Cost-effectiveness of adrenocorticotropic hormone versus oral steroids for infantile spasms.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of adrenocorticotropic hormone (ACTH) and oral steroids as first-line treatment for infantile spasm resolution, we performed a systematic review, meta-analysis, and cost-effectiveness study. METHODS: A decision analysis model was populated with effectiveness data from a systematic review and meta-analysis of existing literature and cost data from publicly available prices. Effectiveness was defined as the probability of clinical spasm resolution 14 days after treatment initiation. RESULTS: We included 21 studies with a total of 968 patients. The effectiveness of ACTH was not statistically significantly different from that of oral steroids (.70, 95% confidence interval [CI] = .60-.79 vs. .63, 95% CI = .56-.70; p = .28). Considering only the three available randomized trials with a total of 185 patients, the odds ratio of spasm resolution at 14 days with ACTH compared to high-dose prednisolone (4-8 mg/kg/day) was .92 (95% CI = .34-2.52, p = .87). Adjusting for potential publication bias, estimates became even more favorable to high-dose prednisolone. Using US prices, the more cost-effective treatment was high-dose prednisolone, with an incremental cost-effectiveness ratio (ICER) of $333 per case of spasms resolved, followed by ACTH, with an ICER of $1 432 200 per case of spasms resolved. These results were robust to multiple sensitivity analyses and different assumptions. Prednisolone at 4-8 mg/kg/day was more cost-effective than ACTH under a wide range of assumptions. SIGNIFICANCE: For infantile spasm resolution 2 weeks after treatment initiation, current evidence does not support the preeminence of ACTH in terms of effectiveness and, especially, cost-effectiveness.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Cost-effectiveness of somatostatin analogues in the treatment of acromegaly.

INTRODUCTION: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly. AREAS COVERED: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method. EXPERT COMMENTARY: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.

Selective Perioperative Administration of Pasireotide is More Cost-Effective Than Routine Administration for Pancreatic Fistula Prophylaxis.

BACKGROUND: In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective. STUDY DESIGN: Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide. RESULTS: Among 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved $30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of $831,916. CONCLUSION: Preoperative clinical characteristics can be used to characterize patients' risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

Pasireotide for the Prevention of Pancreatic Fistula Following Pancreaticoduodenectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF). SUMMARY: PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system. METHODS: A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model. RESULTS: Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving. CONCLUSIONS: Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

The Cost of Postoperative Pancreatic Fistula Versus the Cost of Pasireotide: Results from a Prospective Randomized Trial.

OBJECTIVE: The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use. SUMMARY OF BACKGROUND DATA: We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006]. METHODS: An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$). RESULTS: Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571). CONCLUSIONS: The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.

Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

PURPOSE: Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. METHODS: A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. RESULTS: Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. CONCLUSION: Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

Prophylactic pasireotide administration following pancreatic resection reduces cost while improving outcomes.

BACKGROUND AND OBJECTIVES: Pasireotide decreases leak rates after pancreatic resection, though significant drug cost may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile. METHODS: A cost-effectiveness model compared pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify influential clinical components of the model. RESULTS: With the cost of pasireotide included, per patient costs of pancreatectomy, including those for readmission, were lower in the intervention arm (41,769 versus 42,159$; net savings of 390$, or 1%). This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9-9.2%). Pasireotide cost would need to increase by over 15.4% to make the intervention strategy more costly than usual care. Sensitivity analyses exploring variability of key model inputs demonstrated that the three strongest drivers of cost were (i) cost of pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A. CONCLUSIONS: Prophylactic pasireotide administration following pancreatectomy is cost savings, reducing expensive post-operative sequealae (major complications and readmissions). Pasireotide should be utilized as a cost-saving measure in pancreatic resection. J. Surg. Oncol. 2016;113:784-788. © 2016 Wiley Periodicals, Inc.

Budget impact of pasireotide LAR for the treatment of acromegaly, a rare endocrine disorder.

BACKGROUND: Acromegaly is a rare disorder characterized by the over-production of growth hormone (GH). Patients often experience a range of chronic comorbidities including hypertension, cardiac dysfunction, diabetes, osteoarthropathy, and obstructive sleep apnea. Untreated or inadequately controlled patients incur substantial healthcare costs, while normalization of GH levels may reduce morbidity and mortality rates to be comparable to the general population. OBJECTIVE: To assess the 3-year budget impact of pasireotide LAR on a US managed care health plan following pasireotide LAR availability. METHODS: Two separate economic models were developed: one from the perspective of an entire health plan and another from the perspective of a pharmacy budget. The total budget impact model includes costs of drug therapies and other costs for treatment, monitoring, management of adverse events, and comorbidities. The pharmacy cost calculator only considers drug costs. RESULTS: The total estimated budget impact associated with the introduction of pasireotide LAR is 0.31 cents ($0.0031) per member per month (PMPM) in the first year, 0.78 cents ($0.0078) in the second year, and 1.42 cents ($0.0142) in the third year following FDA approval. Costs were similar or lower from a pharmacy budget impact perspective. For each patient achieving disease control, cost savings from reduced comorbidities amounted to $10,240 per year. LIMITATIONS: Published data on comorbidities for acromegaly are limited. In the absence of data on acromegaly-related costs for some comorbidities, comorbidity costs for the general population were used (may be under-estimates). CONCLUSIONS: The budget impact of pasireotide LAR is expected to be modest, with an expected increase of 1.42 cents PMPM on the total health plan budget in the third year after FDA approval. The efficacy of pasireotide LAR in acromegaly, as demonstrated in head-to-head trials compared with currently available treatment options, is expected to be associated with a reduction of the prevalence of comorbidities.

A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer.

Breast cancer is a global health concern. In fact, breast cancer is the primary cause of death among women worldwide and constitutes the most expensive malignancy to treat. As health care resources are finite, decisions regarding the adoption and coverage of breast cancer treatments are increasingly being based on "value for money," i.e., cost-effectiveness. As the evidence about the cost-effectiveness of breast cancer treatments is abundant, therefore difficult to navigate, systematic reviews of published systematic reviews offer the advantage of bringing together the results of separate systematic reviews in a single report. As a consequence, this paper presents an overview of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer to inform policy and reimbursement decision-making. A systematic review was conducted of published systematic reviews documenting cost-effectiveness analyses of breast cancer treatments from 2000 to 2014. Systematic reviews identified through a literature search of health and economic databases were independently assessed against inclusion and exclusion criteria. Systematic reviews of original evaluations were included only if they targeted breast cancer patients and specific breast cancer treatments (hormone therapy, chemotherapy, and targeted therapy only), documented incremental cost-effectiveness ratios, and were reported in the English language. The search strategy used a combination of these key words: "breast cancer," "systematic review/meta-analysis," and "cost-effectiveness/economics." Data were extracted using predefined extraction forms and qualitatively appraised using the assessment of multiple systematic reviews (AMSTAR) tool. The literature search resulted in 511 bibliographic records, of which ten met our inclusion criteria. Five reviews were conducted in the early-stage breast cancer setting and five reviews in the metastatic setting. In early-stage breast cancer, evidence about trastuzumab value differed by age. Trastuzumab was cost-effective only in women with HER2-positive breast cancer younger than 65 years and over a life-time horizon. The cost-effectiveness of trastuzumab in HER2-positive metastatic breast cancer yielded conflicting results. The same conclusions were reached in comparisons between vinorelbine and taxanes. In both early stage and advanced/metastatic breast cancer, newer aromatase inhibitors (AIs) have proved cost-effective compared to older treatments. This overview of systematic reviews shows that there is heterogeneity in the evidence concerning the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. The cost-effectiveness of these treatments depends not only on the comparators but the context, i.e., adjuvant or metastatic setting, subtype of patient population, and perspective adopted. Decisions involving the cost-effectiveness of breast cancer treatments could be made easier and more transparent by better harmonizing the reporting of economic evaluations assessing the value of these treatments.

Use of Chinese medicine correlates negatively with the consumption of conventional medicine and medical cost in patients with uterine fibroids: a population-based retrospective cohort study in Taiwan.

BACKGROUND: Chinese medicine is commonly used and covered by health insurance to treat symptoms of uterine fibroids in Taiwan. This retrospective cohort study compared the consumption of conventional western medicine and medical cost between Chinese medicine (CM) users and nonusers among patients with uterine fibroids. METHODS: We extracted 44,122 patients diagnosed with uterine fibrosis between 1996 and 2010 from the National Health Insurance reimbursement database, which is a population-based database released by a government-run health insurance system. Multivariate linear regression models were used to find association between using Chinese medicine and the consumption of conventional medicine, and between using Chinese medicine and medical cost. RESULTS: The total fibroid-related conventional western medicine consumed by CM users was less than that by nonusers (ß = -10.49, P < 0.0001). Three categories of conventional medicines, including antianemics (-3.50 days/year/patient, P < 0.0001), hemostatics (- 1.89 days/year/patient, P < 0.0001), and hormone-related agents (-3.13 days/year/patient, P < 0.0001), were used less in patients who were CM users. Moreover, although using CM increased 16.9 USD per patient in CM users annually (P < 0.0001), the total annual medical cost for treating fibroid was 5610 USD less in CM users than in nonusers (P < 0.0001). CONCLUSIONS: Our results suggested that CM reduced the consumption of conventional medicine, and might be a potential therapeutic substitute for conventional western medicines to treat uterine fibroids with low cost.

A cost analysis of somatostatin use in the prevention of pancreatic fistula after pancreatectomy.

BACKGROUND: Studies have shown that somatostatin reduces the occurrence of postoperative pancreatic fistula. However, no study to date has analyzed the cost effectiveness of this treatment. The purpose of this study was to analyze the cost effectiveness of prophylactic somatostatin use with respect to pancreatectomy. METHODS: Review of prospectively collected 2002 patient hepato-pancreatico-biliary database from January 2007 to May 2012. Patients received somatostatin prophylactically at the discretion of their surgeon. Data were analyzed using univariate analysis to determine if somatostatin had an effect on imaging costs, lab costs, "other" costs, PT/OT costs, surgery costs, room and board costs, and total hospital costs. RESULTS: A total of 179 patients underwent pancreatectomy at a single teaching institution. Median total hospital costs were 90,673.50 (59,979-743,667) for patients who developed a postoperative pancreatic fistula versus 86,563 (39,190-463,601) for those who did not (p = 0.004). Median total hospital costs were 89,369 (39,190-743,667) for patients who were administered somatostatin versus 85,291 (40,092-463,601) for patients who did not (p = 0.821). CONCLUSIONS: Pancreatic fistulas significantly increase hospital costs, and somatostatin has been shown to decrease the rate of pancreatic fistula formation. Somatostatin has no significant effect on hospital costs.

Growth-promoting technologies decrease the carbon footprint, ammonia emissions, and costs of California beef production systems.

Increased animal performance is suggested as one of the most effective mitigation strategies to decrease greenhouse gas (GHG) and ammonia (NH(3)) emissions from livestock production per unit of product produced. Little information exists, however, on the effects of increased animal productivity on the net decrease in emission from beef production systems. A partial life cycle assessment (LCA) was conducted using the Integrated Farm System Model (IFSM) to estimate GHG and NH(3) emissions from representative beef production systems in California that use various management technologies to enhance animal performance. The IFSM is a farm process model that simulates crop growth, feed production, animal performance, and manure production and handling through time to predict the performance, economics, and environmental impacts of production systems. The simulated beef production systems compared were 1) Angus-natural, with no use of growth-enhancing technologies, 2) Angus-implant, with ionophore and growth-promoting implant (e.g., estrogen/trenbolone acetate-based) application, 3) Angus-ß2-adrenergic agonists (BAA; e.g., zilpaterol), with ionophore, growth-promoting implant, and BAA application, 4) Holstein-implant, with growth implant and ionophore application, and 5) Holstein-BAA, with ionophore, growth implant, and BAA use. During the feedlot phase, use of BAA decreased NH(3) emission by 4 to 9 g/kg HCW, resulting in a 7% decrease in NH(3) loss from the full production system. Combined use of ionophore, growth implant, and BAA treatments decreased NH(3) emission from the full production system by 14 g/kg HCW, or 13%. The C footprint of beef was decreased by 2.2 kg carbon dioxide equivalent (CO(2)e)/kg HCW using all the growth-promoting technologies, and the Holstein beef footprint was decreased by 0.5 kg CO(2)e/kg HCW using BAA. Over the full production systems, these decreases were relatively small at 9% and 5% for Angus and Holstein beef, respectively. The growth-promoting technologies we evaluated are a cost-effective way to mitigate GHG and NH(3) emissions, but naturally managed cattle can bring a similar net return to Angus cattle treated with growth-promoting technologies when sold at an 8% greater premium price.

Use of alternative and hormonal therapies in male infertility.

OBJECTIVES: To examine the patterns of use of alternative and hormonal therapies in men presenting for infertility evaluation. METHODS: We administered a questionnaire on the use of alternative and hormonal therapies to 500 consecutive men presenting for infertility evaluation at our male infertility clinic. The questionnaire asked about the use of specific therapies (eg, vitamins, herbal medicine, or hormones), the monthly cost of these therapies, and whether the principal healthcare provider had been made aware of the use of therapies. RESULTS: Of the 481 men who completed the questionnaire, 147 (31%) admitted to using one or more alternative therapies. Most of the men using alternative therapies (92 of 147, 63%) were taking one or more antioxidant vitamins or minerals (ie, vitamins C, E, selenium, zinc), and 18 men admitted to using herbal medicines. Of concern, 25 men reported using agents with clear hormonal activity (testosterone, clomiphene citrate), and 6 of these men had not informed their principal healthcare provider of this. CONCLUSIONS: Our data suggest that a significant percentage ( approximately 30%) of men presenting for infertility evaluation do use alternative therapies. It is important to inquire about the use of these therapies because some of these treatments may be toxic to the gonads.