2 ND U.S. WHO Drug Dictionary User Group Meeting

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.

[email protected] (847) 458-2900 x222

mailto:[email protected]


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


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


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

http://www.whocc.no/atcddd

http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_dpd_e.html

http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_dpd_e.html


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


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)


*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)


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


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


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**








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


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.


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


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


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


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.


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!


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!








Data Presentations: Listings• Verbatim reported name• “Preferred” name

• Seq1 = 01• Seq2 = 001

• ATC Level (possibly)


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…)


Data Presentations: Tables

Choose ATC level to group by:• ATC1: Anatomical• ATC2: Therapeutic• Other


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…)


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








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


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


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








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


ATC Codes: Strategies for Adding Value

Instead of Confusion

George B. StomsVital Systems, Inc.

[email protected] (847) 458-2900 x222

mailto:[email protected]

Boston, MAApril 20, 2006

2ND U.S. WHO Drug DictionaryUser Group Meeting

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