Overview

1. Including the Patient Voice in Safety ReportingEthan Basch, MD, MScHealth Outcomes GroupDepartments of Medicine and Epidemiology/BiostatisticsMemorial Sloan-Kettering Cancer CenterJune 2009

2. Overview • Background on PROs • PROs for Adverse Event Reporting • Research • Regulatory issues • CALGB 70501

3. What is a PRO? FDA Definition: “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” - Guidance (2006)

4. FDA Definition of PRO • Any experience the patient knows best • Symptoms • HRQL • Functional status • Therapy compliance • Satisfaction with care • Treatment preferences • Guide clinical practice • Support clinical trial endpoints • Safety monitoring • AEs in clinical trials • Postmarket surveillance

5. Adverse Event Monitoring Essential activity in treatment trials • To ensure patient safety • To provide data about drug effects Core activity in routine cancer care • To guide therapy and supportive care

6. Standard Approach to AE Monitoring NCI-sponsored treatment trials: CTCAE ~1000 individual items, ordinal scale or patients?

7. EXAMPLE: DIARRHEA

8. 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

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

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

11. Rationales for Using PROs for Adverse Symptom Monitoring in Oncology • Improve efficiency, quality, completeness of data collection in clinical trials • Eliminating data collection steps, reducing errors • Providing more direct account of patient experience • Improve delivery of clinical care • Enhancing patient-clinician communication • Providing capacity to monitor patients between visits • Enabling automated alerts to address toxicities earlier • Trotti & Basch: J Clin Oncol, 2007

12. Developed Initial Patient Questionnaire • Adaptations of CTCAE symptom items • Health literacy/patient education experts • Focus groups • Cognitive debriefing • Basch: JCO, 2005

13. Items Loaded to Web Platform • Online interface • Patient self-reporting • Longitudinal report • Automated alerts • Administration • Touchscreen kiosks and wireless tablet computers in clinic waiting areas • Home computers between visits • Basch: J Am Med Informatics Assoc, 2007

14. STAR (1)

15. STAR (2)

16. STAR (3) --Patient Name--

17. STAR (4)

18. STAR (5)

19. Feasibility Studies • Patients receiving chemotherapy • Most patients are willing and able to self-report CTCAE symptoms at clinic visits • Including non-web avid, elderly, and end-stage with high symptom burdens • No attrition in login rates up to 1.5 years • Basch, JCO, 2005 • Basch, JCO, 2007

20. Satisfaction • High patient satisfaction • Wish to continue using • Would recommend to others • Clinician impressions and actions • Accurate portrayal of patient status • Altered chemotherapy doses based on patient-reported information

21. Implications • If PROs were adopted for monitoring adverse symptoms in oncology, how might this alter the frequency or severity of documented toxicities? • Do patients report toxicities differently from clinicians?

22. Patient vs. Clinician Reporting (1) • Paper survey • 400 patient-clinician pairs • Cancer outpatient clinics • Patients and clinicians answered the same CTCAE items • Basch, Lancet Oncol, 2006

23. Patient vs. Clinician Reporting (2) • Basch, Lancet Oncol, 2006

24. Longitudinal Reporting Patient-reporting Clinician-reporting CTCAE Grade-2 (Moderate) CTCAE Grade-3 (Severe) Patient-reporting Clinician-reporting • Basch, JNCI, 2009

25. Prediction Model • Clinician-reported CTCAE symptoms • More predictive of death and hospitalization • Patient-reported CTCAE symptoms • More correlated with daily health status • Complementary information • Both have value in characterizing patient experience with disease and treatment • Basch, JNCI, 2009

26. Drug Labels • Should both be included in clinical trial results and labels? • Would this cause confusion? • Instructive to consider examples outside of healthcare

27. Metacritic.com

28. CNET Reviews

29. Tripadvisor

30. Docetaxel Drug Label

31. NCI Contract Awarded 9/08 NCI HHSN261200800043C

32. NCI Survey • 729 stakeholders • Administered at cooperative groups / NCI listservs 11/08-2/09 *Not mutually exclusive

33. Survey Results

34. 77 CTCAE Items Identified for PRO

35. NCI Contract • Patient interviews • Building technology • Validation study

36. CALGB 70501 • Stand-alone companion trial • Linked to selected treatment trials

37. 70501 Aims • Assess feasibility of patient CTCAE reporting in cooperative group trials • Compare patient vs. clinician reporting Accrual goal: 175

38. Eligibility • Any patient enrolling in a linked treatment trial can also enroll in 70501, anytime prior to cycle/visit #2 • To participate, a site must be listed with CALGB (contact us or CALGB) • Additional accrual / cancer control credit assigned for 70501 enrollment

39. Currently Linked Treatment Trials CALGB 30607:Randomized, phase III, double-blind placebo-controlled trial of sunitinib as maintenance therapy in non-progressing patients following an initial four cycles of platinum-based combination chemotherapy in advanced, stage IIIB/IV non-small cell lung cancer CALGB 30704:A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer CALGB 40502:A randomized phase III trial of weekly paclitaxel compared to weekly nanoparticule albumin bound nab-paclitaxel or ixabepilone combined with bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer CALGB 40503:Endocrine therapy in combination with anti-VEGF therapy: a randomized, double-blind, placebo-controlled phase III trial of endocrine therapy alone or endocrine therapy plus bevacizumab for women with hormone receptor-positive advanced breast cancer CALGB 40601:Randomized phase III trial of paclitaxel combined with trastuzumab, lapatinib, or both as neoadjuvant treatment of HER2-positive primary breast cancer CALGB 40603: Randomized phase II 2 x 2 factorial trial of the addition of carboplatin +/- bevacizumab to neoadjuvant weekly paclitaxel followed by dose-dense AC in hormone receptor-poor/HER2-negative resectable breast cancer CALGB 70604:A randomized, phase III study of standard dosing versus longer dosing interval of zoledronic acid in metastatic cancer CALGB 80405:A phase II trial of irinotecan/5-FU/leucovorin or oxaliplatin/5-FU/leucovorin with bevacizumab, or cetuximab (C225), or with the combination of bevacizumab and cetuximab for patients with untreated metastatic adenocarcinoma of the colon or rectum

40. Schema

41. Interested Sites for 70501 Contact: • Ethan Basch (basche@mskcc.org) • Laura Sit (sitl@mskcc.org)