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Qualità della Vita Legata allo Stato di Salute in

Farmacoeconomia

Luciana Scalone

Centro di FarmacoeconomiaUniversità degli Studi di Milano

Problem

• Needs are unlimited• resources are limited• Resources allocated (devoted) to an intervention can

not be allocated to another one• Somebody has to decide which interventions will be

financed and the priorities

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Trends

Increase of health care expenditure, incompatiblewith the increase of GDP (last two decades)

REASONS• Population ageing• Increase of expectacies• Modern technologies, more effective and more costly• Intercations between these aspects

Population ageing

Proportion of people aged > 60 years (%)36

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35 3330 29 28

2018 19

2217

ITALY GERMANY JAPAN FRANCE UK USA

19902030

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Approaches to the problem

Rationing vs Rationalising(cost containment) (maximun outcome from

available resources)

• Rationing: Uni-dimensioanl task because the expenditure is the only target variable

• Ratioanlising: bi-dimensional task because costs are referred to outcomes

EconomicsEconomics isis... ... ““... ... study of how societies use scarce resources to

produce valuable commodities and distribute them among different people””

PaulPaul A A SamuelsonSamuelson, Nobel Laureate 1970, Nobel Laureate 1970

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maximizingutility resourceslimitedapplicable to alternative uses

Economics

Pharmaco-

application to the pharmaceuticalcontext of

-Economics

•Maximization•Utility•Resources•Scarcity•Alternative uses

Pharmacoeconomics

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Pharmacoeconomics

It is a research method that estimatesthe costs and the outcomes of medical

technologies to comparealternative approaches, at least one

concerning drug therapy

Key elements

• COSTS• EFFECTS• ALTERNATIVES• PERSPECTIVE• TECHNIQUE• TIME HORIZON• SENSITIVITY

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CostsCosts and and EffectsEffects of of anan InterventionIntervention

CCC EEE

++ =+ +

Costs and effectsCosts and effects

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Costs and Effects

Direct

Indirect

Intangible

Not medical

medical

Alternatives

• Pharmacological• Not Pharmacological• No intevention

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Perspective

• Third-party payer• Services supplyers• Patient

Society

Techniques

• Cost Effectiveness Analysis (CEA)• Cost Minimization Analysis (CMA)• Cost Utility Analysis (CUA)• Cost Benefit Analysis (CBA)

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Clinical parametersSurvival

LYS/LYG

Cost effectiveness analysis (CEA)

Quality adjusted life yearsQALY’s

Cost utility analysis (CUA)

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Cost benefit analysis (CBA)

Possible results

Effe

ct

Evaluate

REFUSE

ACCEPT(dominant)

Evaluate

-

-Cost+

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Cost-benefit analysis ’70s, criticismCost-effectiveness analysis ’80s, life expectancyCost-utility analysis ’90s, quality of life, utilitiesCost-benefit analysis going beyond health outcomes

Techniques

• Before 70s the tool most commonly used was CBA, but concerns were raised over whether it was ethical and possible to value human life in monetary terms. This led to the adoption of the CEA

• In 80s an extension of CEA was promoted, to consider not just the “quantity of life” but also the “quality” of that life (QALYs). The focus of QALYs was anyway on health outcomes

• In 90s a debate began concerning the inclusion of non health outcomes (waiting time, location of treatment). This led to the reintroduction of CBA

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Quality of Life

• In the past, the most important objective in healthcare was the recovery from the diseases and the survival

Quality of Life

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• As a result of successful technologies, years have been added to the life of individuals

• As a result of higher life expectancy, the incidence and prevalence of chronic diseases suchas cancer, CVD and dementia have beenincreasing

• People often live with these conditions for manyyears

Quality of Life

• People, in general healthier and wealthier than in the past, have higher expectations: they expectmore than just being alive

• So, more people live longer, but perhaps some of them might feel their longer life is not worthliving!

Quality of Life

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Definition of Quality of Life (QoL)

• Difficult. The most widely used definition is the one by the World Health Organization (The WHOQOL Group, 1995):

“ QoL is individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, concerns. …term incorporating physical health, psychological state, level of indipendence, social relationships”

Definition of Quality of Life (QoL)

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• The impact of an accident/disease and of the relatedtreatment on involved individuals’ QoL

Health Related Quality of Life (HRQoL) is

• The interest in measuring QoL in health care hasincreased in last 2 decades

• Many instruments have been developed and used

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Instruments

• Generic vs Specific• Indexes vs profiles• Self administered, interview, proxy responders• Paper, computer based• etc

Instruments

• Generic vs Specific• Indexes vs profiles• Self administered, interview, proxy responders• Paper, computer based• etc

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Instruments

• Generic vs SpecificGeneric instruments: evaluate HRQoL as a whole.

Appliable to a wide range of different people withdifferent type and severity of diseases, different cultures. Useful for comparinsons and decision-making acrossdifferent diseases and interventions

Specific instruments: have been developed on specificgroups. They focus on the phenomenon of interest, can be more sensitive, more acceptable, do not allowcomparisons

EQ-5D profile

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EQ-5D VAS

Examples of clinical areas where EQ-5D is used

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Available language versions

In which countries EQ-5D is being used?

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Instruments

• Generic vs SpecificGeneric instruments: evaluate HRQoL as a whole.

Appliable to a wide range of different people withdifferent type and severity of diseases, differentcultures…Useful for comparinsons and decision-makingacross diseases, interventions

Specific instruments: have been developed on specificgroups. They focus on the phenomenon of interest, can be more sensitive, more acceptable, do not allowcomparisons

ISSQoL

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Instruments

• Indexes vs profilesThe index is a number quantifying HRQoLThe profile describes HRQoL in their domains

Index

0 (death)

100 (perfect health)

80

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Instruments

• Indexes vs profilesThe index is a number quantifying HRQoLThe profile describes HRQoL in their domains

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EQ-5D profile

Test Chi-quadrato (2X2):

0.046 0.007 0.037 NS NS

32.3%47.6%

77.4%93.7%

55.4%72.6%

19.6%28.6%51.2%58.1%

67.7%52.4%

21.4%6.3%

43.5%27.4%

73.8%69.8%

43.4%38.7%

0.0%1.2% 1.6%6.5%0.0% 0.0% 1.2% 0.0% 5.4% 3.2%

0%

20%

40%

60%

80%

100%

mobility self-care usual activities pain/discomfort anxiety/depressionsevere problemssome problemsno problem

sev mod sev mod sev mod sev mod sev mod

COCHE Study, podium presentation at ISPOR, 6-8 November 2005

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SF-36

PF=Physical Functioning, RP=Role-Physical, BP=Bodily Pain, GH=General Health, VT=Vitality/Energy, SF=SocialFunctioning, RE=Role-Emotional, MH=Mental Health

67.0 62.857.8

45.6

61.069.5 68.6 68.8

59.150.5

88.282.2 78.8

68.8 66.1

80.5 80.0

43.1

53.7

63.566.3

71.370.0

71.3

0

20

40

60

80

100

PF RP BP GH VT SA RE MH

COCHE (232)

COCIS (50)

Italian malepopulation (999)

COCHE Study, podium presentation at ISPOR, 6-8 November 2005

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Instruments

• Indexes vs profilesThe index, if appropriate, can be used in economic

evaluations (CUAs)The profile can be more useful in clinical practice

Quality adjusted life yearsQALY’s

Cost utility analysis (CUA)

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Utility valueUtility value

0death

1Perfecthealth

0,5

0,48

Computing the QALYComputing the QALY

1 year of lifeWith utility level = 0.48

6 months of life With perfect health

(Utility x years of life) = QALY

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HRQoL and utility index

• To be considered in economic evaluations, HRQoL has tobe given a value

• Indicator of that value is the maximum amount of a resource the individual is willing to give up to have higher levels of HRQoL, according to his/her preferences

• These preferences depend on his/her current health state perception, expectations etc

• The higher the willingness to give up, the lower the value given to the current HRQoL

Instruments to estimate utility

VAS (does not consider preferences)Standard GambleTime Trade OffDiscrete Choice Experiment

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Index

0 (death)

100 (perfect health)

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Standard Gamble

CurrentHealthstate

Current health state

UncertainTotal recovery: P

Death: 1 - P

Certain

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50 years old men.Choose between 2 alternatives:

1-Do not accept and stay in the current state = 21222

2-accept and you can have:better state = 11111 with porworse state = 33333 with 1-p

Time-Trade-Off

X T

Health i

Life duration (years)

Health y

Health y = current health stateHealth i = health state with better quality of life but shorter duration

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50 years old men.Choose between 2 alternatives:

1-Current state for the next 35 years = 21223

2-Better state = 11111 until deathin 35-x years

Discrete Choice Experiment

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Discrete Choice Experiment

• Choice-based method• The individual chooses between alternatives• By sacrifying the benefit of something, he/she

will have the benefit from the alternative at his/her disposal

• By making this choice, the individual gives his/her own value to the good/service and itscharacteristics

DCE• Based on Lancaster’s theory: a good is a set of attributes and the

value of the good is a function of each attribute of the good;• Based on random utility theory,• consistent with the neoclassic economic theory

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DCE• Based on Lancaster’s theory: a good is a set of attributes and the

value of the good is a function of each attribute of the good*;• Based on random utility theory,• consistent with the neoclassic economic theory

* Lancaster, 1966

650 € for 1000 UI (plasma-derived)929 € for 1000 UI (Second generation recomb fact)1115 € for 1000 UI (+20% of 929)

Price

Home deliveryCommunity pharmacy Hospital/Local Health Unit

Distribution modes

Lyophilized material for reconstitutionReady-to-use solutionPharmaceutical dosage form

Thrice a weekTwice a weekOnce a week

Factor infusion frequency onprophylaxis

Current (1/4 in PUPs)Reduced (1/6 in PUPs)Very reduced (1/10 in PUPs)

Risk of inhibitor development

Second generation recombinant factorsVery highly purified plasma derived factorsPerceived viral safety

LevelsAttributes

Characteristics and levels

Mantovani et al, Haemophilia, 2005

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DC model• Based on Lancaster’s theory: a good is a set of attributes and the

value of the good is a function of each attribute of the good;• Based on random utility theory*,• consistent with the neoclassic economic theory*

* Thurstone, 1927, McFadden, 1973; Manski, 1977

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Neoclassical economic theory

Assumption: the decision-maker is able to compare some alternatives(choice set) using a preference-indifference operator “>”

Using the “>” operator is equivalent to assigning a value (utility) to each alternative and selecting the alternative with the highest utility

Limitation: the human behavior is complex and a choice model should explicitly capture some level of uncertainty.

Random utility theoryAssumes, as the neoclassical economic theory, that the decision-maker has

a perfect discrimination capability. Anyway the analist is supposed to have incomplete information: uncertainty

is taken into accountThe utility is modeled as a random variable, in order to reflect this

uncertainty

i = decision-maker indexj and k = alternatives to be compared, j the one to be chosen

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Random utility modelUij = Vij + εij

Pij = Prob (Uij > Uik) == Prob (Vij + εij > Vik + εik) = = Prob (Vij - Vik > εij - εik) ∀j ≠ k

P(j | a, b, …, n) = exp Vj / Σk exp Vk

i = decision-maker indexj = the chosen alternative over k alternativesa, b, …,n = k alternatives

650 € for 1000 UI (plasma-derived)929 € for 1000 UI (Second generation recomb fact)1115 € for 1000 UI (+20% of 929)

Price

Home deliveryCommunity pharmacy Hospital/Local Health Unit

Distribution modes

Lyophilized material for reconstitutionReady-to-use solutionPharmaceutical dosage form

Thrice a weekTwice a weekOnce a week

Factor infusion frequency onprophylaxis

Current (1/4 in PUPs)Reduced (1/6 in PUPs)Very reduced (1/10 in PUPs)

Risk of inhibitor development

Second generation recombinant factorsVery highly purified plasma derived factorsPerceived viral safety

LevelsAttributes

Characteristics and levels

Mantovani et al, Haemophilia, 2005

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Choice set

Vij = αij + βXij

- αij = alternative specific constant - Xij = attributes - taste weights = β

• Whether an attribute is important• Relative importance of attributes• marginal rates of substitution of attribute n over attribute n+1 (βn/βn+1)

– willingness to pay (WTP) for an attribute (βn/-βprice)– willingness to give up time (βn/-βtime)

• Welfare/benefit (utility) scores

DCE: Useful to estimate

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Milano, 15 novembre 2005

Milano, 15 novembre 2005

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Uses and utilities of HRQoL instruments

• Clinical practice to understand something more about the individuals’ (patients’) health

Uses and utilities of HRQoL instruments

• Clinical practice to understand something more about the individuals’ (patients’) health

• Population based studies to understand the impact of diseases, interventions

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Uses and utilities of HRQoL instruments

• Clinical practice to understand something more about the individuals’ (patients’) health

• Population based studies to understand the impact of diseases, interventions

• Economic Evaluations to understand how to more efficiently allocate the available resouces

Key elements on HRQoL evaluation

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Key elements on HRQoL evaluation

• NO Gold Standard• Compromise and choises according to aims,

resources• Battery