Economic evaluation, reimbursement and context

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Cost-Utility of HPV for Prevention of Cervical Cancer in the State of Roraima (Brazil): A Markov Model Approach.

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Economic evaluation, reimbursement and context

  1. 1. Cost-Utility of HPV for Prevention of Cervical Cancer in the State of Roraima (Brazil): A Markov Model Approach Giacomo Balbinotto Neto (Ph.D) Allex Jardim da Fonseca (M.D) Universidade Federal do Rio Grande do Sul – Brazil. Institute for Health Technology Assessment – Brazil
  2. 2. IntroductionIn Brazil, Cervical Cancer (CC) represents an important public healthproblem.It is estimated that 22.000 new cases of CC will arise in 2012, correspondingto an incidence rate of 17.5 cases per 100.000 women and to a mortalityrate due to CC of 10.2 deaths per 100,000 women.In the Brazilian Amazon Region, the problem is even more serious.Due to a low screening coverage for CC in target population (less than 25%),a high incidence of CC has been registered in Amazonia (up to 46cases/100,000 women), similar to the incidence rates in low-incomecountries, such as Uganda and Mali. 2
  3. 3. RoraimaNacional Institute of Cancer – Brazil, 2011. 3
  4. 4. Brazilian government programs to control CC arebased on secondary prevention and have historicallyfailed to overcome: (i) geographical isolation in the rain forrest ; (ii) cultural barriers. 4
  5. 5. ObjectiveTo assess cost-utility of the HPV vaccination on theprevention of ICC in Brazilian Amazon Region (Stateof Roraima). MethodsA Markov cohort model was developed to simulatethe natural history of HPV and its progress to ICC,considering the current preventive programs andtreatment costs. 5
  6. 6. Analytical Decision ModelThe analysis was performed from the provider’s perspective (Brazils UnifiedHealth System - SUS).The target population was preteen girls under 12 years old.The cohort time horizon was lifetime.The model simulated the natural history of HPV infection until its progressionto invasive cervical cancer, taking into account the prevention programs (Paptest) that are current in Brazil.For each strategy (screening plus vaccination or screening only), the modelincorporated health state transition probabilities and the target populationwas followed from adolescence until death in a hypothetical cohort. 6
  7. 7. The 1-year transitionprobabilities werebased mainly onempirical data oflocal and nationalstudies.The model evaluatedthe addition of thevaccine to 3 cervicalcancer screeningscenarios (0, 3 or 10exams throughoutlife). 7
  8. 8. Analytical Decision ModelThe model incorporated the transition probabilitiesof mutually exclusive health states that refer to one-year cycles.The model simulated the transition probabilities for70 years from the age of vaccination (12 years old).At each transition, the model attributed the costs,quality of life, and death expectation according tothe individual’s health condition. 8
  9. 9. Analytical Decision ModelThe transition probabilities were based on empiricaldata from medical literature and referred totransitions from a healthy state to a possible HPVinfection and low-grade squamous intraepitheliallesion (LSIL) induction, which could regress overtime to normality, persist, or progress to high-gradesquamous intraepithelial lesion (HSIL).This, in turn, could persist, regress to normality, orprogress to localized, regional, or metastatic invasivecancer. 9
  10. 10. Analytical Decision ModelAt each screening event, cervical lesions would befound according to the criteria (Pap test sensitivityand specificity) described by national studies.The detection of cervical lesions would requirefollow-up evaluations or treatment (colposcopy,cryosurgery, and/or surgery), for which they havebeen assigned a likelihood of success, costs, andimplications for the quality of life of the individuals ofthe cohort model. 10
  11. 11. Analytical Decision ModelThe economic analysis has adopted a 3% annualdiscount rate for the cost and outcome, with theintent to convert future values into present values.The model was calibrated by adjusting the incidenceof precursor lesions of CC to adequately simulate theresults of cancer incidence as recorded in theBrazilian Amazon Region. 11
  12. 12. Analytical Decision ModelThe fundamental structure of the model is based on clinicalpractice that is consistent with the clinical program proceduresadvocated by the VIVA MULHER, program from the BrazilianMinistry of Health.Abnormal screening examinations were forwarded tocolposcopy, and tissues were evaluated by biopsy. If HSIL werehistologically confirmed, then the patient would be subjected tocryotherapy treatment or surgery.The costs related to each procedure were taken from the fundsallocation table of the Ministry of Health of Brazil. 12
  13. 13. Analytical Decision ModelThe probabilities of death by cancer at each stage wereextracted from the global survival curves of longitudinal studies. The five-year survival rate varied from 92.0% for localizedcancer to 55.7% for regional cancer and 16.5% for metastaticcancer.The annual incremental costs were estimated at 10% of theinitial value of the cancer treatment and refer to screeningexaminations, control of sequelae, and treatment-relatedtoxicities or costs related to tumor recurrence. Only direct coststhat were assigned to cancer were computed and arerepresented in international dollars (US$). 13
  14. 14. Analytical Decision ModelThe model multiplies the years of life by the utilityimplicated in the health status to adjust survival byquality of life, with the final outcome of effectivenessbeing quality-adjusted life years (QALYs).In the base case, vaccination coverage was assumedat 70% of the target population. 14
  15. 15. Analytical Decision ModelIn this model, it was determined that the vaccine providesimmunity throughout life after three doses in the course ofone year. However, simulations on the need for booster dosesthroughout life to maintain immunity (one booster dose everyten years) were also performed.The reduction in the incidence of CC-inducing lesions as aresult of vaccination was based on studies that originallyreported the effectiveness of the quadrivalent vaccine . 15
  16. 16. Analytical Decision ModelThe cost of vaccination (three doses + implementation costs)for the base case was estimated at US$ 268.There are no references for the price of the vaccine in Brazilfor the large-scale public sector; since the vaccine has notbeen incorporated into public health protocols yet.However, it was reported that the average price of vaccination(three doses) in the American market is US $360 (LIPPMAN,2007). For the public sector, the value negotiated by theCenters for Disease Control in the United States was US $290(CDC, 2010). 16
  17. 17. Preventive Strategies Cost per Quality- Incremental QALYs ICER individual adjusted life cost (US$) saved per (US$/QALY) years (QALYs) individual (US$)Non-screening scenario Vaccination 467 24.80 -42 0.2 Dominant No vaccination (natural history) 510 24.60Scenario of 3 screeningsthroughout the lifetime (basecase) Vaccination + screening 511 29.6 188 0.2 1,374 Only screening 322 29.4Scenario of 10 screeningsthroughout the lifetime Vaccination + screening 772 34.5 438 0.2 2,518 Only screening 334 34.3 17
  18. 18. Preventive Strategies Cost per Quality- Incremental QALYs ICER individual adjusted life cost (US$) saved per (US$/QALY) years (QALYs) individual (US$)Non-screening scenario Vaccination 467 24.80 -42 0.2 Dominant No vaccination (natural history) 510 24.60Scenario of 3 screeningsthroughout the lifetime (basecase) Vaccination + screening 511 29.6 188 0.2 1,374 Only screening 322 29.4Scenario of 10 screeningsthroughout the lifetime Vaccination + screening 772 34.5 438 0.2 2,518 Only screening 334 34.3 18
  19. 19. Preventive Strategies Cost per Quality- Incremental QALYs ICER individual adjusted life cost (US$) saved per (US$/QALY) years (QALYs) individual (US$)Non-screening scenario Vaccination 467 24.80 -42 0.2 Dominant No vaccination (natural history) 510 24.60Scenario of 3 screeningsthroughout the lifetime (basecase) Vaccination + screening 511 29.6 188 0.2 1,374 Only screening 322 29.4Scenario of 10 screeningsthroughout the lifetime Vaccination + screening 772 34.5 438 0.2 2,518 Only screening 334 34.3 19
  20. 20. Preventive Strategies Cost per Quality- Incremental QALYs ICER individual adjusted life cost (US$) saved per (US$/QALY) years (QALYs) individual (US$)Non-screening scenario Vaccination 467 24.80 -42 0.2 Dominant No vaccination (natural history) 510 24.60Scenario of 3 screeningsthroughout the lifetime (basecase) Vaccination + screening 511 29.6 188 0.2 1,374 Only screening 322 29.4Scenario of 10 screeningsthroughout the lifetime Vaccination + screening 772 34.5 438 0.2 2,518 Only screening 334 34.3 20
  21. 21. Sensitivity AnalysisAll economic assessments show a certain degree of uncertainty,inaccuracy, or methodological controversy (PETITI, 2000;MUENNING, 2002; RASCATI, 2010). Therefore, sensitivity analyses (one-way) were performed forvariables with uncertainty over the base case values to assessthe robustness of the present study findings.These analyses recalculate the ICER considering the variationsin a given parameter. 21
  22. 22. Sensitivity AnalysisThe variables that were evaluated were the cost ofvaccination, the effectiveness of vaccination, thescenario of the pre-existing screening program,vaccination coverage, time of immunity, annualdiscount rate and the characteristics of the Pap test(sensitivity).For such analyses, the variation values represent ourjudgment regarding the uncertainty of the studyparameter or the variations in the results that havebeen published in the medical literature. 22
  23. 23. ResultsThe primary outcome for the calibration of the model was theincidence of invasive cancer.In the scenario of the natural history of HPV infection, withoutscreening exams, the model simulated a 4.2% lifetime risk ofcancer, which equates to 34.1 invasive CC cases per 100,000women, considering the demographic structure of the regionstudied (IBGE, 2007b).In the scenario with screening three times throughout anindividual’s lifetime, the risk of cancer was estimated at 3.4%(equivalent to 27.5 cases per 100,000 women). 23
  24. 24. ResultsFigure below illustrates the CC incidence rate adjustedfor each age group, according to the data of theincidence recorded for the population studied(described as "observed") and compares thesimulations of this incidence rate (from the Markovmodel developed) considering 2 baseline strategies:no screening (natural history) and three screeningsthroughout a woman’s lifetime. 24
  25. 25. The scenario of three Pap tests resulted in satisfactory calibration (base case). 25
  26. 26. PredictionThe prediction in the three-screeningsscenario corresponded satisfactorily to thegross incidence rate of invasive CC as recordedin Amazon region in 2010 (FONSECA, 2010)(28.2 cases per 100,000 women) and will beconsidered as the baseline strategy to becompared with the addition of vaccination. 26
  27. 27. Base Case AnalysisWith a vaccination coverage rate of 70%, thevaccination strategy for preteen girls of the BrazilianAmazon Region would reduce the lifelong incidenceof CC by 35% in this population and would reducethe mortality due to CC by approximately 33.4%.The addition of the vaccine generated an incrementalcost of approximately US$ 188 per woman to thecurrent strategy. The incremental cost-effectivenessratio was US$ 1,374/QALYs saved. 27
  28. 28. Base Case AnalysisFigure below compares the reduction in the incidence of CCfor the various strategies (combination of cytologicalscreening and vaccination), given the different vaccinecoverage levels simulated by this model.We note that the goal of a 50% reduction in CC incidencecould be achieved by combining high vaccination coverage(>70%) with existing screening procedures (>three lifetimePap tests). 28
  29. 29. Base CaseThe addition of HPV vaccination would reduce by45% the incidence of invasive CC (70% vaccination coverage). 29
  30. 30. ResultsThe sensitivity analyses reveal that vaccinationtends to provide a favorable profile from acost-effectiveness point of view despitechanges in the base case parametersproposed by the sensitivity analysis. 30
  31. 31. Base Case AnalysisThe population vaccination coverage implies wide variationsin ICER, surpassing US$ 2,150/QALYs for vaccine coveragelevels of less than 50%. The vaccination strategy tends to dominate the cytologicalscreening (3x) in isolation, i.e., it is less costly and moreeffective (ICER ≤ 0) for vaccination costs lower than US$ 53 (alldoses for primary immunization). For vaccination costs in excess of US$ 537, the vaccinationstrategy requires approximately US$ 3,225to save 1 QALY. 31
  32. 32. Base Case AnalysisA vaccination effectiveness (reduction in theincidence of precursor lesions) of above 40%maintains the ICER below US$1,612/QALY comparedto the basal strategy. Increases in the sensitivity ofthe Pap test tends to modestly increase the ICER ofadded vaccination by improving the efficiency of thebaseline strategy and leading to a relative reductionin the additional benefit of the vaccine. 32
  33. 33. 33
  34. 34. DiscussionThe present study revealed that the addition of HPV vaccinationto the existing preventive strategy exhibits a favorable cost-effectiveness and cost- utility profile in the Brazilian AmazonRegion (State of Romaima).Except for the simulation of vaccination coverage rates below30%, the ICER of the addition of vaccination does not exceedthe conventional limit of the GDP value per capita (about US$10,000 for Brazil) for any other uncertainty simulation. If thecost of vaccination is reduced to US$53 or less, with avaccination coverage rate of 70%, then adding vaccinationtends to dominate the cytological screening strategy alone. 34
  35. 35. Limitations to the Present Study(i) First, because of the lack of national data, someparameters have been calibrated based on international data.(ii) Second, the adherence to strategic programs in Braziltends to be opportunistic (VALE, 2010), favoring thevaccination of women who would have good adherence toexisting cytological screening to the detriment of non-participating women in higher-risk situations.(iii) Finally, the Markov assumption itself establishes thattransition probabilities depend exclusively on the currenthealth state, not on a sequence of past health states(DRUMMOND, 2001). 35
  36. 36. Therefore …The results of the present study should be considered as aconservative estimate of ICER of HPV vaccination in a BrazilianAmazon Region (State of Roraima) with a high incidence of CC.However, the satisfactory calibration of the proposed modelparameters and the alignment with other researchers’ studiesstrengthen the results that vaccination is cost-effective in theBrazilian Amazon Region (GOLDIE, 2007; GOLDIE, 2008;COLANTÔNIO, 2009). 36
  37. 37. Political ImplicationsThe high risk of invasive CC in Amazon Region impliesan urgent need to rethink the current CC preventivepolicy, especially for underprivileged regions of thecountry. The present study was the first cost-effectivenessanalysis of a CC preventive strategy that was directedtoward a specific region of the country (State ofRoraima). 37
  38. 38. Political ImplicationsThe cost-efectiveness analysis of HPV vaccine for AmazonRegion showed a better profile when compared to studiesaddressing this topic to Brazil as a whole, as in the analysispublished by Colantônio et al. (ICER = US$10,181/QALY) andGoldie et al. (ICER = US$9,600/QALY).Regarding public health, these results lead to the conclusionthat public policies on womens health, particularly on CCprevention programs, should be decentralized (adjusted toterritorial reality) and not uniform since the heterogeneityinherent in a country of continental proportions, such asBrazil. 38
  39. 39. Political ImplicationsLarge-scale preteen vaccination in the Amazon region can be consideredan investment in the future to prevent the premature deaths of hundredsof women in the coming decades, who have historically been neglected inpreventive government programs.Although it is difficult to accurately measure and evaluate this benefit, itwould translate into families and children who would not lose theirmothers to CC and resources that would not be allocated to the treatmentof this disease (direct and indirect costs) (COLANTÔNIO, 2008). These results may provide the basis for accelerating the incorporation ofthe vaccine for HPV 16 and 18 in preventive programs that serveunderprivileged women in disadvantaged regions of Brazil like AmazonRegion. 39
  40. 40. ConclusionsVaccination has a favorable profile in terms ofcost-utility in the State of Roraima (AmazonRegion in Brazil).Its inclusion in the immunization schedulewould result in substantial reduction inincidence and mortality of invasive CC inBrazilian Amazon region. 40
  41. 41. Thanks ! Obrigado ! Gracias !giacomo.babinotto@ufrgs.br 41
  42. 42. 42

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