Quality of Life Assessment in Clinical Trials

1. Quality of Life Assessment in Clinical Trials Adapted from www.biostat.wisc.edu/training/courses/542slides/09-qol.pdf Introduction to Clinical Trials Biostatistics and Medical Informatics University of Wisconsin at Madison

2. Why are we interested in Quality of Life (QOL)? • The FDA has stated that efficacy with respect to overall survival and/or improvements in QOL might provide the basis for drug approval. Shaughnessy JA, Wittes RE, Burke G et al. Commentary concerning demonstration of safety and efficacy of Investigational anticancer agents in clinical trials. Journal of Clinical Oncology 1991 (9) 2225-32

3. Discussion Issues in QOL • Background • Data Collection Considerations • DeMets’ Perspective (Biostats professor at U Wisc) on QOL in clinical trials

4. Measuring QOL How are you feeling today? Happy Miserable

5. What is QOL? • 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 about nausea and fatigue • Fundamental Principle: QOL IS ASSESSED BY THE PATIENT

6. QOL (1) • Definition depends on context: • Cancer vs. MI vs. hypertension • Early instruments for measuring QOL were disease-specific • Later instruments, “general health status” • POMS = Profile of Mood • SIP = Sickness Impact Profile • Difficulties with Concept • No agreement on definition • Lack of standardized measures

7. QOL (2) • One definition (Levine and Croog) has two components: • Functioning • Social (major component): get along with family and friends • Physical: perform daily activities • Emotional: stability and self-control • Intellectual: decision-making ability • Perceptions • Life satisfaction: sense of well-being • Health Status: compared to others

8. Factors influencing QOL • Interventions/Treatment • Disease Processes • Labeling: diagnosis brings on ‘change’ • Concomitant Care • Non-related life events (e.g. death in the family)

9. Rationale in Clinical Trials • QOL assesses effect of intervention/treatment • Primary response (treatment less toxic?) • Side effects (treatment toxic?) • Economic aspects (low risk/cost of treatment but high benefit?) • Another setting: Treatment for pain • Primary response (pain lessened?) • Side effects (interact with disease? Other side effects?) • Economic aspects

10. Assessing QOL • Hardest part! • Determine QOL objective • Choose instrument to measure QOL • Reliable, valid, responsive, feasible • Global measures, disease-specific measures, symptom checklists • Select assessment time points • Develop analysis plan

11. Data Collection • Mode: self-administered vs. interview • Self-admin: Reading ability, fine-motor skills • Interview: Hearing problems, age/gender/ethnicity sensitivity, training of interviewer • Either: language • Content • Instrument validity, sensitivity, specificity • Sensitivity of questions • Frame of reference (cognitive skills, privacy, cultural background) • Source(s) • Patient vs family vs health care provider

12. DeMets’ Perspective • Off-the-shelf (i.e. general) 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 silly questions for trial population • May take long time to complete • May impact negatively on compliance

13. DeMets Perspective • “Tailor Made” Instruments • Quick and simple • Standardized but targeted to disease • Validated, normed to trial population • Selects subsets of off-the-shelf instruments • Home-Made Instruments • Often designed by graduate student or comparable • Often too long • Often not validated or ‘normed’ or field tested in the patient population of interest

14. Analytic Issues • “Measurement” • QOL measured by multiple indicators • Need validated overall ‘score’ • Or, can use fancier multivariate methods • Usually, treat ‘score’ as observed level of QOL and proceed with analysis. • Problems: • sometimes the ‘score’ is not a valid measure of QOL in the patient population • These types of measures tend to be fraught with measurement error.

15. Other QOL issues • Often interested in whether or not survival with poor quality of life is better than death without suffering. • “QALY”= Quality Adjusted Life Years • Example: • Cancer: many patients would rather not get toxic therapies and have more enjoyable end of life • The general idea is to down-weight time spent in periods of poor quality of life. • Methodologically challenging: • How to determine the weights? • Different settings might need different weights.

16. Quality Adjusted Survival • QTWIST: Quality-Adjusted Time Without Symptoms of disease and Toxicity. • Evaluate therapies based on both quantity and quality of life through survival analysis • Based on QALYs. • Define QOL health states, including one with good health (minimal symptoms). • Patients progress through health states and never back-track. • Partition the area under the Kaplan-Meier Curve and calculate the average time spent in each clinical health state. • Compare treatment regimens using weighted sums durations, weights are utility based. • Example: 5 year survival Quality of Life for Individual 3 adjusted years of life Compare the average QTWIST in two treatment groups. Could be that on treatment A, people live longer, but QOL is worse.

17. References: • www.biostat.wisc.edu/training/courses/542slides/09-qol.pdf • Fairclough and Gelber, “Quality of Life: Statistical Issues and Analysis.” From Quality of Life and Pharmacoeconomics in Clinical Trials, Second Edition, ed. B. Spiker. 1996.