The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000.

IntroductionWell- 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.MethodsThe 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.ResultsThe 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.ConclusionsPatients 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.FundingIpsen Pharma.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0653-1) contains supplementary material, which is available to authorized users.

BackgroundGastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rare cancers most often found in the gastrointestinal system or the pancreas. However, patient-reported health state utilities based on clinical trials have not been previously reported in this disease area.MethodsThe CLARINET study collected EORTC QLQ-C30 data from patients in both stable and progressive disease states, although data for the latter were only available during the early stage of progression due to trial design. Using published algorithms, data were mapped to EQ-5D utility values. Random-effects generalised least squares models were used to investigate the impacts of progression status, tumour site and other patient characteristics on mapped utility values.ResultsIn total, 1053 observations from 204 patients were mapped to EQ-5D utilities using the McKenzie mapping algorithm. The final random-effects model included age, gender, baseline utility and progression status as covariates; it was not feasible to investigate time-to-death utility due to a limit number of deaths in the CLARINET study. Tumour location (midgut vs pancreas) does not seem to affect utility. However, the difference in utilities based on progression status is statistically significant (p < 0.05) in the base case analysis, and the estimated utilities for stable and progressive disease are 0.776 and 0.726, respectively. Furthermore, scenario analyses showed that utility for progressive disease is numerically lower than for stable disease, but this may not be statistically significant in scenarios where alternative Longworth mapping algorithm was used.ConclusionsPatients with GEP-NETs experience worse utility values in the progressive disease state compared to the stable disease state, based on patient-reported health-related quality of life (HRQL) data from the CLARINET study. The decline of utility in the progressive disease state may be underestimated because progressive HRQL data were only collected shortly after the progression event in the trial. The estimated trial-based utilities can be used in future economic evaluations for GEP-NET treatments and to provide more insights to physicians on patient-reported quality of life outcomes in GEP-NETs.Trial registrationCLARINET EU Clinical Trials Register Number, 2005–004904-35.

The objective was to estimate the cost‐of‐illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) in Sweden in 2013 in a population‐based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP‐NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost‐of‐illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600–€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300–€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600–€24,500) for patients with other GEP‐NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP‐NETs in Sweden was €25,500 per patient and year.

Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are neoplasms derived from the endocrine system in the gastrointestinal tract and pancreas. Treatment options include surgery; pharmacological treatments like somatostatin analogues (SSA), interferon alpha, molecular targeted therapy and chemotherapy; and peptide receptor radionuclide therapy.The objective of this study was to describe treatment patterns and survival among patients with metastatic GEP-NET grade 1 or 2 in Sweden.Methods: Data was obtained via linkage of nationwide registers. Patients diagnosed with metastatic GEP-NET grade 1 or 2 in Sweden between 2005 and 2013 were included (n=811; National population). In addition, medical chart review was performed for the subpopulation diagnosed at Sahlgrenska University Hospital, Gothenburg (n=127; Regional population). Treatment patterns, including treatment sequences, and overall survival were assessed.Results: Most patients had small intestinal NET (76%). In the regional population, 72% had grade 1 tumours; 50% had functioning tumours. The two most common first-line treatments were surgery (57%) and SSA (25%). After first-line surgery, 46% received SSA, while 40% had no further treatment. After first-line SSA, 52% received surgery, while 27% had no further treatment. Overall median survival time from date of diagnosis was 7.0 years (95% CI 6.2-not reached). Among patients with distant metastases, pancreatic NET (vs. small intestinal NET) was associated with poorer survival (HR 1.9; 95% CI 1.1-3.3), as were liver metastases (HR 3.2; 95% CI 1.5-7.0).Conclusions: First-line surgery was typically followed by SSA or no further treatment. Among patients with distant metastases, pancreatic NET or liver metastases were associated with a poorer survival.

Background. Although an increasing number of treatments have become available for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), there remains little consensus on treatment sequence and its impact on health care resource use (HRU). We sought to describe treatment patterns and HRU, in a cohort of patients with metastatic GEP-NETs treated at a tertiary referral center in the U.S. Materials and Methods. We identified patients with a welldifferentiated, metastatic GEP-NET evaluated at Dana-Farber Cancer Institute between July 2003 and May 2015. For these patients, we describe the sequence of treatment regimens received for their disease, together with associated HRU. Results. We identified 682 patients with advanced GEP-NETs. Of these patients, 597 (87.0%) initiated ≥1 treatment over the follow-up period. The mean age at diagnosis was 58.5 years, 50.2% were men, and 94.0% were white. A total of 83.1% initiated a somatostatin analog (SSA) as their firstline treatment, with 55% and 31% of patients continuing with second-and third-line therapies. A total of 31.2% of patients with SSAs underwent dose escalation to above standard dose. In this setting, patients with pancreatic neuroendocrine tumors were more commonly treated with cytotoxic regimens than other NET tumor types and also had higher HRU. Conclusion. Our study suggests that, at a tertiary referral center, patients with advanced NETs commonly received multiple courses of treatments. Our data suggest a clear preference for use of SSAs as a first-line treatment for patients with advanced NETs, with SSAs commonly escalated and continued throughout the course of treatment in combination with other regimens. The Oncologist 2020;25:e644-e650 Implications for Practice: The current study demonstrates the common use of somatostatin analog as a first-line therapy for patients with advanced gastroenteropancreatic neuroendocrine tumors as well as the incorporation of multiple different treatment regimens in the treatment course of patients with this disease. Jalbert, Casciano, Meng et al. e645 3. Rinke A, Muller HH, Schade-Brittinger C et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors:

A385Objectives: PAH-SYMPACT ® is a patient reported outcome (PRO) instrument developed based on interviews with patients with pulmonary arterial hypertension (PAH) and following the FDA's PRO guidance. Its psychometric characteristics are being evaluated using data from the phase IIIb PAH SYMPHONY study. After item reduction, the final instrument consists of 11 symptom items across 2 domains (cardiopulmonary and cardiovascular symptoms) and 11 impact items across 2 domains (physical impact and cognitive/emotional impacts). The objective of this analysis was to evaluate the psychometric properties of the PAH-SYMPACT< sup> ®< /sup> domain scores. MethOds: In SYMPHONY, patients completed generic and disease-specific questionnaires, while clinicians provided assessment of severity and changes in symptomatology. Internal consistency and test-retest reliability, knowngroup and construct validity and sensitivity to change were evaluated. Instrument performance based on oxygen use was also assessed. Results: Data from 278 patients (79% female, mean age 60 years) were included in the analysis. 59% of patients were in WHO functional class III, 41% were on background therapy with a phosphodiesterase type-5 inhibitor and 34% used oxygen therapy at any given time. Individual item scores did not differ based on oxygen use. For all 4 domains, internal consistency reliability was very good (Cronbach's alpha > 0.80) and test-retest reliability (assessed in stable patients) was high (intra-class correlation coefficient 0.84-0.94). Correlations with CAMPHOR and SF-36 were moderate-to-high with correlations slightly lower in the cardiovascular domain than the cardiopulmonary domain. The instrument differentiated well between patients with different disease severity levels. Domain scores were sensitive to changes in clinician-and patientreported disease severity levels. cOnclusiOns: The PAH-SYMPACT ® performed well -with good psychometric properties. The domain scores were reproducible, differentiated between patients of different severity, correlated with other instruments measuring similar constructs, and were sensitive to change. This PRO has the potential to become an important outcome measure in PAH.

Objectives: Estimates of medical care costs attributable to diabetes mellitus (DM) from association analyses may be biased. This study utilizes the hereditary component of DM risk in an instrumental variable (IV) framework to estimate the causal effect of DM on total annual medical care costs. MethOds: Data for the year 2013 from Clalit Health Services (CHS), the largest health fund in Israel, were used to estimate models of health care cost. Included in the study were all CHS members aged between 50 and 60 years whose parents were also members of CHS and thus parental information was available. Average marginal effects (AME) of DM on total medical care costs were estimated using a two-part model using probit and log-linear regression models, controlling for socio-demographic factors. Parental DM was used as an instrumental variable for DM status in the models. All costs were reported as a percentage of the average yearly cost (PAYC) of all CHS members. Results: Of 446,646 CHS members aged 50 to 60, 91,167 had parental data available and were included in the main analysis. Of those, 12,085 (13.2%) had a diagnosis of DM. The average cost of a diabetic member was 220 PAYC, while average cost of a non-diabetic member was only 91 PAYC. The AME of DM, using a non-IV regression model was 71.18 PAYC (standard error 3.33) compared to an estimate of 113.04 PAYC (standard error 27.32) using IV regression. cOnclusiOns: The association of DM with medical care costs is substantial, even in the 50 to 60 years old age group. Although the precision of the IV estimate is limited, the estimate is considerably higher than that from the non-IV model. These findings suggest that the causal effect of diabetes on medical care spending may be higher than estimates based on association analysis alone.Objectives: The rise in type 2 diabetes (T2DM) in Turkey and surrounding regions represents a heavy burden for the healthcare budget. This analysis aims to estimate the cost of managing T2DM and its complications in Turkey. MethOds: Data on diabetes-related healthcare resource use were obtained from the fifth wave of the International Diabetes Management Practice Study (IDMPS). Costs obtained from published literature and IMS data were reported in 2015 Turkish lira (TL). Data on prevalence and proportion of treated patients was from the International Diabetes Federation Atlas 7thedition and the TURDEP II study. Mean annual costs per patient was calculated by multiplying the unit costs by the annual estimates of consumption for all healthcare used items from the IDMPS. Mean annual costs per patient were then multiplied by the total number of diagnosed and treated T2DM patients in Turkey (3,069,397) to obtain cost at a national level. Results: 842 T2DM adults were analysed, 55.5% were females; mean age was 57.4 years (SD11.4); mean duration since diagnosis was 8.7 years (SD6.8). 47% of patients reported diabetes-related complications. Total cost of managing T2DM and its complications was 9,056,237,801TL (€ 2,753,481,254) at a national level ba...