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2 ND U.S. WHO Drug Dictionary User Group Meeting. Boston, MA April 20, 2006. ATC Codes: Strategies for Adding Value Instead of Confusion. George B. Stoms Vital Systems, Inc. George.Stoms@VTLsys.com (847) 458-2900 x222. Presentation Overview. ATC classifications – quick primer - PowerPoint PPT Presentation
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2ND U.S. WHO Drug DictionaryUser Group Meeting
Boston, MAApril 20, 2006
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 2
ATC Codes: Strategies for Adding Value
Instead of Confusion
George B. StomsVital Systems, Inc.
George.Stoms@VTLsys.com (847) 458-2900 x222
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 4
Presentation Overview• ATC classifications – quick primer
• What should we capture in a Clinical Trial Database?
• Data Reduction / Presentation Techniques
• Analysis Techniques
• Strategies for using the WHO Drug Dictionary to enhance value
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 5
ATC System - History• 1969: Olso symposium “The Consumption of Drugs”
– Drug Utilization Research Group (DURG) established.– European Pharmaceutical Market Research Association
(EPhMRA) classification system modified = ATC classification• 1975: Nordic Council on Medicines (NLN) published
ATC/DDD• 1981: WHO Regional Office for Europe recommends
ATC for drug utilization studies.• 1982: WHO Collaborating Centre for Drug Statistics
Methodology established• 1996: Oversight moved to WHO Headquarters in
Geneva for international integration
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 6
ATC System - Currently• Published annually by the
WHO Collaborating Centre for Drug Statistics Methodologyhttp://www.whocc.no/atcddd
• Becoming more commonly used in Canada, currently managed by Health Canadahttp://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_dpd_e.html
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 7
ATC classification• Anatomical
– The organ or system on which a drug acts• Therapeutic (& Pharmacological)
– Indication for typical use(s)– Pharmacological Form
• Chemical – Compound structure and properties
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 8
ATC: 5 Class LevelsATC Level ATC Code ATC Text
1 Anatomical Main Group
A Alimentary tract and metabolism
2 Therapeutic Subgroup
A10 Drugs used in diabetes
3 Pharmacological Subgroup
A10B Oral blood glucose lowering drugs
4 Chemical Subgroup A10B A Biguanides
5 Chemical Substance A10B A02 Metformin(DRecNo: 827)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 9
*New Herbal ATC: 5 Class LevelsATC Level ATC Code ATC Text
1 Anatomical Main Group
A Alimentary tract and metabolism
2 Therapeutic Subgroup
A06 Herbal laxatives
3 Pharmacological Subgroup
A06A Laxatives
4 Chemical Subgroup A06A B Contact laxatives
5 Chemical Substance A06A B5001 Aloe ferox extract(DRecNo: 16518)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 10
Level 1 - Anatomical Groups (14)A ALIMENTARY TRACT AND METABOLISM
B BLOOD AND BLOOD FORMING ORGANS
C CARDIOVASCULAR SYSTEM
D DERMATOLOGICALS
G GENITO URINARY SYSTEM AND SEX HORMONES
H SYSTEMIC HORMONAL PREPARATIONS, EXCL.
J ANTIINFECTIVES FOR SYSTEMIC USE
L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
M MUSCULO-SKELETAL SYSTEM
N NERVOUS SYSTEM
P ANTIPARASITIC PRODUCTS,INSECTICIDES AND REPELLENTS
R RESPIRATORY SYSTEM
S SENSORY ORGANS
V VARIOUS
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 11
Level 2 – Therapeutic GroupsATC2 Selected ExamplesA10 DRUGS USED IN DIABETES
B05 BLOOD SUBSTITUTES AND PERFUSION SOLUTIONS
C02 ANTIHYPERTENSIVES
C07 BETA BLOCKING AGENTS
H03 THYROID THERAPY
L04 IMMUNOSUPPRESSIVE AGENTS
M03 MUSCLE RELAXANTS
N01 ANESTHETICS
S01 OPHTHALMOLOGICALS
S02 OTOLOGICALS
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 12
Level 3 - Pharmacological GroupsATC3 Selected ExamplesA02A ANTACIDS
A06A LAXATIVES
A10A INSULINS AND ANALOGUES
N05A ANTIPSYCHOTICS
N06A ANTIDEPRESSANTS
* S01 = OPHTHALMOLOGICALS (eye) ** S02 = OTOLOGICALS (ear)
S01A ANTIINFECTIVES*
S01C ANTIINFLAMMATORY AGENTS & ANTIINFECTIVES IN COMB*
S02A ANTIINFECTIVES**
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 13
Presentation Overview• ATC classifications – quick primer
• What should we capture in a Clinical Trial Database?
• Data Reduction / Presentation Techniques
• Analysis Techniques
• Strategies for using the WHO Drug Dictionary to enhance value
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 14
Clinical Trial Databases• What should we capture in the CTDB?• Options:
– Drug Record Number– Drug Code (DRecNum + Seq1 + Seq2)– Medicinal Product ID– ATC code– Verbatim Text
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 15
Drug Record Number
Example: Advil (DRecNum=1092)Ibuprofen DoloflamAdvil HaltranAdvil Liqui-gels IbubufenActiprofen IbusprayZofen MotrinNuprin Boots fever and pain reliever
DRecNum allows for grouping of all “synonyms” for the drug, including various companies, brands, generics, countries, preparations, etc.
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 16
Drug Code: DRecNum + Seq1 + Seq2• Seq1: Salt or Ester (Herbal: Plant part) Seq2: Trade Name or Synonym (generics)
DRecNum Seq1 Seq2 Name000005 01 001 Ampicillin000005 01 002 Ampicin000005 01 003 Binotal000005 02 001 Ampicillin Sodium000005 02 002 Binotal000005 02 003 Polycillin-n000005 03 001 Ampicillin Trihydrate
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 17
Drug Code: DRecNum + Seq1 + Seq2 Seq1: Salt or Ester• Seq2: Trade Name or Synonym (generics)
DRecNum Seq1 Seq2 Name000005 01 001 Ampicillin000005 01 002 Ampicin000005 01 003 Binotal000005 02 001 Ampicillin Sodium000005 02 002 Binotal000005 02 003 Polycillin-n000005 03 001 Ampicillin Trihydrate
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 18
Medicinal Product IDThe MP ID is new to version “C” of the WHO dd.It is unique to each entry in the dictionary.
MP ID DRecNum Seq1 Seq2 Name000143 000005 01 001 Ampicillin083950 000005 01 002 Ampicin083951 000005 01 003 Binotal000225 000005 02 001 Ampicillin Sodium084022 000005 02 002 Binotal084023 000005 02 003 Polycillin-n000251 000005 03 001 Ampicillin Trihydrate
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 19
ATC codes: comments• Each product has at least one ATC code.
• The same product may have more than one ATC code, because it could be used for different indications.
• The drug code and MP ID are mapped to all ATCs in the dictionary hierarchy.
• ATC classifications can change over time with dictionary updates.
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 20
Verbatim Text• From source (CRF, progress notes, DCF)
– Drug name • as reported by investigator or subject• as clarified by data management (strength, etc.)
– Start/Stop dates and times– Dosage, Route– Indication
• Taken for an Adverse Event (AE / SAE / ADR)• Taken as a concomitant medication or supplement• Previously ongoing therapy
Caution:
Don’t lose sight of the purpose!
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 22
So, what should we capture in the CTDB?
• See discussion in “Guide”• Determine needs/goals of:
– Statisticians / Programmers– Medical Writers (for CSR)– Drug Safety Group / Surveillance Team– DSMB– Future Licensing Partners (ISS, ISE, etc.)
• Weigh benefits versus effort at data mgt level• Plan for versioning through regulatory life cycle• Capture the dictionary version in the CTDB!
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 23
Presentation Overview• ATC classifications – quick primer
• What should we capture in a Clinical Trial Database?
• Data Reduction / Presentation Techniques
• Analysis Techniques
• Strategies for using the WHO Drug Dictionary to enhance value
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 24
Data Presentations: Listings• Verbatim reported name• “Preferred” name
• Seq1 = 01• Seq2 = 001
• ATC Level (possibly)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 25
Listing 14B: Concomitant Medications During Treatment Period Subj Tx ----------------------- Medication Name -------------------- Start Stop For
ID cohort Age Sex Reported Preferred* date date AE
2103 5 mg 37 M XYLOCAIN LIDOCAINE 07 JUL 2004 07 JUL 2004 NO
ULTRACAIN ARTICAINE 07 JUL 2004 07 JUL 2004 NO
RIZATRIPTAN RIZATRIPTAN 13 JUL 2004 13 JUL 2004 YES
2104 5 mg 35 M CITALOPRAM 20MG CITALOPRAM 01 JAN 2004 ONGOING NO
BISOPROLOL 5MG O/D BISOPROLOL 01 JUN 2004 28 JUL 2004
TYLENOL EXTRA STR PARACETAMOL 06 JUL 2004 06 JUL 2004 YES
ACETAMINOPHEN PARACETAMOL 12 JUL 2004 12 JUL 2004 YES
PARACETAMOL 750 MG PARACETAMOL 12 JUL 2004 19 JUL 2004 YES
PARACETAMOL 1G PARACETAMOL 14 JUL 2004 14 JUL 2004 YES
2107 5 mg 46 M VALERON TILIDINE 01 MAR 2002 ONGOING NO
VALORON 150/12MG TILIDINE 01 MAR 2002 ONGOING
NEURONTIN GABAPENTIN 01 MAR 2002 ONGOING NO
METOCLOPRAMID METOCLOPRAMIDE 12 JUL 2004 ONGOING YES
NEURONTIN 600MG GABAPENTIN 01 MAR 2002 ONGOING
(continues…)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 26
Data Presentations: Tables
Choose ATC level to group by:• ATC1: Anatomical• ATC2: Therapeutic• Other
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 27
Table 13B: Concomitant Medications During Treatment Period by Treatment Cohort
Safety Evaluable Population 5 mg 10 mg 20 mg All
Drug Class (ATC) (N = 8) (N = 8) (N = 8) (N = 24)
Preferred Name n (%) n (%) n (%) n (%)
SUBJECTS WHO TOOK CONCOMITANT MEDS 4 (50.0) 4 (50.0) 5 (62.5) 13 (54.2)
ANALGESICS 4 (50.0) 2 (25.0) 1 (12.5) 7 (29.2)
ANTIGRIPPINE 0 (0.0) 1 (12.5) 0 (0.0) 1 (4.2)
DOLORIN 0 (0.0) 0 (0.0) 1 (12.5) 1 (4.2)
GABAPENTIN 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
PARACETAMOL 2 (25.0) 1 (12.5) 1 (12.5) 4 (16.7)
RIZATRIPTAN 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
SUMATRIPTAN 0 (0.0) 1 (12.5) 0 (0.0) 1 (4.2)
TILIDINE 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
ANESTHETICS 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
ARTICAINE 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
LIDOCAINE 1 (12.5) 0 (0.0) 0 (0.0) 1 (4.2)
(continues…)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 28
What about “double counting” ATCs?
• Since a drug may have more than one ATC, it will could show up in multiple sections of a table. The totals won’t sum correctly. Isn’t this a problem?
– Only if it is not understood and explained (footnote)
– The table’s purpose is to show how many subjects dosed with a med of a certain “type”.
– Even if the med was taken for a different reason (indication/ATC) is still belongs to each “type”.
– Only the totals across “types” become irrelevant
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 29
Presentation Overview• ATC classifications – quick primer
• What should we capture in a Clinical Trial Database?
• Data Reduction / Presentation Techniques
• Analysis Techniques
• Strategies for using the WHO Drug Dictionary to enhance value
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 30
Analysis Techniques• “Bottom Up”
• Prohibited Med; Over-represented in ATC
• “Top Down”• eg: ATC group; multi-ingredients; responder analysis
• “Co-medication Profiles”– AE profiles within ATC levels, or– ATC profiles within AE groupings
• “Guide” discussion and example
• Precautions• Demographics (age/sex), Disease/Treatment, Population
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 31
Analysis: ATC Co-Med ProfileATC ATC Text 4th 3rd 2nd A01 STOMATOLOGICAL PREPARATIONS 21
A01A STOMATOLOGICAL PREPARATIONS 21
A01AA CARIES PROPHYLACTIC AGENTS 0
A01AB ANTIINFECT. AND ANTISEPT. FOR LOCAL ORAL TREATMENT 3
A01AC CORTICOSTEROIDS FOR LOCAL ORAL TREATMENT 18
A01AD OTHER AGENTS FOR LOCAL ORAL TREATMENT 0
A02 DRUGS FOR ACID RELATED DISORDERS 101
A02A ANTACIDS 60
A02AA MAGNESIUM COMPOUNDS 21
A02AB ALUMINIUM COMPOUNDS 0
A02AC CALCIUM COMPOUNDS 3
A02AD COMB AND COMPL. OF ALUMIN., CALC. AND MAGNES. COMP 6
A02AF ANTACIDS WITH ANTIFLATULENTS 9
A02AG ANTACIDS WITH ANTISPASMODICS 12
A02AH ANTACIDS WITH SODIUM BICARBONATE 0
A02AX ANTACIDS, OTHER COMBINATIONS 9
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 32
Analysis: AE vs ATC Profile
ATC
Total co-med
profile (%)Reaction
(%)A01 4.2 5A01A 4.2 5A01AA 0 1A01AB 0.6 1A01AC 3.6 3A01AD 0 0A02 20 25A02A 12 13.6A02AA 4.2 3.8A02AB 0 0A02AC 0.6 0
ATC
Total co-med
profile (%)Reaction
(%)A02AD 1.2 0A02AF 1.8 2.4A02AG 2.4 5.4A02AH 0 0A02AX 1.8 2A02B 8 8.1A02BA 0 0A02BB 2.2 2.5A02BC 1.8 1.6A02BD 1.4 1A02BX 2.6 3
A02AG = ANTACIDS WITH ANTISPASMODICS
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 33
Presentation Overview• ATC classifications – quick primer
• What should we capture in a Clinical Trial Database?
• Data Reduction / Presentation Techniques
• Analysis Techniques
• Strategies for using the WHO Drug Dictionary to enhance value
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 34
WHOdd: Value Enhancement Strategies
• Co-medication Investigations– Safety Profiles (risks / protections)– Efficacy (synergism / suppression)– Economics (drug sparing)
• DSMB / Surveillance / Vigilance • Development Partnerships / Licenses • Secondary Indications• Residual Subject Recruitment
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006 Slide 36
ATC Codes: Strategies for Adding Value
Instead of Confusion
George B. StomsVital Systems, Inc.
George.Stoms@VTLsys.com (847) 458-2900 x222
Boston, MAApril 20, 2006
2ND U.S. WHO Drug DictionaryUser Group Meeting
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