Costs of treatment change following first-line somatostatin analog monotherapy among patients with neuroendocrine tumors.

BACKGROUND: This study describes treatment characteristics and healthcare costs prior to and following treatment change from somatostatin analog (SSA) monotherapy among a privately-insured NET patient population in the US. METHODS: Patients with newly diagnosed NET and treated with SSA monotherapy were retrospectively identified in IBM MarketScan claims between 1/1/2014 and 3/31/2019. NET treatment change was captured ≥30 days after the SSA start date (earliest new treatment = index date). Healthcare costs (reimbursed amount in 2019 dollars) were reported for 1, 3, and 6 months pre- and post-index intervals. RESULTS: A total of 305 patients were identified (mean age: 58 years; female: 52%; metastatic disease: 49%). Most patients started on octreotide (81%) vs. lanreotide (19%). Common treatment changes included alternate SSA (38%), targeted therapy (30%), or chemotherapy (23%). Total costs increased on average by $13,272 between the month preceding and following treatment change (p < .001), with the highest increase among patients changing to targeted therapy ($19,677, p < .001) vs. an alternate SSA ($10,240, p < .001) or chemotherapy ($4,057, p = .155). The trajectory in mean cost difference using a 1, 3, and 6-month time period followed an increasing trend for patients who changed to targeted therapy (Δ$19,677, Δ$34,856, Δ$58,387) but was flat for patients who changed to the alternate SSA (Δ$10,240, Δ$10,026, Δ$11,727). CONCLUSIONS: Higher total healthcare costs were observed following treatment change from first-line SSA. Switching to the alternate SSA was associated with a fixed, one-time cost; whereas, switching to targeted therapy was associated with both an initial switching cost and a persistent monthly increase.

Cost-Utility of Acromegaly Pharmacological Treatments in a French Context.

Objective: Efficacy of pharmacological treatments for acromegaly has been assessed in many clinical or real-world studies but no study was interested in economics evaluation of these treatments in France. Therefore, the objective of this study was to estimate the cost-utility of second-line pharmacological treatments in acromegaly patients. Methods: A Markov model was developed to follow a cohort of 1,000 patients for a lifetime horizon. First-generation somatostatin analogues (FGSA), pegvisomant, pasireotide and pegvisomant combined with FGSA (off label) were compared. Efficacy was defined as the normalization of insulin-like growth factor-1 (IGF-1) concentration and was obtained from pivotal trials and adjusted by a network meta-analysis. Costs data were obtained from French databases and literature. Utilities from the literature were used to estimate quality-adjusted life year (QALY). Results: The incremental cost-utility ratios (ICUR) of treatments compared to FGSA were estimated to be 562,463 € per QALY gained for pasireotide, 171,332 € per QALY gained for pegvisomant, and 186,242 € per QALY gained for pegvisomant + FGSA. Pasireotide seems to be the least cost-efficient treatment. Sensitivity analyses showed the robustness of the results. Conclusion: FGSA, pegvisomant and pegvisomant + FGSA were on the cost-effective frontier, therefore, depending on the willingness-to-pay for an additional QALY, they are the most cost-effective treatments. This medico-economic analysis highlighted the consistency of the efficiency results with the efficacy results assessed in the pivotal trials. However, most recent treatment guidelines recommend an individualized treatment strategy based on the patient and disease profile.

Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

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.

Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study.

Purpose: Acromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China. Methods: This is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform. Results: In total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were <1 year. The most common first-line therapy was surgery with a transsphenoidal (76.1%) or transcranial approach (3.2%). Somatostatin analogues or dopamine agonists were administered in 20.5% of the patients as first-line therapies and in 41.7% as adjuvant therapies. Radiotherapy was performed in 32.1% of patients, 99.3% of whom received radiotherapy as an adjuvant therapy. After a median 5-year follow-up, 46.2% achieved biochemical control. Comorbidities were reported in 88.2% of the patients at follow-up; memory deterioration and thyroid nodules were the most common. Controlled patients had greater improvements in symptoms and comorbidities during follow-up than uncontrolled patients. The annual per-capita cost-of-treatment was $11013 in 2018, with medical treatments being the largest contributor (67%). Medical insurance covered 47.2% of all treatment costs. Conclusion: This study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies.

Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.

BACKGROUND: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. METHODS: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. RESULTS: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. CONCLUSIONS: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

CONTEXT: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. OBJECTIVE: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly. DESIGN AND SETTING: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. PATIENTS: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. INTERVENTION: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day). MAIN OUTCOME MEASURE: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. RESULTS: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%. CONCLUSIONS: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

A Budget Impact Model of the Addition of Telotristat Ethyl Treatment to the Standard of Care in Patients with Uncontrolled Carcinoid Syndrome.

BACKGROUND: Carcinoid syndrome, a rare condition in patients with neuroendocrine tumours, characterised by flushing and diarrhoea, severely affects patients' quality of life. The current carcinoid syndrome standard of care includes somatostatin analogues, but some patients experience uncontrolled symptoms despite somatostatin analogue therapy. Telotristat ethyl is a novel treatment approved by the European Medicines Agency (EMA) and US FDA that significantly reduces bowel movement frequency in patients with uncontrolled carcinoid syndrome. OBJECTIVE: We developed a model to evaluate the 5-year budget impact of introducing telotristat ethyl to standard care in Swedish patients with uncontrolled carcinoid syndrome. METHODS: Treatment response in the 12-week phase III TELESTAR trial (NCT01677910) informed telotristat ethyl efficacy; subsequently, health states were captured by a Markov model using 4-week cycles. TELESTAR open-label extension data informed telotristat ethyl discontinuation. The number of treatment-eligible patients was estimated from literature reviews reporting the prevalence, incidence and mortality of carcinoid syndrome. A Swedish database study informed real-world costs related to carcinoid syndrome and carcinoid heart disease costs. Telotristat ethyl market share was assumed to increase annually from 24% (year 1) to 70% (year 5). RESULTS: Over the 5-year model horizon, 44 patients were expected to initiate telotristat ethyl treatment. The cumulative net budget impact of adding telotristat ethyl to current standard of care was €172,346; per-year costs decreased from €66,495 (year 1) to €29,818 (year 5). Increased drug costs from adding telotristat ethyl were offset by reduced costs elsewhere. CONCLUSIONS: The expected budget impact of adding telotristat ethyl to the standard of care in Sweden was relatively low, largely because of the rarity of carcinoid syndrome.

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.

Management of Diarrhea in Patients With Carcinoid Syndrome.

Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.

Burden of Carcinoid Heart Disease in Patients With Carcinoid Syndrome Initiating Somatostatin Analogues.

PURPOSE: As a result of overproduction of serotonin, patients with uncontrolled carcinoid syndrome (CS) may develop carcinoid heart disease (CaHD). However, the prevalence and health care resources to manage CaHD are not well understood. This study investigated the prevalence and economic burden of CaHD among adults with CS in the United States. METHODS: This retrospective study analyzed insurance claims of patients with CS initiating somatostatin analogue (SSA) therapy. Eligible patients had ≥1 medical claim for CS with continuous insurance coverage for 1 year before and at least 30 days after initiating SSA therapy. Markers for CaHD were identified using a predetermined list of medical and/or procedural claims based on the clinical experience of a practicing cardiologist. Case subjects had a documented medical/procedural claim for a marker of CaHD during the study period; control subjects had no markers for CaHD. Baseline characteristics were assessed during the pre-SSA treatment initiation period. Economic outcomes (health care resources and expenditures) were assessed in the follow-up period after SSA treatment initiation and compared between incident case subjects and control subjects. Descriptive statistics were used to assess demographic and clinical characteristics. Univariate and multivariate models were used to assess differences in health care resource use and costs between case subjects and control subjects. FINDINGS: A total of 654 patients met the eligibility criteria; 248 (38%) had a prevalent marker of CaHD and were excluded from the economic analysis. The analytic sample included 406 patients with CS, 185 (46%) of whom had an incident CaHD marker (case subjects) and 221 were controls. Baseline characteristics between the case subjects and control subjects were similar with the exception that case subjects tended to be older. Average health care resource use and costs were higher among case subjects (total costs, $51,825 vs $29,068; P < 0.01), driven by average hospital admissions (1.4 vs 0.7) with increased length of stay (4.3 vs 2.0 days), office visits (22.8 vs 19.8), and outpatient services (22.3 vs 15.4; all, P < 0.05). IMPLICATIONS: CaHD may be common among patients with CS before initiating SSA therapy and within 2 years of starting SSA therapy, suggesting suboptimal control of serotonin production. Patients with CaHD incur substantial economic costs in addition to the clinical morbidity compared with patients with CS and no CaHD.

The effects of pre-operative somatostatin analogue therapy on treatment cost and remission in acromegaly.

PURPOSE: To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. METHODS: The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. RESULTS: The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn't achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn't alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). CONCLUSIONS: Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn't persist long term.

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.

LanroNET - A Non-Interventional Prospective Study to Assess the Resource Utilisation and Cost of Lanreotide Autogel 120 mg in the Population of Polish Patients with Symptomatic Neuroendocrine Tumours.

Wstep: Celem badania LanroNET byla ocena wykorzystania zasobów medycznych oraz kosztów objawowego leczenia polskich chorych na nowotwory neuroendokrynne z zastosowaniem lanreotydu autogel 120 mg. Material i metody: LanroNET to wieloosrodkowe, nieinterwencyjne, obserwacyjne, prospektywne badanie przeprowadzone w 12 osrod-kach w Polsce. W badaniu uczestniczyli dorosli chorzy na wydzielajace nowotwory neuroendokrynne leczeni lanreotydem autogel 120 mg od przynajmniej 3 miesiecy przed wlaczeniem do badania. Podczas 24-miesiecznej obserwacji rzeczywistej praktyki klinicznej zbierano dane dotyczace wykorzystania zasobów medycznych oraz przebiegu terapii chorych z wydzielajacymi nowotworami neuroendokrynnymi. WYNIKI: W badaniu uczestniczylo 54 chorych na wydzielajace nowotwory neuroendokrynne. Przecietny czas stosowania lanreotydu wynosil 1,7 roku (zakres 0,0-2,2 lata). Badanie ukonczylo 33 pacjentów, najczestsza przyczyna przedwczesnego zakonczenia leczenia (8/16) byla progresja choroby. Calkowity sredni koszt wykorzystanych zasobów bez kosztów farmakoterapii oszacowano na 26 307 zl/EUR 6.030,35 na pacjenta/rok. W czasie badania sredni odstep miedzy wstrzyknieciami lanreotydu wynosil 31,7 dni (6,7). Pod koniec obserwacji, po 24 miesiacach od follow-up, 7 pacjentów stosowalo 42-dniowe odstepy miedzy dawkami. Sredni rzeczywisty koszt lanreotydu autogel 120 mg wyniósl 4216,30 zl/966,49 EUR na pacjenta/28 dni we wspólnej perspektywie platnika i pacjenta i byl nizszy o 554,16 zl/127,02 EUR niz koszt stosowania standardowych 28-dniowych odstepów miedzy dawkami. WNIOSKI: Badanie LanroNET jest pierwszym w Polsce obserwacyjnym dwuletnim badaniem chorych na czynne hormonalnie nowotwo-ry neuroendokrynne zoladkowo-jelitowo-trzustkowe oceniajacym koszty codziennej praktyki klinicznej i koszty leczenia lanreotydem autogel.

68 Ga-somatostatin analogue PET-CT: Analysis of costs and benefits in a public hospital setting.

INTRODUCTION: Between 2009 and 2012, 68 Ga-somatostatin analogue PET-CT progressively replaced 111 In-octreotide scintigraphy for imaging neuroendocrine tumours in WA public hospitals due to published literature demonstrating improved diagnostic accuracy and increased availability. Despite significantly improved sensitivity and specificity, 68 Ga-somatostatin analogue PET is currently unfunded in Australia. This study sought to undertake cost analysis of the two modalities in a public hospital setting and to compare them with regard to patient factors such as imaging time and radiation dose. METHODS: This analysis was based on retrospective clinical data from 95 111 In-octreotide scintigraphies performed in 2007 and 2008 at Sir Charles Gairdner (SCGH) and Royal Perth (RPH) hospitals and 219 68 Ga-somatostatin analogue PET-CT studies performed in 2013 at SCGH. Whole body effective radiation dose was derived from the radiopharmaceutical and low-dose CT scan. The cost analysis included radiopharmaceutical and imaging costs. RESULTS: The median imaging time for an 111 In-octreotide scintigraphy was 152 min at SCGH, 100 min at RPH and 20 min for a 68 Ga-somatostatin analogue PET-CT scan. The mean effective radiation dose for 111 In-octreotide scintigraphy was 18.1 mSv at SCGH and 13.8 mSv at RPH. The effective dose for 68 Ga-somatostatin analogue PET-CT was 8.7-10.8 mSv. The average cost of 68 Ga-somatostatin analogue PET-CT was four times less than 111 In-octreotide scintigraphy. CONCLUSION: 68 Ga-somatostatin analogue PET-CT is not only more accurate than 111 In-octreotide scintigraphy, this study has also shown that it is significantly less expensive, delivers a lower radiation dose to patients and requires less imaging time for patients and staff. 68 Ga-somatostatin PET-CT provides an important combination of both reduced cost and improved clinical care for patients.

Cost-effectiveness analysis of telotristat ethyl for treatment of carcinoid syndrome diarrhea inadequately controlled with somatostatin analogs.

AIMS: This study evaluated the cost-effectiveness of telotristat ethyl (TE) added to somatostatin analog octreotide (SSA + TE) compared to octreotide alone (SSA) in patients with carcinoid syndrome diarrhea (CSD) whose symptoms remain uncontrolled with SSA alone. MATERIALS AND METHODS: A deterministic Markov model evaluated the costs and quality-adjusted life-years (QALY) gained with SSA + TE vs SSA per a third-party US payer perspective. The model reflected clinical practice and resource use estimates based on current standards of care, with utility estimates based on similar symptoms from ulcerative colitis. Treatment efficacy was based on the phase III clinical trial of SSA + TE vs SSA alone [TELESTAR, NCT01677910]. According to TELESTAR, 44% of SSA + TE and 20% of SSA patients responded to therapy after 12 weeks. At each 4-week assessment period, SSA patients not adequately controlled received increasing doses of SSA and SSA + TE patients discontinued TE and moved to SSA only. Drug costs for adequately and not adequately controlled patients were $4,291.75 and $5,890.57 for SSA, respectively, and $9,456.07 and $5,890.57 for SSA + TE, respectively. RESULTS: The base-case analysis demonstrated lifetime QALYs of 1.67 at a cost of $495,125 for the SSA cohort and 2.33 ($590,087) for SSA + TE with an incremental QALY for SSA + TE of 0.66 for an additional $94,962. The incremental cost per QALY gained was $142,545. Sensitivity analyses demonstrated high probability (>99%) of SSA + TE being cost-effective at thresholds for rare diseases and orphan drugs of $300,000-$450,000. LIMITATIONS: The recent availability of TE precluded the incorporation of clinical and economic inputs based on real-world practice patterns. The scarcity of epidemiology and utility information for this rare condition required the use of some proxy estimates. CONCLUSIONS: This analysis demonstrated TE is a cost-effective treatment option when used on top of standard of care in CSD patients.

Development of a Framework Based on Reflective MCDA to Support Patient-Clinician Shared Decision-Making: The Case of the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the United States.

INTRODUCTION: Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making. METHODS: The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing. RESULTS: The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option. CONCLUSIONS: Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives. FUNDING: Ipsen Pharma.

Budgetary Impact of Telotristat Ethyl, a Novel Treatment for Patients with Carcinoid Syndrome Diarrhea: A US Health Plan Perspective.

PURPOSE: Telotristat ethyl (TE) was recently approved for carcinoid syndrome diarrhea (CSD) in patients not adequately controlled with somatostatin analog long-acting release (SSA LAR) therapy alone. A budget impact model was developed to determine the short-term affordability of reimbursing TE in a US health plan. METHODS: A budget impact model compared health care costs when CSD is managed per current treatment patterns (SSA LAR, reference drug scenario) versus when TE is incorporated in the treatment algorithm (SSA LAR + TE, new drug scenario). Prevalence of CSD, proportion of patients not adequately controlled on SSA LAR, monthly treatment costs (pharmacy and medical), and treatment efficacy were derived from the literature. In the reference drug scenario, an escalated monthly dose of SSA LAR therapy of 40 mg was assumed to treat patients with CSD not adequately controlled on the labeled dose of SSA LAR. In the new drug scenario, TE was added to the maximum labeled monthly dose of SSA LAR therapy of 30 mg. The incremental budget impact was calculated based on an assumed TE market uptake of 28%, 42%, and 55% during Years 1, 2, and 3, respectively. One-way sensitivity analyses were conducted to test model assumptions. FINDINGS: A hypothetical health plan of 1 million members was estimated to have 42 prevalent CSD patients of whom 17 would be inadequately controlled on SSA LAR therapy. The monthly medical cost per patient not adequately controlled on SSA LAR in addition to pharmacotherapy was estimated to be $3946 based on the literature. Based on the observed treatment response in a clinical trial of 20% and 44% for the base case reference and new drug scenarios, total per patient per month costs were estimated to be $7563 and $11,205, respectively. Total annual costs in the new drug scenario were estimated to be $2.3 to $2.5 million during the first 3 years. The overall incremental annual costs were estimated to be $154,000 in Year 1, $231,000 in Year 2, and $302,000 in Year 3. This translated to an incremental per patient per month cost of $0.013, $0.019, and $0.025 for Years 1, 2, and 3. These results remained robust in 1-way sensitivity analyses. IMPLICATIONS: The availability of TE for patients not adequately controlled on SSA LAR therapy provides a novel treatment option for CSD. This model showed that providing access to this first-in-class oral agent would have a minimal budget impact to a US health plan.