Drug safety in EMBASE

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Drug safety in EMBASE

• The indexing of safety aspects of therapeutic
  drugs and other chemical compounds in EMBASE

Irene Elsevier Elsevier Bibliographic Databases
April 2006
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EMBASE index basic elements

• Section assignment ( classification)
• Medical descriptors
• General descriptors
• Disease terms ( disease links)
• Check tags
• Drug descriptors ( drug links)
• Drug trade names/manufacturers
• CAS registry numbers
• Medical devices/trade names/manufacturers

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Today focus on

• Drug descriptors links adverse drug reaction
  (ADR) and drug toxicity (TOX) (introduced in
  1988)
• Medical descriptors Disease terms link side
  effect (SID)
• Section 38 Adverse reaction titles
• Check tags (human study types)

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Today focus on

• Drug descriptors links adverse drug reaction
  (ADR) and drug toxicity (TOX) (introduced in
  1988)
• Medical descriptors Disease terms link side
  effect (SID)
• Section 38 Adverse reaction titles
• Check tags (human study types)

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Real drugs versus other drugs

• Title ... Therapeutic drugs and other chemical
  compounds...
• EMBASE
• real drugs compounds, factors or preparations
  that are in clinical use or have a potential
  clinical use, as therapeutic, palliative,
  prophylactic or diagnostic agent
• other drug terms (e.g. solvents, environmental
  chemicals, starting compounds, etc.)
• Real drugs all drug links (including ADR and
  TOX)
• Other drugs only endogenous compound (END) and
  drug toxicity (TOX)

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ADR versus TOX

• ADR undesired side effects of drugs used at
  therapeutic dose ranges in humans
• TOX toxicity of drugs or other chemicals in
  animals (including LD50 tests), in animal or
  human cellstissues use for humans only at
  non-therapeutic dose ranges or for lasting damage
  at therapeutic dose range

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ADR or TOX?

• Real drug or other drug?
• Human subject or animal, animal/human
  tissuecells?
• Dose?
• Undesired effect transient or lasting?

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Today focus on

• Drug descriptors links adverse drug reaction
  (ADR) and drug toxicity (TOX) (introduced in
  1988)
• Medical descriptors Disease terms link side
  effect (SID)
• Section 38 Adverse reaction titles
• Check tags (human study types)

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Medical descriptors

• Disease terms ? disease links
• e.g. headache, rash
• Non-disease terms ? no disease links
• e.g. blood pressure, sedation

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Disease term SID

• Drug ADR Disease SID
• Drug TOX Disease (no SID)
• Exception when TOX is used for lasting damage

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SID special cases (1)

• ... Adverse effects found were headache, ...
• headache side effect
• ... Decreased liver function was shown by
  abnormal ALT values...
• liver dysfunction side effect
• alanine aminotransferase blood level
• ...Adverse effects were mild and consisted of
  irritability, ...
• irritability
• side effect side effect
• ...Drug A caused an elevated blood
  pressure... blood pressure
• side effect side effect

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SID special cases (2)

• ... Clonidine was well tolerated and no adverse
  effects were found ...
• absence of side effects side effect (2006)
• ... Clonidine was well tolerated and only mild
  adverse effects were found ...
• unspecified side effect side effect (2006)
• ...Patients were monitored for blood toxicity
  but none was found ...
• blood toxicity side effect
• ... Patients were monitored for blood toxicity
  but none was found, nor were any other side
  effects reported...
• blood toxicity side effect
• absence of side effects side effect (2006)

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SID special cases (3)

• Original versus non-original information
• Non-original publication (e.g. review) all
  adverse effects indexed in depth
• Original publication only original information
  is indexed general/background information is
  omitted
• Only findings are indexed, no speculations,
  general statements etc.
• e.g. ... We do not recommend drug A as it
  normally causes severe rash...
• rash is not indexed as a side effect

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Overindexing (1)

• Customer queries
• Adverse effects not mentioned in the abstract are
  indexed
• Negative finding of an adverse effect is still
  indexed
• The term side effect side effect makes no sense

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Overindexing (2)

• EMBASE
• not a diagnostic, therapeutic or safety handbook,
  but
• a tool to help you finding articles containing
  information you are looking for

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Today focus on

• Drug descriptors links adverse drug reaction
  (ADR) and drug toxicity (TOX) (introduced in
  1988)
• Medical descriptors Disease terms link side
  effect (SID)
• Section 38 Adverse reaction titles
• Check tags (human study types)

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Section 38 Adverse Reaction Titles

• Each article containing drug ADR assigned to
  and classified for Section 38
• 46 classifications, based on drug groups
  antidepressive drugs, antibiotics, antifungal
  drugs, hormones, antineoplastic drugs, etc.
• Abstracts of articles important for drug safety
  are published in abstract booklets, organized per
  drug category

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Today focus on

• Drug descriptors links adverse drug reaction
  (ADR) and drug toxicity (TOX) (introduced in
  1988)
• Medical descriptors Disease terms link side
  effect (SID)
• Section 38 Adverse reaction titles
• Check tags (human study types)

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Check tags (key descriptors)

• Medical descriptors
• scope notes (exact definitions)
• actively looked for
• highly consistent use
• Examples
• human/nonhuman, study types, age, gender, etc.
• Use limit your search to e.g. humans only,
  clinical trials

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Summary thus far

• Real drugs vs. other chemical compounds
• ADR vs. TOX
• Disease side effect
• Special cases
• Overindexing
• Section 38
• Check tags

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EMTREE (1)

• Disease terms facet C2-C7 (physical disease by
  ... ) and F3 (mental disease)
• Adverse drug reaction or side effect (explosion
  terms C6), e.g. drug fatality, drug eruption,
  injection site reaction, drug hypersensitivity,
  etc.

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EMTREE (2)

• Drug and disease links have scope notes, normal
  EMTREE terms not
• Indexers index what is in the article
• Consequence
• e.g. drug toxicity as drug link is clearly
  defined, liver toxicity as index term not ?
• liver toxicity can be indexed as side effect
  whereas it concerns an adverse drug reaction

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EMBASE compared to Medline (1)

• Medline drug qualifiers
• Adverse effects (AE) real drugs at normal dosage
  in therapeutic etc. use. Not limited to drugs
  also for complications arising from other medical
  procedures (e.g. surgery)
• Toxicity (TO) experimental studies on drugs
  chemicals in humans animals, including safety
  studies at various dose levels

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EMBASE compared to Medline (2)

• Medline disease qualifier
• Chemically induced (CI) used for biological
  phenomena, diseases, syndromes, etc. caused by
  endogenous or exogenous substances

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EMBASE compared to Medline (3)

• EMTREE richer in specific drug terms than MeSH
• EMBASE all specific drugs mentioned in article
  indexed in descriptor field
• Medline many specific drugs only indexed as
  substance name, not as MeSH heading
• EMBASE all drugs can have drug links
• Medline only drugs indexed as MeSH heading can
  have qualifiers, not the drugs terms indexed as
  substance name

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EMBASE compared to Medline (4)

• Example Adverse effects of clopidogrel (Dialog
  DataStar)
• EMBASE
• clopidogrel-ae.DE.
• Medline
• Clopidogrel heading mapped to
  ticlopidine/analogs and derivatives
• ticlopidine-aa.DE. AND ticlopidine-ae.DE. AND
  clopidogrel.NM.

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Why EMBASE if you have Medline?

• Journal coverage
• 3000 titles in both EMBASE and Medline
• 1800 titles EMBASE unique
• 1800 titles Medline unique
• EMBASE more comprehensive in drug indexing
• EMBASE.com EMBASE plus Medline, deduplicated

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EMBASE.com

• ca. 6600 journal titles
• 1800 EMBASE unique EMBASE indexing
• 3000 EMBASE/Medline overlap EMBASE indexing
• 1800 Medline unique Medline index converted to
  EMBASE indexing (MeSH vs. EMTREE mapping)

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EMBASE on Dialog DataStar

• clopidogrel-ae.de.
• clopidogrel-to.de.
• bleeding-si.de.
• bleeding-si.de.
• bleeding-si.mj.
• Floating subheadings
• si.fs.
• ae.fs.
• to.fs.

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EMBASE on OVID

• clopidogrel/ae
• clopidogrel/to
• bleeding/si
• exp bleeding/si
• exp bleeding/si
• Floating subheadings
• si.fs.
• ae.fs.
• to.fs.

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Use of EMBASE in practice (1)
Developing efficient search strategies to
identify reports of adverse effects in MEDLINE
and EMBASE Su Golder et al., Health Information
and Libraries Journal, 23 (2006) 3 12.
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Use of EMBASE in practice (2)

• Strategies (drug term text and index term of 7
  drugs)
• drug term AND exp liver disease/si
• exp vigabatrin/ae,to
• drug term AND (ae OR co).fs.
• drug term AND (free text search on safe OR side
  effect OR ..)
• drug term AND (exp adverse drug reaction OR exp
  side effect)
• drug term AND (case-control-study OR cohort-study
  OR clinical trial).de. OR DRUG INDEXING TERMS/ae
• Sensitivity precision of each strategy and
  combined strategies ? high sensitivity, low
  precision

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Use of EMBASE in practice (3)

• drug term AND exp liver disease/si
• Free text, no index term not relevant?
• exp vigabatrin/ae,to ? Toxicity dose?
• drug term AND (ae OR to OR co).fs. ??
  Complication NO
• drug term AND (free text search on safe OR side
  effect OR ..) ? Free text not linked to drug

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Use of EMBASE in practice (4)

• drug term AND (exp adverse drug reaction OR exp
  side effect) ? exp ADR and exp SID same results
  info not linked to drug term
• drug term AND (case-control-study OR cohort-study
  OR clinical trial).de. OR DRUG INDEXING TERMS/ae
  ? case control study and cohort analysis no check
  tags better drug link clinical trial DRUG
  INDEXING TERM/ct,ae

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Use of EMBASE in practice (5)

• Conclusion
• Higher precision
• use drug index terms
• use drug links ADR (and TOX)
• extra use drug link CTR

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Thank you very much for your attention!Questions?

• Contact
• Lisette Cleyndert (product manager EMBASE)
• l.cleyndert_at_elsevier.com
• Irene Elsevier
• i.elsevier_at_elsevier.com