CTCAE v4.

0
Common Terminology Criteria for Adverse Events

Presented by:
Vicki Duvall and Michele Copersino
May 28, 2010

Objectives

• Summarize use of CTCAE

• Describe rationale for CTCAE v3.0 revision

• Define MedDRA

• Identify status quo and minor changes CTCAE v3.0 to

CTCAE v4.0

• Review resources available for CTCAE v4.0 materials

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CTCAE Definition, Rationale, Evolution
• List of Adverse Event (AE) terms commonly encountered
in oncology
• Each AE is accompanied by a grading (severity) scale

• CTCAE is the agreed upon terminology for the

designation, reporting and grading of AEs

• Evolution
• 1984 CTC v1.0 49 AE terms
• 1998 CTC v2.0 300 AE terms *
• 2003 CTCAE v3.0 1059 AE terms*
• 2009 CTCAE v4.0 790 AE Terms (MedDRA LLTs)
*Mapped to MedDRA (Medical Dictionary for Regulatory Activities) terminology

Impetus for 2009 Revision

• 2006 MedDRA Meeting
• AE Reporting: MedDRA vs. CTCAE

• 2007 NCI/CTEP, FDA discussions

• AE data analysis MedDRA vs. CTCAE

• 2008 Evaluation of CTCAE v3.0 as a standard terminology

• Non-standardized AE terminology
• Non-machine interpretable
• No definitions

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 Relax!
v4.0 is fundamentally unchanged

CTCAE pdf

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CTCAE v4.0 What’s the Same?
Components

v3.0

v4.0

Unchanged

CTCAE v4.0
Remains a list of AE terms
associated with a 5-point
Grading (severity) scale

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CTCAE v4.0 What’s New?
Use of MedDRA
• Introduction to MedDRA
• Clinically validated international medical terminology used by
regulatory authorities and the biopharmaceutical industry
• multiple languages
• Hierarchical (terms arranged form highest to lowest level)
• System Organ Class (SOC) 26 CTCAE v4.0
• High Level Group Term (HLGT)
• High Level Term (HLT)
• Preferred Term (PT)
• Lowest Level Term (LLT) > 66,000 CTCAE v4.0 (small subset of total)

What’s New?
v3.0 Category is v4.0 SOC (System Organ Class)
CTCAE v3.0 CATEGORY CTCAE v4.0 SOC
Count 28 Count 26

AUDITORY/EAR Ear and labyrinth disorders

DERMATOLOGY/SKIN Skin and subcutaneous tissue
disorders
ENDOCRINE Endocrine disorders
INFECTION Infections and infestations
PULMONARY/UPPER RESPIRATORY Respiratory and thoracic disorders
VASCULAR Vascular disorders
What’s New?
v3.0 Category is v4.0 SOC (System Organ Class)
CTCAE v3.0 CATEGORY CTCAE v4.0 SOC

CARDIAC ARRYTHMIA
Cardiac disorders

CARDIAC GENERAL
Nervous system disorders
NEUROLOGY
Psychiatric disorders

What’s New?
Some v3.0 Categories deleted in v4.0
CTCAE v3.0 CTCAE v4.0 SOC
CATEGORY
DEATH General disorders and administration site conditions
(Death NOS; Death neonatal; Sudden death NOS)

Pregnancy, puerperium and perinatal conditions

(Fetal death)
GROWTH & Musculoskeletal and connective tissue disorders
DEVELOPMENT
PAIN System – specific SOC (Ear and labryinth disorders;
Gastrointestinal disorders; Renal and urinary disorders;
HEMORRHAGE
etc. )
SYNDROMES Blood and lymphatic system disorders; Cardiac
disorders; Immune system disorders; Metabolism and
nutrition disorders; Neoplasms benign, malignant and
unspecified (incl cysts and polyps); etc.
What’s New?
Example of v4.0 use of MedDRA SOC
- SOC General disorders and administration site conditions
- HLGT General system disorders NEC
- HLT Asthenic Conditions
- PT Fatigue
- LLT Fatigue (CTCAE v4 term)
Chronic fatigue
Exhaustion
Fatigue ability
Fatigue extreme
Tired all the time
Tiredness
Tired out
+ 13 more LLTs (related terms)

CTCAE v4.0 SOC replaces CATEGORY

v3.0

v4.0

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What’s New?
v4.0 AE terms are MedDRA LLTs

v3.0

CTCAE v3.0 Multiple concepts were mapped to MedDRA: Fatigue 10016256

v4.0

CTCAE v4.0 AE terms are single concept MedDRA terms

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What’s New?
v4.0 AE terms are MedDRA LLTs
CTCAE v3.0 CTCAE v3.0 AE CTCAE CTCAE v4.0 AE
CATEGORY Term v4.0 SOC Term
PULMONARY/ Voice changes/ Respiratory, Voice alteration
UPPER RESPIRATORY dysarthria (e.g., thoracic and
hoarseness, loss or mediastinal
alteration in voice, disorders
laryngitis)
Hoarseness
Laryngeal inflammation
Nervous Aphonia
system
disorders
Dysarthria
Infections Laryngitis
and
infestations
What’s New?
v3.0 Infection + ANC combinations Deleted

What’s New?
Infection term - Select Deleted
What’s New?
Short Name Deleted

v3.0

v4.0

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What’s New?
v3.0 Supra-ordinate term – Select Deleted

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v4.0

v4.0

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Summary
Comparison CTCAE v3.0 to v4.0

CTCAE v3.0 CTCAE v4.0

CATEGORY (28) SOC (26)
Combination AE terms Single concept MedDRA LLTs
Short Names None
Supra-ordinate terms None
1,059 AE terms (28 = Other, specify) 790 AE terms (26 = Other, specify)
Summary
CTCAE v4.0 AE Terms
• Each AE term is
• A MedDRA LLT
• Listed within the LLT Primary SOC
• Accompanied by a definition
• Associated with ‘related terms’

CTCAE v4.0 Documentation

• Publications
• Limited number of handbooks
• CTEP website
• CTCAE v4.0 ‘pdf version’
• CTCAE mapping v3.0 to v4.0
• BiomedGT Wiki
• CTCAE v4.0 ‘interactive version’
CTCAE on the CTEP website

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Multiple formats of CTCAE

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CTCAE v4.0 on BiomedGT Wiki

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CTCAE Terms Organized by SOC

CTCAE SOCs
Example: Click on
Blood and lymphatic
system disorders

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All AEs
within SOC
displayed

Example: Click on Febrile Neutropenia

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Options regarding Febrile Neutropenia

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Example: Click on Definition

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Example: Click on Related Terms

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 Example: Click on Factbox

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Click on FAQ to see if question or issues

issue has
beenbeen
has previously
previously
addressed
addressed

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For More Information
• CTEP
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_v40

• BiomedGT Wiki
http://biomegt.nci.nih.gov/wiki/index.php/CTCAE4

Special Thanks
• Ann Setser, CBIIT, NCI