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Challenges in cost-utility analysis in the critical care setting { Ville Pettilä MD, PhD, A/P Helsinki University Hospital SFAI- veckan / Kalmar CCM 2006 CCM 2006 - only 19 papers - max $958,423/ QALY -$1,150 - $575,000 / life-year - many < $50,000 /QALY - 41 studies in critical/intensive care quality assessed as poor to moderate Boston- CEA RegistryQuality of cost-utility analyses { .. In the ideal world Sintonen 1994 { ARDS N=200 Angus D AMJRCCM 2001 Quality-adjusted survival Angus DC et al. CCM 2006 Challenge No 1: Inter-patient variability { Costs and QALYs – the real world in the ICU Cost-effectiveness planes for a treatment Räsänen P et al. HQLO 2006 Crit Care Med 2003 Challenge No 2: Inter-diagnoses variability { Challenge No 3: How to adjust for non-survivors? { Angus D et al. CCM 2006 Challenge No 4: Which instrument to use for quality of life (QOL)? { { SF- (RAND- 36) EQ-5D Nottingham Health Profile (NPH) SIP etc. (1) What is an OPTIMAL QOL measure ? EQ-5D *simple *ESICM recommendation *one number between 0 and 1 * enables QALY calculations { (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? (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 ! { (4) QOL- follow-up and adjustment ? { Were all patients followed ? What is the optimal time for QOL measurement ? Dowdy et al ICM 2006 - 8894 references - 111 studies - 21 different patient populations - 21 studies included - Different instruments, patient populations Dowdy et al. ICM 2005 Challenge No 5: How to calculate/ estimate quality of life (QOL)? { Challenge No 6: { How accurate are the costs? Indirect costs ? Costs after hospital discharge? Challenge No 7: { What is the time-frame? Should it be life-time? Kaarlola A, Tallgren M, Pettilä V CCM 2006 QALYs after critical care [N=2873] Kaarlola et al. CCM 2006 Cost-utility after intensive care [N=2873] Kaarlola et al. CCM 2006 Cost per QALY in severe sepsis (Finnsepsis study) N=480 Key finding: The estimated life-time cost-utility using QOL at 2 years after discharge is very reasonable (median 1720€/QALY) { Karlsson et al CCM 2009 Cost per QALY in acute respiratory failure (FINNALI study) N=958 Cost (euro) QALY (year) 40000 50 35000 45 40 30000 35 25000 30 20000 25 15000 20 cost, mean 15 10000 10 5000 5 0 0 1624 2534 3544 4554 5564 6574 cost/QALY, mean QALY, mean 74- >81 80 Age groups 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-utility – acute respiratory failure – life-time scale –FINNALI -2007 n Gained survival (yrs) QALYs (yrs) Cost/hospital survivor Cost/QALY mean (SD) mean (SD) € € Age (yrs) ≤51 252 36 (19) 25 (16) 19195 670 52-63 236 17 (11) 11 (8) 21069 1582 64-74 251 9 (8) 6 (6) 21499 2620 ≥75 219 4 (5) 3 (3) 21737 5263 ≤31 253 28 (18) 20 (15) 15187 726 32-43 246 18 (16) 11 (12) 22545 1656 44-55 222 13 (15) 8 (11) 23565 2026 ≥56 237 8 (13) 5 (9) 24760 2560 Elective 133 16 (14) 12 (12) 17273 1283 Emergency 821 17 (18) 11 (13) 21462 1410 NIV only 105 15 (17) 11 (14) 13154 956 Invasive ventilation only 775 17 (17) 12 (13) 20065 1313 NIV and invasive ventilation before 6 hours 43 11 (16) 6 (9) 42625 3733 NIV and invasive ventilation after 6 hours 35 13 (17) 8 (11) 44971 3499 Sepsis 136 14 (15) 9 (12) 37219 2599 Cardiac insufficiency 192 9 (12) 6 (8) 27322 2779 Pneumonia 114 14 (16) 9 (12) 26368 2106 Post-operative with ventilatory support<1 day 132 17 (15) 12 (12) 11025 836 SAPS II (points) Admission type Ventilatory support ARF risk factors 48 hours before Linko et al Critical Care 2010 Challenge No 8: Discount for costs and QALYs included in the calculations? { Challenge No 9 How to present willingness to pay and probabilities? { Challenge No 9: How to present willingness to pay and probabilities? CEACcost effectiveness acceptability curve { Cost-effectiveness acceptability curves-CEACs Subgroups of patients according to gained QALYs Conclusions Cost utility studies in critical care lack scientific validity and robustness Conclusions 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 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 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