|Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer
|Reed SD, Scales CD, Stewart SB, Sun J, Moul JW, Schulman KA, Xu J
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.
This study assessed the cost-effectiveness of chemoprevention of prostate cancer using finasteride, compared with no chemoprevention, considering risk groups. At a threshold of 100,000 US dollars per quality-adjusted life-year, chemoprevention might be cost-effective, especially for men with a family history of disease and a high number of risk alleles. Genetic targeting could reduce overall expenditure. The methods were valid, but the sources of data were not described and the authors’ conclusions need to be supported by further studies.
Type of economic evaluation
This study assessed the cost-effectiveness of chemoprevention of prostate cancer using finasteride, compared with no chemoprevention, considering risk groups defined by the patient's family history and number of risk alleles (genetic polymorphism).
Finasteride (5mg per day) was taken for 25 years or until prostate cancer developed. The comparator was no chemoprevention. Patients were selected for chemoprevention by genetic testing for risk alleles and on the basis of their family history. Patients with a family history of prostate cancer received chemoprevention without genetic testing. Those with no family history underwent genetic testing, with chemoprevention given based on the of number of risk alleles, with various thresholds tested.
The analysis was based on a Markov model with a lifetime horizon. The authors stated that the perspective of the health care system was adopted.
The clinical data were from a selection of relevant studies, with most of the epidemiological data selected from US databases. The relative risk of prostate cancer with finasteride was a key input of the model.
Monetary benefit and utility valuations:
The utility values were from a published study on radical prostatectomy and they were reported as disutilities.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and they were discounted at an annual rate of 3%.
The economic analysis included the cost of finasteride, the costs of out-patient medications (alpha-blockers for patients with benign prostatic hyperplasia, and androgen suppression therapy for patients with biochemical recurrence or metastatic disease), and the costs of prostate cancer in the year after diagnosis, the year before death, and all intervening years. The prostate cancer costs were from a published study, while the drug costs were based on average wholesale prices. The cost of a genetic test was added for patients with no family history of prostate cancer and this was based on assumptions. All costs were in US dollars ($) and were discounted at an annual rate of 3%. The price year was 2009.
Analysis of uncertainty:
A probabilistic sensitivity analysis was undertaken using a Monte Carlo simulation, with predetermined distributions for the inputs. These probability distributions were reported. Confidence intervals were generated around the model outcomes. The impact of individual inputs on the model outcomes was investigated, focusing on the risks of high- and intermediate-grade cancer with finasteride, the starting age for chemoprevention, the duration of chemoprevention, the absence of a beneficial effect of finasteride on benign prostatic hyperplasia, the disutilities associated with benign prostatic hyperplasia and chemoprevention, and the costs of chemoprevention and prostate cancer treatment. Variations in the age-specific incidence of prostate cancer were considered.
In the whole sample of patients, chemoprevention led to a gain of 101.2 QALYs (95% CI 60.2 to 151.1) per 1,000 patients and an additional cost of $9,043 (95% CI 8,549 to 9,498), compared with no chemoprevention. The incremental cost per QALY gained was $89,300 (95% CI 58,800 to 149,800).
Without a genetic test, in patients with a family history of prostate cancer, the incremental cost-effectiveness ratio was $64,193 per QALY gained, while in those with no family history this increased to $101,025.
The ratio fell to $43,400 for patients with a family history and 14 or more risk alleles and rose to $128,600 for those with no family history and seven or fewer risk alleles. The ratio only exceeded $100,000 for patients with no family history and up to 11 risk alleles. All ratios were generally 36% lower for patients with a family history, across varying numbers of risk alleles.
Assuming the introduction of a genetic test at $400 per person, the cost-effectiveness for patients with no family history ranged from $98,128 with chemoprevention for those with 14 or more alleles to $103,213 with chemoprevention for those with eight alleles or more.
The risk of high-grade tumours with finasteride and the utility weights assigned to benign prostatic hyperplasia and finasteride were influential inputs.
The authors concluded that, at a threshold of $100,000 per QALY, chemoprevention with finasteride might be cost-effective, especially for men with a family history of disease and a high number of risk alleles. Genetically targeted therapy could reduce the overall expenditure associated with chemoprevention.
The selection of the comparators was valid as chemoprevention, with or without risk assessment, was compared against no chemoprevention and the threshold number of risk alleles was varied.
The approach used to identify the relevant sources of data was not reported and relevant data might have been missed. No information on the methods and the patient groups examined in these studies was provided. This makes it impossible to judge the validity of the clinical inputs. US epidemiological data were used, where available. The clinical data were varied extensively in the sensitivity analysis. QALYs were an appropriate benefit measure because of the impact of the disease on both survival and quality of life. They also allow cross-disease comparisons. No details of the sources used to obtain the disutilities were provided.
The cost categories appear to have been consistent with the perspective. Limited information on the key source of economic data was given, reducing the transparency of the analysis. The price year and discounting were appropriately reported. Some details of the unit costs were reported, but no clear information was provided on the patterns of resource consumption. The impact of alternative assumptions for the costs was considered in the sensitivity analyses.
Analysis and results:
The results were clearly presented and an incremental analysis was carried out to synthesise the costs and benefits of the strategies. The authors discussed the issues around the selection of the optimal cost-effectiveness threshold. The uncertainty was appropriately investigated, using both a deterministic and a probabilistic approach, and the findings were clearly reported and illustrated. As little information was given about the unit costs and resource quantities, the study may be difficult to transfer to other settings.
The methods were valid, but no details were given of the sources used to populate the decision model. The authors’ conclusions need to be supported by further studies.
Supported by a grant from the National Cancer Institute, USA.
Reed SD, Scales CD, Stewart SB, Sun J, Moul JW, Schulman KA, Xu J. Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer. Journal of Urology 2011; 185(3): 841-847
Subject indexing assigned by NLM
5-alpha Reductase Inhibitors /economics /therapeutic use; Aged; Cost-Benefit Analysis; Finasteride /economics /therapeutic use; Humans; Male; Middle Aged; Polymorphism, Genetic; Prostatic Neoplasms /economics /genetics /prevention & control
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Date abstract record published