Health Care Utilization and Economic Burden in Patients with Central Precocious Puberty: An Assessment of the Commercially Insured and Medicaid Populations.

BACKGROUND: Central precocious puberty (CPP), early onset of puberty caused by the premature activation of the hypothalamic-pituitary-gonadal axis, is a rare disease affecting children of both sexes. There is limited evidence that quantifies the economic burden of CPP. OBJECTIVE: To characterize the health care resource utilization (HRU) and costs among patients with CPP who were treated with gonadotropinreleasing hormone (GnRH) agonists, for those insured commercially and with Medicaid. METHODS: Eligible CPP patients for this retrospective cohort analysis were aged ≤ 12 years; were diagnosed between January 1, 2010, and September 30, 2014; and had at least 1 prescription for an FDA-approved GnRH agonist: leuprolide or histrelin (first prescription = index date). CPP patients had to be continuously enrolled in the MarketScan Commercial or Medicaid Database for at least 12 months before and after the index date. Control patients were randomly selected from all eligible non-CPP patients and N:1 matched on demographic characteristics with up to 20 controls per case. Clinical comorbidities, HRU, and costs were compared between study cohorts. Health care costs were examined via multivariable analysis to adjust for baseline differences between patients and controls. Treatment patterns among CPP patients were also characterized. RESULTS: There were 1,236 CPP patients and 24,206 controls with commercial insurance and 673 CPP patients and 11,965 controls with Medicaid insurance who met the inclusion criteria. Across payers, the mean age of CPP patients ranged from 7.6 years (Medicaid) to 8.5 (commercial), and 80%-87% were female. The mean observed duration (SD) of treatment with any approved GnRH agonist was 1.51 (0.98) years for commercial patients and 1.22 (1.04) for Medicaid patients. The mean age of discontinuation among patients who ceased GnRH agonist treatment ranged from 8.7 to 9.6 years. In the first year post-index, CPP patients had a greater number of unique diagnosis codes, unique medications, and comorbid conditions than controls. They also had significantly higher all-cause and diseasemonitoring related HRU. After adjusting for baseline characteristics, CPP patients with Medicaid insurance spent 6.42 times more ($16,768 [$31,460] vs. $2,610 [$4,897]), and patients with commercial insurance spent 12.25 times more ($19,940 [$20,132] vs. $1,628 [$1,645]) on health care in the year following treatment initiation than matched controls. CONCLUSIONS: Patients with CPP have substantially more comorbidities and greater HRU and costs than their non-CPP peers. DISCLOSURES: All funding for this study was provided by AbbVie, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Soliman and Grubb are employed by AbbVie and hold stock in AbbVie. Bonafede and Nelson are employed by IBM Watson Health, which received funding from AbbVie to conduct this study. Klein is a paid consultant of AbbVie but was not compensated for any work on development of this manuscript for publication. Portions of this work were presented at Pediatric Academic Societies (PAS) 2018 Meeting, May 5-8, 2018, in Toronto, Canada, as a poster presentation titled "Examination of Economic Burden Among Commercially Insured Patients with Central Precocious Puberty (CPP)."

Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Drug therapy for adenomyosis: a prospective, nonrandomized, parallel-controlled study.

Objective To provide novel insights into the clinical treatment of adenomyosis. Methods Two hundred patients with adenomyosis were enrolled in this prospective, nonrandomized, parallel-controlled study with a 1-year follow-up in our hospital. Group 1 was treated with 3.75 mg leuprorelin acetate (LA) (n = 40), Group 2 was treated with 1.88 mg LA (n = 40), Group 3 underwent Mirena implantation (n = 40), Group 4 underwent Mirena implantation after treatment with 3.75 mg LA (n = 40), Group 5 underwent Mirena implantation after treatment with 1.88 mg LA (n = 20), and Group 6 received San-Jie-Zhen-Tong capsules alone (n = 20). Uterine volume, pain, cancer antigen 125 level, ovary function, adverse effects, and Mirena expulsion were evaluated. Results The uterine volume and pain scores were lower in the groups treated with 1.88 than 3.75 mg LA, but the lower dose was associated with significantly fewer hot flashes and sweating. The 1-year Mirena expulsion rate was higher in Group 3 than in Groups 4 and 5 (10.00% vs. 3.33%, respectively). Costs were significantly higher in Groups 1 and 4 than in Groups 2 and 5. Conclusion Administration of 1.88 mg LA may be an alternative therapy for Asian patients with adenomyosis. The combination of LA and Mirena could enhance the therapeutic effect. Registration number: ChiCTR-IPR-15005971.

Cost analysis of leuprorelin acetate in Japanese prostate cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: This study aimed to evaluate the economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot from a societal perspective in Japanese prostate cancer patients. METHODS: The cost analysis estimated the reduction in direct and indirect costs as well as intangible costs saved by having one less injection. Claims data were used for the analyses of direct and indirect costs reduction. A discrete choice experiment based on a web-based survey estimated the monetary value of the intangible costs for one injection. Another web-based survey of prostate cancer patients, who had received treatment with leuprorelin acetate injections, was carried out to calibrate the results of the discrete choice experiment. RESULTS: Reductions in medical costs and loss of productivity for having one less injection in prostate cancer patients receiving leuprorelin acetate were JPY 5,670 and JPY 1,723, respectively. Intangible costs saved by using a 6-month depot formulation instead of a 3-month depot formulation for the injection of leuprorelin acetate were estimated to be JPY 19,872, including the values for a reduction in pain (JPY 3,131), injection site reactions (JPY 11,545), waiting time (JPY 9,479), and subtracting the value of medical consultation (JPY 4,283). The total cost reduction for having one less injection was JPY 27,265. LIMITATIONS: The respondents from the internet panel provided by a survey company are not necessarily a representative population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot has an advantage in monetary value in the reduction in medical costs, loss of productivity, and intangible costs for having one less injection in prostate cancer patients compared with leuprorelin acetate 3-month depot. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Cost analysis of leuprorelin acetate in Japanese pre-menopausal breast-cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: The aim in this study is to evaluate economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot in Japanese pre-menopausal breast cancer patients from a societal perspective. METHODS: The cost analysis was conducted by estimating direct and indirect cost, and intangible costs associated with one 6-month injection compared with two 3-month injections. Claims data were used for the analyses of direct and indirect cost and Medical Fee Schedule Table for direct cost. Discrete choice experiments were conducted by web-based survey to determine the intangible costs. Another web-based survey was also conducted on premenopausal breast cancer patients with injections of leuprorelin acetate, to calibrate the results of discrete choice experiments. RESULTS: The medical costs saved for having one less injection in pre-menopausal breast cancer patients with leuprorelin acetate injection were JPY 6,183. The productivity loss saving was JPY 1,419. An estimation of intangible costs saved for having one less injection of leuprorelin acetate was JPY 58,430, which included the disbenefit due to pain (JPY 8,535), injection site reactions (JPY 44,051), waiting time (JPY 9,595), and subtracting value in medical consultation (JPY 3,751). The total cost saved for having one less injection was JPY 66,032. LIMITATIONS: The respondents from the internet panel provided by a survey company do not necessarily reflect a population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot demonstrates a higher value than leuprorelin acetate 3-month depot through saving medical costs and loss of productivity, as well as intangible costs saved for having one less injection when treating pre-menopausal breast cancer patients. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

[Cost effectiveness of GnRH antagonists in patients with prostate cancer and cardiovascular risk : Comparative analysis against Leuprorelin by the Number Needed to Treat]. / Kosteneffektivität von GnRH-Antagonisten bei Patienten mit Prostatakarzinom und kardiovaskulärem Risiko : Vergleichende Analyse gegenüber Leuprorelin anhand der Number Needed to Treat.

BACKGROUND: Recent studies suggest that androgen deprivation therapy (ADT) is associated with increased cardiovascular (CV) risk for patients with hormone-sensitive prostate cancer (PCa) and pre-existing CV disease. This risk seems to be different for the gonadotropin-releasing hormone (GnRH) agonists leuprolide and goserelin and GnRH antagonists, whereas the slightly more expensive GnRH antagonist shows a beneficial risk profile. The present study assesses the cost effectiveness of degarelix compared to leuprolide for PCa patients with increased CV risk. METHODS: This analysis is based on a pooled analysis of six phase III, randomized, controlled trials comparing the GnRH agonists leuprolide and goserelin with the GnRH antagonist degarelix. For the combined endpoint of CV events or death a superiority of degarelix was determined with a Number-Needed-to-Treat of 12. From the perspective of German statutory health insurance, this evaluation estimates and compares the additional drug costs of degarelix treatment to the cost of one (avoided) CV event. The CV event costs were estimated via emergency treatment and transportation, inpatient treatment, and rehabilitation. The difference of these two cost pools divided by 12 yields the average saving per patient and year. RESULTS: For every 12 PCa patients with CV history that are treated with GnRH antagonists to prevent one CV event, there will be additional drug costs in comparison with leuprolide treatment of € 3111 per year. Costs of € 8447 per year are prevented. Therefore, each patient with a history of CV who is treated with degarelix instead of a leuprolide generates savings of € 445 per patient and year. CONCLUSIONS: Compared to leuprolide, degarelix is cost effective for patients with increased CV risk.

Ulipristal acetate for pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands: cost minimization analysis and budget impact analysis.

OBJECTIVE: Ulipristal acetate has been found to be non-inferior to other pre-operative treatments of uterine fibroids, particularly leuprolide. The objective of this study was to assess the pharmacoeconomic profile of ulipristal acetate compared to leuprolide for the pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands. The analysis was performed and applied within the framework of the ulipristal acetate submission for reimbursement in 2012. METHODS: A decision model was developed to compare the total costs of ulipristal acetate compared to leuprolide, the standard care in The Netherlands. The target population of this study corresponded to the type of patients included in the PEARL II clinical trial; i.e. women of reproductive age requiring pre-operative treatment for uterine fibroids. Sensitivity analysis was implemented to assess uncertainties. Data regarding costs, effects, and other input parameters were obtained from relevant published literatures, the Dutch Healthcare Insurance Board, and expert opinion obtained by means of a panel of experts from several medical centers in The Netherlands. RESULTS: In The Netherlands, the total costs of ulipristal acetate and leuprolide were estimated at €4,216,027 and €4,218,095, respectively. The annual savings of ulipristal acetate were, therefore, estimated at €2,068. The major driver of this cost difference was the cost of administration for leuprolide. Sensitivity analyses showed that ulipristal acetate mostly remained cost-saving over a range of assumptions. The budget impact analysis indicated that the introduction of ulipristal acetate was estimated to result in cost savings in the first 3 years following the introduction. The results of this study were used in the decision on reimbursement of ulipristal acetate according to the Dutch Reference Pricing system in 2012. CONCLUSION: Ulipristal acetate was cost saving compared to leuprolide and has the potential to provide substantial savings on the healthcare budget in The Netherlands.

Treatment costs for advanced prostate cancer using luteinizing hormone-releasing hormone agonists: a solid biodegradable leuprorelin implant versus other formulations.

AIM: To compare treatment costs with alternative luteinizing hormone-releasing hormone (LHRH) agonist preparations and determine whether a leuprorelin solid implant is associated with potential cost savings. PATIENTS & METHODS: A hypothetical population of 1000 prostate cancer patients was apportioned between the three most commonly-prescribed LHRH agonist preparations. Differentiated annual costs for 1- and 3-monthly formulations were calculated for France, Germany, Italy, Spain, the UK (EU5) and Sweden, and compared with the leuprorelin solid implant. RESULTS: Compared with alternative formulations, leuprorelin solid implants had potential annual cost savings/1000 patients of €353,000 (EU5) and €699,000 (Sweden; 1-month formulations), and €259,000 (EU5) and €300,000 (Sweden; 3-month formulations). CONCLUSION: The leuprorelin solid implant was associated with potential cost savings compared with the most commonly used LHRH agonist preparations.

A cost-utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom.

OBJECTIVE: To determine the cost-effectiveness of the treatment of advanced hormone-dependent prostate cancer with degarelix compared to luteinizing hormone-releasing hormone (LHRH) agonists in the UK using the latest available evidence and the model submitted to AWMSG. METHODS: A cost-effectiveness model was developed from the perspective of the UK National Health Service evaluating monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti-androgen flare cover for the first-line treatment of patients with advanced (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov process model was constructed using the patient population characteristics and efficacy information from the CS21 Phase III clinical trial and associated extension study (CS21A). The intention-to-treat (ITT) population and a high-risk sub-group with a PSA level >20 ng/mL were modeled. RESULTS: In the base-case analysis using the patient access scheme (PAS) price, degarelix was dominant compared to leuprorelin with cost savings of £3633 in the ITT population and £4310 in the PSA > 20 ng/mL sub-group. The chance of being cost-effective was 95% in the ITT population and 96% in the PSA > 20 ng/mL sub-group at a threshold of £20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained dominant when PSA progression was assumed equal and only the benefits of preventing testosterone flare were taken into account. Treatment with degarelix also remained dominant in both populations when the list price was used. The additional investment required to treat patients with degarelix could be offset in 19 months for the ITT population and 13 months for the PSA > 20 ng/mL population. The model was most sensitive to the hazard ratio assumed for PSA progression between degarelix and leuprorelin and the quality-of-life (utility) of patients receiving palliative care. CONCLUSION: Degarelix is likely to be cost-effective compared to leuprorelin plus anti-androgen flare cover in the first-line treatment of advanced hormone-dependent prostate cancer.

Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Medical versus surgical androgen suppression therapy for prostate cancer: a 10-year longitudinal cost study.

PURPOSE: We provide a relative cost comparison of medical versus surgical androgen suppressive therapy for prostate cancer. MATERIALS AND METHODS: Comparison is based on a cohort of 96 patients who began androgen suppressive therapy for prostate cancer between 1988 and 1990. Patients were followed until death or the end point of study in June 2000 at which time 15% were alive. Current Medicare orchiectomy reimbursements were compared to 1999 wholesale drug costs. RESULTS: For an individual patient the cost of luteinizing hormone releasing hormone (LH-RH) agonist treatment surpassed the cost of surgery at less than 4.2 to 5.3 months, and for combined androgen blockade (LH-RH agonists and nonsteroidal antiandrogens) at less than 2.7 to 3.4 months. For 5 (5.2%) patients on combined androgen blockade and 6 (6.3%) on LH-RH agonists alone, medical therapy would have had a cost advantage over bilateral orchiectomy. For the androgen suppression cohort the cost of LH-RH agonist treatment was 10.7 to 13.5 times and combined androgen blockade was 17.3 to 20.9 times the cost of bilateral orchiectomy. Urology resource use comparisons are provided. These findings significantly underestimate the cost advantage of surgery. A seventh of the patients were alive at study end point, and prostate specific antigen induced stage shifting and changes in practice patterns resulted in earlier and more frequent androgen suppressive treatment. CONCLUSIONS: Except for patients with short anticipated survivals current medical androgen suppressive treatment options are more costly than bilateral orchiectomy. There is a need for a cost comparable medical option to orchiectomy.

The cost value of medical versus surgical hormonal therapy for metastatic prostate cancer.

PURPOSE: The cost of luteinizing hormone releasing hormone analogue and antiandrogen for prostate cancer is being scrutinized by the Health Care Finance Administration and other insurers. We compared the discounted present value cost of medical hormonal therapy to that of orchiectomy as well as the value created by these treatments from the insurer and patient perspectives. MATERIALS AND METHODS: We performed a telephone survey of 42 patients receiving hormonal therapy to estimate the value created by medical versus surgical castration from the patient perspective. The cost of medical hormonal therapy was discounted back to the present value and compared with the cost of bilateral orchiectomy. RESULTS: The total cost of bilateral orchiectomy was $2,022, while the discounted present value cost using the average wholesale price for 30 months of medical hormonal therapy was $13,620. Therefore, medical hormonal therapy costs $11,598 more than orchiectomy ($13,620 - $2,022). A discounted payment of $386 per month for 30 months is necessary to recoup the $11,598 difference. All surveyed patients on medical hormonal therapy stated that avoiding orchiectomy was worth $386 per month and it was an appropriate insurer expense. If patients paid $386 per month out-of-pocket, 22 of the 42 (52%) would pay the additional monthly expense, while 20 (48%) indicated that they could not afford the additional expense. CONCLUSIONS: These results indicate that medical hormonal therapy costs significantly more than bilateral orchiectomy but creates positive value for men with prostate cancer by enabling them to avoid orchiectomy.

Evaluation of Lovelace Health Systems chronic pelvic pain protocol.

Although laparoscopy has been considered the gold standard for the diagnosis of endometriosis, it often fails to detect the disease and provide lasting pain relief. Motivated by concerns for patient well-being, treatment efficacy, and cost containment, Lovelace Health Systems of Albuquerque, New Mexico, turned to the Lovelace Chronic Pelvic Pain Protocol, based on a chronic pelvic pain algorithm used to identify potential candidates for therapy with gonadotropin-releasing hormone agonist (GnRH agonist). Since the protocol's introduction in January 1997, empiric therapy with GnRH agonist has proved beneficial to patients, physicians, and healthcare system budgets.

Chronic pelvic pain: presumptive diagnosis and therapy using GnRH agonists.

Chronic pelvic pain has a prevalence of 15% to 30% of reproductive-age women. It causes a sizable minority of all gynecological visits, and is responsible for much physical and psychological suffering. Although laparoscopic inspection, plus treatment, for pelvic pain has been considered ideal, it is often unnecessary, fruitless, and even hazardous, besides being expensive. Therefore, empirical medical therapy has much to recommend it. Foremost is the fact that endometriosis is the most frequent source of chronic pelvic pain, and responds well to medical treatment. In fact, GnRH analogs (agonists) used for 6 months can reduce AFS endometriosis scores by one-half, with cure rates at 5 years of three-fourths of responders who had minimal disease and one-third of responders with severe disease. Danazol and oral contraceptives plus NSAIDs have been used, too. The latter treatment is best reserved for cases involving dysmenorrhea. The objections to empirical treatment-lack of exact knowledge of the entity being treated and the potential of overlooking cancer-are discussed here in the context of pain treatment, with an emphasis on history taking, diagnostic imaging, and careful observation.

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

OBJECTIVES: With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. SEARCH STRATEGY: The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. SELECTION CRITERIA: We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. DATA COLLECTION AND ANALYSIS: The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. MAIN RESULTS: Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)