1. Is t he ‘Child’s Voice’ from Diagnosis to End-of-Life Trustworthy? Pamela S. Hinds, PhD, RN, FAAN Director, Department of Nursing Research and Quality Outcomes Associate Director, Center for Translational Research Children’s National Health System Professor, Department of Pediatrics The George Washington University

2. Children’s National Medical Center Washington, D.C.

3. Disclosure I do not have any conflicts of interest to disclose. Funding sources for the data included in this presentation include the National Institute of Nursing Research, the National Cancer Institute, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Association of Critical Care Nurses, the Oncology Nursing Foundation, and Alex’s Lemonade Foundation

4. Child Voice Considered as Part of the Family Voice

5. Most Excellent Co- Investigators  Judy Hicks, LCSW  Wayne Furman, MD  Linda Oakes, MSN  Deo Kumar Srivastava, PhD  Justin Baker, MD  Sheri Spunt, MD  Johanna Menard, BSN  Chris Feudtner, MD  Nancy West, BSN  Brent Powell, MDiv  Shana Jacobs, MD  Scott Mauer, MD  Michele Pritchard, PhD, RN  Jami Gattuso, MSN  Chris Feudtner, MD  Tessie October, MD

6. Most Excellent Co- Investigators Bryce Reeve, PhD David Freyer, DO, MPH Lillian Sung, M.D., PhD Catriona Mowbray, PhD, RN Kathy Kelly, PhD, RN Steven Joffee, M.D. Janice Wythcombe, PhD, RN Jichuan Wang, PhD Changrong Yuan, PhD, RN

7. Overview of Comments Provide a description of the child’s voice –an overview of the evolution of child - reported outcomes in clinical investigations describe the parallel science of parent and clinician reports of child treatment

8. Overview of Comments Describe research methods to solicit the child’s voice –Address using the child’s voice Describe future steps to document and apply the child’s voice in clinical investigations and care

9. The Child’s Voice - What is it? Why seek it? How do we seek it? When do we seek it? How do we use it?

10. The Child’s Voice What is ‘the child’s voice’? –Literature review –Reflection on completed pediatric studies –Dialogue with pediatric and family researchers –Review of federal policies

11. The Child’s Voice The direct reports of children using qualitative (e.g., words, colors, photos, depictions), quantitative or both approaches to convey to others the quality of their illness experiences during a defined period of time.

12. The Child’s Voice What it is not: –Body and facial expressions not included: require interpretation –Age not included: variation –Parent voice –Clinician voice

13. The Child’s Voice: What is in the voice? Availability Intensity/ Degrees Meaning

14. The Child’s Voice What evidence do we have that the child’s voice is real?

15. The Child’s Voice: Is it Real? Symptoms –Pain - presence, location, intensity, change Eland, 1975; 1978 Awareness of Serious Illness –Not going to go home from the hospital –Not going to get better –Able to compare self to others Bluebond-Langer, 1978

16. Pediatric Self-Report Evolution of the Past Three Decades Clinician Reports (CTCAE) Use of Adult Measures (HUI) Proxy Reports (Play Performance Scale) No Conceptual definitions for Pediatrics Pediatric Definitions/Descriptions Proxy Reports Formatting changes to match Child Development (Rand) ●●● ● ● ● IQ Assessments

17. Can an Ill Child Report? Evidence for ability to report symptoms –>130 reports in past 32 years Instrumentation studies Theory testing Intervention

18. Can an Ill Child Report? >500 children 5 to 18+ years of age Time of Diagnosis Following the first course or 6 weeks of treatment 3 months into treatment 6 months into treatment End of treatment Survivorship

19. Can an Ill Child Report? Age of child reports: QoL –3 and 4 year olds – quantitative - pain –5 years of age and older - quantitative – quality of life Up to 20% of 5 year olds uncomfortable with selecting a score Up to 15% of 6 year olds uncomfortable Up to 10% of 7 year olds uncomfortable

20. Can an Ill Child Report? Aspect of TIME in the description of ‘the Child’s Voice’ –Ability to report changes over time Past 7 days/Past 30 days –Influence of maturation and of the moment

21. Can an Ill Child Report? Quality of Life Symptoms Satisfaction with Care Preference for Decision Making

22. Evolution of Pediatric Self-Report Measures for the Past Four Decades Clinician Reports (CTCAE) Use of Adult Measures (Hill) Proxy Reports (Play Performance) No Conceptual definitions for Pediatrics Patient-Reported Outcomes as Primary Pediatric Definitions/Descriptions Government Role Proxy Reports Formatting changes to match Child Development (Rand) ●●● ● ● ● ●

23. National Initiatives and PROs Food and Drug Administration Guidelines-1 “Guidance for Industry—Patient-reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” (December, 2009) Content Overview –Appropriate role of PRO in development of medical products –Evaluation of PRO instruments (multiple criteria) –Clinical Trial Designs –Approaches to Data Analysis FDA accepts PRO endpoints in reviewing product applications Further highlights importance of PROs at national level

24. National Initiatives and PROs Food and Drug Administration Gludeliens-2 Criteria for evaluating a PRO as a clinical trial endpoint Conceptual framework underlying instrument Selection of concepts relevant to disease, population and treatment being evaluated Key properties of instrumentation –Reliability Test-retest Internal consistency –Validity Content Construct –Clinical sensitivity (ability to detect change)

25. National Initiatives and PROs Food and Drug Administration Guidelines-3 Considerations for Children and Adolescents In general, PRO review criteria similar to adults Additional age-related criteria –Age-related vocabulary –Language comprehension –Comprehension of health concept being measured –Duration of recall Proxy-reported outcome measures are discouraged –Observer reports should include only those events or behaviors that are directly observable

26. Evolution of Pediatric Self-Report Measures for the Past Four Decades Clinician Reports (CTCAE) Use of Adult Measures (HUI) Proxy Reports (Play Performance Scale) No Conceptual definitions for Pediatrics Patient-Reported Outcomes as Primary Pediatric Definitions/Descriptions Government Role Proxy Reports Formatting changes to match Child Development (Rand) ●●● ● ● ● ● Child Voice Incorporated into research and care

27. Evolution: Practice Guidelines

28. Research Priority Recommendations

29. Measuring the Child’s Voice Evolution from disease-specific instruments to document ill child’s voice Comparability across clinical contexts –Core instruments i.e., Pediatric PROMIS measures –Pediatric PROMIS use with children diagnosed with cancer, sickle cell disease, asthma, kidney disease

30. Soliciting Pediatric Reported Outcomes Future Next Steps

31. Can Ill Children Report Treatment Toxicity? Common Terminology Criteria for Adverse Events (CTCAE), v. 4.03, 2010 –Mandatory report by clinicians (DHHS/NIH/NCI) 147 clinicians identified AEs that children 7 to 20 years of age could report (subjective experiences) RO1 to create and validate the Pediatric CTCAE

32. Cognitive Interviewing Age GroupPediatric Form A (x items) Pediatric Form B (x items) Pediatric Form C (x items) Pediatric Form D (x items) Totals 7-8 years6 children 6 proxies 6 children 6 proxies 6 children 6 proxies 6 children 6 proxies 48 English speaking children and proxies (24 dyads) 9-12 years6 children 6 proxies 6 children 6 proxies 6 children 6 proxies 6 children 6 proxies 48 English speaking children and proxies (24 dyads) Age GroupAdult Form A (x items) Adult Form B (x items) Adult Form C (x items) Totals 13-15 years8 children 8 proxies 8 children 8 proxies 8 children 8 proxies 48 English speaking youth and proxies (24 dyads) 16-20 years8 children 8 proxies 8 children 8 proxies 8 children 8 proxies 48 English speaking youth and proxies (24 dyads)

33. Cognitive Interviewing - Spanish Age GroupPediatric Form A (x items) Pediatric Form B (x items) Pediatric Form C (x items) Pediatric Form D (x items) Totals 7-13 years5 children 5 proxies 5 children 5 proxies 5 children 5 proxies 5 children 5 proxies 40 Spanish speaking children and proxies (20 dyads)

34. Soliciting the Child’s Voice ‘Please tell me what you are hoping for now.’

35. When Would a Child’s Voice be Silent? Able but not invited to speak Able but not wanting to report –Lack of confidence in self –Lack of confidence in those asking –Fear of outcomes –Protecting others Not Able to speak –Not understanding the method –Too ill

36. Soliciting the Child’s Voice Future Next Steps

37. Can Ill Children Report Treatment Toxicity? Common Terminology Criteria for Adverse Events (CTCAE), v. 4.03, 2010 –Mandatory report by clinicians (DHHS/NIH/NCI) 147 clinicians identified AEs that children 7 to 20 years of age could report (subjective experiences) RO1 to create and validate the Pediatric CTCAE

38. How Do We Validate the Ill Child’s Voice?

39. Can a Very Ill Child Report? Evidence for ability to report symptoms –>130 reports in past 15 years; <5% at end of lif e

40. Ill Child Reports at End of Life: 2007

41. Ill Child Reports at End of Life: 2012

42. Timing of Soliciting the Very Ill Child’s Voice Before the child loses his/her voice Soliciting child preferences –Method flexibility –Method blending

43. Ill child and parent agreement –Measuring agreement over time Challenging current approaches to ‘agreement’ –Estimation of change, concern –Effect of training to report –Other voices other than parent/guardian? Can There be Only One Voice?

44. Child Voice/ Family Voice ILL CHILD THE PARENT THE WELL SIBLING

45. Child and Parent Voices at End of Life Parent: –Doing as my child would prefer Child: – Thinking about my relationships with others

46. Single Unit of Analysis and Interpretation Child Reports Exclusionary Informed Collaborative Delegation: Allowed to choose Parent Reports Exclusionary Informed Collaborative Delegation: Allowed to choose

47. Combining Voices: Dyad, Triad and More  Family Level of Analysis  Family and Clinician Level of Analysis

48. Primary Points Ill children can self-report during illness and end-of-life care Parent s and clinicians add important voices to the ill child’s treatment and end-of-life experiences Single unit analyses and interpretations (ill child, parent, clinician) are informative but insufficient

49. The Child’s Voice - What is it? Why seek it? How do we seek it? When do we seek it? How do we use it?

50. Of What Benefit is the Child’s Voice in Research and Care? Accurate symptom and quality of life assessments Impact of therapy Impact of care Patient and parent trust of clinicians and satisfaction with care –Relationship with treatment decision- making

51. Do We Trust the Child’s Voice? If we do not trust the child’s voice, we will not ask If we do not trust the child’s voice, we will not act on the voice If we ask, it is like a promise to the child to listen, to act in respect of the child’s voice