Setting The setting was outpatient, primary care. The economic study was carried out in Germany.

Transcription

1 An economic analysis of human papillomavirus triage for the management of women with atypical and abnormal Pap smear results in Germany Sheriff S K, Petry K U, Ikenberg H, Crouse G, Mazonson P D, Santas C C 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 The study compared three management strategies for atypical and abnormal Papanicolau (Pap) smears conducted during cervical cancer screening. These were repeat Pap smear, triage with human papillomavirus (HPV) DNA testing, and immediate treatment. Type of intervention Screening. Economic study type Cost-effectiveness analysis. Study population Three hypothetical populations were modelled separately. Specifically, German women attending routine cervical screening, who had baseline smear results of PapIIw, PapIII or PapIIId. Setting The setting was outpatient, primary care. The economic study was carried out in Germany. Dates to which data relate Data for the model parameters were drawn from studies published between 1993 and The unit costs were reported in 2005 values. Source of effectiveness data Estimates of the prevalence of cervical intraepithelial neoplasia (CIN) 2+ in the starting populations and individual test specificities and sensitivities were used to estimate the following: the proportion of women for whom CIN2+ is detected and treated; the proportion of women with CIN2+ that was not detected; and the proportion of women with <CIN2 that received unnecessary treatment. Other parameters included compliance with screening and follow-up. Modelling Three models were designed, each evaluating the three management strategies used for populations with PapIIw, Pap III Page: 1 / 5

2 or PapIIId smear results. Management strategy 3, immediate treatment, was used only in the PapIII and PapIIId populations. Each model simulated 1 year- follow-up for 1,000 women with abnormal or atypical Pap smears. Diagrams of the model pathways were provided and described in the publication. Sources searched to identify primary studies Four published papers (1993 to 2003) provided data on the prevalence of CIN2+ for PapIIw and PapIIId, and the sensitivity for CIN2+ of repeat Pap and HPV DNA triage. Unpublished data were used to obtain the prevalence of CIN2+ PapIII estimate. Expert opinion was used to justify the following assumptions: compliance with screening, treatment and follow-up was 100%; the initial screening was performed using conventional cytology, which requires a second visit for sample collection if HPV triage is performed; the sensitivity and specificity of repeat Pap and HPV testing were considered independent of the baseline screening results; the sensitivity and specificity of second repeat Pap were assumed identical to those for first repeat Pap, as reported in the literature; and women with a baseline abnormal result, who had a first repeat Pap with a normal result, returned for a confirmatory follow-up in 3 months (assumed to be normal) and would then return to routine screening the following year. Methods used to judge relevance and validity, and for extracting data Data were abstracted from the published literature. Single estimates were applied to each of the model inputs, with gaps filled following personal communication with experts. The process used to identify the data was not reported and no inclusion criteria were given. The methods used to select the estimates were neither reported nor discussed. Measure of benefits used in the economic analysis The outcome used in the economic analysis was the incremental number of cases of CIN2+ detected and treated. Direct costs Pap smear testing, HPV testing, office visits for screening (physician payment only) and large loop excision treatment costs were included in the model. Resource use was driven by assumptions within the treatment strategies. The unit costs were taken from national published codes and reimbursement levels (EBM - described as the uniform valuation standard for the German fee schedule) and were reported separately. The price year was Statistical analysis of costs The costs were treated deterministically. Indirect Costs In line with the perspective adopted, productivity costs were not included. Currency Euros (EUR). Sensitivity analysis Page: 2 / 5

3 One-way sensitivity analyses were conducted on key inputs. Specifically, the costs were varied by +/- 100%, prevalence and sensitivity or specificity rates were varied between 0 and 1, and compliance with follow-up testing and treatment was varied from 50 to 100%. Threshold analyses were presented in some detail for each of the three model populations. Estimated benefits used in the economic analysis The number of incremental cases with HPV testing compared with repeat Pap was 19 in the PapIIw population, 69 in the PapIII population and 176 in the PapIIId population. Compared with HPV testing, there were 4 incremental cases for immediate treatment in the PapIII population and 11 in the PapIIId population. Cost results For repeat Pap, the mean cost per patient was EUR 40 in the PapIIw population, EUR 100 in the PapIII population and EUR 121 in the PapIIId population. For HPV testing, the mean cost per patient was EUR 81 in the PapIIw population, EUR 156 in the PapIII population and EUR 207 in the PapIIId population. The mean cost per patient was EUR 321 for immediate treatment in both the PapIII and PapIIId populations. The incremental cost per patient for HPV testing compared with repeat Pap was EUR 41 in the PapIIw population, EUR 56 in the PapIII population and EUR 86 in the PapIIId population. For immediate treatment compared with HPV testing, the incremental cost per patient was EUR 165 in the PapIII population and EUR 114 in the PapIIId population. Synthesis of costs and benefits Average cost-effectiveness ratios were reported and incremental cost-effectiveness ratios were calculated. For patients with initial PapIIw, III and IIId results, the incremental costs per additional case of CIN2+ detected and treated for HPV triage versus repeat Pap were EUR 2,232 for PapIIw, EUR 815 for PapIII and EUR 487 for PapIIId. The number of cases treated in a hypothetical population of 1,000 women increased from 17 to 35 for the PapIIw population, from 61 to 130 for the PapIII population, and from 157 to 332 for the PapIIId population. For patients with PapIII and IIId results, immediate treatment of 1,000 patients detected 4 and 11 additional cases, respectively, compared with HPV triage, at incremental cost-effectiveness ratios of EUR 39,684 and EUR 10,716. PapIIw model results were most sensitive to changes in the cost of HPV and Pap testing, and to the cost of follow-up visits. PapIII and PapIIId model results were somewhat sensitive to changes in the cost of treatment, HPV and Pap test sensitivity and HPV test specificity. Authors' conclusions For each of the populations evaluated, human papillomavirus (HPV) triage was the most cost-effective management strategy when compared with either repeat smear or immediate treatment. The results were considered insensitive to changes in model inputs within the ranges reported in the literature. CRD COMMENTARY - Selection of comparators The authors justified their choice of the comparators fully in the paper. In addition, they provided full justification for Page: 3 / 5

4 the exclusion of other possible screening techniques. You should decide whether all relevant comparators for your own setting have been included. Validity of estimate of measure of effectiveness The parameters were derived from published research, unpublished data, expert opinion and author assumptions. The methods of searching for and the retrieval and selection of published data were not provided. No justification for the parameter estimates was given. It was unclear whether a synthesis of the evidence had taken place as no details were included. It is therefore impossible to judge the validity of the estimates chosen, although the authors later stated that data were drawn from studies with different designs and patient populations, which implies that it might not have been appropriate to combine the data in a single model. Assumptions about the sensitivity and specificity of the tests might have been important in the PapIII and PapIIId models, the results of which were shown to be sensitive to these inputs. Validity of estimate of measure of benefit The estimate of benefit was a disease-specific measure derived from the decision-analytic model. The authors suggested that the complexity and uncertainty surrounding the natural history of the disease prevented them from conducting an analysis based on a lifetime benefit, such as survival or quality-adjusted life-years. Validity of estimate of costs The perspective adopted was that of the German health system, but the omission from the analysis of some relevant costs (e.g. costs of adverse events and outpatient facilities) might have had an impact on the results. Resource quantities were determined by the management and treatment strategies chosen (by expert opinion and author assumption), therefore it is difficult to evaluate whether they truly reflected the treatment setting. The costs and the quantities were reported separately, thus allowing greater generalisability of the model. The price year was reported and the unit costs were derived from an appropriate source of health system prices. Other issues The authors made appropriate comparisons with other studies conducted outside Germany, which generally supported their results. They did not assess the impact of any variations due to different treatment provision in different settings, but did emphasise the tailoring of their analysis to the specific German setting chosen. The results were presented in full and the conclusions reflected the scope of the analysis. The authors reported a number of limitations to their study. First, published data were not available for all inputs, thus requiring expert opinion to fill in the gaps, and were combined from several sources varying in study design and patient populations. Second, the management and treatment strategies were, from necessity, simplified in the models despite high levels of variation in German clinical practice. Finally, the analysis was limited to 1 year although cost-effectiveness ratios are ideally reported in terms of lifetime benefits. Implications of the study The authors suggested that further data concerning the longitudinal nature of HPV infection and cervical cancer are required, and that the present results should then be refined. Source of funding Supported by Roche Diagnostics. Bibliographic details Sheriff S K, Petry K U, Ikenberg H, Crouse G, Mazonson P D, Santas C C. An economic analysis of human papillomavirus triage for the management of women with atypical and abnormal Pap smear results in Germany. European Journal of Health Economics 2007; 8(2): PubMedID Page: 4 / 5

5 Powered by TCPDF ( DOI /s Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Costs and Cost Analysis; Decision Trees; Disease Management; Female; Germany; Humans; Papanicolaou Test; Papillomaviridae /isolation & purification; Triage; Uterine Cervical Neoplasms /diagnosis /virology; Vaginal Smears /economics AccessionNumber Date bibliographic record published 30/11/2007 Date abstract record published 30/11/2007 Page: 5 / 5