Cost Effectiveness of a Human Papillomavirus Vaccine in reducing the risk of cervical cancer in Ireland using a

transmission dynamic model.

Cara Usher1, Lesley Tilson1, Cathal Walsh2, Jens Olsen3, Martin Rudbeck Jepsen4, Michael Barry1.

1. National Centre for Pharmacoeconomics, Dublin, Ireland. 2. Dept. of Statistics, Trinity College Dublin, Ireland.3. University of Southern Denmark, Odense, Denmark. 4. Statens Serum Institut, Copenhagen, Denmark.

Aim

To evaluate the cost effectiveness of a combined primary (vaccination) and secondary (screening)

approach to managing pre-cancerous and cancerous lesions

vsA population-based cervical cancer screening

programme alone in Ireland.

Human Papilloma Virus (HPV)

More than 100 different types of HPV infection have been characterised:

– High risk – most common are HPV 16, 18, 45 and 31.

– Low risk- include HPV types 6, 11.

Cause ~70% of cervical cancersCause ~ 90%

of anogenital warts

Two vaccines currently developed:

1.Gardasil® – protects against HPV types 16, 18, 6 and 11.

2.Cervarix ® – protects against HPV types 16 and 18.

Efficacy demonstrated for up to 5.5 years after vaccination.

Requirement for booster dose at later time not established.

Routine cytology screening still required, as vaccines do not protect against all oncogenic types of HPV.

Human Papilloma Virus (HPV) Vaccine

Natural history of HPV

Normal Cervix

Infection

Clearance

HPV infectedCervix

(CIN 1)

Progression

Regression

CIN 2/3

Cancer

Methods

Framework• Scope of analysis agreed with economic modelling groupin Denmark and EAG in Ireland.

Comparator• Population-based cervical cancer screening programme

Perspective• Healthcare payer

Model Structure

Transmission model Cost Effectiveness Model Simulated infection causedby HPV 16&18 only, using

sexual behaviour patterns1.

HPV type-specific prevalence

- Artistic trial2.

Calibration: Estimates CIN1-3, CC incidence

1. Layte et al, 2006.2. Kitchener et al, 2006.

Outputs from transmission modelcombined with resource use and cost data

Incremental effects( incidence CIN 1-3, CC)

Incremental costs(costs of vaccination vs no vaccination)

Model Inputs

• Epidemiological data

• Sexual behaviour patterns• HPV-type distribution• Prevalence of HPV infection• Incidence of premalignant and invasive CC

• Resource use data

• Vaccination costs• Direct medical costs• Unit cost data

Model Inputs• Time Horizon

• 70 yrs (9 – 79 years)

• Outcome Measure

• Life Years Gained

• Vaccine Coverage

• 80% (based on Men C catch-up programme).

• Discounting

• 3.5% costs & benefits

Scenario Coverage

12 yr old females 80%

12 yr olds + catch-up to 15 yrs

80%

12 yr olds + catch-up to 17 yrs

80%

12 yr olds + catch-up to 19 yrs

80%

12 yr olds + catch-up to 26 yrs

80% 30% (GP)

Model Inputs(Summary)

Vaccine efficacy 95.2%

Duration of vaccine protection

Lifelong

Screening 25-44 yrs, 80% screened every 3 yrs45-60 yrs, 80% screened every 5 yrs

Proportion of CIN 1-3 caused by HPV 16 & 18

74% CC50% CIN 2/3, 35% CIN 1

Cost of vaccine €100

Administration costs €30 (<19 yrs)€58 (>19 yrs)

Direct Medical Costs• CIN 1• CIN 2/3• Invasive cancer

€617€1,632€18,160

Discount Rate 3.5% (costs & benefits)

Parameter One-Way SA

Probabilistic SA

Vaccine Efficacy 88% - 99% Beta (35, 2)

Duration of vaccine protection

10 yrs/booster

Bernoulli (0, 5)

Vaccine Coverage 60% Beta (20, 5)

Screening 62% Beta (20, 5)

Proportion of CIN 1-3 and CC caused by HPV 16 / 18

60% CC40% CIN 2/321% CIN 1

Beta (60, 20) CCCIN 2/3 in proportion

CIN 1

Cost of vaccine (per dose) €80 - €120 N (100, 10)

Administration costs (per dose)

€15 - €45 N(30, 7) truncated to be +ive

Direct Medical Costs 20% N (0, 0.1)

Discount rate 0 and 6% Triangular (0, 3.5, 6%)

Results (1) – Simulation Model

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Time from intervention

Fem

ale

Inci

den

ce [

%]

No vaccination HPV16

No vaccination HPV18

Base case HPV16

Base case HPV18

HPV16 catch-up

HPV18 catch-up

Results (2) – Cases Averted

Health state

Estimated total number of cases

in 2004

Average annual number of cases averted due to

HPV vaccination

CIN 1 7,259 2,245

CIN2/3 3,515 1,435

Cervical cancer

200 111

Deaths from cervical cancer

93 52

Results (3) – Cost Effectiveness of the base-case vaccination programme

(HPV vaccination & screening vs screening alone)

Incremental costs

(discounted)

Incremental life years gained (discounted)

 

ICER

€ 6,984,496 401.8 years € 17,383 / LYG

Results (3) – Cost Effectiveness of catch-up vaccination programmes

0

1

2

3

4

5

6

7

8

9

10

11

12

0 50 100 150 200 250 300 350 400 450

Incremental LYG

Incr

emen

tal c

ost

mill

ion

€

Scenario 1

Scenario 2

Scenario 3

Scenario 4

Scenario 5

No vaccination

ICER €17,383/LYG

ICER €18,893/LYG

ICER €20,646/LYG

ICER €22,038/LYG

ICER €24,534/LYG

12 yr olds + Catch-Up to 15 yrs: ICER €52,968/LYG.

Results (4) – Sensitivity Analysis: Probabilistic

2.5 centile

97.5 centile

Results (5) – Sensitivity Analysis: One-Way

0 5000 10000 15000 20000 25000 30000 35000 40000 45000

ICER

Discount rate (0-6%)

Direct medical Costs (+/-20%)

Cost of vaccine (80-120 per dose)

Cost of administration of vaccine (15-45 per dose)

Vaccine coverage (60%)

Booster dose at 10 years

Vaccine efficacy (85-99%)

Proportion caused by HPV 16/18 (60% Cervicalcancer, 40% CIN 2/3, 21% CIN 1)

Population screening coverage (62%)€17,383/LYG

Summary

• Cost-effectiveness of base-case vaccination programme ICER €17,383/LYG

• Cost-effectiveness of catch-up vaccination programmes

ICER €52,968/LYG (12-15 yr olds)

Strengths / Limitations

• Study framework, i.e. a collaborative approach to assessing cost-effectiveness of an intervention in a short timeframe.

• Uncertainty with data.• cross-protection• requirement for booster• vaccine efficacy against types 6 & 11

Conclusions

• Epidemiological impact of vaccination

• Cost effective to vaccinate 12 yr old females

• Cost effective to vaccinate 12 – 15 yr old females

Minister for Health Approves Introduction Of Cervical Cancer Vaccination Programme

5th August 2008

“It is clear the main priority now is to move to the introduction of the vaccination programme for 12 year old girls to commence in

September 2009” .

Acknowledgements