A Cost-Effectiveness Analysis of Alternative Human papillomavirus (HPV) Vaccination Strategies

About This Presentation
Title:

A Cost-Effectiveness Analysis of Alternative Human papillomavirus (HPV) Vaccination Strategies

Description:

Genital warts 90 % Recurrent respiratory papillomatosis ... What is the sensitivity of vaccine health impact (HPV, CIN, cervical cancer, genital warts) to: ... – PowerPoint PPT presentation

Number of Views:125
Avg rating:3.0/5.0

less

Transcript and Presenter's Notes

Title: A Cost-Effectiveness Analysis of Alternative Human papillomavirus (HPV) Vaccination Strategies


1
A Cost-Effectiveness Analysis of Alternative
Human papillomavirus (HPV) Vaccination Strategies
  • Elamin H. Elbasha
  • Merck Research Laboratories, USA

2
Presentation outline
  • HPV infection and disease
  • HPV vaccines
  • Merck model
  • Public health impact
  • Economic impact
  • Summary and conclusions

3
HPV infection
  • HPV is small, non-enveloped, encapsulated,
    double-stranded DNA virus
  • HPV encodes two structural proteins
  • L1 codes for major capsid protein
  • L2 codes for minor capsid proteins
  • Enormous HPV diversity
  • More than 100 HPV genotypes
  • More than 40 types infect ano-genital tract
  • At least 13 high-risk types cause cervical cancer
  • Ubiquitous
  • Lifetime Risk of HPV infection up to 70 among
    sexually active
  • Major risk factor for HPV acquisition number of
    sexual partners

4
Neoplasm or external genital warts
Asymptomatic or common warts
5
HPV infection life cycle
Goodman A., Wilbur D. C. Case 32-2003 A
37-Year-Old Woman with Atypical Squamous Cells on
a Papanicolaou Smear. N Engl J Med 2003
3491555-1564
6
Conditions associated with HPV types 16, 18, 6,11
  • HPV 16, 18 Estimated attributable
  • Cervical cancer 70
  • High grade cervical abnormalities 50
  • Low grade cervical abnormalities 30
  • Anal cancer 70
  • Vulva / Vagina / Penile 40
  • Head and neck cancers 3-12
  • HPV 6, 11
  • Low grade cervical abnormalities 10
  • Genital warts 90
  • Recurrent respiratory papillomatosis (RRP) 90

Clifford, BJ Ca 2003 Munoz Int J Cancer 2004
Brown J Clin Micro 1993 Carter Cancer Res 2001
Clifford Cancer Epi Biomarkers Prev 2005 Gissman
Proc Natl Acad Science 1983 Kreimer Cancer
Epidemiol Biomarkers Prev 2005
7
By end of presentation, 16 women would die from
cervical cancer
Second most common cancer among women 274,000
deaths from cervical cancer in 2002
Globocan 2002
8
Immunologic Basis for HPV vaccines
  • L1 HPV major capsid protein self-assembles into
    empty virus-like particles (VLPs)
  • In animal models of papillomavirus infection
    using species-specific VLPs
  • Vaccination results in protection from infection
    and disease
  • Efficacy associated with development of
    neutralizing antibodies
  • Transfer of serum from vaccinated to unvaccinated
    animals transfers protective efficacy
  • Protection is prophylactic, not likely to be
    therapeutic
  • Protection is likely to be type-specific

9
HPV vaccines
  • Prepared from virus-like particles
    (non-infectious)
  • Produced by recombinant technology
  • Do not contain any live biological product or DNA
  • GARDASIL prophylactic quadrivalent HPV
    (6,11,16,18) vaccine licensed in U.S. other
    countries
  • First vaccine to prevent cervical cancer,
    precancerous genital lesions, and genital warts
  • Series of three injections over a six-month
    period
  • Safe and highly efficacious
  • CERVARIX prophylactic bivalent HPV (16,18)
    vaccine in final stages of clinical testing

10
Research questions
  • What are the epidemiologic consequences of HPV
    vaccination?
  • What is the sensitivity of vaccine health impact
    (HPV, CIN, cervical cancer, genital warts) to
  • vaccine characteristics (e.g., duration of
    protection)?
  • vaccination strategies (females and males,
    females-only, catch-up, etc.)?
  • What is the cost-effectiveness of programs using
    a quadrivalent HPV (6/11/16/18) vaccine?

11
Methods
  • Direct and indirect herd immunity effects of
    vaccination
  • Describe transmission of the virus and resulting
    disease in a population
  • Assess impact of vaccine on vaccinees and their
    contacts
  • An integrated disease transmission model and
    cost-utility analysis
  • Demographic model
  • Behavioral model
  • HPV infection and disease models
  • Economic model
  • US healthcare system data and perspective
  • Assumes existing screening practices

12
Transfer diagram, no vaccine compartments
13
Transfer diagram, vaccine compartments
14
Transfer diagram, CIN compartments
15
Vaccine characteristics data and assumptions
  • Vaccine take ( of vaccinees with vaccine effect)
  • HPV 16/18 100, HPV 6/11 100
  • Vaccine degree of protection
  • HPV 16/18, HPV 6/11 against infection 90
    (CI74?100)
  • HPV 16/18, HPV 6/11 against disease 100
    (CI87?100)
  • Vaccine duration of protection
  • HPV 16/18, HPV 6/11 10 years to lifetime
  • Breakthrough infections
  • Infectiousness and clearance same as natural
    infections

16
Vaccination strategies
Description Definition
A. Routine 12-year-old females Vaccinate females before reaching age 12
B. Routine 12-year-old females and males Vaccinate females and males before reaching age 12
C. 12-year-old females 1224-year-old females catch-up Strategy A a temporary catch-up program targeting 1224-year-old females
D. 12-year-old females and males 1224-year-old females catch-up Strategy B a temporary catch-up program targeting 1224-year-old females
E. 12-year-old females and males 1224-year-old females and males catch-up Strategy B a temporary catch-up program targeting 1224-year-old females and males
17
Vaccination penetration rates assumptions
  • Routine 12-year olds
  • increase vaccine penetration linearly from 0 in
    Year 0 to 70 in Year 5 and after
  • Catch-up 12?24-year olds
  • All cohorts (12?24) increase vaccine penetration
    linearly from 0 in Year 0 to 50 in Year 5
  • Program stops after 5 years

18
Impact of vaccination strategies diagnosed HPV
16/18-related cervical cancer incidence, females
(12y), lifelong duration
19
Impact of vaccination strategies diagnosed HPV
16/18-related CIN 2/3 incidence- females (12y)
lifelong duration
20
Impact of vaccination strategies diagnosed HPV
6/11/16/18-related CIN 1 incidence - females
(12y) lifelong duration
21
Impact of vaccination strategies diagnosed HPV
6/11-related genital warts incidence - females
(12y) lifelong duration
22
Impact of vaccination strategies diagnosed HPV
6/11-related genital warts incidence - males
(12y) lifelong duration of protection
23
Cumulative quality-adjusted life years
24
Cumulative costs
25
Cost-effectiveness analysis of HPV vaccination
strategies
Discounted total Discounted total Incremental Incremental Incremental
Strategy Costs QALYs Costs QALYs /QALYs
No vaccination 72,659,302 2,698,711
12-year-old females 74,042,990 2,699,178 1,383,687 467 2,964
12-year-old females and males 78,707,825 2,699,327 4,664,835 149 dominated
12-year-old females 12?24-year-old females catch up 74,815,667 2,699,343 3,892,159 16 4,666
12-year-old females and males 12?24-year-old females catch up 79,746,357 2,699,461 4,930,690 118 41,803
12-year-old females and males 12?24-year-old females and males catch up 81,761,210 2,699,506 2,014,853 45 45,056
Assumes cost of vaccination series is 360 and
duration of protection is lifelong. Compared
with the preceding non-dominated strategy.
26
Sensitivity analysis Impact of vaccination
strategiesdiagnosed HPV 16/18-related CIN 2/3
incidence- females (12y) 10-years duration vs.
lifetime
27
Impact of Vaccination StrategyCervical Cancer
Incidence - Females (1285y) Lifelong duration,
50 coverage
28
Impact of Vaccination StrategyCervical Cancer
Incidence - Females (1285y) Lifelong duration,
90 coverage
29
Sensitivity analyses Incremental
cost-effectiveness ratio (/QALY) vs. duration of
protection cost
Input range/Program Vaccination costs Vaccination costs
Input range/Program 300 500
Vaccine duration of protection lifelong
12-year-old females 12?24-year-old females catch up 2,422 9,900
12-year-old females males 12?24-year-old females males catch up 36,161 65,810
Vaccine duration of protection 10-Years
12-year-old females 12?24-year-old females catch up 16,194 32,619
12-year-old females males 12?24-year-old females males catch up 44,562 79,115
30
Sensitivity analyses Incremental
cost-effectiveness ratio (/QALY) vs. vaccine
coverage and cost
Input range/Program Vaccination costs Vaccination costs
Input range/Program 300 500
Vaccine coverage 50
12-year-old females 12?24-year-old females catch up 2,056 9,271
12-year-old females males 12?24-year-old females males catch up 28,845 53,479
Vaccine coverage 90
12-year-old females 12?24-year-old females catch up 2,925 10,739
12-year-old females males 12?24-year-old females males catch up 82,241 142,830
31
Limitations outstanding research questions
  • Vaccine characteristics (e.g., duration of
    protection) are influential
  • Need more and better epidemiologic and natural
    history of disease data to support model
  • Need to analyze the impact on other important
    HPV-related diseases such as vulvar and vaginal
    neoplasias and cancers, recurrent respiratory
    papillomatosis
  • Need to reflect the indirect costs of HPV-related
    disease
  • Need to model HPV types interaction/cross
    protection
  • If screening practices change, the model can
    reflect the shifting impact of vaccination

32
Summary
  • A prophylactic quadrivalent HPV vaccine can
    substantially reduce the incidence of cervical
    cancer, CIN, and genital warts
  • Catch up vaccination can provide earlier and
    greater reductions in HPV-related disease
  • Vaccinating males and females before age 12
    combined with a temporary 12?24-year olds catch
    up program can be cost-effective and efficiently
    added to current screening programs

33
Acknowledgement
  • Erik J. Dasbach, PhD
  • Ralph P. Insinga, PhD
  • Merck Research Laboratories, USA
Write a Comment
User Comments (0)