Patient-Reported Outcomes: Introducion and Overview

1. Patient-Reported Outcomes:Introducion and Overview Pythia Nieuwkerk, PhD Department of Medical Psychology Academic Medical Center, Amsterdam

2. Outline presentation • What are patient–reported outcomes (PROs)? • How do PROs complement traditional clinical outcome measures? • How can we measure PROs? • Type of measures • How are PROs used in clinical research? • Examples

3. What is a Patient-Reported Outcome? • 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.1 • The term PRO addresses the source of the report, and not the concept or content of the report.2 1. FDA, 2009, 2. Patrick et al. 2007

4. What concepts do PRO instruments measure? • Concepts measured by PROs differ in their degree of complexity: • From simple • eg, presence of a symptom • To more complex concepts • eg, ability to carry out activities of daily living • To even more complex concepts • eg, health-related quality of life

5. What is health-related quality of life? Health: A state of complete physical, social, and mental well-being, not merely the absence of disease or infirmity WHO, 1948

6. WHO-based consensus of “Quality of Life” Multi-dimensional Physical Functioning Social Functioning Mental Functioning Affected by disease/treatment Subjective

7. Subjectivity and Objectivity HRQoL is not subjective in the usual sense of the term It can be measured accurately in an individual, and in a group It is “subjective” in that it: derives from the individual patient. represents what is important to the individual patient.

8. How do PROs complement traditional clinical outcome measures?

9. WILSON-CLEARY MODEL OF HEALTH OUTCOMES Characteristics of Individual Biological and Physiological Variables Symptoms Functional Status General Health Perceptions Quality of Life Characteristics of Environment Wilson & Cleary JAMA (1995)

10. Motivations for PRO/QOL research • Changing the concept of treatment model • Switching from biomedical model to patient-centered model • Living longer and comfortable, especially for cancer patients, elderly population, etc.

11. Number of papers on “quality of life” published each year (PubMed)

12. Motivations for PRO/QOL research • Some treatment effects are known only to the patient • eg, pain intensity and fatigue • Capturing different aspects of health outcomes extended beyond biomedical / clinical indicators • eg, symptoms and functioning, comprehensive assessment of impact of disease and treatment

13. When are PROs most relevant • When no survival gain is expected (e.g. palliative treatments) • When no significant differences in survival are expected • Where survival is gained at the expense of major toxicity and treatment burden

14. How can we measure PROs?

15. www.proqolid.org

16. Type of health outcomes instrument HEALTH PROFILE Health states and impact on daily functioning and well-being Generic measure Disease-specific measure SF-36 WHOQOL-100 MOS-HIV EORTC QLQ C30

17. Generic instrument- SF-36 Health profile: 8 domains • Physical functioning (10 items) • Role limitations/physical (4 items) • Role limitations/emotional (3 items) • Social functioning (2 items) • Emotional well-being (5 items) • Energy/fatigue (4 items) • Pain (2 items) • General health perceptions (5 items)

18. Does your health now limit you in walking more than a mile? (If so, how much?) No, not limited at all Yes, limited a little Yes, limited a lot

19. How much of the time during the past 4 weeks have you been happy? None of the time A little of the time Some of the time Most of the time All of the time

20. Physical Health Physical function Role function-physical Pain General Health SF-36 Physical Health

21. Mental Health Emotional Well-Being Role function-emotional Energy Social function SF-36 Mental Health

22. Generic instrument – WHOQOL-100 Health profile: 6 domains • Physical health (12 items) • Psychological health (20 items) • Level of independence (16 items) • Social relationship (12 items) • Environment (32 items) • Spirituality, religiousness & personal beliefs (4 items)

23. Same domain, different content Social domain: Social functioning versus social well being • Social functioning: limitations due to disease/treatment (SF36, EORTC-QLQ-C30) • More likely to respond to medical treatment • Social wellbeing: closeness with family and friends (FACT-G) • More likely to respond to psychosocial interventions

24. Generic versus Disease specific PROs Generic PRO • Intended for use across broad chronic disease populations • Allow comparisons across these groups • Disadvantage: may not permit adequate disease-specific focus • Disease caused symptoms • Treated related symptoms

25. Type-2 Diabetes Depression Congestive Heart Failure Average Adult Average Well Adult Chronic Lung Disease Asthma 30 40 50 34 36 55 SF-36’s Physical Component Summary (PCS) RELATIVE DISEASE BURDEN: Generic PROs allow for cross-disease comparison of disease impact Ware & Kosinski, 2001

26. Generic versus Disease specific PROs Disease specific PRO • Focus on the impact of a particular condition on the patient’s functioning and experience • Responsive to disease-related changes • Cannot be used across populations with other diseases

27. WILSON-CLEARY MODEL OF HEALTH OUTCOMES Characteristics of Individual Biological and Physiological Variables Symptoms Functional Status General Health Perceptions Quality of Life Characteristics of Environment Wilson & Cleary JAMA (1995)

28. Combining PRO measures Disease-specific and Generic PROs are complementary: • When both are included in a study, it is possible to capture: • Disease-specific concepts • Generic concepts, compare to norm: (relative) burden of illness / benefit of treatment

29. Measuring PROs/HRQL • No standard scale, need to specify what we want to measure • What is your research question? • Who are your patients? • What do you anticipate what will happen? • Appropriateness of the measure to the question or issue of concern. • Correspondence between the content of the measure and goals of the study.

30. How are PROs used in clinical research?

31. Study Goals • Characterizing the burden of disease and treatment • Characterizing treatment-specific outcomes for use in shared decision making • Predicting patient outcomes • Evaluating the effectiveness of interventions

33. The EORTC QLQ-C30 Physical functioning Role functioning Functional scales Cognitive functioning Emotional functioning Social functioning

34. The EORTC QLQ-C30 Physical functioning Role functioning Functional scales Cognitive functioning Emotional functioning Social functioning Fatigue Nausea andVomiting Pain Symptoms Dyspnea Insomnia Appetiteloss Constipation Diarrhea Financial difficulties

35. The EORTC QLQ-C30 Physical functioning Role functioning Functional scales Cognitive functioning Emotional functioning Social functioning Fatigue Nausea and Vomiting Pain Symptoms Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties Global health status scale Global health status Overall QoL

36. The EORTC QLQ-C30 Standardized score Physical functioning Role functioning Range 0 - 100 Functional scales Cognitive functioning Emotional functioning Social functioning Fatigue Nausea and Vomiting Pain Symptoms Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties Global health status scale Global health status Overall QoL

37. The EORTC QLQ-C30 Standardized score Physical functioning Role functioning Range 0 - 100 A higher score indicates a higher level of functioning Functional scales Cognitive functioning Emotional functioning Social functioning Fatigue Nausea and Vomiting Pain A higher score indicates a higher level of symptoms Symptoms Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties A higher score indicates a higher level of QoL Global health status scale Global health status Overall QoL

38. Profiles 100 = Good QOL 0 = Poor QOL 71 96 Physical functioning 63 93 Role functioning 83 94 Functional scales Cognitive functioning 62 Emotional functioning 77 Social functioning 71 91 Global health status 64 71 O= No symptoms 100 = Many symptoms 14 38 Fatigue 2 10 Nausea and Vomiting 14 Pain 31 6 Dyspnea 28 Symptoms scales Insomnia 34 14 4 20 Appetite loss 2 11 Constipation 4 Diarrhea 7 Healthy women (50-59 years) (Schwarz et al. Eur J Cancer, 2001) Metastatic breast cancer baseline (Bottomley et al 2003) Metastatic breast cancer at cycle 2 of doxorubicin/cyclophosphamide

39. Study Goals • Characterizing the burden of disease and treatment • Characterizing treatment-specific outcomes for use in shared decision making • Predicting patient outcomes • Evaluating the effectiveness of interventions

40. Changes in HRQL from start to 18 months of antiretroviral therapy for HIV-infection Cognitive function Physical function Health distress Social function General health Role function Mental health Overall QoL Vitality Pain

41. Study Goals • Ccharacterizing the burden of disease and treatment • Characterizing treatment-specific outcomes for use in shared decision making • Predicting patient outcomes • Evaluating the effectiveness of interventions

42. Predicting survival in HIV infection • 560 HIV infected patients starting HAART. • Completed the MOS HIV between 1998-2000. • All cause mortality established in March 2008. • 66 patients (11.8%) died during follow-up. • Physical Health Summary score (MOS HIV) significant predictor of survival, independent of other (clinical) parameters. de Boer-van der Kolk: CID 2010

43. Physical Health summary score (MOS-HIV) de Boer-van der Kolk: CID 2010

44. Predicting Outcomes • Baseline HRQL has been shown to be an independent predictor for overall survival • Overview of 36 trials that assessed baseline PROs and mortality (Gotay, JCO 26:1355, 2009) • PRO is a complex biomarker that can be highly predictive • Help signal those patients who are in need of medical attention • Can be an early warning useful for clinical decision making • Can be used as a stratification variable in research

45. Study Goals • Characterizing the burden of disease and treatment • Characterizing treatment-specific outcomes for use in shared decision making • Predicting patient outcomes • Evaluating the effectiveness of interventions

46. VITAL study Prevention of Coronary Heart Disease Intervention to enhance adherence to statin therapy and life-style recommendations

47. Risk counseling • Protocolized (nurse practitioner). • Identification individual risk factors. • Calculation Absolute Cardiovascular Risk (Framingham risk score) • Graphical presentation personal risk  Risk Passport. • Life style counseling (stop smoking, weight reduction)

48. Risk Passport

49. Inclusion Criteria > 18 yrs Indication for statin therapy- primary prevention- secondary prevention Subjects (n = 201, from outpatient clinics)

50. Study endpoints • Primary endpoints • LDL cholesterol levels • Adherence to statins • Anxiety • Secondary endpoint • Quality of Life (QOL)