caBIG Population Sciences SIG

1. caBIG Population Sciences SIG Ethan Basch, MD, MSc Memorial Sloan-Kettering Cancer Center PRO-CTCAE A system for patient self-reporting of adverse symptoms in oncology trials May 7, 2009

2. Overview • Background • Adverse Event reporting in oncology • PRO-CTCAE contract overview • System/functionality requirements • Demonstration

3. Adverse Event Monitoring Essential activity in clinical trials • To ensure patient safety • To provide data about drug effects • Trialists, regulators, clinicians, patients Core activity in routine cancer care • To guide therapy and supportive care

4. Standard Approach to AE Monitoring NCI-sponsored treatment trials: CTCAE v3 ~1000 individual items and patients

5. Patient Experiences Symptom Current Model for Adverse Symptom Reporting in Oncology Trials Clinician Interprets Symptom Clinician interviews patient at visit Chart Representation of Symptom Clinician writes in chart Data Manager Interpretation of Symptom Manual data entry Data manager abstracts chart Research Database

6. Patient Experiences Symptom Patient direct reporting of symptoms (1) Research Database

7. Patient Experiences Symptom Clinician Patient direct reporting of symptoms (2) Research Database

8. Increasing Regulatory Interest in PROs • FDA DEFNITION OF PATIENT-REPORTED OUTCOME (PRO): “Any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient’s response by a clinician or anyone else”

9. Rationales for Patient-Reported Outcomes Approach to Adverse Symptom Reporting • Improve efficiency of data collection • Eliminating data collection steps, reducing errors • Provide more direct account of patient experience • Eliminating filtering of patient reports by others • Engage patients as active participants in trials • Enable real-time data capture (ePROs) • Automated alerts, between-visit reporting • Provide subsequent patients with AE information reported by their peers, not clinical staff • Harmonize CTCAE with current standards for symptom measurement using PROs • Eg, FDA guidance • Trotti, Colevas, Setser, Basch: JCO, 2007

10. Prior Research Findings • Patients willing and able to report CTCAE symptoms via computer at clinic visits • Patient reporting is discrepant from clinician reporting • Patients generally self-report worse severity • Patient reports better reflect day-to-day experience • Clinicians will accept patient-reported AEs for treatment decisions and documentation

11. Currently no standard approach or technology platform for collecting patent-reported adverse symptoms in oncology trials

12. NCI Contract HHSN261200800043C • 2-Year Contract • Started on 10/1/08

13. Overall Mission of Project • Employ rigorous scientific methods to create a system for patient self-reporting of adverse symptoms in cancer trials (called the PRO-CTCAE), which is widely accepted and used; generates useful data for investigators, regulators, clinicians and patients; and is compatible with existing adverse event reporting systems

14. SOWMultiple Interrelated Tasks • Generate White Paper identifying barriers, ideal conditions, and solutions to implement PRO-CTCAE • Create PRO-CTCAE items • Build/evaluate electronic PRO-CTCAE platform • Evaluate measurement properties of items • Develop training materials • Design cooperative group study YEAR 1 YEAR 2

15. Task-Based Framework for Project

16. Expert Investigative Team and Subcontracts

17. Overview of Project • Brief review of relevant non-technology tasks of project

18. Progress to Date (1)Task 1: Create White Paper • Survey of 729 stakeholders *Not mutually exclusive

19. Progress to Date (2)Task 1: Create White Paper • Survey results

20. Progress to Date (3)Task 1: Create White Paper • Potential barriers to CTCAE PROs

21. Progress to Date (4)Task 1: Create White Paper • Solutions: funds and new computers

22. Progress to Date (5)Task 2: Develop Items • 77 CTCAE symptoms identified amendable to patient self-reporting • PRO-CTCAE items created • Different in format from CTCAE • Can be viewed on Wiki

23. PRO-CTCAE Item List

24. Progress to DateTask 2: Develop Items • For each symptom, evaluate multiple dimensions • Frequency, severity, interference with activities • Developed structure of questionnaire items

25. Generic Structure of Items FREQUENCY: How OFTEN did you have XXXX: • Never, Rarely, Occasionally, Frequently, Almost Constantly SEVERITY: At its worst, what was SEVERITY of your XXXX: • None / Mild / Moderate / Severe / Very severe INTERFERENCE: How much did XXXX INTERFERE with your (daily activities): • Not at all / A little bit / Somewhat / Quite a bit / Very much

26. Task 5: Platform Development • Envisioned a system to allow PIs to create forms for electronic administration of PRO-CTCAE items to patients at clinic visits

27. Platform Components/Functionality • Components • Form builder • Study calendar • Patient interface • Study-level reports • Patient-level reports • Automated alerts/notifications • Skip pattern rules • User-level access/permissions • Interoperability with caAERS

28. Publishing Tool and FormBuilder

29. Task 5: Approach • Subcontract to SemanticBits LLC • Weekly teleconferences since 10/08 • Committee: investigators, research study personnel, oncologists, patient representatives, psychometricians, FDA representatives, NCI representatives • DEMONSTRATION: • Ram Chilukuri, SemanticBits LLC