1. { Challenges in cost-utility analysis in the critical care setting Ville Pettilä MD, PhD, A/P Helsinki University Hospital 23.9.2011 1 VP SFAI- veckan / Kalmar

2. CCM 2006

3. - only 19 papers - max $958,423/ QALY -$1,150 - $575,000 / life-year - many < $50,000 /QALY -

4.   41 studies in critical/intensive care   quality assessed as poor to moderate

5. Boston- CEA Registry- Quality of cost-utility analyses

6. {.. In the ideal world 23.9.2011 6 VP

7. Sintonen 1994

8. {

9. 23.9.2011VP 9

10. Angus D AMJRCCM 2001 ARDS N=200

11. Angus DC et al. CCM 2006 Quality-adjusted survival

12. { Challenge No 1: Inter-patient variability

13. Costs and QALYs – the real world in the ICU

14. Räsänen P et al. HQLO 2006 Cost-effectiveness planes for a treatment

15. Crit Care Med 2003

16. { Challenge No 2: Inter-diagnoses variability

18. { Challenge No 3: How to adjust for non-survivors?

19. Angus D et al. CCM 2006

20. { Challenge No 4: Which instrument to use for quality of life (QOL)?

21. { (1) What is an OPTIMAL QOL measure ?   SF- (RAND- 36)   EQ-5D   Nottingham Health Profile (NPH)   SIP   etc.

22. {   EQ-5D   *simple   *ESICM recommendation   *one number between 0 and 1   * enables QALY calculations

23. { (2) QOL – target population ?   selected vs. unselected   defined vs. all   trauma ?, sepsis? ARDS?   timing of measurement 6(-12) months post/ICU ?   a cohort or an RCT?

24. { (3) QOL- missing data   Proportion of missing data - < 10%?   How to handle missing data ?   Comparison of patients with missing data to those with available data !   Adequate sample size !

25. { (4) QOL- follow-up and adjustment ?   Were all patients followed ?   What is the optimal time for QOL measurement ?

27. Dowdy et al ICM 2006

28. - 8894 references - 111 studies -21 different patient populations -21 studies included -Different instruments, patient populations Dowdy et al. ICM 2005

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31. { Challenge No 5: How to calculate/ estimate quality of life (QOL)?

32. { Challenge No 6: How accurate are the costs? Indirect costs ? Costs after hospital discharge?

33. { Challenge No 7: What is the time-frame? Should it be life-time?

34. Kaarlola A, Tallgren M, Pettilä V CCM 2006

35. QALYs after critical care [N=2873] Kaarlola et al. CCM 2006

36. Cost-utility after intensive care [N=2873] Kaarlola et al. CCM 2006

37. { Cost per QALY in severe sepsis (Finnsepsis study) N=480 Karlsson et al CCM 2009 Key finding: The estimated life-time cost-utility using QOL at 2 years after discharge is very reasonable (median 1720€/QALY)

38. Mean of costs, costs/QALYs and estimated QALYs with 95% CIs in different age groups for acute respiratory failure patients. FINNALI, Linko et al. Critical Care 2010 Cost per QALY in acute respiratory failure (FINNALI study) N=958 23.9.2011 38 VP

39. Table 3. Predicted cost-utilities in subgroups of patients with acute respiratory failure. n Gained survival (yrs)QALYs (yrs) Cost/hospital survivor Cost/QALY mean (SD) € € Age (yrs) ≤5125236 (19)25 (16)19195 670 52-6323617 (11)11 (8)21069 1582 64-742519 (8)6 (6)21499 2620 ≥752194 (5)3 (3)21737 5263 SAPS II (points) ≤3125328 (18)20 (15)15187 726 32-4324618 (16)11 (12)22545 1656 44-5522213 (15)8 (11)23565 2026 ≥562378 (13)5 (9)24760 2560 Admission type Elective13316 (14)12 (12)17273 1283 Emergency82117 (18)11 (13)21462 1410 Ventilatory support NIV only10515 (17)11 (14)13154 956 Invasive ventilation only 77517 (17)12 (13)20065 1313 NIV and invasive ventilation before 6 hours4311 (16)6 (9)42625 3733 NIV and invasive ventilation after 6 hours3513 (17)8 (11)44971 3499 ARF risk factors 48 hours before Sepsis13614 (15)9 (12)37219 2599 Cardiac insufficiency1929 (12)6 (8)27322 2779 Pneumonia11414 (16)9 (12)26368 2106 Post-operative with ventilatory support<1 day13217 (15)12 (12)11025 836 Chronic diseases: chronic obstructive pulmonary disease, chronic restrictive pulmonary disease, chronic heart disease, diabetes mellitus, immunodeficiency, neuromuscular disease Linko et al. Critical Care 2010 accepted Cost-utility – acute respiratory failure – life-time scale –FINNALI -2007 Linko et al Critical Care 2010 23.9.2011 39 VP

40. { Challenge No 8: Discount for costs and QALYs included in the calculations?

41. { Challenge No 9 How to present willingness to pay and probabilities?

42. { Challenge No 9: How to present willingness to pay and probabilities? CEAC- cost effectiveness acceptability curve

43. Cost-effectiveness acceptability curves-CEACs Subgroups of patients according to gained QALYs

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46.  Cost utility studies in critical care lack scientific validity and robustness Conclusions 23.9.2011VP 46

47.  Cost utility studies in critical care lack scientific validity and robustness  No consensus regarding utility instrument, calculations, adjustment for missing data, and representation of data exist Conclusions 23.9.2011VP 47

48.  Cost utility studies in critical care lack scientific validity and robustness  No consensus regarding utility instrument, calculations, adjustment for missing data, and representation of data exists  At their best the available cost utility studies in critical care may be seen as clinically valuable estimations of benefit/ harm of the treatment Conclusions 23.9.2011VP 48

49. Conclusion Cost-utility –studies…. …..the gold standard 1. Representative non-selected population 2. Defined diagnostic group 3. Standardized utility instrument 4. Life-time scale for QALYs gained 5. Preferably all hospital costs/reliable estimate 6. Discount rate 7. Sensitivity analysis regarding different age and severity of disease 8. Cost-effectivenss plane 9. CEA-curve 23.9.2011 49 VP