1. 542-07-#1 STATISTICS 542 Intro to Clinical Trials Quality of Life Assessment

2. 542-07-#2 Why Are We Interested in the Quality of Life? The United States Food and Drug Administration has stated that efficacy with respect to overall survival and/or improvements in QOL might provide the basis for drug approval “Live longer – feel better” Shaughnessy JA, Wittes RE, Burke G et al. Commentary concerning demonstration of safety and efficacy of investigational anticancer agents in clinical trials. J Clin Oncol 1991; 9:2225-32.

3. 542-07-#3 Outline for Quality of Life General background Data collection considerations DeMets’ Perspective

4. 542-07-#4 Your Quality of Life How are you feeling this afternoon? Mood HappyMiserable

5. 542-07-#5 What is Quality of Life? WHO:“Health is not only the absence of infirmity and disease, but also a state of physical, mental and social well being Multiple domains include: physical, cognitive, emotional and social functioning, pain, sexual functioning, health perceptions, and symptoms such as nausea and fatigue Fundamental principle: quality of life is assessed by the patient

6. 542-07-#6 Quality of Life (1) Definition depends on context Cancer vs. MI vs. hypertension Some instruments are disease specific Others are "general health status" instruments –POMS = Profile of Mood –SIP = Sickness Impact Profile Difficulties with concept –No agreement on definitions –Lack of standardized measures

7. 542-07-#7 Quality of Life (2) One definition (Levine & Croog) Two Components - Functioning 1.Social (Major component) - Get along with family & friends | sense of worth 2.Physical - Perform daily life activities 3.Emotional - Stability and self control 4.Intellectual - Decision making ability -Perceptions 1.Life Satisfaction - Sense of well being 2.Health Status - Compared to others

8. 542-07-#8 Factors Which Influence Quality of Life 1.Intervention 2.Disease Process 3."Labeling"  Need a control group -Diagnosis brings on change 4.Concomitant Care 5.Non-related life events (e.g. death in family)

9. 542-07-#9 Rationale in Clinical Trials Quality of life may assess effect of intervention –primary response (treatment less toxic?) –side effects (treatment toxic?) –economic aspects (low risk/cost treatment but benefit high?)

10. 542-07-#10 How To Assess Quality of Life Determine your QoL Objective Choose an instrument –Reliable, valid, responsive, feasible –Global measures, disease-specific measures, symptom checklists Select your assessment time points and administration format Develop an analysis plan

11. 542-07-#11 Data Collection Considerations (1) Mode –Self-administered glasses, reading skills, fine-motor skills –Personal interview training/background of interviewer sensitivity to gender/ethnicity/age hearing impairment

12. 542-07-#12 Data Collection Considerations (2) Content –instrument validity, sensitivity & specificity –sensitivity of questions –frame of reference for answers (cognitive skills, privacy, cultural background) Source(s) –participant, family or support network, health care providers

13. 542-07-#13 Off the Shelf Instruments Off-the-shelf instruments –Designed to distinguish sickness from wellness –May not be sensitive to particular aspect of a given trial –May not be validated or "normed" in population being tested –May ask ridiculous questions for trial pop. –May take hours to complete –May impact negatively on compliance

14. 542-07-#14 Off-the-Shelf Instruments Off-the-Shelf Instruments (Example-NOTT) Design –Advanced Chronic Obstructive Pulmonary Disease –24 vs. 12 hours of O 2 –Quality of life 1 0 outcome (No norms in this pop!) Quality of Life Results  –Patients were sick –Patients got worse –No treatment difference BUT –Mortality ratio was 2/1 (p<.01)

15. 542-07-#15 DeMets’ Perspective "Tailor Made" Instruments –Can be Quick and simple –Standardized but targeted to disease –Must be Validated for trial population –Select subsets of off-the-shelf instruments

16. 542-07-#16 DeMets’ Perspective “Home-made" Instruments –Often designed by a graduate student –Often too long –Often not validated or field tested on your patient population

17. 542-07-#17 Quality of Life Instruments Can be simple and short Classic examples for –Cancer –Congestive Heart Failure

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21. 542-07-#21 Quality of Life Analysis Analytic methods likely to be based on a scoring system Methods often rank based Challenging to design/ compute sample size