1. Alice Chen, MD, FACP Investigational Drug Branch, CTEP, DCTD National Cancer Institute CTCAE Version 4

2. 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)

3. 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

4. General Characteristics of Grading Scale Grade 0No AE or within normal limits. Grade 1Mild AE (minor; no specific medical intervention; asymptomatic laboratory findings only, radiographic findings only; marginal clinical relevance) Grade 2Moderate AE (minimal intervention; local intervention; noninvasive intervention [packing, cautery] indicated); AE limiting instrumental ADL (e.g., shopping, laundry, transportation, ability to conduct finances).

5. 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

6. General Characteristics of Grading Scale Grade 4Life-threatening AE (the patient is at risk of death at the time of the event if immediate intervention is not undertaken) Grade 5Fatal Adverse Event

7. 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

8. 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

9. Comparison CTCAE v3.0 to Draft 1 CTCAE v3.0Draft 1 Broad Grouping of TermsCATEGORYSOC AE TermsMultiple concepts; non- MedDRA Single concept MedDRA Number of Terms1,059~800 Grading Scale0 – 50 - 5 Other Components Short NameYesNo Also ConsiderYesTBD Navigation NoteYesTBD Representation as a Formal Vocabulary NoYes DefinitionsNoYes Formal Ongoing Governance NoYes

10. 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