Potential health and economic impact of adding a human papillomavirus vaccine to screening programs Kulasingam S L, Myers E R Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Various strategies using prophylactic vaccine targeted against human papillomavirus (HPV), in addition to conventional cytological screening, were examined. Details of the age at which each strategy was commenced, and the intervals at which each strategy was conducted, are reported in the 'Modelling' section. Type of intervention Vaccination and screening. Economic study type Cost-effectiveness analysis. Study population The study population comprised hypothetical females aged 12 years (and followed-up until aged 85 years) who, at the start of the simulation, had never had sex and were disease free. Setting The economic analysis was conducted in the Department of Obstetrics and Gynecology and Center for Clinical Health Policy Research, Duke University, Durham, USA. Dates to which data relate The dates to which the effectiveness and cost data related were not reported. Prices for 2001 were used. Source of effectiveness data The effectiveness data were derived from a published systematic review and from the authors' assumptions. Modelling A health state-transition Markov model (described elsewhere) was used to simulate the natural history of HPV infection and cervical cancer, and also to estimate the health, cost and life expectancy associated with three strategies. The model was revised to separately simulate high- and low-risk HPV infection. Screening intervals of 1, 2, 3 and 5 years and starting ages for screening of 18, 22, 24, 26 and 30 years were chosen for two strategies (conventional cytological screening alone and vaccination followed by screening). The authors fixed the age of first screening for the screening only strategy as 18 years. The delayed ages of first screening were 30 years for screening every 5 years, 26 years for screening every 3 years, 24 years for screening every 2 years, and 22 years for annual screening. Outcomes assessed in the review Page: 1 / 6
The outcomes assessed in the review and used as model inputs were the sensitivity and specificity of cytology, the proportion of HPV infections that progress directly to cervical intraepithelial neoplasia (CIN) 2-3, and the efficacy of the vaccine. The other transition probabilities were described in detail in other published studies. Study designs and other criteria for inclusion in the review Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Twelve studies were included in the review. Methods of combining primary studies Investigation of differences between primary studies Not performed. Results of the review The sensitivity of cytology (for the detection of CIN 2-3) was 55.6% (plausible range: 51-95) and the specificity was 95.7% (plausible range: 80-97). The proportion of HPV infections that progressed directly to CIN 2-3 was 10% (plausible range: 0-10). The vaccination efficacy was 90% (plausible range: 25-100). Methods used to derive estimates of effectiveness The authors made several base-case assumptions for screening, treatment, vaccination and the natural history of highrisk HPV infection. The authors used published literature and assumptions to derive health states utilities, all of which were subsequently tested in the sensitivity analyses. Estimates of effectiveness and key assumptions The following assumptions were made. The HPV vaccine did not differentially affect HPV infection progression to CIN 1 and CIN 2-3. The vaccine would be targeted at a proportion of high-risk HPV types rather than one or two high-risk HPV types, and this proportion would be constant as the cohort aged. Page: 2 / 6
Compliance with primary screening, follow-up and treatment was 100%. Colposcopy had perfect sensitivity and specificity for the detection of CIN 2-3. Women with no underlying disease confirmed at colposcopy would return to routine screening. Women with treated CIN would receive annual screening for the remainder of their lifetime, or until hysterectomy for other indications. Women who were screened and successfully treated would have a 95% reduction in the risk of developing CIN. Vaccine efficacy was constant over a 10-year period. There were no significant adverse effects due to vaccination. The entire cohort of 12-year-old girls would be vaccinated once and immunisation would be successful for all of the girls. Measure of benefits used in the economic analysis The health benefits were measured in terms of the life-years saved or quality-adjusted life-years (QALYs) saved. The authors did not include health-related quality of life in the base-case because no published utilities were applicable to all states. The QALYs were calculated in the sensitivity analysis using utilities derived from the literature and assumptions. The expected reductions in cancer incidence and deaths were also calculated. Life expectancy was discounted at an annual rate of 3%. Direct costs In the base-case analysis, the direct costs included only the medical costs. The perspective adopted was not clear, but it is likely to have been that of the health care system. In the sensitivity analysis, a broader societal perspective was adopted that included the indirect costs. The medical costs included conventional cytology, vaccine, colposcopy and biopsy, CIN 1, CIN 2-3, and cervical stages. The cost estimates for screening and diagnoses were derived from MEDSTAT, the National Ambulatory Medical Care Survey, and Medicare data. The vaccine costs were derived from an Institute of Medicine report on future vaccine development (a 3-vaccine series). The vaccine was assumed to be administered within current health care visits. The dates to which the cost data related were not reported. The costs were expressed in 2001 US dollars using the medical care component of the consumer price index from the Bureau of Labour statistics. The costs and the quantities were not reported separately. The costs were discounted at 3%. Statistical analysis of costs No statistical analysis of the costs was carried out. Indirect Costs The indirect costs for vaccination were used in the sensitivity analysis. The indirect costs were for the parents' time for three office visits. The costs were discounted at 3%. The source of the indirect costs, and the dates to which these costs related, were not reported. Currency US dollars ($). Sensitivity analysis One-way and two-way sensitivity analyses were carried out to test the authors' assumptions. The sensitivity analyses included the indirect costs and quality of life measures. Page: 3 / 6
Estimated benefits used in the economic analysis A total of 40 strategies were compared. However, the authors focused their analysis on 12. For the base-case, compared with no intervention, vaccination resulted in a 16.8% reduction in cancer incidence and a 17.7% reduction in cervical cancer deaths. When screening every 5 years beginning at 18 years was compared with no intervention, there was a 59.3% reduction in cancer incidence and a 71.2% reduction in cervical cancer deaths The reductions were 92.1% (cancer incidence) and 96% (cervical cancer deaths), respectively, with screening every year. When vaccination and delayed screening every 5 years beginning at age 30 years was compared with no intervention, there was a 62.1% reduction in cancer incidence and a 72.6% reduction in cervical cancer deaths. There was a 65.5% reduction in cancer incidence and a 75.7% reduction in cervical cancer deaths when comparing vaccination and delayed screening every 5 years beginning at age 18 years with no intervention. The corresponding reductions were 92.4% (cancer incidence) and 96% (cervical cancer deaths) for vaccination and delayed screening every year beginning at age 22 years, and 93.2% (cancer incidence) and 96% (cervical cancer deaths) for vaccination and delayed screening every year beginning at age 18 years. The life expectancy was 28.712 years with no intervention and 28.7261 years with vaccination alone. The life expectancy was 28.745 years with screening every 5 years beginning at age 18, and 28.7518 years with screening every 3 years beginning at age 18. The life expectancy was 28.7563 years with vaccination and delayed screening every 2 years beginning at age 24, 28.7578 years with vaccination and delayed screening every 2 years beginning at age 18, and 28.7612 years with vaccination and delayed screening every year beginning at age 18. Cost results The mean discounted lifetime cost was $284 with no intervention and $417 with vaccination alone. The mean discounted lifetime cost was $483 with screening every 5 years beginning at age 18, and $632 with screening every 3 years beginning at age 18. The mean discounted lifetime cost was $834 with vaccination and delayed screening every 2 years beginning at age 24, $973 with vaccination and delayed screening every 2 years beginning at age 18, $1,374 with vaccination and delayed screening every year beginning at age 22, and $1,563 with vaccination and delayed screening every year beginning at age 18. Synthesis of costs and benefits A strategy of vaccination alone was not cost-effective. Screening only was preferred at less frequent screening intervals (every 5 years and every 3 years). Compared with no intervention, the incremental cost-effectiveness ratio (ICER) of screening every 5 years was $6,030 per life-year saved. Compared with no intervention, the ICER of screening every 3 years was $21,912 per life-year saved. At more frequent screening intervals, a combination of vaccination and screening was preferred. The ICER ranged from $44,889 (for vaccination and delayed screening every 2 years beginning at age 24 compared with screening every 3 years) to $236,250 (for vaccination and delayed screening every year beginning at age 18 compared with the same strategy with interval beginning at age 22). Page: 4 / 6
In terms of the sensitivity analysis, assumptions about the natural history of HPV infection and response to vaccine, the impact of treatment of CIN, the differential impact of a type-specific vaccine on CIN 1 compared with CIN 2-3 and cancer, and assumptions about women who do not respond to vaccination were all considered with regard to the costeffectiveness results. The results were numerous (see original paper for more details). Authors' conclusions Using $50,000 per life-year saved as a threshold, the most attractive strategy appeared to be vaccination plus biennial screening beginning at age 24. CRD COMMENTARY - Selection of comparators The reason for the choice of the comparators was clear. The comparators represented potential alternatives to vaccination followed by screening. You should consider the applicability of these approaches to your own setting. Validity of estimate of measure of effectiveness The authors stated that a systematic review of the literature had been undertaken and the methodology used was reported in published studies (Myers et al. and Maxwell et al., see Other Publications of Related Interest). It is possible that the authors used data from the available studies selectively. The authors did not consider the impact of differences between the primary studies when estimating the effectiveness. They also justified some of the assumptions with reference to the medical literature. The estimates were investigated in a sensitivity analysis, which used what appear to have been appropriate ranges. Validity of estimate of measure of benefit The estimation of benefits was modelled using a Markov simulation model, which was appropriate. The health benefits were discounted. The QALYs were calculated in the sensitivity analysis using utilities derived from the literature and assumptions. The authors used QALYs to provide comparability with other published results. They acknowledged that assumptions on utility values may have a substantial impact on the ICER calculations. Validity of estimate of costs The perspective adopted was not clear, but it was likely to have been that of the health care system. A broader societal perspective, which included the costs of the parents' time, was adopted in the sensitivity analysis. The costs and the quantities were not reported separately. No statistical analysis of the quantities was performed. Other issues The authors did not compare their findings with those from other studies. However, they did refer to cost-effectiveness thresholds in the sensitivity analyses. The issue of generalisability to other settings was not addressed. The authors do not appear to have presented their results selectively. They also reported further limitations of their study. First, there is uncertainty in both the probability and cost estimates. Second, the use of utilities for cancer and preinvasive lesions should be interpreted with caution. Implications of the study The findings suggest that a vaccine that reduces the incidence of oncogenic HPV types during the peak ages of infection (generally the late teens and early 20s) can be economically attractive, especially if it allows for a delay in the onset of screening. Future research needs to be focused on the optimal time to offer vaccination. Research into understanding the feasibility and acceptability of vaccination at different ages should be given high priority. Source of funding Supported by a grant from Merck Research Laboratories. Page: 5 / 6
Powered by TCPDF (www.tcpdf.org) Bibliographic details Kulasingam S L, Myers E R. Potential health and economic impact of adding a human papillomavirus vaccine to screening programs. JAMA 2003; 290(6): 781-789 PubMedID 12915431 DOI 10.1001/jama.290.6.781 Other publications of related interest Myers ER,McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. American Journal of Epidemiology 2000;151:1158-71. Maxwell GL, Carlson JW, Ochoa M, Krivak T, Rose GS, Myers ER. Costs and effectiveness of alternative strategies for cervical cancer screening in military beneficiaries. Obstetrics and Gynecology 2002;100:740-8. Goldie SJ, Kuhn L, Denny L, Pollack A, Wright TC. Policy analysis of cervical cancer screening strategies in lowresource settings: clinical benefits and cost-effectiveness. JAMA 2001;285:3107-15. Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cervical Intraepithelial Neoplasia /pathology /prevention & control /virology; Colposcopy /economics; Cost-Benefit Analysis; Disease Progression; Female; Humans; Life Expectancy; Markov Chains; Mass Screening /economics; Middle Aged; Models, Theoretical; Papillomaviridae /immunology /isolation & purification; Papillomavirus Infections /pathology /prevention & control; Papillomavirus Vaccines; Quality-Adjusted Life Years; Tumor Virus Infections /pathology /prevention & control; Uterine Cervical Neoplasms /pathology /prevention & control /virology; Vaccination /economics; Vaginal Smears /economics; Viral Vaccines /administration & dosage /economics AccessionNumber 22003008221 Date bibliographic record published 31/12/2003 Date abstract record published 31/12/2003 Page: 6 / 6