The cost-effectiveness of adjuvant chemotherapy for early breast cancer: A comparison of no chemotherapy and first, second, and third generation regimens for patients with differing prognoses.

BACKGROUND: The risk of recurrence following surgery in women with early breast cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces this risk; however, increasingly effective regimens are associated with higher costs and toxicity profiles, making it likely that different regimens may be cost-effective for women with differing prognoses. To investigate this we performed a cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy, (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third generation regimen). These adjuvant chemotherapy regimens were used in three large UK-led randomised controlled trials (RCTs). METHODS: A Markov model was used to simulate the natural progression of early breast cancer and the impact of chemotherapy on modifying this process. The probability of a first recurrent event within the model was estimated for women with different prognostic risk profiles using a parametric regression-based survival model incorporating established prognostic factors. Other probabilities, treatment effects, costs and quality of life weights were estimated primarily using data from the three UK-led RCTs, a meta-analysis of all relevant RCTs, and other published literature. The model predicted the lifetime costs, quality adjusted life years (QALYs) and cost-effectiveness of the four strategies for women with differing prognoses. Sensitivity analyses investigated the impact of uncertain parameters and model assumptions. FINDINGS: For women with an average to high risk of recurrence (based upon prognostic factors and any other adjuvant therapies received), FEC-D appeared most cost-effective assuming a threshold of £20,000 per QALY for the National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to be the optimal strategy and, for some older low risk women, the model suggested a policy of no chemotherapy was cost-effective. For no patient group was CMF chemotherapy the preferred option. Sensitivity analyses demonstrated cost-effectiveness results to be particularly sensitive to the treatment effect estimate for FEC-D and the future price of docetaxel. INTERPRETATION: To our knowledge, this analysis is the first cost-effectiveness comparison of no chemotherapy, and first, second, and third generation adjuvant chemotherapy regimens for early breast cancer patients with differing prognoses. The results demonstrate the potential for different treatment strategies to be cost-effective for different types of patients. These findings may prove useful for policy makers attempting to formulate cost-effective treatment guidelines in the field of early breast cancer.

Information technology facilitates cost-effectiveness analysis in developing countries: an observational study of breast cancer chemotherapy in Taiwan.

Health information technology offers a powerful tool to monitor the performance of a healthcare system. Advances in computer technology and capacity combined with lower start-up costs will allow developing countries to achieve greater impact when they initiate electronic health information systems. We focused on the integrated health information system that was established in Taiwan in conjunction with the launch of the National Health Insurance (NHI) programme. We used data from that health information system to conduct a cost-effectiveness analysis of chemotherapy use among breast cancer patients. We then used this analysis to discuss what policy makers can learn from this type of analysis. We identified a cohort of patients in the NHI Research Database who had been diagnosed with breast cancer in 2001 and had received chemotherapy following surgical removal of the tumour. We followed these patients for 3 years and conducted a cost-effectiveness analysis from the payer's perspective. Using the net benefit regression approach, we compared the cost effectiveness of the two most commonly prescribed first-line chemotherapy regimens for the treatment of breast cancer in 2001 in Taiwan. The dependent variable of the regression model was the individual-level net benefit, and the independent variables included a binary variable indicating the choice of chemotherapy regimen, the patients' age, co-morbidity, type of surgery, geographic region and type of treatment facility. We employed both frequentist and Bayesian approaches in our net benefit regression analyses. In the Bayesian analysis, we applied non-informative priors to all parameters in the base-case analyses. We then explored the use of informative priors in the sensitivity analysis, using cost-effectiveness data published in the literature to form the prior distributions for the relevant parameters. Over 60% of surgically treated breast cancer patients received either CMF (cyclophosphamide, methotrexate, fluorouracil) or CEF (cyclophosphamide, epirubicin, fluorouracil). A comparison of patient characteristics indicated that patients in the CEF group tended to be younger (47.8 vs 49.1 years; p = 0.016), and were significantly more likely to have undergone a mastectomy (84% vs 76%; p < 0.001) and to have been treated in a teaching hospital (26% vs 13%; p < 0.001). We also observed significant variations in geographic region of the location of facilities between treatment groups. On average, CEF was not cost effective in the treatment of patients with breast cancer in Taiwan, although analyses stratified by geographic region suggested a wide variation across regions. At a societal willingness to pay (WTP) of new Taiwanese dollar ($NT)1 500 000 ($US80 000), the probability that CEF was more cost effective than CMF was 0.0%, 0.0%, 0.0% and 3.9% for the Taipei metropolitan area, and the north, middle and the combined south and east region, respectively; the probability became 0.6%, 0.0%, 1.3% and 54.5%, respectively, at a WTP of $NT5 000 000 ($US270 000). After co-variate adjustments, the probabilities were 0.0%, 0.0%, 0.0% and 0.8%, respectively at a WTP of $NT1 500 000, and were 0.0%, 0.0%, 1.4% and 34.7% at $NT5 000 000. Sensitivity analyses showed that CEF potentially could have been more cost effective than CMF within a reasonable range of societal WTP (i.e. $NT1 000 000-3 000 000 or $US55 000-160 000) had the optimal dosage level for CEF been established for breast cancer patients in Taiwan. A population-based, fully integrated electronic health information system provides useful data to assess the cost effectiveness of competing treatments and interventions in current practice. This research may potentially inform policy makers of modifications that can be instituted to improve the cost effectiveness of a new therapy. However, findings from this study need to be interpreted with caution because the study provided information only on the short-term cost effectiveness (i.e. 3 years) of CEF compared with CMF. It is possible that a future analysis will reach a different conclusion when more years of follow-up data become available.

Adjuvant fluorouracil, epirubicin and cyclophosphamide in early breast cancer: is it cost-effective?

Adjuvant chemotherapy (ACT) in breast cancer exposes patients to morbidity, but improves survival. The FEC (fluorouracil, epirubicin, cyclophosphamide) regimen has taken over the prior role of CMF (cyclophosphamide, methotrexate, fluorouracil). In this model, efficacy, tolerability and quality of life (QoL) data from the literature were incorporated with Norwegian practice and cost data in a cost-effectiveness approach. The FEC efficacy was calculated 3-7% superior CMF. There was no difference in quality of life. An 80-100% dose intensity range was employed, one Euro was calculated NOK 8.78 and a 3% discount rate was used. The total cost of FEC employing the friction cost method on production loss, including amount spent on drugs, administration and travelling ranged between 3,278-3,850 Euros (human capital approach 12,143-12,715 Euros). Money spent on drugs alone constituted 15-48%, depending on method chosen. A cost-effectiveness analysis revealed a cost per life year (LY) saved replacing FEC by CMF of 3,575-15,125 Euros. Adjuvant FEC is cost effective in Norway.