1. outcome research 1 Outcome/ instruments selection Wei-Chu Chie Preventive Medicine

2. outcome research 2 A review of outcomes –Clinical Death: binary/Disease: any type/Utilization of care –Functional/QOL Discomfort, QOL/Disability –Perceptual Dissatisfaction/satisfaction, QOL –Financial –Behavioral true behaviors/self-efficacy/utilization of care

3. outcome research 3 A review of criteria for good instruments Precision –free of random error Accuracy –free of systematic error

4. outcome research 4 Principles of outcome & instrument selection Outcome and instrument are related Basic principles –goal(s) of the research –nature of outcome –time span of outcome assessment –criteria of good instruments

5. outcome research 5 Endpoints and outcome An index selected to describe outcome usually used in experimental researches –primary/secondary/tertiary –time to event/clinical/surrogate/behavioral,...

6. outcome research 6 Research goal and nature of endpoints Primary endpoints –of biological or clinical importance –form the basis of the objectives of the trial/study –not be highly correlated –sufficient statistical power –relatively few (< 4)

7. outcome research 7 Research goal and nature of endpoints Secondary endpoints –of biological or clinical importance but less adequate statistical power –potentially important but highly correlated with primary endpoints –address other important but ancillary objectives

8. outcome research 8 Research goal and nature of endpoints Tertiary endpoints –exploratory –not of major importance

9. outcome research 9 Time span of outcome assessment Long-term: event or time to event –mortality –morbidity Mid-term: clinical, QOL Short-term: behavioral or satisfaction

10. outcome research 10 Long-term outcomes –Time to events (change of status) –events: mortality/survival (final) recurrence onset of an expected disease/adverse effect –‘ hard ’ endpoints: more objective –two components: time or person-time event: binary, clear-cut: occurred/censored

11. outcome research 11 Long-term outcomes Strengths –objective: ‘ hard ’ endpoints –accurate and precise –easy to access and measure Weakness –time consuming –too much simplified/insensitive –too late in prevention

12. outcome research 12 Mid-term outcomes Clinical symptoms, signs, laboratory findings, … –biochemistry, physiology, … Quality of Life* Sometimes as surrogate endpoints to ‘ time-to-event ’ endpoints

13. outcome research 13 Mid-term outcomes Strengths –less time consuming –more sensitive to treatment/predictors Weakness –not necessarily predictive to final events –less accurate and precise: somewhat ‘ soft ’ –more difficult to measure

14. outcome research 14 Short-term outcomes Behavioral –response to education/counseling, … Satisfaction –toward treatment and disease/health status

15. outcome research 15 Short-term outcomes Strengths –less time consuming –sensitive to treatments Weakness –not necessarily predictive to final events –less accurate and precise: ‘ soft ’, subjective –more difficult to measure

16. outcome research 16 Special use of QOL Ever seen/used as –a ‘ soft ’ endpoint –compensation of the failure in curative treatments Current extension of its role –a necessary efficacy index –economic analysis if used with survival: QALY or QAS

17. outcome research 17 QOL Generic –cross different diseases/condition/population –format: based on definition of health health profile (multi-dimensional questionnaire) utility (single index or multi-dimensional) –visual analog scale/standard gamble/time-trade- off –purposes description/treatment effect/economic evaluation cross disease/condition … transferable

18. outcome research 18 QOL Specific –disease/condition/population-specific –format: extended from generic + specific problems health profile (multi-dimensional questionnaire) –purposes description/treatment effect evaluation not cross-disease transferable

19. outcome research 19 Example Evaluation of the effect of a diet & exercise education program on patients with CAD –long-term: fatal MI/non-fatal MI –mid-term: serum lipid profile, BMI, QOL –short-term: diet & exercise pattern

20. outcome research 20 A review of criteria for good instruments Precision: free of random error –the degree to which a variable has nearly the same value when measured several times –coefficient of variation (C.V.) –reliability test-retest internal consistency inter- and intra-observer consistency

21. outcome research 21 A review of criteria for good instruments Accuracy: free of systematic error –the degree to which a variable actually represent what it is supposed to represent –validity –with gold standard sensitivity specificity predictive validity

22. outcome research 22 A review of criteria for good instruments Accuracy: free of systematic error –without gold standard face validity & content validity criterion-related validity –convergence validity –divergence validity construct validity

23. outcome research 23 Access to data/instrument selection Event/time-to-event –primary data: follow-up –secondary data: electronic or paper mortality: national mortality registry cancer: cancer registry other special registries NHI database hospital records

24. outcome research 24 Access to data/instrument selection Clinical data –sources primary: select precise and accurate clinical instruments secondary: medical record or laboratory work –format manual/paper/automatically- generated/electronic –QA & QC: good calibration/training

25. outcome research 25 Access to data/instrument selection QOL/Symptoms/Satisfaction/Behavio r –questionnaire/primarily from the subject self-design vs. using existing or translated translate existing Foreign questionnaire read validation reports/instructions carefully –observation/use of markers/informants –secondary utilization of care: from NHI or hospital records use existing data base of previous researches

26. outcome research 26 Multiple outcomes/endpoints Positive side –enrich the results –take care of different aspects/time frames Negative side –confusing: which one is the most important? –opportunistic: one significant is significant

27. outcome research 27 Putting all information together Construct a composite index –QALY or QAS –QOL * survival Develop a time-sequence model –time-dependent predictors eg. weight, cholesterol –path analysis