Transcript WHOdd

2ND 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.
[email protected]
(847) 458-2900 x222
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 2
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 4
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 5
ATC System - Currently
• Published annually by the
WHO Collaborating Centre for Drug
Statistics Methodology
http://www.whocc.no/atcddd
• Becoming more commonly used in
Canada, currently managed by Health
Canada
http://www.hc-sc.gc.ca/hpfb-dgpsa/tpddpt/index_drugs_dpd_e.html
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 6
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 7
ATC: 5 Class Levels
ATC 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 8
*New Herbal ATC: 5 Class Levels
ATC 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 9
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 10
Level 2 – Therapeutic Groups
ATC2
Selected Examples
A10
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 11
Level 3 - Pharmacological Groups
ATC3
Selected Examples
A02A
ANTACIDS
A06A
LAXATIVES
A10A
INSULINS AND ANALOGUES
N05A ANTIPSYCHOTICS
N06A ANTIDEPRESSANTS
S01A
ANTIINFECTIVES*
S01C ANTIINFLAMMATORY AGENTS & ANTIINFECTIVES IN COMB*
S02A
ANTIINFECTIVES**
* S01 = OPHTHALMOLOGICALS (eye)
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
** S02 = OTOLOGICALS (ear)
Slide 12
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 13
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 14
Drug Record Number
DRecNum allows for grouping of all “synonyms”
for the drug, including various companies,
brands, generics, countries, preparations, etc.
Example: Advil (DRecNum=1092)
Ibuprofen
Doloflam
Advil
Haltran
Advil Liqui-gels
Ibubufen
Actiprofen
Ibuspray
Zofen
Motrin
Nuprin
Boots fever and pain reliever
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 15
Drug Code: DRecNum + Seq1 + Seq2
• Seq1: Salt or Ester (Herbal: Plant part)
Seq2: Trade Name or Synonym (generics)
DRecNum Seq1 Seq2 Name
000005
01
001
Ampicillin
000005
01
002
Ampicin
000005
01
003
Binotal
000005
02
001
Ampicillin Sodium
000005
02
002
Binotal
000005
02
003
Polycillin-n
000005
03
001
Ampicillin Trihydrate
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
• Seq2: Trade Name or Synonym (generics)
DRecNum Seq1 Seq2 Name
000005
01
001
Ampicillin
000005
01
002
Ampicin
000005
01
003
Binotal
000005
02
001
Ampicillin Sodium
000005
02
002
Binotal
000005
02
003
Polycillin-n
000005
03
001
Ampicillin Trihydrate
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 17
Medicinal Product ID
The 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 Name
000143
000005
01
001
Ampicillin
083950
000005
01
002
Ampicin
083951
000005
01
003
Binotal
000225
000005
02
001
Ampicillin Sodium
084022
000005
02
002
Binotal
084023
000005
02
003
Polycillin-n
000251
000005
03
001
Ampicillin Trihydrate
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 18
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 19
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
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 20
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!
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 22
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 23
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 24
Listing 14B: Concomitant Medications During Treatment Period
Subj
Tx
ID
cohort
Age
Sex
2103
5 mg
37
M
2104
2107
5 mg
5 mg
----------------------- Medication Name --------------------
35
46
M
M
Start
Stop
For
date
date
AE
Reported
Preferred*
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
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
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 25
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 26
Table 13B: Concomitant Medications During Treatment Period by Treatment Cohort
Safety Evaluable Population
Drug Class (ATC)
5 mg
10 mg
20 mg
All
(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 27
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 28
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 29
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 30
Analysis: ATC Co-Med Profile
ATC
A01
A01A
A01AA
A01AB
A01AC
A01AD
A02
A02A
A02AA
A02AB
A02AC
A02AD
A02AF
A02AG
A02AH
ATC Text
STOMATOLOGICAL PREPARATIONS
STOMATOLOGICAL PREPARATIONS
CARIES PROPHYLACTIC AGENTS
ANTIINFECT. AND ANTISEPT. FOR LOCAL ORAL TREATMENT
CORTICOSTEROIDS FOR LOCAL ORAL TREATMENT
OTHER AGENTS FOR LOCAL ORAL TREATMENT
DRUGS FOR ACID RELATED DISORDERS
ANTACIDS
MAGNESIUM COMPOUNDS
ALUMINIUM COMPOUNDS
CALCIUM COMPOUNDS
COMB AND COMPL. OF ALUMIN., CALC. AND MAGNES. COMP
ANTACIDS WITH ANTIFLATULENTS
ANTACIDS WITH ANTISPASMODICS
ANTACIDS WITH SODIUM BICARBONATE
A02AX
ANTACIDS, OTHER COMBINATIONS
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
4th
3rd
2nd
21
21
0
3
18
0
101
60
21
0
3
6
9
12
0
9
Slide 31
Analysis: AE vs ATC Profile
ATC
Total
co-med
profile (%)
Total
co-med
profile (%)
Reaction
(%)
Reaction
(%)
A01
4.2
5
A02AD
1.2
0
A01A
4.2
5
A02AF
1.8
2.4
A01AA
0
1
A02AG
2.4
5.4
A01AB
0.6
1
A02AH
0
0
A01AC
3.6
3
A02AX
1.8
2
A01AD
0
0
A02B
8
8.1
A02
20
25
A02BA
0
0
A02A
12
13.6
A02BB
2.2
2.5
A02AA
4.2
3.8
A02BC
1.8
1.6
A02AB
0
0
A02BD
1.4
1
A02AC
0.6
0
A02BX
2.6
3
ATC
A02AG = ANTACIDS WITH ANTISPASMODICS
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 32
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 33
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 34
ATC Codes:
Strategies for Adding Value
Instead of Confusion
George B. Stoms
Vital Systems, Inc.
[email protected]
(847) 458-2900 x222
2nd U.S. WHO Drug Dictionary User Group Meeting - Boston, MA - Apr 20, 2006
Slide 36
2ND U.S. WHO Drug Dictionary
User Group Meeting
Boston, MA
April 20, 2006