A cost-effectiveness analysis of vaginal carbon dioxide laser therapy compared with standard medical therapies for genitourinary syndrome of menopause-associated dyspareunia.

BACKGROUND: Topical vaginal estrogen therapy is considered the gold standard treatment for genitourinary syndrome of menopause-associated dyspareunia, but early investigations of energy-based devices show promise for patients with contraindications or those who are refractory to vaginal estrogen cream therapy. Although evaluating safety, efficacy, and long-term outcomes for novel technologies is critically important when new technologies become available to treat unmet healthcare needs, evaluation of the costs of these new technologies compared with existing therapies is also critically important but often understudied. OBJECTIVE: We sought to perform a cost-effectiveness analysis of 3 therapies for genitourinary syndrome of menopause, including vaginal estrogen therapy, oral ospemifene therapy, and vaginal CO2 laser therapy and determine if vaginal laser therapy is a cost-effective treatment strategy for dyspareunia associated with genitourinary syndrome of menopause. STUDY DESIGN: An institutional review board-exempt cost-effectiveness analysis was performed by constructing a decision tree using decision analysis software (TreeAge Pro; TreeAge Software, Inc, Williamstown, MA) using integrated empirical data from the published literature. Tornado plots and 1-way and 2-way sensitivity analyses were performed to assess how changes in the model's input parameters altered the overall outcome of the cost-effectiveness analysis model. RESULTS: All 3 treatment methods were found to be cost-effective below the willingness-to-pay threshold of $50,000.00 per quality-adjusted life year for moderate dyspareunia. The incremental cost-effectiveness ratio for vaginal CO2 laser therapy was $16,372.01 and the incremental cost-effectiveness ratio for ospemifene therapy was $5711.14. Although all 3 treatment strategies were on the efficient frontier, vaginal CO2 laser therapy was the optimal treatment strategy with the highest effectiveness. In a 1-way sensitivity analysis of treatment adherence, vaginal CO2 laser therapy was no longer cost-effective when the adherence fell below 38.8%. Vaginal estrogen cream and ospemifene therapies remained cost-effective treatment strategies at all ranges of adherence. When varying the adherence to 100% for all strategies, oral ospemifene therapy was "dominated" by both vaginal CO2 laser therapy and vaginal estrogen cream therapy. In a 2-way sensitivity analysis of vaginal CO2 laser therapy adherence and vaginal CO2 laser therapy cost, vaginal CO2 laser therapy still remained the optimal treatment strategy at 200% of its current cost ($5554.00) when the adherence was >55%. When the cost fell to 20% of its current cost ($555.40), it was the optimal treatment strategy at all adherence values above 29%. CONCLUSION: This study showed that vaginal fractional CO2 laser therapy is a cost-effective treatment strategy for dyspareunia associated with GSM, as are both vaginal estrogen and oral ospemifene therapies. In our model, vaginal CO2 laser therapy is the optimal cost-effective treatment strategy, and insurance coverage should be considered for this treatment option if it is proven to be safe and effective in FDA trials.

Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

The selective estrogen receptor modulators in breast cancer prevention.

BACKGROUNDS: Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). METHODS: Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. RESULTS: To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. CONCLUSION: A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

Hormonal prevention of breast cancer.

Breast cancer prevention can be provided by using SERMs or aromatase inhibitors depending on the ovarian status, with a global risk reduction of 50 to 60%. Prophylactic annexectomy offered to reduce ovarian risk in BRCA mutation carriers also lowers breast cancer risk by 50%. Main side effects include deep vein thrombosis for SERMs, hot flushes and joint pain (although less frequently than initially suspected) with aromatase inhibitors. Other strategies based on progesterone, insulin or prolactin signaling modulation may be offered in the future. Criteria for candidate selection remain to be established.

Cost-effectiveness of bazedoxifene incorporating the FRAX® algorithm in a European perspective.

UNLABELLED: The cost-effectiveness of bazedoxifene was compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX® for both fracture risks and for treatment efficacy. Cost/QALY differences were explained to a large extent by differences in fracture risk. INTRODUCTION: In cost-effectiveness modelling of osteoporosis treatments, the fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior fracture. However, knowledge of additional clinical risk factors contributes to fracture risk assessment as demonstrated by the FRAX® tool. Bazedoxifene, a new selective estrogen receptor modulator for the treatment and prevention of osteoporosis, has been shown in a phase III clinical trial to reduce the risk of osteoporotic fractures in women. In an analysis using FRAX®, the efficacy of bazedoxifene was greater in patients with higher fracture risk. METHODS: The aim of this study was to evaluate the cost-effectiveness of bazedoxifene compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX®. A Markov cohort model was adapted to incorporate the FRAX® risk factors. FRAX® produces relative risks for hip fractures and major osteoporotic fractures. Patients were given a 5-year intervention, reducing the risk of fractures in a risk-dependent manner. The effect of treatment on fractures was assumed to decline linearly over 5 years after the intervention. RESULTS: There are large cost/quality-adjusted life year variations between countries in the European setting studied. The base case values ranged from cost saving (Sweden) to EUR 105,450 (Spain) in 70-year-old women with a T-score of -2.5 SD and a prior fracture. CONCLUSION: Bazedoxifene can be a cost-effective treatment for postmenopausal osteoporosis. The variability between countries was explained to a large extent by differences in fracture risk, and the estimated cost-effectiveness was highly dependent on the population's FRAX®-estimated probability of major osteoporotic fracture.

Endocrine therapy use among elderly hormone receptor-positive breast cancer patients enrolled in Medicare Part D.

BACKGROUND: Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators [SERMs] or aromatase inhibitors [AIs]) for five years following diagnosis. OBJECTIVE: To examine utilization and adherence to therapy for SERMs and AIs in Medicare Part D prescription drug plans. DATA: Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. STUDY DESIGN: We identified 15,542 elderly women diagnosed with hormone-receptor positive breast cancer in years 2003-2005 (the latest SEER data at the time of the study) and enrolled in a Part D plan in 2006 or 2007 (the initial years of Part D). This permitted us to compare utilization and adherence to therapy at various points within the recommended five-year timeframe for endocrine therapy. SERM and AI use was measured from claim records. Non-adherence to therapy was defined as a medication possession ratio of less than 80 percent. PRINCIPAL FINDINGS: Between May 2006 and December 2007, 22 percent of beneficiaries received SERM, 52 percent AI, and 26 percent received neither. The percent receiving any endocrine therapy decreased with time from diagnosis. Among SERM and AI users, 20-30 percent were non-adherent to therapy; out-of-pocket costs were higher for AI than SERM and were strongly associated with non-adherence. For AI users without a low income subsidy, adherence to therapy deteriorated after reaching the Part D coverage gap. CONCLUSIONS: Many elderly breast cancer patients were not receiving therapy for the recommended five years following diagnosis. Choosing a Part D plan that minimizes out-of-pocket costs is critical to ensuring beneficiary access to essential medications.

A comparison between bisphosphonates and other treatments for osteoporosis.

Since their development 30 years ago, bisphosphonates are now one of the standard therapy in the management of osteoporosis. Improvements in terms of anti-resorptive potency have leaded to new molecules available either orally or intravenously, from weekly to yearly administration. Overall tolerance of bisphosphonates is good with regards to the risk of mandibular necrosis, not comparable with those observed in cancer treatment, and with no causal link yet established in osteoporotic patients. Compliance remains poor and should be improved by a better education of the patients about their treatment. Other treatments like teriparatide, raloxifene or strontium ranelate are now also available and give more therapeutic options but also more questions on the best molecule to choose for each patient. There is currently no valid basis for distinguishing in a formal and objective manner the different new-generation bisphosphonates, in terms of efficacy against either vertebral, peripheral or hip fractures. In a same way, comparison between bisphosphonates and the other treatments available for osteoporosis is hard in absence of proper randomised controlled study. This review gives an overview of the recent data on the efficacity and tolerance of bisphosphonates in the different forms of osteoporosis and compares them to the other treatments currently available.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

INTRODUCTION: The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. AIM: The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. MAIN OUTCOME MEASURES: The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. METHODS: Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. RESULTS: A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. CONCLUSION: CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

[The necessity of cost-effectiveness analysis in osteoporosis]. / De la nécessité des études coût-efficacité en ostéoporose.

Economic evaluations are increasingly being used by decision-makers to estimate the cost-effectiveness of interventions. Major changes have recently occurred in the treatment of osteoporosis. The development of a valid economic model (Markov) in the field of osteoporosis is discussed, as well as these limitations. Intervention, such hip protectors, calcium and vitamin D, bisphosphonates, hormonal replacement therapy, SERMs, strontium ranélate, analogue of parathyroid hormone are analysed in the light of cost-effectiveness analyses.

Comparative economic analysis of aromatase inhibitors and tamoxifen in the treatment of hormone-dependent breast cancer.

Within the past 2 years three separate groups reported marked improvements in relapse-free survival when trastuzumab was added to adjuvant chemotherapy in patients with HER2-overexpressing breast cancer. Notwithstanding the significance of this molecular target, the discovery of the estrogen receptor (ER) may be of even greater importance. Although tamoxifen has long been considered the hormonal therapy of choice for patients with estrogen-responsive breast cancer, accumulating clinical data suggest the new generation of aromatase inhibitors (AIs) is more effective and less toxic. With the availability of new information, guidelines have been updated and reformulated regarding the use of AIs as first-line hormonal therapy in postmenopausal women with ER-positive breast cancer. This paper, a product of the ongoing advances in oncology, incorporates two distinct, yet important, features of oncology; first, clinical concepts related to hormone-dependent breast cancer and second, pharmacoeconomic evaluation of the antiestrogen tamoxifen and the new generation of antiaromatase agents.

Cost-effectiveness of switching to exemestane versus continued tamoxifen as adjuvant therapy for postmenopausal women with primary breast cancer.

BACKGROUND: Sequential tamoxifen/exemestane therapy reportedly improves disease-free survival in women with primary breast cancer compared with continued tamoxifen therapy. The objective of the current study was to assess the cost-effectiveness of switching to exemestane after 2 to 3 years of tamoxifen versus continued tamoxifen in postmenopausal women with primary breast cancer for a total of 5 years of adjuvant therapy. METHODS: A Markov model based on the Intergroup Exemestane Study (IES) population compared switching to exemestane versus continued tamoxifen for 2.5 years of therapy and 5 years of postadjuvant therapy follow-up. Disease progression and hazards ratios (HR) for recurrence and survival were determined from datasets (IES and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute) and from the published literature. An expert panel validated treatment patterns, outcomes, and resource utilization. Direct medical costs were included based on published sources. Cost-effectiveness ratios were determined, and extensive sensitivity analyses were conducted. RESULTS: Exemestane was found to be more effective than tamoxifen alone with regard to disease-free survival (2.6% absolute improvement), life-years gained (0.1028 LY), and quality-adjusted life-years gained (0.1195 QALY), at an additional cost of 2,889 Can dollars per person over 7.5 years. Incremental cost-effectiveness ratios were 28,119 Can dollars/LY gained and 24,185 Can dollars/QALY gained. The model was most sensitive to distant recurrence HR but was robust to variations in clinical, cost, and utility parameters. CONCLUSIONS: Switching to adjuvant exemestane after 2 to 3 years of tamoxifen is cost-effective in postmenopausal women with primary breast cancer.

SERMs: meeting the promise of multifunctional medicines.

The successful development and clinical evaluation of the selective estrogen receptor modulators in the Study of Tamoxifen and Raloxifene trial provides an occasion to reflect on the milestone that has been achieved and the potential for further progress in the chemoprevention of breast cancer. The evolution of tamoxifen from a successful treatment for breast cancer to the first chemopreventive for any cancer took two decades. Clinicians gained an enormous amount of experience with the use of tamoxifen as a treatment, and, as a result, there were few surprises in terms of efficacy or the side effect profile when the medicine was used to prevent breast cancer in high-risk women. In contrast, raloxifene emerged via the novel path of the evidence-based hypothesis that a drug targeted at one disease, osteoporosis, could also prevent breast cancer. Changes in health care strategies to implement chemoprevention take time, but the evidence now suggests that chemoprevention has become a reality in clinical practice.

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective.

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

When to recommend and to pay for first-line adjuvant breast cancer treatment? A structured review of the literature.

A structured review of studies on the health-economic evaluation of systemic adjuvant therapy for early-stage breast cancer was carried out. Of the eight articles that have been identified four were related to the cost-effectiveness of chemotherapy, three compared chemotherapy with combined chemotherapy and hormonal therapy and one compared tamoxifen (TAM) with third-generation aromatase inhibitors (ATIs). Results of the review indicate that the cost-utility of adjuvant breast cancer therapy is within the range of other oncological interventions. Adjuvant chemotherapy is most cost-effective in pre-menopausal women with node-positive breast cancer while cost-effectiveness decreases considerably with increasing age. Endocrine therapy with TAM is most cost-effective in ER-positive tumours with no significant age effect. The cost-utility of using the ATI anastrozole instead of TAM in adjuvant therapy cannot be conclusively assessed on the basis of the existing evidence.

Benefit-risk assessment of raloxifene in postmenopausal osteoporosis.

Raloxifene, a nonsteroidal benzothiophene, is a second-generation selective estrogen receptor modulator (SERM) that is an antiresorptive agent. Raloxifene is a non-hormonal agent that binds to the estrogen receptor and results in estrogen agonist effects on bone and the cardiovascular system and estrogen antagonist effects on endometrial and breast tissue. Raloxifene has diverse pharmacodynamic properties due to its differential interactions with the estrogen receptor and tissue selectivity. Raloxifene was the first SERM to be approved for the prevention and treatment of postmenopausal osteoporosis. In this review, we conducted a systematic search of the literature for trials that evaluated the following outcomes: bone density, fractures, quality of life, cardiovascular outcomes, safety and adverse events. Raloxifene at the approved dosage of 60 mg/day increased lumbar spine bone density by 2.5% relative to control after 2 years of therapy. A large fracture prevention trial confirmed that treatment with raloxifene 60 mg/day for 3 years decreased the relative risk of incident vertebral fractures by 30-50% in women with prevalent fractures or osteoporosis. Extraskeletal effects of raloxifene include a reduction in total cholesterol and low density lipoprotein cholesterol levels. Assessment of the safety profile revealed that raloxifene was not associated with endometrial hyperplasia and that there was a 72% reduction in the incidence of invasive breast cancer in raloxifene-treated postmenopausal women with osteoporosis. Adverse events associated with raloxifene included an increase in the absolute risk of venous thromboembolism and an increase in the risk of hot flashes and leg cramps. In comparison to other osteoporosis therapies, raloxifene has a lesser impact on bone mineral density, a similar effect on the occurrence of vertebral fractures, but no effect on the frequency of non-vertebral fractures. Raloxifene can be recommended for the prevention of vertebral fractures in women with osteopenia/osteoporosis who are not at high risk of non-vertebral fractures and who do not have a past history of venous thromboembolism.

Cost effectiveness of raloxifene in the treatment of osteoporosis in Sweden: an economic evaluation based on the MORE study.

BACKGROUND: The Multiple Outcomes of Raloxifene Evaluation (MORE) study showed that treatment with raloxifene reduces the risk of vertebral fracture and breast cancer in postmenopausal women with osteoporosis. OBJECTIVE: Based on the MORE study the aim of the present study was to assess the cost effectiveness of raloxifene (compared with no treatment) for the treatment of osteoporosis in postmenopausal women in Sweden. DESIGN: A revised version of a previously developed computer simulation model was used. The impact of the risk-reducing effect of raloxifene on vertebral fractures and breast cancer on cost effectiveness was analysed using a clinical and a morphometric definition of vertebral fracture. Benefits of raloxifene treatment were measured in quality-adjusted life-years (QALYs) and life-years gained. The study estimated the cost effectiveness mainly from a healthcare perspective but the cost effectiveness taking a societal perspective was also analysed. RESULTS: Intervention costs (in Swedish kronor [SEK] and euros [euro], year 2001 values) in postmenopausal women with a relative risk of vertebral fracture of 2 were SEK372000 (euro40000), SEK303000 (euro33000) and SEK263000 (euro28000) per QALY for women aged 60, 70 and 80 years, at start of treatment, respectively, when the clinical vertebral definition was used. The cost effectiveness using a clinical morphometric vertebral fracture definition was similar to the cost effectiveness using a clinical vertebral fracture definition. CONCLUSIONS: In relation to accepted threshold values for cost per QALY in Sweden, this model indicates, with its underlying assumptions and data, that raloxifene (compared with no treatment) is cost effective for the treatment of postmenopausal women at an increased risk of vertebral fracture, from the Swedish healthcare and societal perspectives.