NCI-sponsored treatment trials: CTCAE v4• 790 individual items

Standard Approach to AE Monitoring

CATEGORY EXAMPLE DATA SOURCE

Laboratory Neutropenia Laboratory report

Observable Retinal tear Clinical staff

Symptoms Nausea Clinical staff vs. patients

Development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

•Contract initiated October 2008– Project Officer: Bryce Reeve– Awarded to MSKCC

NCI Contract HHSN261200800043C

Mission

Employ rigorous scientific methods to create a system for patient self-reporting of adverse symptoms in cancer trials, which is widely accepted and used; generates useful data for investigators, regulators, clinicians and patients; and is compatible with existing adverse event reporting software systems

Scope

1. Produce a White Paper2. Conduct stakeholder survey identifying

barriers and potential solutions for implementing patient AE reporting in cooperative group trials

3. Create patient adaptations of CTCAE symptom items (“PRO-CTCAE items”)

4. Build software platform5. Conduct a “validation” study

NCI

ADVISORS TECH

NETWORK

NCCCP

PRO-CTCAE Network

MSKCCCoordinating

Center

Dana-Farber

MD Anderson

Mayo

Duke

Penn

FDACooperative Groups Industry

Christiana

Hartford

OLOL

Spartanburg

St. Joseph - Orange

SemanticBits

PerceptivePatient

Advocates

DCPDCCPS DCTD CBIIT

Progress to Date

Survey Highlights*729 Stakeholders in Cooperative Groups

QUESTION AGREE NEUTRAL DISAGREESystems to collect PROs in clinical trials should be developed 89% 5% 6%

In clinical trials, adverse events should be reported by patients 88% 8% 4%

POTENTIAL BARRIERS AGREE NEUTRAL DISAGREELack of computers 69% 15% 16%

Limited personnel 57% 18% 25%

SOLUTIONS TO OVERCOME BARRIERS AGREE NEUTRAL DISAGREEFunding (for personnel, dedicated space, training) 79% 13% 8%

Computers 72% 21% 7%

* Full survey results and White Paper available on project Wiki (https://wiki.nci.nih.gov/x/cKul)

Item Development

• 78 CTCAE adverse event items identified as amendable to patient self-reporting

• To develop patient versions of these items, generic question structures were created based on existing questionnaires– Simple grading scales– Clear to patients from diverse backgrounds– Amenable to translation

Item Development

• Lay terms for each symptom identified– Removed medical jargon– Mapped to CTCAE v4 and MedDRA

• Identified which “attributes” are appropriate to characterize each symptom– Frequency, severity, interference– Up to 3 attribute items per symptom

Example: Mucositis

CTCAE v4 Term Grade 1 Grade 2 Grade 3 Grade 4

Mucositis oral Asymptomatic or mild symptoms; intervention not indicated

Moderate pain; not interfering with oral intake; modified diet indicated

Severe pain; interfering with oral intake

Life-threatening consequences; urgent intervention indicated

Two PRO-CTCAE v1 Items Responses

What was the severity of your MOUTH OR THROAT SORES at their worst?

NoneMildModerate SevereVery Severe

How much did MOUTH OR THROAT SORES interfere with your usual activities?

Not at allA little bitSomewhatQuite a bitVery much

Item Refinement

• Multicenter “cognitive interviewing” study to assure comprehension across diverse patient populations– N=150– Focus on lower education and regional diversity– Status: Final interviews being completed now

Software Platform

Hosted on NCI servers

Form Builder

Integrated Study Calendar

Planned future integration with Patient Study Calendar (PSC)

Simple Patient Interface

Secondary conditional

item

Reports

Real-Time Alerts

Software “Usability” Testing

• 3 cancer centers– 120 patients, 60 staff members

“Validation” Study

• Assessment of validity, reliability, sensitivity, and appropriate recall period for items– 900 patients • 5 cancer centers • 5 NCCCP sites

– Status: Accrual starting in May