The cost of prostate cancer chemoprevention: a decision analysis model Svatek R S, Lee J J, Roehrborn C G, Lippman S M, Lotan Y

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1 The cost of prostate cancer chemoprevention: a decision analysis model Svatek R S, Lee J J, Roehrborn C G, Lippman S M, Lotan Y 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 use of daily finasteride treatment for the prevention of prostate cancer (PC). Type of intervention Primary prevention. Economic study type Cost-effectiveness analysis. Study population The study population comprised a hypothetical cohort of 50-year-old men with a prostate-specific antigen (PSA) level of <= 3.0 mg/ml, a normal digital rectal exam, and an American Urological Association symptom score of less than 20. Setting The setting was primary care. The economic study was carried out in the USA. Dates to which data relate The effectiveness data were derived from studies published between 1995 and No dates for resource consumption were explicitly reported. The price year was Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies. Modelling A Markov model with a lifetime horizon and annual cycles was constructed to assess the long-term clinical and economic impact of chemoprevention with finasteride, compared with no preventive treatment, in a hypothetical cohort of men aged 50 years. The men were assumed to receive the intervention drug for 20 years or until PC was diagnosed. The simulation considered progression in a fixed sequence of health states: cancer-free, PC (Gleason grades 8-10, 7, 6, or 2-5), biochemical recurrence of PC, metastatic disease and death. A graphical representation of the model was provided. At the end of each cycle, patients could remain in the same state, progress to a more advanced stage, or die of unrelated causes. Patients diagnosed with cancer received immediate radical retropubic prostatectomy and pelvic lymph node dissection (without adjuvant or neoadjuvant therapy). Biochemical recurrence was managed initially with watchful waiting. Patients who entered the metastatic disease health state were assumed to be treated with androgen ablation therapy using leuprolide acetate. Outcomes assessed in the review Page: 1 / 6

2 The outcomes estimated from the literature were: the probability of developing PC; the transition probabilities across health states; the prevalence of benign prostatic hyperplasia; and the effect of finasteride on benign prostatic hyperplasia. Study designs and other criteria for inclusion in the review It was unclear whether a systematic review of the literature was undertaken to identify primary studies, which might have been identified selectively. Much of the clinical data were derived from the PCPT, in which 18,882 men were randomised to receive finasteride or placebo and then followed for 7 years. The effect of finasteride on benign prostatic hyperplasia was derived from the Medical Therapy of Prostatic Symptoms Trial. No information on the other sources of data was provided. Sources searched to identify primary studies Criteria used to ensure the validity of primary studies The use of data derived mainly from a large clinical trial ensures a high internal validity. Methods used to judge relevance and validity, and for extracting data Number of primary studies included Five primary studies provided the clinical data. Methods of combining primary studies Investigation of differences between primary studies Results of the review The 7-year prevalence of PC was reduced by 24.8% in the finasteride group in comparison with the placebo group. However, there was an increase of high-grade prostate tumours with finasteride (37% versus 22.2%). The lifetime probability of developing PC was estimated to be 12.5% with finasteride and 16% without finasteride. Transition probabilities across health states depended on the Gleason score and the follow-up period (presented for 5, 10 or 15 years). For example, the probabilities of moving from 'no evidence of disease' to 'biochemical recurrence' were: 0.25 after 5 years, 0.43 after 10 years, and 0.50 after 15 years for patients with a Gleason score of 8-10; 0.21 after 5 years, 0.35 after 10 years, and 0.42 after 15 years for patients with a Gleason score of 7; Page: 2 / 6

3 0.15 after 5 years, 0.25 after 10 years, and 0.31 after 15 years for patients with a Gleason score of 6; and 0.12 after 5 years, 0.20 after 10 years, and 0.23 after 15 years for patients with a Gleason score of 2-5. The transition probabilities across the other health states of the model were also reported. The prevalence of benign prostatic hyperplasia was 0.15 (range: 0.10 to 0.20) in men younger than 65 years of age and 0.22 (range: 0.14 to 0.30) in men aged 65 years or older. The relative effect of finasteride on benign prostatic hyperplasia compared with placebo was 60% (range: 50 to 100). Measure of benefits used in the economic analysis The summary benefit measure used was the number of life-years (LYs) associated with the two strategies under examination. An annual discount rate of 3% was used. The LYs were estimated using the decision modelling approach. Direct costs The analysis of the costs included the direct medical costs associated with medications (finasteride, leuprolide acetate and alpha-blockers), specific disease states (biochemical recurrence and metastatic disease), terminal care for PC, radical retropubic prostatectomy, complications from retropubic prostatectomy, physician visits, PSA laboratory test and transurethral resection of prostate. The unit costs were not presented separately from the quantities of resources used, as limited information on resource consumption was provided. The costs were derived from published studies, average wholesale prices and local estimates, and reflected costs not charges. Discounting was relevant, as the long-term costs were evaluated, and an annual rate of 3% was used. All costs were inflated to 2005 values using the Gross Domestic Product Deflator Inflation Calculator. Statistical analysis of costs The costs were treated deterministically. Indirect Costs The indirect costs were not included in the economic evaluation. Currency US dollars ($). Sensitivity analysis Two- and three-way sensitivity analyses were carried out to assess the robustness of the cost-effectiveness ratios to simultaneous variations in the relative risk reduction associated with finasteride, the cost of finasteride, and the lifetime prevalence of PC. Alternative ranges of values were either derived from the literature or based on authors' opinions. A further analysis was performed in which it was assumed that a quarter of men with PC diagnosis received salvage therapy following PSA recurrence and one half of men with metastatic disease received chemotherapy. A further, alternative scenario assumed that finasteride did not increased the incidence of high-grade disease Estimated benefits used in the economic analysis In the base-case analysis, chemoprevention with finasteride led to a gain of 13.7 LYs per 1,000 men in comparison with placebo. In the scenario where finasteride did not increase the incidence of high-grade disease, chemoprevention with finasteride led to a gain of 21.4 LYs per 1,000 men in comparison with placebo. Page: 3 / 6

4 Cost results In the base-case analysis, chemoprevention with finasteride led to an additional cost of $9,631 per person in comparison with placebo. In the scenario where finasteride did not increase the incidence of high-grade disease, chemoprevention with finasteride led to an additional cost of $9,607 per person in comparison with placebo. Synthesis of costs and benefits Incremental cost-effectiveness ratios (ICERs; i.e. the incremental cost per LY gained) were calculated to combine the costs and benefits. In the base-case analysis, the ICER associated with finasteride over placebo was $703,847. In the scenario where finasteride did not increase the incidence of high-grade disease, the ICER associated with finasteride over placebo was $434,113. The results of the sensitivity analysis showed that in a population of high-risk individuals (lifetime prevalence > 30%), the cost of finasteride would have to be reduced from its current monthly cost ($62) to $15 for the ICER to fall below the threshold of $50,000 per LY gained. At a monthly cost of $62, the ICER was greater than $100,000 unless the prevalence was greater than 40% and the risk reduction was greater than 50%. Other changes did not substantially affect the ICER. Finasteride was generally not cost-effective, assuming a threshold of $100,000 per LY gained. Authors' conclusions Chemoprevention with finasteride led to a reduction in the lifetime prevalence of prostate cancer (PC) in men aged 55 years and older, but it was not cost-effective except in scenarios with substantial reductions in the cost of the agent and in high-risk men. In effect, given the low prevalence of disease, a substantial proportion of the cost would be generated by giving finasteride to men who, even without chemoprevention, would never develop PC. CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear since the actual pattern of care (no prevention) was used as the comparator for the new preventive agent. You should decide whether they are valid comparators in your own setting. Validity of estimate of measure of effectiveness The effectiveness data were derived from published studies, although it was not stated whether a systematic review of the literature had been undertaken. Therefore, the primary studies might have been identified selectively. The bulk of the evidence came from a large clinical trial, the randomised design of which ensures the robustness of the clinical data. Limited information on the other sources of evidence was provided. The authors did not address the issue of heterogeneity amongst the primary studies and did not report which approach was used to combine the primary estimates, whenever required. The sensitivity analysis focused on those parameters that were considered uncertain or relevant. Validity of estimate of measure of benefit The use of LYs as the summary benefit measure was appropriate as expected survival is a relevant aspect of health for patients at risk of developing PC. Discounting was performed, as recommended by guidelines for economic evaluations. Validity of estimate of costs The analysis of the costs was restricted to direct medical costs, which makes the perspective of the third-party payer Page: 4 / 6

5 relevant for the analysis. The authors stated that the inclusion of indirect costs associated with productivity losses would have been interesting. The costs were presented as macro-categories, and few details of the unit costs and quantities of resources used were presented. This will limit the possibility of replicating the analysis in other settings. The costs were mainly derived from published studies but a detailed breakdown of the cost items was not provided. Statistical analyses of the costs were not carried out, and only the price of chemoprevention was varied in the sensitivity analysis. The price year was reported, which will assist reflation exercises in other time periods. Other issues The authors reported details of a published economic evaluation of finasteride, the results of which were comparable to those observed in the current study although the data were derived from different sources. The issue of the generalisability of the study results to other settings was not explicitly addressed, but alternative epidemiological scenarios were considered in the sensitivity analysis. However, the costs were not varied in these sensitivity analyses (except for the unit cost of finasteride). The authors noted some limitations of their analysis, which was intentionally biased in favour of finasteride. However, despite this bias, the results were unfavourable for chemoprevention. Implications of the study The study results did not support the use of finasteride for the prevention of PC in men aged 55 years or older. The authors stated that targeting a high-risk population might make chemoprevention more cost-effective. Source of funding None stated. Bibliographic details Svatek R S, Lee J J, Roehrborn C G, Lippman S M, Lotan Y. The cost of prostate cancer chemoprevention: a decision analysis model. Cancer Epidemiology, Biomarkers and Prevention 2006; 15(8): Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information Thompson JM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349: Zeliadt SB, Etzioni RD, Penson DF et al. Lifetime implications and cost-effectiveness of using fanasteride to prevent prostate cancer. Am J Med 2005;118: McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349: Indexing Status Subject indexing assigned by NLM MeSH Aged; Chemoprevention; Cost-Benefit Analysis; Decision Support Techniques; Enzyme Inhibitors /economics /therapeutic use; Finasteride /economics /therapeutic use; Health Care Costs; Health Services Research /economics; Humans; Male; Markov Chains; Middle Aged; Models, Econometric; Prostatic Neoplasms /economics /epidemiology /prevention & control; Sensitivity and Specificity Page: 5 / 6

6 Powered by TCPDF ( AccessionNumber Date bibliographic record published 31/03/2007 Date abstract record published 31/03/2007 Page: 6 / 6