DEFINING QUALITY OF LIFE FOR ONCOLOGIC DRUG APPROVAL

1. DEFINING QUALITY OF LIFE FOR ONCOLOGIC DRUG APPROVAL Carol M. Moinpour, PhD Southwest Oncology Group Statistical Center Fred Hutchinson Cancer Research Center Seattle, Washington/USA ODAC QUALITY OF LFE SUBCOMMITTEE February 10, 2000

2. What is Quality of Life? • Subjective • Patient perception is critical • Health-related • Yes, we are primarily measuring health status • Multidimensional • Which dimensions are relevant? • Usually not driven by psychosocial theories

3. Proposal: Data Source Expert re: “patient benefit” = patient Best equipped to evaluate claims about impact of treatment

4. Quality of Life Vs Health-Related QOL (HRQL) • Not feasible to measure the myriad of non-medical influences • Restrict QOL domains likely to be affected by medical intervention (HRQL) • Attribution problem • Randomization addresses unmeasured factors • Combine quality with quantity of life?

5. Proposal: QOL vs HRQL • Restrict quality of life assessments to HRQL • Patients asked to report current status • Address known covariates • HRQL can include duration of life • A complicated question deserving our attention

6. HRQL Domains

7. Examples of Quality of Life Domains Physical Functioning Spirituality Occupational/Role Functioning Future Orientation Social Functioning Sexuality/Intimacy Emotional Functioning Health Concerns Symptom Status Family Well-Being Financial Concerns Satisfaction w/Care Global/Overall Perception of Quality of Life

8. HRQL Domains • Inclusion of symptoms important because • Corroborate physician-rated toxicities • Document palliation in advanced stage disease • Need to examine the “reach” of better/worse symptoms to general functioning

9. Assessment of Multiple HRQL Dimensions • Specifies how treatments affect patients • Complements physician-related toxicity information • Informs patients and physicians about risks/benefits tradeoffs • Identifies ways to improve cancer treatments • Identifies survivors rehabilitation needs

10. Proposal: HRQL Domains • Three basic domains • Psychological • Physical • Social • [Global HRQL vs summary score?] • Measure symptoms but also document their effect on basic domains

11. Proposal: HRQL Domains • Symptom status is not a manifestation of patient HRQL • Sx outcomes alone should not be called HRQL • Sx outcomes alone may be appropriate in Phase II, single institution, or supplemental submissions • Sx outcomes can be designated primary • Clinical issues should drive content of sx measures

12. Proposal: Role of Theory • Psychological or social science theories usually not driving HRQL assessment design • Psychometric theory has done so • First obligation: identify HRQL issues critical to evaluating treatments • Can suggest broad impacts on the patient • Tx rationale usually doesn’t address HRQL

13. Additional Slides

14. HRQL Research Issues • Independence of HRQL dimensions • Incorporation of importance ratings? • Impact of substantial individual variation conclusions re: patient benefit • Integration of symptom and basic domain data • To document scope of patient benefit/harm • Validity of total scores with symptom component • Role of methodological and theory-driven research in defining HRQL for drug claims?

15. Problem with Single Item Measures • Only 1 chance to capture concept or dimension • OK for detecting moderate to large differences • Attractive for clinical trials (burden issue) • Likely to miss differences at individual patient level • Compromise - brief, multi-item scales

16. World Health Organization Definition “Health is not only the absence of infirmity and disease but also a state of physical, mental and social well-being.”