 'toxicology'/exp OR

'toxicity testing'/exp OR 'carcinogenesis'/exp OR toxicity OR 'drug

carcinogenicity'/exp OR carcinogenicit* OR 'drug hypersensitivity'/exp OR

hypersensitivit* OR 'mutagenicity'/exp OR 'morbidity'/exp OR 'mortality'/exp))

Pharmacovigilance search using Emtree

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'ivadantin'/'drug toxicity','adverse drug reaction' OR

(‘ivadantin'/de AND ('adverse drug reaction'/exp OR 'side effect'/exp OR 'drug safety'/exp OR 'drug

toxicity'/exp OR safety OR complication* OR toxicity OR adrs OR (adverse OR side OR undesirable)

NEXT/2 (effect* OR reaction* OR event* OR outcome*) OR 'toxicity and intoxication'/exp OR 'fertility'/exp

OR 'toxicology'/exp OR 'toxicity testing'/exp OR 'carcinogenesis'/exp OR 'drug carcinogenicity'/exp OR

carcinogenicit* OR 'drug hypersensitivity'/exp OR hypersensitivit* OR 'mutagenicity'/exp OR 'morbidity'/exp

OR 'mortality'/exp OR

'reproduction'/exp OR 'reproduction' OR 'pregnancy disorder'/exp OR 'lactation'/exp OR 'lactation' OR

'pregnancy disorders of endocrine origin'/exp OR 'breast feeding'/exp OR 'breast milk'/exp OR 'breast'

NEXT/2 ('feeding' OR 'milk') OR 'prenatal disorder'/exp OR 'embryonic and fetal functions'/exp OR

'parameters concerning the fetus, newborn and pregnancy'/exp OR 'pregnancy'/exp OR 'pregnancy' OR

'teratology'/exp OR 'prenatal drug exposure'/exp OR 'prenatal exposure'/exp OR 'prenatal' OR embryo* OR

'newborn' OR 'fetus' OR 'perinatal' OR 'perinatal drug exposure'/exp OR 'maternal exposure'/exp OR

'maternal exposure' OR 'elderly'/exp OR 'elderly' OR 'aged' OR 'addiction'/exp OR 'addiction' OR 'drug

withdrawal'/exp OR 'drug withdrawal' OR 'treatment failure'/exp OR 'drug treatment failure'/exp OR

'treatment failure' OR 'drug resistance'/exp OR 'drug resistance' OR 'drug tolerance'/exp OR 'drug tolerance'

OR 'drug induced' OR 'drug induced disease'/exp OR 'drug abuse'/exp OR 'substance abuse'/exp OR 'drug

misuse'/exp OR 'drug overdose'/exp OR abuse OR misuse OR overdose OR 'medication error'/exp OR

'medication error' OR 'off label drug use'/exp OR 'occupational exposure'/exp OR 'occupational exposure'

OR 'overdose' OR 'off label use' OR 'off label drug use' OR 'drug efficacy'/exp OR 'drug efficacy' OR

'death'/exp OR 'death' OR 'drug interaction'/exp OR 'drug interaction' OR 'intoxication' OR 'drug

contraindication'/exp OR 'drug contraindication' OR 'congenital disorder'/exp OR 'congenital disorder' OR

'case report'/exp OR 'case report' OR 'treatment contraindication'/exp OR 'treatment contraindication'))

Drug subheadings and generic adverse effects terms and special situations

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Set up an Alert

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Where to Find more Information

Help file (support hub):

• News item for July 31st release

• What are triple links (triple indexing)?

• How do I apply filters to identify drug, disease and device

information found in Triple Links?

• How do I write search queries to identify drug, disease and device

information found in 'Triple Links'?

• What are subheadings in Embase?

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Thank you!

• Q&A will be sent to you by email. For more information and

questions please contact your regional office

• Our next Embase webinar is on October 28th and will focus on

Embase indexing.

• Please fill out the survey that appears on your screen after leaving

the webinar.

Any questions?

Thank you!

Any questions?

Ivan Krstic, PhD

Product Development Manager EMBASE

i.krstic@elsevier.com