111

PPharmacoharmacoEEconomic evaluation of conomic evaluation of newer atypical antipsychotics and newer atypical antipsychotics and

bipolar disorserbipolar disorser

25 Jun 2011

Yen Kuang Yang M.D.Department of Psychiatry NCKU Taiwan /

22

2008 Gross Domestic Product 2008 Gross Domestic Product Per CapitaPer Capita

(IMF) (IFS) June 2008(IMF) (IFS) June 2008Unit: USD

33

Percentage of Medical Demand in GDPPercentage of Medical Demand in GDP

44

Direct and Indirect CostsDirect and Indirect Costs

UK Australia Korea

Unemployment was identified as the largest component of overall cost

1 Mangalore, R. et al. (2007). J Ment Health Policy Econ, 10(1), 23-41.2 Access Economics: SANE Australia 20023 Chang, S. M. et al. (2008). J Korean Med Sci, 23(2), 167-175.

35.6%

64.3%70.1%

29.9%

Annual total 2005: $3,175 in US$M

55

87%

13%

The average cost for each patients The average cost for each patients with schizophrenia in Taiwanwith schizophrenia in Taiwan

Direct Cost: $71,742 (US$2,174)

Direct Cost: $71,742 (US$2,174)

Indirect Cost: $477,213(US$14,461)

Indirect Cost: $477,213(US$14,461)

( Lee et al Psychiatr Res 2008)

66

InstitutionServices

34.4%

CommunityServices

0.5%

FolkTherapy15.7%

Others5.8%

Drugs43.6%

Direct costsDirect costs

NonNon--psychiatric psychiatric medical servicesmedical services

( Lee et al Psychiatr Res 2008)

77

Indirect costIndirect cost

PatientJoblessness

50%Caregiver

Joblessness43%

other7%

( Lee et al Psychatr Res 2008)

88

Three tasks for pharmacoeconomic Three tasks for pharmacoeconomic evaluation evaluation

1. Long acting risperidone (1. Long acting risperidone (ConstaConsta))Yang YK et al Psychiatry and Clinical Neuroscience 2005; 138:385Yang YK et al Psychiatry and Clinical Neuroscience 2005; 138:385--9494

2. Paliperidone oral tablet (2. Paliperidone oral tablet (InvegaInvega))Puw RF et al Taiwanese J of Psychiatry 2010;24:280Puw RF et al Taiwanese J of Psychiatry 2010;24:280--90 90

3. Medical cost of bipolar disorder (3. Medical cost of bipolar disorder (New New indicationindication))Tang et al Bipolar disorders 2010;35:107Tang et al Bipolar disorders 2010;35:107--10 10

999

Long acting risperidone Long acting risperidone ((ConstaConsta))

Yang YK et al Psychiatry and Clinical Neuroscience 2005; 138:385Yang YK et al Psychiatry and Clinical Neuroscience 2005; 138:385--9494

(/)

1010

Original DesignOriginal Design

1111

Diagram 1: Decision Tree Diagram 1: Decision Tree Depot RisperidoneDepot Risperidone--ResponseResponse BranchBranch

1212

Executive Executive committeecommittee (expert opinion)(expert opinion)

6 senior psychiatrists 6 senior psychiatrists 2 2 pharmacoecomonistspharmacoecomonists / statistic specialists/ statistic specialists1 representative of pharmaceutical company1 representative of pharmaceutical company

1313

Probability of efficacy: by anonymous expertsProbability of efficacy: by anonymous experts

Clinical research agent Clinical research agent (CRO)(CRO)Their clinical experience in psychiatry is more than Their clinical experience in psychiatry is more than 15 years.15 years.Currently, they actively provide clinical services for Currently, they actively provide clinical services for schizophrenic patients, particularly inpatient service .schizophrenic patients, particularly inpatient service .Their administration load is minimal.Their administration load is minimal.They are not fullThey are not full--time child psychiatrists.time child psychiatrists.They are not full time psychotherapists.They are not full time psychotherapists.The The risperidonerisperidone, , depot haloperidoldepot haloperidol and and olanzapaineolanzapaineare available for more than 2 years in their hospital are available for more than 2 years in their hospital or institution. or institution. They are not numbers of the executive committee in They are not numbers of the executive committee in this study.this study.

1414

The therapeutic options in the modelThe therapeutic options in the model

Initial agents Long-acting risperidone

Depot haloperidol Olanzapine

1st option Olanzapine Long-acting risperidone

Long-acting risperidone

2nd option Clozapine Olanzapine Clozapine 3rd option Depot haloperidol Clozapine Depot haloperidol

1515

Patient populationPatient population

BPRS

1717

Estimated CostEstimated CostUnit cost: 0.9% population of TaiwaneseUnit cost: 0.9% population of TaiwaneseFourFour--month cost ( treatment package) month cost ( treatment package)

Model : full adherence

Model : as needed

cost

Time

1818

Table 3. Table 3. The average fourThe average four--month costs for different month costs for different

medical states in Modelsmedical states in Modelsand and

Cost items/medical status Response CD IR

Model Model Model Model Model Model

Outpatient clinic 1,898 1,447 1,239 839 1,119 757

Intensive care 8,578 84,637 23,901 101,993 37,939

Home care 412 38 412 77 348 1,021

Emergency service 165 768 1,471 906 1,120

Total costs 11,052 1,485 87,056 26,603 104,365 41,287

Unit: New Taiwan dollar (NT$) CD: Clinical deterioration IR: Inadequate response

Yang YK et al 2005

1919

Table 4. Models Table 4. Models andand: two: two--year costyear cost--effectiveness effectiveness

analysis among three strategiesanalysis among three strategies

Strategies Effectiveness Costs(NT$) C/E ratio (NT$) Model Model Model Model

Long-acting risperidone

0.55 374,187 252,885 678,367 458,457

Depot haloperidol 0.32 315,834 167,036 1,000,741 529,265 Olanzapine 0.45 381,285 244,055 841,875 538,872 NT$: New Taiwan dollar C/E: Cost-effectiveness

Yang YK et al 2005

2020

Table 5. Sensitivity analysis (Model I) of the impact of Table 5. Sensitivity analysis (Model I) of the impact of increasing the response rate of longincreasing the response rate of long--acting risperidone by acting risperidone by 0%~15%0%~15%

NT$ New Taiwan Dollar *The incremental response rate was added only at the first episode (the first 4 month of this trial).

ProbabilityProbability

Cost (NT$)Cost (NT$) EffectivenessEffectiveness Cost/Effectiveness (NT$)Cost/Effectiveness (NT$)

Risperidone Risperidone longlong--actingacting

HaloperidoHaloperidol depotl depot

OlanzapinOlanzapinee

Risperidone Risperidone longlong--actingacting

HaloperidHaloperidol depotol depot

OlanzapineOlanzapine Risperidone Risperidone longlong--actingacting

Haloperidol Haloperidol depotdepot

OlanzapineOlanzapine

0.75 (0.75 (--0%)0%) 383,866383,866 315,834315,834 381,285381,285 0.500.50 0.320.32 0.450.45 765,436765,436 1,000,7411,000,741 841,875841,875

0.79 (0.79 (--5%)5%) 379,027379,027 315,834315,834 381.285381.285 0.530.53 0.320.32 0.450.45 719,763719,763 1,000,7411,000,741 841,875841,875

0.83 (0.83 (--10%)10%) 347,187347,187 315,834315,834 381.285381.285 0.550.55 0.320.32 0.450.45 678,367678,367 1,000,7411,000,741 841,875841,875

0.87 (0.87 (--15%)15%) 369,348369,348 315,834315,834 381.285381.285 0.580.58 0.320.32 0.450.45 640,451640,451 1,000,7411,000,741 841,875841,875NT$ New Taiwanese dollars *The incremental response rate was added only at the first episode (the first 4 month of this trial).

Yang YK et al 2005

2121

Table 6. Sensitivity analysis (model I) of the impact of longTable 6. Sensitivity analysis (model I) of the impact of long--acting risperidone price variation by 0%~15%acting risperidone price variation by 0%~15%

Constant PriceConstant Price(25mg; 37.5mg)(25mg; 37.5mg)

Cost (NT$) Cost (NT$) EffectivenessEffectiveness Cost/Effectiveness (NT$) Cost/Effectiveness (NT$)

Risperidone Risperidone long long --actingacting

Haloperidol Haloperidol depotdepot

OlanzapineOlanzapine Risperidone Risperidone long long --actingacting

Haloperidol Haloperidol depotdepot

OlanzapineOlanzapine Risperidone Risperidone long long --actingacting

Haloperidol Haloperidol depotdepot

OlanzapineOlanzapine

4,367; 5,8954,367; 5,895(0%)(0%) 374,187374,187 315,834315,834 381,285381,285 0.550.55 0.320.32 0.450.45 678,367678,367 1,000,7411,000,741 841,875841,875

4,585; 6,1904,585; 6,190(+5%)(+5%) 382,357382,357 318,964318,964 383,449383,449 0.550.55 0.320.32 0.450.45 693,178693,178 1,010,6591,010,659 846,653846,653

4,804; 6,4854,804; 6,485(+10%)(+10%) 390,527390,527 322,095322,095 385,613385,613 0.550.55 0.320.32 0.450.45 707,989707,989 1,020,5801,020,580 851,431851,431

5,022; 6,7795,022; 6,779(+15%)(+15%) 398,697398,697 325,226325,226 387,777387,777 0.550.55 0.320.32 0.450.45 722,801722,801 1,030,5011,030,501 856,209856,209

NT$: New Taiwan dollar

(Yang YK et al 2005)

2222

INVEGAINVEGA: Min. Peak: Min. Peak--toto--trough trough FluctuationFluctuation

Mean % peak-to-trough fluctuation (Cmax Cmin Cav)RIS-INT-32 & SCH-101

140%

65%

40%

0%

20%

40%

60%

80%

100%

120%

140%

Risperdal IR(4mg)Risperdal Consta 25mg Invega 12mg

% p

eak-

to-t

rough f

luct

uations

2323

Acute modelAcute model LongLong--term modelterm model

Invega CostInvega Cost--Effectiveness modelEffectiveness model

2424

StudytasksStudytasks

Literature reviewLiterature reviewTo apply To apply National Health Insurance (NHI)National Health Insurance (NHI)data of data of schizophrenia in 2005 from schizophrenia in 2005 from National Health Research InstituteNational Health Research Institute (unit (unit cost of medical resource utilization)cost of medical resource utilization)To conduct expert interview via structured To conduct expert interview via structured questionnairequestionnaire (N=10)(N=10) conducted by conducted by CROCRO (())To conduct To conduct expert meetingexpert meeting (N=4+2)(N=4+2)

2525

Acute modelAcute model

2626

Acute model Acute model -- 11Response rate in acute model

Normalized response rate in acute model

2727

30%30% ppt with discontinuation will seek medical t with discontinuation will seek medical help.help.

Acute model Acute model -- 22

Discontinuation rate within 6 weeks prior to receiving medication

2828

Acute model + LongAcute model + Long--term model term model (())

2929

OneOne--year treatment complianceyear treatment complianceRisperidoneRisperidone68.3%68.3%Olanzepine : 74.6%Olanzepine : 74.6%QuentiapineQuentiapine 60.0%60.0%Paliperidone : Paliperidone : 73.3 %73.3 %

(Dossenbach etal J Clin Psychiatry 2005)IC-SOHO

3030

Acute model + LongAcute model + Long--term model term model (())

3131

Long Term model (one year)Long Term model (one year)Relapse/ worsen rate 20.2%~37.0% (N.S. Relapse/ worsen rate 20.2%~37.0% (N.S. 21.8%).21.8%).

Hospitalization rate Hospitalization rate 9.2%9.2% (NS) (NS)

21.8%+9.2%= 31.0%21.8%+9.2%= 31.0% ( Dossenbach etal 2005 )( Dossenbach etal 2005 )

The mean of hospitalization was The mean of hospitalization was 1.71.7 times times per year per year ( 2005 NHRID )( 2005 NHRID )

3232

Acute model + LongAcute model + Long--term model term model (())

3333

OneOne--year model (year model ()) no response & switchno response & switch

Switch rate : Switch rate : 54.4%54.4%(California Medicaid data(California Medicaid data Menzin et al Menzin et al Psychiatry Service 2003, CATIE)Psychiatry Service 2003, CATIE)

3434

Acute model + LongAcute model + Long--term model term model (())

3535

Duration of switchDuration of switch

Treatment duration under different condition

3636

Daily cost for drugsDaily cost for drugs

Daily cost for drugs

Avg. daily dose Avg. daily medication cost (NTD)

*Assumption: calculated from 300mg*1+200mg*2+25mg*2, 89NTD for 300mg, 65NTD for 200mg and 20.4NTD for 25mg (NHI price on Sep 1, 2007)

3737

EPSEPS

8%7%

3%

0%1%2%3%4%5%6%7%8%9%

Paliperidone ER Olanzapine Quetiapine

EPS rate

Avg. EPS rate of olanzapine andrisperidone in CATIE study

EPS rate in each group

Paliperidone 6 weeks trial-EPS related adverse event rate

3838

Average costAverage cost--effectiveness in effectiveness in acute phaseacute phase

174,096

183,707231,340

0

50,000

100,000

150,000

200,000

250,000

Paliperidone ER Olanzapine Quetiapine

(NTD)

Average cost effectiveness in acute model

Ave

rage

cos

t effe

ctiv

enes

s(N

TD)

3939

Average costAverage cost--effectiveness in longeffectiveness in long--term phaseterm phase

537.3 537.6

615.2

480500520540560580600620640

Paliperidone ER Olanzapine Quetiapine

(NTD)

Average cost effectiveness in long-term model

4040

$179,893

$184,573

$166,518$167,674

$155,000

$160,000

$165,000

$170,000

$175,000

$180,000

$185,000

$190,000Olanzapine Paliperidone ER

40% improve 20% improve

Avg. cost per patient per yearAvg. cost per patient per year

414141

Long acting risperidone (Long acting risperidone (New New indicationindication))

(/)

4242

Aug/31/2010 42Medical costs and relapse rates for BD in Taiwan

SubjectsSubjectsat least one acute admission based upon principal at least one acute admission based upon principal

diagnosis of BD (ICDdiagnosis of BD (ICD--99--CM code: 296.0X, CM code: 296.0X, 296.1X, 296.4X, 296.5X, 296.6X, 296.7X, 296.1X, 296.4X, 296.5X, 296.6X, 296.7X, 296.80, or 296.89) between 296.80, or 296.89) between January 1, 2006 January 1, 2006 and December 31, 2006and December 31, 2006if each admission occurring within 14 days of if each admission occurring within 14 days of the discharge date of a previous one, the two the discharge date of a previous one, the two events being regarded as one hospitalization events being regarded as one hospitalization episode. episode. 4,267 cases for analysis in this study ((4,4014,401--134 134 loss of NHI beneficiary statusloss of NHI beneficiary status ))

4343

Aug/31/2010 43Medical costs and relapse rates for BD in Taiwan

Relapse vs. RehospitalizationRelapse vs. Rehospitalization

Emergency Service Care

4444

Aug/31/2010 44Medical costs and relapse rates for BD in Taiwan

Time to first relapse within 12 months of the index Time to first relapse within 12 months of the index dischargedischarge

(by gender and age group)(by gender and age group)

4545

CoCo--morbidities Prevalence rate morbidities Prevalence rate (Hsieh M Het al)(Hsieh M Het al)

*3

*1 *2

4646

BipolarBipolar(N=2,173(N=2,173) ) (Hsieh MHet al)(Hsieh MHet al)

*Prevalence rate: 2006/**E-code: 1.Self-harm(Self-harm): 'E950', 'E956', 'E958', 'E959', 'E952', 'E957', 'E953', 'E9512.Accident(Self-harm): 'E885', 'E929', 'E860', 'E866', 'E917', 'E920', 'E884', 'E819', 'E968', 'E849', 'E853', 'E878', 'E852', 'E924', 'E812', 'E927', 'E816', 'E818', 'E988', 'E826', 'E858', 'E879', 'E880', 'E883', 'E906', 'E915', 'E989', 'E815', 'E854', 'E855', 'E876', 'E893', 'E898', 'E899', 'E905', 'E918', 'E9693.Others (Self-harm):'E928', 'E939', 'E936', 'E980', 'E888', 'E947', 'E960', 'E887', 'E937', 'E931', 'E933', 'E943', 'E945'

4747

Conclusion

Model selectionUnit price for different treatment To estimate compliance ratesTo figure out different treatment ratesTarget population/durationData selection/experts

484848

(/)Thanks for your attention!