Health care resource use and costs among patients with carcinoid syndrome in France: Analysis of the National Health Insurance Database.

OBJECTIVES: Carcinoid syndrome (CS) develops in approximately 20% of patients with neuroendocrine tumours (NET). This study described healthcare resource utilization and its associated costs among patients with NET and CS, using the French national health care data system. METHODS: Patients were included if they had a hospital stay associated with the code E34.0 "CS" and at least one delivery of a somatostatin analogue (SSA) between 01/01/2012 and 31/12/2016. The end of the analysis was either 31/12/2017 or the date of death, whichever occurred first. Mean overall costs were described by item of expenditure and by periods. RESULTS: 646 patients were included: 64yo, 55% men, 64% and 15% had NET from the small-intestine or lung, respectively. Among them, 309 patients were incident and 271 died during the study period. Mean overall cost per person per month (PPPM) was €2,892: €3,273 for the first year following diagnosis, €2,574 in "middle-years" and €5,039 within the year preceding death. The two most costly expenditure items were drugs (€1,695 PPPM) and hospital stays (€870 PPPM). CONCLUSION: The first year following diagnosis and the year preceding death are the two periods representing the highest costs for CS care in France. Successful disease management may contribute to lower costs in the intermediate period.

Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study.

PURPOSE: To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS: A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS: Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION: This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.

Development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index.

OBJECTIVE: To develop a symptom-focused index to evaluate representative symptoms, treatment side effects, and emotional and functional well-being of patients with carcinoid syndrome (CS). METHODS: The development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index (FACT-CSI) followed US Food and Drug Administration guidelines for the development of patient-reported outcome (PRO) measures and involved the following: (a) literature review; (b) interviews with 14 CS patients; (c) interviews with 9 clinicians; and (d) instrument development involving input from a range of PRO measure development and CS experts. The resulting draft instrument underwent cognitive interviews with 7 CS patients. RESULTS: Forty-six CS sources were reviewed. Analysis of patient interviews produced 23 patient-reported symptoms. The most frequently endorsed physical symptoms were flushing, diarrhea, abdominal pain, fatigue, and food sensitivity/triggers. Seven priority CS emotional and functional themes were also identified by patients. Expert interviews revealed 12 unique priority symptoms - the most common being diarrhea, flushing, wheezing, edema, abdominal pain/cramping, fatigue, and 8 emotional and functional concerns. Through an iterative process of team and clinical collaborator meetings, data review, item reduction and measure revision, 24 items were selected for the draft symptom index representing symptoms, emotional concerns, global assessment of treatment side effects, and functional well-being. Cognitive interview results demonstrated strong content validity, including positive endorsement of item clarity (>86% across items), symptom relevance (>70% for most items), and overall measure content (86%). CONCLUSIONS: The FACT-CSI is a content-relevant, symptom-focused index reflecting the highest priority and clinically relevant symptoms and concerns of people with CS.

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.

Cost-of-illness of metastatic gastroenteropancreatic neuroendocrine tumours in Sweden-A population-based register-linkage study.

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.

Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease: a retrospective Swedish study.

OBJECTIVES: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns. MATERIALS AND METHODS: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group. RESULTS: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography. CONCLUSIONS: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.

Healthcare and economic impact of diarrhea in patients with carcinoid syndrome.

AIM: To examine healthcare resource utilization patterns and costs accrued by carcinoid syndrome (CS) patients with and without diarrhea. METHODS: We conducted a retrospective cohort study using MarketScan® data from 1/1/2002-12/31/2012. Newly diagnosed CS patients had 1 medical claim for CS (ICD-9-CM code 259.2) plus either ≥ 1 additional claim for CS or for carcinoid tumors (ICD-9-CM 209.x), and had no evidence of CS for 1 year prior to index CS diagnosis, in commercially-insured patients < 65 years old. Patients were required to have continuous enrollment one year prior and after index date (first claim with CS diagnosis in the ID period). We identified patients with evidence of non-infectious diarrhea (ICD-9-CM codes 564.5 and 787.91) within one year from the index date. Overall and CS-related healthcare resource utilization and costs were compared between patients with and without non-infectious diarrhea during the one year period after the index date. RESULTS: There were 2822 newly diagnosed CS patients; 534 (18.9%) had evidence of non-infectious diarrhea. Compared to patients without non-infectious diarrhea, non-infectious diarrhea patients more commonly had at ≥ 1 CS-related hospitalization (13.7% vs 7.2%), ≥ 1 CS-related ED visit (11.0% vs 4.4%), and CS-related office visits in one year (6.9 vs 4.1; all P < 0.001). After adjusting for demographics, region, number of chronic conditions and the Charlson Comorbidity Index, the proportions of patients with any and with CS-related hospitalizations were 9.7% and 6.8% higher, respectively, among non-infectious diarrhea patients compared to those with without non-infectious diarrhea (P < 0.001). Unadjusted costs were significantly higher among non-infectious diarrhea patients vs those without non-infectious diarrhea. The non-infectious diarrhea group was also more costly, with adjusted mean annual costs of $81610, compared to $51719 in the group without non-infectious diarrhea (P < 0.001). CONCLUSION: Diarrhea is burdensome and costly in CS patients. Reduction of CS-related healthcare expenditures may be achievable through preventive treatment and appropriate management of diarrhea in CS.