Ethan Basch , M.D. Memorial Sloan-Kettering Cancer Center PROJECT OVERVIEW May 24, 2010

1. PRO-CTCAE Face-To-Face Meeting #2Advancing the Science of Adverse Symptom Monitoring in Cancer Treatment Trials Ethan Basch, M.D. Memorial Sloan-Kettering Cancer Center PROJECT OVERVIEW May 24, 2010 National Cancer Institute

2. Outline • Introductions • Project background • Progress to date • Goals of the day

3. Introductions

4. Background “A PRO is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else” http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdfz

5. Background • PROs are standard in multiple settings • Symptom efficacy evaluation in clinical trials • HRQL • Patient satisfaction • Patient preferences • But not standard for adverse symptom reporting

6. Patient Experiences Symptom Current Model for Adverse Symptom Reporting in Cancer Trials Clinician Interprets Symptom Chart Representation of Symptom Data Manager Interpretation of Symptom Research Database

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

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

9. Patient Experiences Symptom Clinician Patient direct reporting of symptoms (4) Assign attribution; initiate expedited reporting Research Database

10. Patient Experiences Symptom Clinician Enhance clinical care Patient direct reporting of symptoms (5) Assign attribution; initiate expedited reporting Research Database

11. Clinicians systematically downgrade symptoms compared with patients Basch: NEJM, 2010 Fromme: JCO, 2004 Stromgren: ActaAnesth, 2001 Weingart: Arch Intern Med, 2005 Pakhomov: Am J Man Care, 2008 Sprangers, ActaOncologica, 2000

12. Patient adverse symptom reports better correlate with functional status than clinician reports • Basch: JNCI, 2009

13. Clinician CTCAE Reporting is Unreliable N=393 Seen by 1st clinician in office, then 2nd clinician ~15 minutes later • Atkinson: SBM, 2010

14. PROs Better Identify SAEs Early • NCCTG 9741: Phase III trial comparing regimens for metastatic colorectal cancer • Closed after 841/1,125 patients enrolled due to unexpected excess of early deaths in Arm 1 (“IFL”) • Associated with “GI syndrome” including severe diarrhea • Diarrhea reporting: • Clinicians reported CTCAE each cycle (diarrhea required) • Patients reported diarrhea via in HRQL every other cycle • Rothenberg: JCO, 2001

15. Clinician-Reported Diarrhea • Dueck: Unpublished Data, 2010

16. Patient-Reported Diarrhea • Dueck: Unpublished Data, 2010

17. Patient vs. Clinician Diarrheain Arm 1 (IFL) • Dueck: Unpublished Data, 2010

18. NCI Contract HHSN261200800043C Development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) • Initiated October 2008

19. Mission Develop 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

20. PRO-CTCAE Network CBIIT DCCPS DCP DCTD Dana-Farber Christiana N E T W O R K N C C C P NCI MD Anderson Hartford Mayo OLOL MSKCC Coordinating Center Duke Spartanburg Penn St. Joseph - Orange SemanticBits ADVISORS T E C H Cooperative Groups FDA Industry Patient Advocates Perceptive

21. Task-Based Project • Task 1: White paper and survey • Task 2: Item development • Task 3: Cultural literacy • Task 4: Cognitive interviews • Task 5: Technology development • Task 6: Usability testing • Task 7: Validation study • Task 8: Feasibility study • Task 9: Educational materials DoneOngoing

22. Logistics • Multidisciplinary committee for each task • NCI representatives • FDA representatives as appropriate • Patient advocates • Methodological expertise • Clinical expertise • Regular web-enabled teleconferences • Digitally recorded • Documentation on Wiki

23. Wiki https://wiki.nci.nih.gov/x/X6_l

24. PRO-CTCAE Presentations (2009-10) • American Society of Clinical Oncology (ASCO) • International Society for Pharmacoeconomics and Outcomes Research (ISPOR) • International Society for Quality of Life Research (ISOQOL) • Drug Information Association (DIA) • caBIG Annual Meeting • Society of Clinical Trials (SCT) • Society of Behavioral Medicine (SBM) • Agency for Healthcare Research and Quality (AHRQ)

25. Goals of the Day • Project update • Information exchange • Discuss future directions and challenges • Feasibility/implementation/dissemination • Methodological/analytic issues • Demonstrating does not generate noise • Technology development • Between-visit reporting • Integration with other systems • Regulatory issues

26. Survey Highlights*729 Stakeholders in Cooperative Groups * Full survey results and White Paper available on project Wiki (https://wiki.nci.nih.gov/x/cKul)

27. Agenda