1. PRO-CTCAE Face-To-Face Meeting #2 Advancing 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 1.Introductions 2.Project background 3.Progress to date 4.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/GuidanceComplianceR egulatoryInformation/Guidance s/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 Clinician Interprets Symptom Chart Representation of Symptom Data Manager Interpretation of Symptom Research Database Current Model for Adverse Symptom Reporting in Cancer Trials

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

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

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

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

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

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 1 st clinician in office, then 2 nd 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 Diarrhea in Arm 1 (IFL) Dueck: Unpublished Data, 2010

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

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 NCI ADVISORS TECHTECH NETWORKNETWORK NCCCPNCCCP 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

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 Done Ongoing

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 1.Feasibility/implementation/dissemination 2.Methodological/analytic issues Demonstrating does not generate noise 3.Technology development Between-visit reporting Integration with other systems 4.Regulatory issues

26. Survey Highlights* 729 Stakeholders in Cooperative Groups QUESTION AGREENEUTRALDISAGREE Systems to collect PROs in clinical trials should be developed89%5%6% In clinical trials, adverse events should be reported by patients 88%8%4% POTENTIAL BARRIERS AGREENEUTRALDISAGREE Lack of computers69%15%16% Limited personnel57%18%25% SOLUTIONS TO OVERCOME BARRIERS AGREENEUTRALDISAGREE 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)

27. Agenda