Rubicon of pharmacoeconomics

Transcription

1 Rubicon of pharmacoeconomics Assoc. Prof. Mitja Kos, M.Pharm., Ph.D. Head, Chair of Social Pharmacy, University of Ljubljana- Faculty of Pharmacy Web:

2 Topics for today Rationale for pharmacoeconomics Outcomes research Study perspective Modelling in pharmacoeconomics What is a cost-effective strategy Health technology assesment Pharmacoeconomics in Slovenia Your wishes

3 Gáj Júlij Cézar (ca pr.n.št.)

4

5 What are the key policy issues/trends in health care? Do we have anything in common?

6 Health Policy Issues Growth in healthcare expenditures: Ageing population Advancements in medical technologies Increasing demands of regulatory bodies Rising expectations of the patients and consumers Limited healthcare budget

7 EUR per capita Targeted oncology drugs Accessibility in EUR per capita 20 IMS data Austria Croatia France Germany Hungary Italy Slovenia UK Obradović M, Mrhar A, Kos M. Market Uptake of Biologic and Small-Molecule Targeted Oncology Drugs in Europe. Clin Ther Dec;31(12):

8 Market share (%) Targeted onc.drugs vs oncology drugs Market share of targeted oncology drugs within the market of oncology drugs (EphMRA=L1&L2) in the selected European countries from 1997 to IMS data Austria Croatia France Germany Hungary Italy Slovenia UK Obradović M, Mrhar A, Kos M. Market Uptake of Biologic and Small-Molecule Targeted Oncology Drugs in Europe. Clin Ther Dec;31(12):

9 What is the key selection criteria?

10 Effectiveness / benefit! What if can not afford all?

11 EUR Drug price => cost A B ciena/trošak

12 Are there any other costs we should take into account when deciding for a certain drug?

13 Could be any similar case!

14 Direct Medical Cost Directly connected with material and medical services: Hospitalisation, Healthcare providers, Laboratory testing, Diagnostics, Drugs: Drug acquisition cost, Monitoring costs, Administration costs, Adverse effects costs Medical Direct Cost Non- medical Indirect Intangible

15 EUR Direct Medical Cost Strategija Strategy A A Strategija Strategy B B 0 zdravilo neželeni učinki hospitalizacija laboratorijski Skupaj Drug Adverse Hospitalisation Lab testi test Sum drug effect

16 EUR Direct Medical Cost Strategija Strategy A A Strategija Strategy B B zdravilo Drug neželeni Adverse učinki drug effect hospitalizacija laboratorijski Skupaj Hospitalisation Lab testi test Sum

17 Economic outcomes Cost Direct Indirect Intangible Medical Non- medical Treatment strategy

18 Direct Medical Cost Cost directly connected with medical services & material: Hospitalisation, Healthcare providers, Laboratory testing, Diagnostics, Drugs: Drug acquisition cost, Monitoring costs, Administration costs, Cost- adverse effects Medical Direct Cost Non- medical Indirect Intangible

19 Direct Medical Cost Fixed: do not change with the amount of service Building, overheads Variable: Drugs, test, material Services Cost Direct Indirect Intangible Medical Non- medical

20 Direct Non-medical Cost Direct cost as a consequence of disease without medical cost of material and services Transportation, Family care, Care givers, Special food Cost Direct Indirect Intangible Medical Non- medical

21 Indirect Cost Cost of lost or reduced productivity resulting from morbidity or premature mortality due to a medical conition or treatment Work loss (days missed from work) SLO average: 30,8 days/ employee (3rd EU-27) Lost productivity while at work (disabled ) Premature death Cost Direct Indirect Intangible Medical Non- medical

22 Intangible Costs Costs assigned to the amount of suffering that occur because of the disease or healthcare intervention Pain Suffering Inconvenience Cost Direct Indirect Intangible Medical Non- medical

23 Discounting P i n 0 Fn (1 r) n P= overall cost F= cost per year n r= discount rate n= year i= number of years LETO STROŠEK PROGRAMA A (EUR) STROŠEK PROGRAMA B (EUR) % % %

24 Case: Vaccine against HPV Perspective: - Patient - Parents - Health care payer - Society - Health care providers

25 Study perspective Patient Health care payer Society Health care providers...

26 Partial evaluation Only Costs => economic outcomes: Burden of ilness: total cost an ilness represents to society Only Consequences: Clinical and humanistic outcomes

27 Donabedian model & Outcomes Research Structure Process Kozma Outcomes

28 Clinical Outcomes Survival/mortality Morbidity: Strokes Fractures MIs

29 Humanistic Outcomes Health related quality of life (QoL) Patient satisfaction Patient preferences/utilities

30 Quality of Life The value assigned to duration of life as modified by the impairments; physical, social and psychological functional states; perceptions and opportunities that are influenced by disease, injury, treatment, or policy Data more meaningful to patients than that typically collected in clinical trials

31 Patient Satisfaction A measurement that focuses on the effectiveness perceived by the patient regarding the consequence of the use of healthcare products, services or programs offered by the practitioner

32 Utility Assesment Similar to QoL values but not equal Different in that QoL is more descriptive where utility assesment involves making decisons in the face of risk and uncertainty (gambles and trade- offs)

33 Humanistic outcomes & Pheco Utility: Perfect health 1 + death 0

34 Utility Utež- uporabnost Quality Adjusted Life Years (QALY) 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 A B 0, Time Čas

35 Utility Utež- uporabnost Quality Adjusted Life Years (QALY) 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 A B 0, Time Čas

36 Utility Utež- uporabnost Quality Adjusted Life Years (QALY) 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 A B B 0, Time Čas

37 Direct methods Standard gamble Time trade-off Rating scale

38 Standard gamble 1-p p Immediate death 100% health Current health

39 Time trade-off t2 100% health t2<t1 t1 Current health

40 Rating scale Does not include uncertainty.

41 Indirect methods for utility assessment Mapping of questionnaires Euro-Qol 5-D, Heath Utility Index 1,2,3 SF-6D Fast & simple

42 EQ-5D Euro-Qol 5-D

43 Quality of life methods

44 Pharmacoeconomics Description and analysis of costs and consequences of interventions and their impact on individuals, health care system and society.

45 Full evaluation Cost-Minimisation Analysis Δ EUR, Effect1=Effect2 Cost-Effectiveness Analysis Δ EUR, Effect1 Effect2 Cost-Utility Analysis Δ EUR/ QALYG Cost-Benefit Analysis Δ EUR/ ΔEUR

46 Type of study? Outcomes?

47 Time horizon?

48 Types of Studies Clinical Studies Observational Studies Model Studies

49 Model Studies Represent the real world with a series of numbers and mathematical/statistical relationships Most common: Decision analysis Markov modeling Other e.g.: Discrete Event Simulation Transition models

50 Decision analysis Problems and processes disaggregated into components that form a model: Possible events (decision, unceratinties, and endpoints) with Relationship among them Decision tree: A branching structure in which each node represents an event that may take place in the future.

51 Decision tree stabilna bolezen 0,5 odziv brez odziva podzi vgef gefitinib # Najboljša podporna oskrba pb S CGef napredovala bolezen # vinorelbin/cisplatin pr ed 1V in Ci s gemcitabin/cisplatin Terapija 2. reda # pred 1GemCis gemcitabin/karboplatin pred 1GemK ar paklitaksel/karboplatin pr ed 1P akk ar odziv EGFR+ bolnik z adenokarcinomom III/IV vinorelbin/cisplatin stabilna bolezen 0,5 podzivv in Cis brez odziva # Najboljša podporna oskrba napredovala bolezen # pb S C Terapija 2. reda # erlotinib p2 Re dc ite rl docetaksel p2 Re dcitdoc gemcitabin/cisplatin [+] gemcitabin/karboplatin [+] paklitaksel/karboplatin [+] pemetreksed/cisplatin [+]

52 Case: Investment of $1000 Risky investment: Huge profit 500 $, probability 30% Small profit 100 $, probability 40% Huge loss -600 $, probability 30% Bank: 5% interest

53 Case: Investment of $1000 Where Kam investirati to $1000? Stock Tvegana market investicija Banka 5% 5% interest obresti 50 Velik Huge dobicek profit 0,3 Small profit Majhen dobicek 0,4 Velika Huge loss izguba 0,

54 Case: Expected value $10 Where Kam investirati to $1000? Stock Tvegana market investicija Banka 5% 5% interest obresti $50 50 Velik Huge dobicek profit 0,3 Small profit Majhen dobicek 0,4 Velika Huge loss izguba 0,

55 Case: Blindness Clinical signs of a possible, but not certain, early-stage autoimmune disorder Disorder: 50% of cases with signs If the condition is present, and if it progresses, blindness will result. Disorder leads to blindness in 12% of cases ($ ) An imperfect test can help determine whether an individual has the disorder ($ 150): Sensitivity= 80% True positive / (true positive + false negative) Specificity= 100% True negative / (true negative + false positive) Treatment: Relatively effective (98,7%) and cheap ($ 680) Adverse effects: included in cost and QALY.

56 Case: Blindness

57 Markov models Andrej Andrejevič Markov Russion mathematician Stochastic (random, nondeterministic) processes

58 Case: cancer in a decision tree Asymptomatic state Progression Death

59 Markov model 1. Define health states and transitions: Absorbing state 2. Markov cicle 3. Allocation of cost and benefits Asimptomatična faza p prog p smrt Progresivna faza p smrt + p smrtbolezen Smrt

60 What is a cost-effective strategy?

61 Cost (EUR) Stroški (EUR) Cost effectiveness graph A ,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Effectiveness Učinkovitost (%)

62 C/E Cost-effectiveness ratio, C/E

63 Cost (EUR) Stroški (EUR) C/E= const a ,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Effectiveness Učinkovitost (%)

64 Cost (EUR) Stroški (EUR) Alternative= B, C/E b a ,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

65 Cost (EUR) Stroški (EUR Alternatives: new B & A B3 b B a B1 A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Effectiveness Učinkovitost (%)

66 Cost (EUR) Stroški (EUR B2 vs A b B a A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

67 Cost Absolute dominance Dominated strategies Reference Effectivenes Dominant strategies Cost effectiveness graph

68 Absolutely dominated strategy When an alternative strategy (dominant) exist that is cheaper and more effective.

69 Cost (EUR) Stroški (EUR B3 vs A B3 b a A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

70 Cost (EUR) Stroški (EUR ICER Incremental cost-efectiveness ratio, ICER ΔC/ ΔE B3 b a A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

71 Fiat

72 Mercedes-Benz

73 Health care budget Fixed budget: Realocation of sources? Loosly fixed budget: Threshold ICER: Europe: EUR/QALYG SLO- Health Council: and EUR/QALYG SLO- Dialysis standard: EUR/QALYG & EUR/LYG FFA- Willingness to pay for a life-year gained from the societal perspective: EUR/LYG

74 Health care budget NICE: Appraising life-extending, end of life treatments, > treshold ICER= /QALYG CEoL.pdf

75 Cost (EUR) Stroški (EUR) ICER vs C/E, alternative= B A ,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

76 Cost (EUR) Stroški (EUR) B1 vs S & A b a S B1 A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Učinkovitost (%) Effectiveness (%)

77 Extended dominance ICER higher than the next more effective stratgey B1 ICER A A ICER B1 S

78 Cost (EUR) Stroški (EUR) Efficient frontier Efficient frontier or cost-effective frontier: connectes all strategies that are not dominated B3 b a S A 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 Effectiveness (QALY) Učinkovitost (%)

79 Case: blindness Ne zdravi Motnja prisotna pmotnja Brez motnje # Slepota pslepost_bz Brez slepote # 0 / 13, / 6,936 0 / 11,56 Moznosti zdravljenja pm OTNJA=0,5 pslepost_bz=0,12 pslepost_z=0,013 test_obcutljivost=0,8 test_specificnost=1, Biopsija Zdravi vse Motnja prisotna pmotnja Brez motnje # Motnja prisotna pmotnja Brez motnje # Pravilen pozitivni test, zdravi z zdravilom test_obcutljivost Napacen negativni test, ne zdravi # Napacni pozitvni test, zdravi z zdravilom # Pravilen negativni test, ne zdravi test_specificnost Slepota pslepost_z Brez slepote # 680 / 12,565 Slepota pslepost_z Brez slepote # Blindness pslepost_bz Brez slepote # 830 / 12, / 13, / 7, / 12, / 7, / 12, / 6, / 11,556 SF-FFA

80 Cost Case: blindness Cost-Effectiveness Analysis At Moznosti zdravljenja $ 2.500,0 $ 2.300,0 $ 2.100,0 $ 1.900,0 $ 1.700,0 $ 1.500,0 $ 1.300,0 $ 1.100,0 $ 900,0 12,30 QALYs 12,60 QALYs 12,90 QALYs Ef fectiveness Ne zdravi Biopsija Zdravi takoj SF-FFA

81 Case: blindness Text report Strategy Cost Incr Cost Eff Incr Eff C/E Incr C/E (ICER) Zdravi takoj $ 940,0 12,53 QALYs 75 $/QALY Biopsija $ 1.110,0 $ 170,0 12,89 QALYs 0,36 QALYs 86 $/QALY 474 $/QALY Ne zdravi $ 2.400,0 $ 1.290,0 12,30 QALYs -0,59 QALYs 195 $/QALY (Dominated) TABLE 2 - all options referenced to a common baseline Zdravi takoj $ 940,0 12,53 QALYs 75 $/QALY Biopsija $ 1.110,0 $ 170,0 12,89 QALYs 0,36 QALYs 86 $/QALY Ne zdravi $ 2.400,0 $ 1.460,0 12,30 QALYs -0,23 QALYs 195 $/QALY TABLE 3 - without dominated options (simple or extended) Zdravi takoj $ 940,0 12,53 QALYs 75 $/QALY Biopsija $ 1.110,0 $ 170,0 12,89 QALYs 0,36 QALYs 86 $/QALY 474 $/QALY TABLE 2 - all options referenced to a common baseline TABLE 3 - without dominated options (simple or extended) Dominance Report: The strategy "Ne zdravi" is dominated by "Biopsija". Extended Dominance Report: No strategies were eliminated by extended dominance. SF-FFA

82 Sensitivity analysis Simple sensitivity analysis Probabilistic sensitivity analysis (PSA)

83 Cost Case: blindness Sensitivity Analysis on test sensitivity test_obcutljivost = 0,79 $ 2.500,0 $ 2.300,0 $ 2.100,0 $ 1.900,0 $ 1.700,0 $ 1.500,0 $ 1.300,0 $ 1.100,0 $ 900,0 $ 700,0 12,300 QALYs 12,700 QALYs Ef fectiveness Ne zdravi Biopsija Zdravi vse SF-FFA

84 Cost Case: blindness Sensitivity Analysis on test sensitivity test_obcutljivost = 0,91 $ 2.500,0 $ 2.300,0 $ 2.100,0 $ 1.900,0 $ 1.700,0 $ 1.500,0 $ 1.300,0 $ 1.100,0 $ 900,0 $ 700,0 12,300 QALYs 12,700 QALYs Ef fectiveness Ne zdravi Biopsija Zdravi vse SF-FFA

85 Stroški (EUR) Cost (EUR) Probabilistic sensitivity analysis E D B C A 0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0 Effectiveness Učinkovitost (QALY)

86 Δ C ICER graph (e.g. strategy E vs C) Threshold ICER Δ E

87 Frequency Frekvenca ICER distribution ICER (EUR/QALYG)

88 Δ C ICER graph EUR/QALY EUR/QALY EUR/QALY Δ E

89 Probability Verjetnost (%) Cost-effectiveness acceptability curve Threshold mejni ICER ICER

90 Cost Case: gefitinib Cost-Effectiveness Analysis At EGFR+ bolnik z adenokarcinomom III/IV 29K EUR 28K EUR 27K EUR 26K EUR 25K EUR 24K EUR 23K EUR 22K EUR 21K EUR 20K EUR 19K EUR 18K EUR 17K EUR 16K EUR 15K EUR 14K EUR 13K EUR 12K EUR 0,930 QALY 1,030 QALY 1,130 QALY Ef fectiveness gefitinib vinorelbin/cisplatin gemcitabin/cisplatin gemcitabin/karboplatin paklitaksel/karboplatin pemetreksed/cisplatin Extended Dominance: 0,052 <= k <= 0,331 0,054 <= k <= 0,484

91 Cost Case: gefitinib CE Scatterpl ot 36K EUR 31K EUR 26K EUR gefitinib vinorelbin/cisplatin gemcitabin/cisplatin gemcitabin/karboplatin paklitaksel/karboplatin pemetreksed/cisplatin 21K EUR 16K EUR 11K EUR 0,80 QALY 1,00 QALY 1,20 QALY 1,40 QALY Ef fectiveness

92 Proportion Cost-Effective Case: gefitinib Acceptability Curve 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 0K 15K 30K 45K 60K 75K 90K Willingness to Pay gefitinib vinorelbin/cisplatin gemcitabin/cisplatin gemcitabin/karboplatin paklitaksel/karboplatin pemetreksed/cisplatin

93 Application Optimal allocation of financial resources in Healthcare Negotitation of drug prizes Formulation of formularies Ph industry decisions: In all phases of drug development e.g. R&D, clinical studies, regulatory issues, marketing Clinical practice: optimal treatment guidelines

94 What is HTA?

95 Health technology Can be defined as any intervention that may be used to promote health, to prevent, diagnose or treat disease or for rehabilitation or long-term care. This includes the pharmaceuticals, devices, procedures and organizational systems used in health care.

96 Health technology assessment (HTA) A multidisciplinary process that summarizes information about the medical, social, economic, and ethical issues related to the use of health technology in a systematic, transparent, unbiased, robust manner.

97 Is HTA in place in your country? Where do you see its elements?

98

99

100

101

102

103 Is pharmacoeconomics used in decision making in your country?

104 Should pheco be used as an explicit criteria?

105 Elementi HTA v Sloveniji Health Council (Zdravstveni svet) Splet: Postopek za vloge: Medicinal products among technologies: Registration: quality, safety, effectivenes Javna agencija za zdravila in medicinske pripomočke: European medicines agency (EMA): Bylaw on medicinal products prizes: Pravilnik o cenah zdravil za uporabo v humani medicini Bylaw on list allocation: Pravilnik o razvrščanju zdravil na listo Poenotenje postopka ambulantna bolnišnična zdravila

106 HTA council/network/agency?

107 Topics for today Rationale for pharmacoeconomics Outcomes research Study perspective Modelling in pharmacoeconomics What is a cost-effectives strategy Health technology assesment

108 Gáj Júlij Cézar (ca pr.n.št.) Alea iacta est! Kocka je pala!