Patient Reported Outcomes Quality of Life Committee PROQOL

1. CP1223416-1 Patient Reported Outcomes Quality of Life Committee(PROQOL) Jeff A. Sloan, PhD Chair Michele Halyard, MD Vice Chair Paul Schaefer, MD Community Co-Chair July 29, 2009 Update  It is my privilege today to report on the activities of the NCCTG Quality of Life Committee. A QOL Working Group was formed in 1999 to facilitate efficient, effective, and systematic incorporation of QOL endpoints into NCCTG treatment trials where appropriate. The QOL Working Group became a Committee in 2001 with a rating of outstanding to excellent in the previous grant application. The present application proposes the QOL Committee as a Discipline-oriented Scientific Committee for the next six years. It is my privilege today to report on the activities of the NCCTG Quality of Life Committee. A QOL Working Group was formed in 1999 to facilitate efficient, effective, and systematic incorporation of QOL endpoints into NCCTG treatment trials where appropriate. The QOL Working Group became a Committee in 2001 with a rating of outstanding to excellent in the previous grant application. The present application proposes the QOL Committee as a Discipline-oriented Scientific Committee for the next six years.

2. CP1223416-2

3. CP1223416-3 Breaking News

4. CP1223416-4 Survival Curves for n=3704 cancer patients (Biomarker Assay (BMA) Positive versus Negative) Kaplan-Meier estimate survival plots displayed here indicated a median survival of 9.2 months among patients whose QOL was clinically deficient, compared to a median survival of 16.8 months for patients who reported a non-deficient qol at baseline. Hence, a patient reported baseline QOL score of 50 or below, corresponded to a 7.6 month deficit in median survival.Kaplan-Meier estimate survival plots displayed here indicated a median survival of 9.2 months among patients whose QOL was clinically deficient, compared to a median survival of 16.8 months for patients who reported a non-deficient qol at baseline. Hence, a patient reported baseline QOL score of 50 or below, corresponded to a 7.6 month deficit in median survival.

5. CP1223416-5 Median survival (months) across sites The survival analysis was repeated for individual tumor types with results displayed in this table. Results for GI, GU, lung and breast cancer patients all indicated survival deficits among patients who reported clinically deficient baseline QOL. The survival analysis was repeated for individual tumor types with results displayed in this table. Results for GI, GU, lung and breast cancer patients all indicated survival deficits among patients who reported clinically deficient baseline QOL.

6. CP1223416-6 Multivariate Cox Model for Survival A cox proportional hazard model was subsequently used to assess the impact of other covariates on the basic finding. Being from a minority population was not a contributing factor for survival in this analysis. Not surprisingly, Tumor type and Performance score contributed to patient survival. However, even after controlling for all these other factors, the indication of a clinically deficient baseline QOL contributed significantly to the prediction of patient survival. A cox proportional hazard model was subsequently used to assess the impact of other covariates on the basic finding. Being from a minority population was not a contributing factor for survival in this analysis. Not surprisingly, Tumor type and Performance score contributed to patient survival. However, even after controlling for all these other factors, the indication of a clinically deficient baseline QOL contributed significantly to the prediction of patient survival.

7. CP1223416-7 Replication of results A recent literature review (n=13,874) indicated that in 36 of 39 studies indicated that analogues of BMA+ were significantly associated with overall survival (Gotay, JCO, 26: 1355 -1363, March 2008) Meta analysis involving over 10,000 patients indicated that BMA+ analogue was prognostic for survival (Efficace, ASCO 2008) The theoretical framework from Wilson and Cleary indicates that Quality of life-related variables such as a patient�s perception of their own well-being can impact treatment outcome. Evidence from the literature for the prognostic capability of patient-reported outcomes has been mounting in recent years. For example, in March of this year, Carolyn Gotay and colleagues reported that based on their literature review they found that in 36 of 39 studies, at least one Patient-reported outcomes was significantly associated with overall survival. Among the patient-reported outcomes s involved, patient Quality of life was indicated as prognostic in 15 studies. The theoretical framework from Wilson and Cleary indicates that Quality of life-related variables such as a patient�s perception of their own well-being can impact treatment outcome. Evidence from the literature for the prognostic capability of patient-reported outcomes has been mounting in recent years. For example, in March of this year, Carolyn Gotay and colleagues reported that based on their literature review they found that in 36 of 39 studies, at least one Patient-reported outcomes was significantly associated with overall survival. Among the patient-reported outcomes s involved, patient Quality of life was indicated as prognostic in 15 studies.

8. CP1223416-8 Is this convincing evidence that BMA+ is a promising prognostic factor for cancer patient survival? What is BMA+?

9. CP1223416-9 BMA+ = a score of 5 or less in patient-reported QOL on a 0-10 scale Subsequently, we replaced the visual analogue scale with a numerical analogue scale. Psychometric comparisons published elsewhere have indicated that the two methods provide virtually identical results (Sloan, 2002; Huschka, 2005; Locke, 2007). Circling a number is easier for the patients and more reflective of the level of precision they can provided than placing an X in a box. Further, technician time is saved. Subsequently, we replaced the visual analogue scale with a numerical analogue scale. Psychometric comparisons published elsewhere have indicated that the two methods provide virtually identical results (Sloan, 2002; Huschka, 2005; Locke, 2007). Circling a number is easier for the patients and more reflective of the level of precision they can provided than placing an X in a box. Further, technician time is saved.

10. 10 QOL as a prognostic indicator Collate findings from multiple cooperative groups, comparing prognostic power of single-item LASAs (ncctg) versus multi-item Primary outcome: overall survival Prognostic variables: overall QOL, fatigue Key advantage: NCCTG uses simple single-item assessments Data being compiled and analyzed

11. 11 Overall QOL and Fatigueas routine assessments To be added to ALL treatment trials Will be part of the on-study form Two simple single-item LASAs Implementation fourth quarter 2009

12. 12 PROMIS

13. 13 Goal of RFA Improve assessment of self-reported symptoms and other domains of health- related quality of life across a wide range of chronic diseases

14. 14 Broad Objectives Develop and test a large bank of items measuring PROs Create a CAT for efficient assessment of PROs across a range of chronic diseases Create a publicly available, adaptable and sustainable system allowing clinical researchers access to a common item repository and CAT

15. 15 Structure Collaborative agreement network: Patient Reported Outcomes Measurement Information System (�PROMIS�) Consisting of: 6 Primary Research Sites Statistical Coordinating Center Steering Committee Scientific Advisory Board

16. 16 PROMIS Network

17. 17 What PROMIS Promises

18. 18 Item Banking and Computerized Adaptive Testing (CAT)

19. 19 NCCTG and PROMIS Grant submitted with aims:

20. CP1223416-20 Roles of the PROQOL Committee The QOL Committee has two roles within the NCCTG: 1) to support the disease-oriented committees to incorporate QOL-related research hypotheses into the evaluation of disease-specific cancer treatments; and 2) to develop and carry out a focused program of research into the assessment of QOL endpoints, using NCCTG clinical trials as an investigational platform.The QOL Committee has two roles within the NCCTG: 1) to support the disease-oriented committees to incorporate QOL-related research hypotheses into the evaluation of disease-specific cancer treatments; and 2) to develop and carry out a focused program of research into the assessment of QOL endpoints, using NCCTG clinical trials as an investigational platform.

21. CP1223416-21 Roles of the PROQOL Committee The QOL Committee has two roles within the NCCTG: 1) to support the disease-oriented committees to incorporate QOL-related research hypotheses into the evaluation of disease-specific cancer treatments; and 2) to develop and carry out a focused program of research into the assessment of QOL endpoints, using NCCTG clinical trials as an investigational platform.The QOL Committee has two roles within the NCCTG: 1) to support the disease-oriented committees to incorporate QOL-related research hypotheses into the evaluation of disease-specific cancer treatments; and 2) to develop and carry out a focused program of research into the assessment of QOL endpoints, using NCCTG clinical trials as an investigational platform.

22. CP1223416-22 Infrastructure Expansion: Liaisons Neuro�����Paul Brown, MD GI������...Axel Grothey, MD, . Joleen Turja, MD Breast��.......�Michele Halyard, MD, Amylou Dueck, PhD Lung�����...Nina Garces, MD, . Nathan Foster, MS Melanoma���.Barb Pockaj, MD, Svetomir Markovic, MD

23. CP1223416-23 Interaction with other groups GOG-0236 � Flexitouch massage therapy for lower extermity lymphedema for patients with gynecologic malignancies, closed due to poor accrual. ACOSOG Z6051: Laporoscopic rectal cancer trial, open and accruing. ACOSOG Z1052: Cryoablation for breast cancer, open and accruing. E3201 � bowel function questionnaire validation data under analysis

24. CP1223416-24 Specific Aims We have specified three research aims for the next grant period. (click) First, we will explore the relationship between genetics and QOL. (click) Second, we will improve the clinical trial patient experience to inform and improve clinical trial design and conduct. (click) Finally, we will continue methodological work on estimating the clinical significance and the value added of QOL assessments.We have specified three research aims for the next grant period. (click) First, we will explore the relationship between genetics and QOL. (click) Second, we will improve the clinical trial patient experience to inform and improve clinical trial design and conduct. (click) Finally, we will continue methodological work on estimating the clinical significance and the value added of QOL assessments.

25. CP1223416-25 Specific Research Questions Are there other genetic markers?(e.g., APOE epsilon 4 allele) Is there consistency across tumor sites? Breast cancer (N063D) Lung cancer (N0222, N01C9) Neuro-oncology (N0577) Which aspects of QOL are more/less influenced by genetics? We will attempt to expand on these preliminary findings presented in the ASCO plenary session by returning to the data in N9741 to include additional genetic markers. For example, we will investigate the role of the APOE epsilon 4 allele which has been indicated as potentially having a relationship to emotional functioning. We also have planned studies in the lung, breast, and neuro-oncology groups to explore possible relationship across other tumors and to identify which aspects of QOL might be more or less influenced by genetics.We will attempt to expand on these preliminary findings presented in the ASCO plenary session by returning to the data in N9741 to include additional genetic markers. For example, we will investigate the role of the APOE epsilon 4 allele which has been indicated as potentially having a relationship to emotional functioning. We also have planned studies in the lung, breast, and neuro-oncology groups to explore possible relationship across other tumors and to identify which aspects of QOL might be more or less influenced by genetics.

26. CP1223416-26 TITLE: Exploring the Relationship between Selected Genetic Polymorphisms of Colorectal Cancer Patients and Quality of Life (QOL) Domains of Mood: A Correlative Study to North Central Cancer Treatment Group (NCCTG) Phase III Trial N9741 PRINCIPAL INVESTIGATORS: Jeff A. Sloan, Ph.D. & Gen Shinozaki, M.D. Potential genetic polymorphsims identified by Dr. Shinozaki in pilot study New Concept

27. CP1223416-27 QOL & Genetics D. Mirjam Sprangers � co-chair of geneqol consortium Research agenda workshop February, 2009, Rochester, MN

28. CP1223416-28 Specific Aims We have specified three research aims for the next grant period. (click) First, we will explore the relationship between genetics and QOL. (click) Second, we will improve the clinical trial patient experience to inform and improve clinical trial design and conduct. (click) Finally, we will continue methodological work on estimating the clinical significance and the value added of QOL assessments.We have specified three research aims for the next grant period. (click) First, we will explore the relationship between genetics and QOL. (click) Second, we will improve the clinical trial patient experience to inform and improve clinical trial design and conduct. (click) Finally, we will continue methodological work on estimating the clinical significance and the value added of QOL assessments.

29. CP1223416-29 Specific Research Questions Are there other genetic markers?(e.g., APOE epsilon 4 allele) (N9741) Is there consistency across tumor sites? Breast cancer (N063A) Lung cancer (N0222, N01C9) Neuro-oncology (N0577) Which aspects of QOL are more/less influenced by genetics? We will attempt to expand on these preliminary findings presented in the ASCO plenary session by returning to the data in N9741 to include additional genetic markers. For example, we will investigate the role of the APOE epsilon 4 allele which has been indicated as potentially having a relationship to emotional functioning. We also have planned studies in the lung, breast, and neuro-oncology groups to explore possible relationship across other tumors and to identify which aspects of QOL might be more or less influenced by genetics.We will attempt to expand on these preliminary findings presented in the ASCO plenary session by returning to the data in N9741 to include additional genetic markers. For example, we will investigate the role of the APOE epsilon 4 allele which has been indicated as potentially having a relationship to emotional functioning. We also have planned studies in the lung, breast, and neuro-oncology groups to explore possible relationship across other tumors and to identify which aspects of QOL might be more or less influenced by genetics.

30. CP1223416-30 TITLE: Exploring the Relationship between Selected Genetic Polymorphisms of Colorectal Cancer Patients and Quality of Life (QOL) Domains of Mood: A Correlative Study to North Central Cancer Treatment Group (NCCTG) Phase III Trial N9741 PRINCIPAL INVESTIGATORS: Jeff A. Sloan, Ph.D. & Gen Shinozaki, M.D. Potential genetic polymorphsims identified by Dr. Shinozaki in pilot study New Concept

31. CP1223416-31 QOL & Genetics Research agenda workshop February 26-28, 2009, Rochester, MN Challenge grant submitted Special session at ISOQOL, New Orleans, October 29-31, 2009 Special section of Quality of Life Research

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33. CP1223416-33 N0392 WIWI now on six open studies, to provide feedback for patient experience, satisfaction, QOL A quality of life assessment of patients participating in phase I clinical trials confirms a decrease during treatment, developed the WIWI

34. CP1223416-34 Improving clinical trial design Compliance issues in completion of patient-reported outcomes in a series of NCCTG/Mayo clinical trials Comparing and Validating Simple measures of Patient-reported Peripheral Neuropathy (PRPN) for NCCTG Clinical Trials: a Pooled Analysis of 2440 Patients

35. 35 Development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) National Cancer Institute, Div of Cancer Control and Pop Sciences The resulting PRO-CTCAE will: 1) be comprehensive to capture a range of symptoms and functioning that enhances monitoring of adverse events; 2) have minimal burden on the patient in terms of survey length and comprehension; 3) be adaptable for translation into multiple languages to accommodate the diversity of patients who participate in NCI-sponsored clinical trials; 4) include both paper and electronic administration; 5) be fully integrated and complement the revised CTCAE (version 4.0); 6) meet the standards of compatibility within the CaBIG specifications; and 7) have minimal administrative burden for health care providers who will collect and interpret data for reporting adverse events and for informing patient care. The contract will also validate the PRO-CTCAE and demonstrate the feasibility of integrating the system within NCI-sponsored trials.

36. 36 PRO-CTCAE Project Items have been drafted Testing of items now happening with patients, cognitive interviews Mayo/NCCTG will be one of the test sites Part of the PROMIS grant project

37. CP1223416-37 REALTIME QOL Assessment QOL committee strategic goal to investigate whether real time use of QOL data in clinical practice adds to patient care Pilots in Rad Onc & Neuro-Onc planned Ultimate goal to look at using QOL data collection in clinic setting Use of LASA 12 instrument Submission for external funding planned Potential for larger NCCTG wide study

38. CP1223416-38 Clinical Significance of Real-time Quality of Life (QOL) Data Specific Aims To determine if patient QOL can be improved by the real-time use of QOL data during radiation treatments To determine whether the availability of real-time QOL assessment data in radiation oncology practice increases the acceptance of and utilization of such information by physicians To evaluate the quality of patient-physician relationship with real-time use of QOL data compared to interactions where the QOL data are not utilized

39. CP1223416-39 Process Flow Physician can view the patient survey for current visit as well as the weekly summary (if available) Absolute value of 5 or more on the measure will be bolded and highlighted in red as alert values Any change of 2 points or more on the measure since the last visit will be bolded and highlighted in green as alert values

40. CP1223416-40 Process Flow LASA survey results table: The table will include the survey results of the current visit as well as all of the previous visits. The QOL change since last visit (if available) will be displayed in the last column of the table.

41. CP1223416-41 Login Page

42. CP1223416-42 Nurse/Staff Data Entry Page

43. CP1223416-43 Patient Survey: LASA

44. CP1223416-44 Survey Summary by Week and QOL Change since last visit (Table)

45. CP1223416-45 Overall QOL Deficit Management (LASA #1� LASA #6g, LASA 10-12)�

46. CP1223416-46 Adult Cancer Pain (LASA #8)

47. CP1223416-47 Deficit in Cancer-Related Fatigue (LASA #9)�

48. CP1223416-48 Cancer-Related Fatigue (ET-4)�

49. CP1223416-49 Implementing a PRO-based treatment process for cancer patients New Concept

50. CP1223416-50 Real-time Projects Pilot open in Mayo Scottsdale Rochester pilot in neuro patients open this year Second pilot in three selected NCCTG sites developed, open 2010

51. CP1223416-51 Prioritization How do we organize all this �stuff�? Tumor groups prioritize their studies via online priority list Annual retreats to produce timeline Master workload lists for staff Perhaps at NCCTG meetings (question?)

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