1. NCI-sponsored treatment trials: CTCAE v4 790 individual items Standard Approach to AE Monitoring CATEGORYEXAMPLEDATA SOURCE LaboratoryNeutropeniaLaboratory report ObservableRetinal tearClinical staff SymptomsNauseaClinical staff vs. patients

2. 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

3. 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

4. Scope 1.Produce a White Paper 2.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 platform 5.Conduct a “validation” study

5. NCI ADVISORS TECHTECH NETWORKNETWORK NCCCPNCCCP PRO-CTCAE Network MSKCC Coordinating Center Dana-Farber MD Anderson Mayo Duke Penn FDA Cooperative Groups Industry Christiana Hartford OLOL Spartanburg St. Joseph - Orange SemanticBits Perceptive Patient Advocates DCPDCCPSDCTD CBIIT

6. Progress to Date

7. Survey Highlights* 729 Stakeholders in Cooperative Groups QUESTIONAGREENEUTRALDISAGREE Systems to collect PROs in clinical trials should be developed89%5%6% In clinical trials, adverse events should be reported by patients88%8%4% POTENTIAL BARRIERSAGREENEUTRALDISAGREE Lack of computers69%15%16% Limited personnel57%18%25% SOLUTIONS TO OVERCOME BARRIERSAGREENEUTRALDISAGREE Funding (for personnel, dedicated space, training)79%13%8% Computers72%21%7% * Full survey results and White Paper available on project Wiki (https://wiki.nci.nih.gov/x/cKul)

8. 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

9. 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

10. Example: Mucositis CTCAE v4 TermGrade 1Grade 2Grade 3Grade 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 ItemsResponses What was the severity of your MOUTH OR THROAT SORES at their worst? None Mild Moderate Severe Very Severe How much did MOUTH OR THROAT SORES interfere with your usual activities? Not at all A little bit Somewhat Quite a bit Very much

11. 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

12. Software Platform Hosted on NCI servers

13. Form Builder

14. Integrated Study Calendar Planned future integration with Patient Study Calendar (PSC)

15. Simple Patient Interface Secondary conditional item

16. Reports

17. Real-Time Alerts

18. Software “Usability” Testing 3 cancer centers – 120 patients, 60 staff members

19. “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