Population-level effectiveness & cost-effectiveness of the 9-valent HPV vaccine

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1 Population-level effectiveness & cost-effectiveness of the 9-valent HPV vaccine Marc Brisson Canadian Research Chair Modeling Infectious Diseases Associate Professor, Université Laval PCC2015 February 21 st, 2015

2 Funding

3 Modeling Team Université Laval Jean-François Laprise Mélanie Drolet Talia Malagon CDC Harrell Chesson Lauri Markowitz Imperial College Marie-Claude Boily Disclaimer The findings and conclusions expressed are those of the author and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC) or the Department of Health and Human Services (DHHS)

4 Context Recent results from a large clinical trial have shown that a 9-valent HPV vaccine is highly effective 1 Published Feb 19 th in the New England Journal of Medicine 1 9-valent includes types HPV-6/11/16/18/31/33/45/52/58 HPV types that cause about 90% of cervical cancers worldwide 2 9-valent HPV vaccine (Gardasil 9) was approved by: U.S. FDA (December 10 th, 2014) Health Canada (February 5 th, 2015) Thursday (Feb 26 th ), the Advisory Committee on Immunization Practices (ACIP) will vote on whether to recommend 9-valent HPV vaccination in the U.S. REF: 1) Joura, NEJM 2015; 2) de Sanjose, Lancet Oncol 2010

5 9-valent HPV vaccine efficacy Phase III study 9-valent (n=7,099) vs Quadrivalent (n=7,105) Population at enrollment: year old females, not infected Results outcomes with HPV types 31, 33, 45, 52, 58 97% efficacy (95%CI:81-100) against incidence of high-grade cervical/vulvar/vaginal disease caused by HPV types 31, 33, 45, 52, 58 97% efficacy (95%CI:92-99) against incidence of any grade 96% efficacy (95%CI:94-97) against six-month persistent HPV infection What we don t know Added benefit in the context of potential cross-protection REF: Joura, NEJM 2015

6 Main criteria considered when making recommendations for new vaccines Safety & Efficacy Preventable burden of illness Effectiveness & Cost-effectiveness Affordability & Programmatic feasibility Equity Public preferences & Politics

7 Objectives To evaluate the: additional population-level effectiveness, and incremental cost-effectiveness of switching from the 4-valent to the 9-valent HPV vaccine, using the U.S. as an example 7

8 Model Overview HPV-ADVISE Model type: Individual-based transmission-dynamic model & Components: Demographic Sexual behaviour & HPV transmission Natural history of disease Vaccination Screening & Treatment Economic Population: Open-Stable, 10 to 100 years of age HPV infections: 18 genotypes, including 6/11/16/18/31/33/45/52/58 Diseases: Anogenital warts Cervical cancer (SCC & adenocarcinoma) Cancers of the anus, oropharynx, penis, vagina & vulva &: Van de Velde et al. JNCI (22): ; Description of model components in extra slides 8

9 Model fit Results 200,000 different combinations of parameters sampled from the prior parameter distributions 50 parameter sets produced model results within the 826 pre-specified data targets

10 Proportion of sexually active women Model Fit sexual behaviour Ex: Proportion sexually active women Data Box plots represent the min, max and median of model predictions Age (years) &: Other examples of model fit in extra slides; Data: NHANES 10

11 Prevalence HPV-16/18 Prevalence HPV-16/18 Prevalence HPV-16/18 Model Fit HPV Prevalence in women Ex: HPV-16/18 prevalence by age and level of sexual activity 30% 25% Low Sexual Activity (L0) 30% 25% Average Sexual Activity (L1) 20% 20% 15% 15% 10% 10% 5% 5% 0% 40% 35% Age (years) High Sexual Activity (L2) 0% Age (years) 30% 25% 20% Data 95%CI Box plots represent the min, max and median of model predictions 15% 10% 5% 0% Age (years) &: Other examples of model fit in extra slides; Data: NHANES 11

12 Incidence of HSIL per 100,000w-y Model Fit Screening Ex: Incidence of HSIL 1, Data Box plots represent the min, max and median of model predictions Age (years) &: Other examples of model fit in extra slides; Data: Insigna

13 Incidence of SCC per 100,000w-y Model Fit Squamous cell carcinoma (SCC) Ex: Incidence of SCC Data Box plots represent medians, and 5, 25, 75, and 95th percentiles Age group (years) &: Other examples of model fit in extra slides; Data: US Cancer Statistics (NPCR/SEER) 13

14 Vaccine efficacy (VE) parameters VE among susceptible females & males 4-valent Base case VE persistent infection (%) 4-valent & 9-valent HPVtype (no cross protection) (cross protection) 16/ / Other HRtypes &: Malagón, Lancet Infectious Disease 2012 : We assume that VE against HPV-16/18 is equal for the 4- and 9-valent vaccines (based on immunogenicity presented at Eurogin 2013) 14

15 Intervention HPV vaccination Decision 4-valent 4-valent 3-dose vaccination 15

16 Intervention HPV vaccination Decision 4-valent 4-valent 4-valent 16

17 Intervention HPV vaccination Decision 9-valent 9-valent 4-valent 4-valent 4-valent 4-valent 17

18 % vaccinated with 3 doses 3-dose Vaccination Coverage Data: National Immunization Survey Used age-specific 3-dose uptake rates: Annual % vaccinated with 3 rd dose among those who had not previously received a 3 rd dose : Observed uptake rates 2014+: Assumed uptake rates constant at 2013 levels Overall vaccination coverage increases until 2017 due to age and time cohort effects 50% 40% 30% 20% 10% 0% Coverage year olds Girls Boys Year 39% 14% 46% 25% Coverage Age (yrs) Girls Boys 13 26% 12% 14 38% 18% 15 48% 27% 16 55% 31% 17 62% 38% 13 to 17 46% 25% 18

19 Population-level effectiveness 19

20 HPV-type specific positivity 9-valent HPV vaccine Potential for additional cancer prevention 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 31/33/45/52/58 16/18 Women Men 0% Cervix Vulva Vagina Anus Oropharynx Penis Anus Oropharynx &: 1) Saraiya, JNCI (under review) 20

21 Number of cases per year 9-valent HPV vaccine Potential for additional cancer prevention in the U.S. 12,000 Women Men 10,000 8,000 31/33/45/52/58 16/18 6,000 4,000 2,000 0 Cervix Vulva Vagina Anus Oropharynx Penis Anus Oropharynx Ref: 1) Jemal JNCI 2013; 2) Saraiya, JNCI (under review) 21

22 % Change in incidence Effectiveness 4-valent vs. 9-valent Base case, No Cross Protection for 4-valent 0% CIN2/3 0% Cervical Cancer -10% -20% -10% -20% -30% -40% -50% -60% -70% -80% 61% -30% -40% -50% -60% -70% 19% 14% -80% 65% -90% -100% -90% -100% valent (No Cross Protection) 9-valent Years since start of vaccination Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 22

23 % Change in incidence Effectiveness 4-valent vs. 9-valent Base case, with & without Cross Protection for 4-valent 0% CIN2/3 0% Cervical Cancer -10% -20% -30% -40% -50% -60% -10% -20% -30% -40% -50% -60% -70% -80% -90% -100% 12% -70% -80% -90% -100% % 4-valent (No Cross Protection) 4-valent (Cross Protection) 9-valent Years since start of vaccination Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 23

24 % Change in incidence Effectiveness 9-valent vs. 9-valent Girls & 4-valent Boys Base case, No Cross Protection for 4-valent 0% CIN2/3 0% Cervical Cancer -10% -20% -30% -40% -10% -20% -30% -40% -50% -60% -70% -50% -60% -70% 0-1% -80% -90% -100% -80% -90% -100% % 4-valent (No Cross Protection) 9-valent Girls & 4-valent Boys (No Cross Cross Protection Protection) 9-valent Years since start of vaccination Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 24

25 % Change in incidence Effectiveness Base case, No Cross Protection for 4-valent 0% Oropharyngeal Cancer 0% Anogenital warts -10% -20% -30% -40% -50% -60% -70% -10% -20% -30% -40% -50% -60% -70% -80% -90% -100% 4-valent No Cross Protection 9-valent Girls & 4-valent Boys No Cross Protection 9-valent -80% -90% -100% valent 9-valent Years since start of vaccination Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 25

26 Number of events averted (Thousands) Health Outcomes Prevented over 70 years Base case valent (No Cross Protection) 4-valent (Cross Protection) 9-valent Girls & 4-valent Boys (No Cross Protection) 9-valent 0 All Cancers Deaths Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 26

27 Number of events averted (Thousands) Health Outcomes Prevented over 70 years Base case, No Cross Protection for 4-valent 800 NNV & =1, K valent (No Cross Protection) 4-valent (Cross Protection) 9-valent Girls & 4-valent Boys (No Cross Protection) 9-valent 300 NNV=4, K All Cancers Deaths &: NNV=(# females vaccinated with 9-valent) (Additional events prevented by vaccinating females with 9-valent); Base case: vaccine-type efficacy=95%, duration=lifelong; Predictions: Mean estimate generated by the 50 best fitting parameter sets 27

28 Number of events averted (Thousands) Health Outcomes Prevented over 70 years Base case, with Cross Protection for 4-valent 800 NNV & =2, K valent (No Cross Protection) 4-valent (Cross Protection) 9-valent Girls & 4-valent Boys (No Cross Protection) 9-valent K NNV=6, All Cancers Deaths &: NNV=(# females vaccinated with 9-valent) (Additional events prevented by vaccinating females with 9-valent); Base case: vaccine-type efficacy=95%, duration=lifelong; Predictions: Mean estimate generated by the 50 best fitting parameter sets 28

29 Number of events averted (Thousands) Health Outcomes Prevented over 70 years Base case, 9-valent vs. 9-valent Girls & 4-valent Boys 800 NNV & =13, valent valent (No Cross Protection) 4-valent (Cross Protection) 9-valent Girls & 4-valent Boys (No Cross Protection) 300 NNV=32, All Cancers Deaths &: NNV=(# boys vaccinated with 9-valent) (Additional events prevented by vaccinating boys with 9-valent); Base case: vaccine-type efficacy=95%, duration=lifelong; Predictions: Mean estimate generated by the 50 best fitting parameter sets 29

30 % Change in incidence Effectiveness 4-valent vs. 9-valent Australia (switch to 9-valent in 2015, Cross Protection) 0% CIN2/3 0% Cervical Cancer -10% -20% -30% -40% -50% -60% -70% -10% -20% -30% -40% -50% -60% -70% -80% -90% 19% -80% -90% 4-valent Australia 9-valent Australia 14% -100% -100% Years since start of vaccination Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 10 best fitting parameter sets 30

31 Summary Population-level effectiveness predictions Current 4-valent vaccination strategies are expected to substantially reduce HPV-related diseases Switching to a 9-valent strategy is expected to further reduce precancerous lesions and cervical cancer, with less impact on other HPV-related outcomes Vaccinating girls with the 9-valent provides the great majority of benefits of a 9-valent program 31

32 Cost-effectiveness 32

33 Economic analysis Perspective: Costs: Outcome Measure: Discounting: Time Horizon: Vaccine Cost : (with administration) Societal All direct medical costs & Cost per QALY gained & 3% for costs and benefits 70 years 4-valent: $145/dose 9-valent: $158/dose QALY=quality-adjusted life-year &: Description of parameters and references available in extra slides : Cost from Merck presentation at the 29th International Papillomavirus Conference,

34 Incremental QALY-gained (1,000) Incremental QALYs-gained Discounted over 70 years 1,200 1,000 AGW consultations Other cancers Cervical lesions Cervical cancer 800 (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] No Cross Protection 9-valent [3 vs 2] No Cross Protection, 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] Cross Protectcon 9-valent [3 vs 2] Cross Protection, 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 34

35 Incremental QALY-gained (1,000) Incremental QALYs-gained Discounted over 70 years 1,200 1,000 AGW consultations Other cancers Cervical lesions Cervical cancer 800 (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] No Cross Protection 9-valent [3 vs 2] No Cross Protection, 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] Cross Protectcon 9-valent [3 vs 2] Cross Protection, 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 35

36 Incremental QALY-gained (1,000) Incremental QALYs-gained Discounted over 70 years 1,200 1,000 AGW consultations Other cancers Cervical lesions Cervical cancer 800 (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] No Cross Protection 9-valent [3 vs 2] No Cross Protection, 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] Cross Protectcon 9-valent [3 vs 2] Cross Protection, 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 36

37 Incremental QALY-gained (1,000) Incremental QALYs-gained Discounted over 70 years 1,200 1,000 AGW consultations Other cancers Cervical lesions Cervical cancer 800 (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] No Cross Protection 9-valent [3 vs 2] No Cross Protection, 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] Cross Protectcon 9-valent [3 vs 2] Cross Protection, 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong Predictions: Mean estimate generated by the 50 best fitting parameter sets 37

38 Incremental Cost offsets ($1,000,000) Incremental Healthcare costs saved Discounted over 70 years 25,000 22,500 20,000 17,500 15,000 12,500 10,000 7,500 5,000 2,500 AGW consultations Other cancers Cervical screening Cervical cancer (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent 0 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] No Cross No Protection, Cross 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] Cross Protection, Cross Protectcon 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean estimate generated by the 50 best fitting parameter sets 38

39 Incremental Cost offsets ($1,000,000) Incremental Healthcare costs saved Discounted over 70 years 25,000 22,500 20,000 17,500 15,000 12,500 10,000 7,500 5,000 2,500 AGW consultations Other cancers Cervical screening Cervical cancer (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent 0 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] No Cross No Protection, Cross 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] Cross Protection, Cross Protectcon 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean estimate generated by the 50 best fitting parameter sets 39

40 Incremental Cost offsets ($1,000,000) Incremental Healthcare costs saved Discounted over 70 years 25,000 22,500 20,000 17,500 15,000 12,500 10,000 7,500 5,000 2,500 AGW consultations Other cancers Cervical screening Cervical cancer (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent 0 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] No Cross No Protection, Cross 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] Cross Protection, Cross Protectcon 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean estimate generated by the 50 best fitting parameter sets 40

41 Incremental Cost offsets ($1,000,000) Incremental Healthcare costs saved Discounted over 70 years 25,000 22,500 20,000 17,500 15,000 12,500 10,000 7,500 5,000 2,500 AGW consultations Other cancers Cervical screening Cervical cancer (1) 4-valent (2) 9-valent Girls, 4-valent Boys (3) 9-valent 0 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] No Cross No Protection, Cross 4-valent 4-valent [1 vs No vacc] 9-valent Girls 4-valent Boys [2 vs 1] 9-valent [3 vs 2] Cross Protection, Cross Protectcon 4-valent Base case: vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean estimate generated by the 50 best fitting parameter sets 41

42 Cost-effectiveness Base Case, No Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 6,866 1,068 6,400 [3,500; 10,100] (2) 9-valent Girls 4-valent Boys 2 vs. 1-2, Cost saving [CS; CS] (3) 9-valent 3 vs ,200 [1,900; >1million] 3 vs. 1-2, Cost saving [CS; CS] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 42

43 Cost-effectiveness Base Case, No Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 6,866 1,068 6,400 [3,500; 10,100] (2) 9-valent Girls 4-valent Boys 2 vs. 1-2, Cost saving [CS; CS] (3) 9-valent 3 vs ,200 [1,900; >1million] 3 vs. 1-2, Cost saving [CS; CS] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 43

44 Cost-effectiveness Base Case, No Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 6,866 1,068 6,400 [3,500; 10,100] (2) 9-valent Girls 4-valent Boys 2 vs. 1-2, Cost saving [CS; CS] (3) 9-valent 3 vs ,200 [1,900; >1million] 3 vs. 1-2, Cost saving [CS; CS] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 44

45 Cost-effectiveness Base Case, No Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 6,866 1,068 6,400 [3,500; 10,100] (2) 9-valent Girls 4-valent Boys 2 vs. 1-2, Cost saving [CS; CS] (3) 9-valent 3 vs ,200 [1,900; >1million] 3 vs. 1-2, Cost saving [CS; CS] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 45

46 Cost-effectiveness Base Case, No Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 6,866 1,068 6,400 [3,500; 10,100] (2) 9-valent Girls 4-valent Boys 2 vs. 1-2, Cost saving [CS; CS] (3) 9-valent 3 vs ,200 [1,900; >1million] 3 vs. 1-2, Cost saving [CS; CS] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 46

47 Cost-effectiveness Base Case, with Cross Protection for 4-valent Change in costs ($ million) Change in QALY-gained (1,000 QALY) ICER ($/QALYgained) (0) No Vaccination (1) 4-valent 1 vs. 0 5,379 1,131 4,800 [1,600; 8,600] (2) 9-valent Girls 4-valent Boys 2 vs. 1-1, Cost saving [CS; CS] (3) 9-valent 3 vs ,400 [4,000;>1million] 3 vs Cost saving [CS; 10,400] ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration=lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Predictions: Mean result of the 50 best fitting parameter sets (25 runs per parameter set) Uncertainty intervals: 10 th and 90 th percentiles of model results based on the 50 best fitting parameter sets, reflects uncertainty in the natural history parameters 47

48 Results: Sensitivity Analysis Influential Variables 48

49 Sensitivity Analysis Incremental cost-effectiveness ($/QALYgained), with Cross Protection for 4-valent 4-valent () vs. No vaccination 9-valent () vs 4-valent () Base case 4,800 Cost saving Duration of Protection 9- & 4-valent=20yrs Cross-protection=20yrs Vaccination Coverage All doses at 13 yrs of age Girls=75%, Boys=69% 6,500 4,900 6,700 9,900 Cost saving Cost saving Cost saving 3,500 Min Health Care Costs 11,700 4,500 Min Burden of Disease 8,000 Cost saving Cervical screening - Co-testing - Cost saving ICER: Incremental Cost-Effectiveness Ratio; QALY=quality-adjusted life-year Base case: Vaccine-type efficacy=95%, duration of protection =Lifelong; 4-valent cost/dose=$145; 9-valent cost/dose=$158 Min: Minimum estimates from the U.S. literature; All doses given at 13 yrs of age: Vaccination coverage Girls=62%, Boys=32%; HPV Co-testing: HPV co-testing every 5 years (30-65 year old women) Predictions: Mean result of the 50 best fitting parameter sets (20 runs per parameter set) 49

50 Max. additional cost/dose for the 9-valent to be cost-effective vs. Quadrivalent in Canada (at $40,000/QALY-gained) Girls-only, Coverage=80%, VE=95%, Quadrivalent X- protection Description Cost diff. BASE CASE 24(6;36) Vaccine duration (VD) VD=Life 16(6;26) Lower nonavalent vaccine efficacy (VE) Nona VE=90% 19(10;36) Nona VE=85% 19(10;35) Vaccination coverage (VC) VC=70% 25(16;35) VC=50% 25(16;43) Disease Burden Max. cancer burden 37(10;50) Min. cancer burden 16(5;30) Max. AGW burden 24(7;34) Min. AGW burden 24(6;36) Disease endpoints Cervical cancer and AGW 24(6;35) Cervical cancer only 24(5;36) Cost-effectiveness threshold $20,000 $100,000 Most favourable scenario for quadrivalent Quad: VE=95%, VD=Life; Nona: VE=85%, VD=20yrs 8(-9;19) REF: Drolet, International Journal Cancer (4;21) 49(13;81) Favourable to nonavalent Cost difference ($)

51 Max. additional cost/dose for the 9-valent to be cost-effective vs. Quadrivalent in Canada (at $40,000/QALY-gained) Girls-only, Coverage=80%, VE=95%, Quadrivalent X- protection Description Cost diff. BASE CASE 24(6;36) Vaccine duration (VD) VD=Life 16(6;26) Lower nonavalent vaccine efficacy (VE) Nona VE=90% 19(10;36) Nona VE=85% 19(10;35) Vaccination coverage (VC) VC=70% 25(16;35) VC=50% 25(16;43) Disease Burden Max. cancer burden 37(10;50) Min. cancer burden 16(5;30) Max. AGW burden 24(7;34) Min. AGW burden 24(6;36) Disease endpoints Cervical cancer and AGW 24(6;35) Cervical cancer only 24(5;36) Cost-effectiveness threshold $20,000 $100,000 Most favourable scenario for quadrivalent Quad: VE=95%, VD=Life; Nona: VE=85%, VD=20yrs 8(-9;19) REF: Drolet, International Journal Cancer (4;21) 49(13;81) Favourable to nonavalent Cost difference ($)

52 Summary 52

53 Summary Cost-effectiveness predictions Current 4-valent HPV vaccination programs are highly costeffective Switching to a 9-valent program is likely cost-effective (and cost saving in the U.S.) Vaccinating girls with the 9-valent provides the majority of cost savings and QALYs-gained of a 9-valent program Results are robust across a range of plausible assumptions with or without cross protection vaccination coverage, price, duration of protection, health care costs, burden of illness 53

54 Thank you! 54

IMPACT OF HPV IMMUNIZATION STRATEGIES & POTENTIAL FOR CERVICAL CANCER ELIMINATION

IMPACT OF HPV IMMUNIZATION STRATEGIES & POTENTIAL FOR CERVICAL CANCER ELIMINATION Marc Brisson Full Professor Université Laval, Canada SAGE meeting October 24, 2018 Geneva 1 Questions A. What is the potential