Mark Jit Modelling and Economics Unit Health Protection Agency, London Case study: Structural uncertainty in human papillomavirus vaccination modelling.

Mark Jit

Modelling and Economics Unit

Health Protection Agency, London

Case study: Structural uncertainty in

human papillomavirus vaccinationmodelling

M Jit1,2, Y Choi1, N Gay1 and WJ Edmunds1,3

1Centre for Infections, Health Protection Agency2University of Birmingham3London School of Hygiene & Tropical Medicine

Outline

• Introduction to the problem

• Representing structural uncertainty

• Selecting optimal scenarios

• Presenting results

GardasilTM • Protects against HPV 6, 11, 16, 18.

• Doses at 0, 2, 6 months.

• Aluminium adjuvanted.

• Licensed widely, in use in several countries.

CervarixTM • Protects against HPV 16, 18.

• Doses at 0, 1, 6 months.

• AS04 adjuvanted.

• Licensed in Europe and Australia.

HPV vaccines

Female HPV prevalence in UK DNA studies

Epidemiological uncertainty

Progression and regression of HPV-related neoplastic states.

Duration of HPV infection.

Prevalence of anogenital warts among HPV 6 and 11 infected people.

Duration of vaccine protection.

Coverage of vaccination programme.

Uncertainty about disease burden

Cost and QoL impact of screening.

Cost and QoL impact of treating neoplasias, cancer, warts.

Accuracy of cytological screening and DNA testing.

Structural uncertainty

Natural regression of HPV-related neoplasias.

Existence of natural immunity to HPV.

Pattern of sexual partnerships between age and risk groups.

Vaccine protection against non-vaccine HPV types.

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Type specific HPV prevalence by

cytological status (ARTISTIC trial)

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Cytological status at time of screening

(Cervical screening programme)

Sexual partnership patterns

(Sexual lifestyle survey 2000)

Cost and quality of life data

(current literature)

Diagnosed anogenital warts

cases

(GP and GUM clinic returns)

Duration, QoL detriment of warts

episode

(York GUM study)

Types of models used

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Jit M, Gay N, Soldan K, Choi YH, Edmunds WJ. Estimating progression rates for human papillomavirus infection from epidemiological data. Medical Decision Making (in press).

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Sexual transmission stage

Changes in disease end points after

vaccine introduction

Natural history stage

Progression and regression rates

Economic stage

Changes in the economic burden

(cost and quality of life)

Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus vaccination in the United Kingdom. BMJ 2008; 337:a769.

Some relevant issues that were raised during this work

When is uncertainty structural rather than parametric?

How should different structural scenarios be weighed or selected?

How can we improve the computational efficiency of structural uncertainty analysis?