WHO Drug Dictionary North American User Group Meeting Chicago (Deerfield), IL October 1, 2009

WHO Drug DictionaryNorth American

User Group MeetingChicago (Deerfield), IL

October 1, 2009

WHO Drug Dictionary User Group Meeting - Chicago/Deerfield, IL - Oct 1, 2009 Slide 2

ATC Coding Revisited

George B. Stoms

Vital Systems, Inc.

[email protected] (847) 458-2900 x222

mailto:[email protected]


Presentation Overview• WHO Drug Dictionary – quick review

• What should we capture in a Clinical Trial Database?

• Data Reduction / Presentation Techniques

• Analysis Techniques

• Change Management


Drug Record Number

Example: Advil (DRecNum=1092)

Ibuprofen Doloflam

Advil Haltran

Advil Liqui-gels Ibubufen

Actiprofen Ibuspray

Zofen Motrin

Nuprin 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 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


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


Medicinal Product IDThe MP ID: 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


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 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


Level 3 - Pharmacological GroupsATC3 Selected Examples

A02A 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**


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, formulations, etc.

• The drug code and MP ID are mapped to all ATCs in the dictionary hierarchy.

• ATC classifications can change over time with dictionary updates.







Do we see clearly what is really needed?

Melbourne's Digital Harbour Port 1010, Australian Customs Service (2006)


Clinical Trial Databases

• What should we capture in the CTDB?

• Options:– Verbatim Text + CRF fields – Drug Record Number– Drug Code (DRecNum + Seq1 + Seq2)– Medicinal Product ID– Generic (Preferred) Name / Decode– ATC code ???


CDISC: SDTM- SDTM 3.1 Implementation Guide, Section 4.1.3.5

…fill CMDECOD with the drug’s generic nameand fill CMCLAS with the drug class only if the dictionary used codes drugs to a single class. When using WHODRUG, for example, CMCLAS would not be filled since a drug may have multiple classes.

… No other intermediate levels or relationships should be stored in the dataset. By knowing the dictionary and version used, the reviewer will be able to obtain intermediate levels ... a drug’s ATC codes (as in WHO Drug).


CDISC: CDASHCDASH (Clinical Data Acquisition Standards Harmonization) Section 5.5

CMTRTMedication Name

CMINDCIndication for taking this medication

CMAENOIdentifier for the Adverse Event that is the

indication CMMHNO

Identifier for the Medical History that is the indication


Difficulties using ATC for consolidation

CRFCM WHO Drug

(version) CMDECOD

DrugCode

CMCLAS

ATC #2?

ATC #1?

ATC #3?


Instead: WHOdrug + MedDRA

CRFCM

CRFMH

CRFAE

MedDRA(version)

WHO Drug(version)

CMMHNO

CMAENO

CMDECOD

DrugCode

CMCLAS

PT

SOC

LLT

MeaningfulGrouping

Medications taken for…








Data Presentations: Listings

• Verbatim reported name

• “Preferred” name• Seq1 = 01• Seq2 = 001

• ATC Level(s) ?

• CRF fields (dose, route, dates, etc)


Listing 16.2.4.6: 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…)


Tables – if grouping by ATC…

Choose ATC level to group by:

• ATC1: Anatomical

• ATC2: Therapeutic

• Other


Tables – if grouping by ATC…Choose an ATC strategy

1. Select a “primary ATC” based on the indication for each individual report

2. Select a “primary ATC” once per drug within the study or program

3. Select a “primary ATC” once per drugwithin the company

4. “Let the dictionary do the walking…”


Table 14.1.4.4: 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…)


Challenges when using ATC for grouping

• 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• Prohibited Meds

• Eligibility Criteria

• Efficacy Suppression

• Efficacy Synergism

• Drug Sparing

• Comparative Effectiveness

• Safety Signals / Pharmacovigilance

• “Co-medication Profiles”

AE profiles within ATC

• Secondary Indications

• Residual Subject Recruitment








Change Management

• Highlighting the problem / “Feel the Pain”• Budget, Staffing, Timelines

• Identify stakeholders• CDM, Statistics, Safety, Regulatory, Licensing• Early preparation / meetings• Anticipate resistance / Bring solutions

• Pilot (concurrent study)

• Plan for implementation

• Feedback Loop ROI


ATC Coding Revisited

George B. Stoms

Vital Systems, Inc.

[email protected] (847) 458-2900 x222

mailto:[email protected]

WHO Drug DictionaryNorth American

User Group MeetingChicago (Deerfield), IL

October 1, 2009

Documents

WHO Drug Dictionary North American User Group Meeting Chicago (Deerfield), IL October 1, 2009