Alice Chen, MD, FACP Investigational Drug Branch, CTEP, DCTDNational Cancer Institute

CTCAE Version 4

CTCAE v3.0 Issues & MedDRA

CTCAE v3.0 Terms– Multiple concepts– One/many element of Grade description is

critical AE concept– Not all MedDRA terms

• 72% CTCAE = mapped to a single MedDRA term/code

• 28% CTCAE = CTEP-only code (with meaning to no one outside CTEP)

CTCAE Revision Status

Phase 1: – Represent terms as single concept – MedDRA terms– Address CTCAE v3.0 Terms only

Phase 2: • Address Grading (severity) scales• Add new terms (Working with MedDRA)

– CTEP Help Desk Requests; Others– Definitions for terms– caBIG VCDE conformity

Public Review: Phase 3:

– Working Group; Steering Committee; Advisory Board Review

Final: May 27 - Publication

General Characteristics of Grading Scale

• Grade 0 No AE or within normal limits. • Grade 1 Mild AE (minor; no specific medical

intervention; asymptomatic laboratory findings only, radiographic findings only; marginal clinical relevance)

• Grade 2 Moderate AE (minimal intervention; local

intervention; noninvasive intervention [packing, cautery] indicated); AE limiting instrumental ADL (e.g., shopping, laundry, transportation, ability to conduct finances).

General Characteristics of Grading Scale

• Severe AE (medically significant but not life-threatening). AEs• in which initial inpatient hospitalization or prolongation of existing

hospitalization is indicated; • that are important medical events that may not be immediately life-

threatening; • that do not result in death. • that do not result in hospitalization but may jeopardize the patient or may

require intervention either to prevent hospitalization or to prevent the AE from becoming life-threatening or potentially resulting in death.

• that are disabling (result in persistent or significant disability or incapacity). • Limit performance of basic activities of self care (getting in and out of

bed, dressing, eating, getting around inside, bathing, or using the toilet).

Grade 3

General Characteristics of Grading Scale

Grade 4 Life-threatening AE (the patient is at risk of death at the time of the event if immediate intervention is not undertaken)

Grade 5 Fatal Adverse Event

AE Terms: Draft 1

• Single concept MedDRA terms that are common in oncology practice

• ~66% of CTCAE v3.0 terms appear in Draft 1 exactly as mapped to MedDRA

• ~33% of CTCAE v3.0 terms have been deleted– Infection with/without/with unknown ANC + site-

specific infections• ~70 New terms• Remainder = Edits

INFECTION CATEGORY

• Infection with unknown ANC – Conjunctiva– MedDRA: Conjunctivitis infective -10010742

• Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) – Conjunctiva

• Infection with normal ANC or Grade 1 or 2 neutrophils - Conjunctiva

CTEP - only

codes

Comparison CTCAE v3.0 to Draft 1

CTCAE v3.0 Draft 1

Broad Grouping of Terms CATEGORY SOC

AE Terms Multiple concepts; non-MedDRA

Single concept MedDRA

Number of Terms 1,059 ~800

Grading Scale 0 – 5 0 - 5

Other Components

Short Name Yes No

Also Consider Yes TBD

Navigation Note Yes TBD

Representation as a Formal Vocabulary

No Yes

Definitions No Yes

Formal Ongoing Governance

No Yes

Summary CTCAE v4.0

• All AEs are MedDRA LLT terms that are common in oncology practice

• AE Terms will be organized by Primary SOC• Grading scales • CTCAE v4.0 DRAFT posted for public review /

comment March 23 – April 10, 2009• Listed on the CTEP website• CTCAE v4.0 publication May 27, 2009• Long term Governance being established