Cost-effectiveness of teduglutide in adult patients with short bowel syndrome - a European socioeconomic perspective.

BACKGROUND: Short bowel syndrome with intestinal failure (SBS-IF) is a rare but devastating medical condition. An absolute loss of bowel length forces the patients into parenteral support dependency and a variety of medical sequelae, resulting in increased morbidity and mortality. Interdisciplinary treatment may include therapy with the effective but expensive intestinotrophic peptide teduglutide. OBJECTIVES: A time-discrete Markov model was developed to simulate the treatment effect [lifetime costs, quality-adjusted life years (QALYs), and life years (LYs)] of teduglutide plus best supportive care compared with best supportive care alone in patients with SBS-IF. METHODS: The health status of the model was structured around the number of days on PS. Clinical data from 3 data sets were used: 1) an Austrian observational study (base case), 2) pooled observational cohort studies, and 3) a prospective study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects. Direct and indirect costs were derived from published sources. QALYs, LYs, and costs were discounted (3% per annum). RESULTS: Under the base case assumption, teduglutide is associated with costs of 2,296,311 € per patient and 10.78 QALYs (13.74 LYs) over a lifetime horizon. No teduglutide is associated with 1,236,816 € and 2.24 QALYs (8.57 LYs). The incremental cost-utility ratio (ICUR) amounts to 123,945 €. In case of the pooled clinical data set, the ICUR increases to 184,961 €. If clinical data based on the study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects were used, the ICUR increased to 235,612 €. CONCLUSIONS: Teduglutide in treating patients with SBS-IF meets the traditional cost-effectiveness criteria from a European societal perspective. Nevertheless, the varying concentrations of teduglutide efficacy leave a degree of uncertainty in the calculations.

The Impact of Teduglutide on Real-Life Health Care Costs in Children with Short Bowel Syndrome.

OBJECTIVES: To analyze the real-life health care costs of home parenteral nutrition (HPN) in children with short bowel syndrome with intestinal failure (SBS-IF) before and after treatment with teduglutide, and to compare those with costs of children with SBS-IF not treated with teduglutide. STUDY DESIGN: All consecutive children with SBS-IF on HPN treated with subcutaneous teduglutide starting from 2018 through 2020 in a tertiary French referral center were retrospectively included. These patients were matched to children with SBS-IF on HPN followed during the same 3-year period who were eligible for the teduglutide but were not treated. HPN direct medical costs included home-care charges, HPN bags, hospital admissions, and teduglutide. A comparison of costs before/after treatment and between patients treated/not treated was performed. RESULTS: Sixty children were included: 30 (50%) were treated with teduglutide and 30 (50%) were untreated. In the treated group, the median total costs of HPN significantly decreased after 1 (P < .001) and 2 years of treatment (P < .001) from 59 454 euros/year/patient to 43 885 euros/year/patient and 34 973 euros/year/patient, respectively. When we compared patients treated and not treated, the total HPN costs/year/patient were similar at baseline (P = .6) but were significantly lower in the teduglutide-treated group after 1 (P = .006) and 2 years of treatment (P < .001). When we added the cost of teduglutide into the analysis, the total cost increased significantly in the treated group and remained much greater even after modeling a reduction in the cost of the drug to one-third the present cost and PN weaning (P < .001). CONCLUSIONS: Treatment with teduglutide is associated with a significant reduction in the annual costs of HPN but still remains expensive because of the drug itself. Finding cost-saving strategies is essential.

Cost-effectiveness of teduglutide in adult patients with short bowel syndrome: Markov modeling using traditional cost-effectiveness criteria.

BACKGROUND: Adults with short bowel syndrome have a high mortality and significant morbidity due to unsuccessful attempts at rehabilitation that necessitate chronic use of parenteral nutrition (PN). Teduglutide is a novel therapy that promotes intestinal adaptation to improve rehabilitation but with a price >$400,000/y. OBJECTIVE: The current study evaluated the cost-effectiveness of using teduglutide in US adult patients with short bowel syndrome. METHODS: A Markov model evaluated the costs (in US dollars) and effectiveness (in quality-adjusted life years, or QALYs) of treatment compared with no teduglutide use, with a presumed starting age of 40 y. Parameters were obtained from published data or estimation. The primary effect modeled was the increased likelihood of reduced PN days per week when using teduglutide, leading to greater quality of life and lower PN costs. Sensitivity analyses were performed on all model parameters. RESULTS: In the base scenario, teduglutide cost $949,910/QALY gained. In 1-way sensitivity analyses, only reducing teduglutide cost decreased the cost/QALY gained to below the typical threshold of $100,000/QALY gained. Specifically, teduglutide cost would need to be reduced by >65% for it to reach the threshold value. Probabilistic sensitivity analysis favored no teduglutide use in 80% of iterations at a $100,000/QALY threshold. However, teduglutide therapy was cost-saving in 13% of model iterations. CONCLUSIONS: Teduglutide does not meet a traditional cost-effectiveness threshold as treatment for PN reduction in adult patients with short bowel syndrome compared with standard intestinal rehabilitation. Subpopulations that demonstrate maximum benefit could be cost-saving, and complete nonuse could lead to financial loss. Teduglutide becomes economically reasonable only if its cost is substantially reduced.

An exclusive human milk diet for very low birth weight newborns-A cost-effectiveness and EVPI study for Germany.

OBJECTIVES: Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow's milk-based fortifiers in very low birth weight newborns. METHODS: A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values. RESULTS: In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent. CONCLUSION: Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany.

Epidemiology and Healthcare Resource Utilization Associated With Children With Short Bowel Syndrome in the United States.

BACKGROUND: There is a lack of large database research relating to the epidemiology and health resource utilization associated with short bowel syndrome (SBS) in the United States. METHODS: We analyzed the Kids' Inpatient Database for the year 2012 and utilized International Classification of Diseases, Ninth Revision, and Clinical Modification ( ICD-9-CM) diagnosis codes to identify patients 0-3 years of age with SBS, who were matched by age and sex to children without SBS. The study variables included patient and hospital demographics, All Patient Refined Diagnosis Related Groups, in-hospital mortality, hospital length of stay, and hospitalization costs. We also determined the most frequent ICD-9-CM diagnostic and procedural codes associated with SBS. RESULTS: Children with SBS demonstrated a higher rate of mortality than that of children without SBS (1.6% vs 0.7%; P < .001). Children with SBS also experienced a longer length of stay (median days [interquartile range]: 8 [15] vs 2 [3]; P < .001) and higher hospital costs ($17,000 [$34,000] vs $3000 [$5000]; P < .001). The most frequent medical diagnoses associated with SBS were infection (62%), anemia (29%), and liver disease (17%). Children with SBS also demonstrated more severe illness as assessed by an All Patient Refined Diagnosis Related Group score of 3 or 4 (94.30% vs 16.20%; P < .001). CONCLUSIONS: Children hospitalized with SBS have a high severity of illness and experience complicated inpatient courses related to their disease. Our study represents the first use of national U.S. data to study the epidemiology and health resource utilization associated with SBS.

The role, yield and cost of paediatric faecal elastase-1 testing.

OBJECTIVE: Faecal elastase-1 (FE1) is a sensitive marker for exocrine pancreatic enzyme insufficiency. Pancreatic insufficiency (EPI) leads to maldigestion and subsequent poor weight gain. Thus, FE1 is performed as work-up for children with failure to thrive (FTT). However, EPI in the paediatric population outside of cystic fibrosis (CF) is rare. This study aimed to identify the indications for FE1 testing and their diagnostic yield in children. The secondary aim was to evaluate the cost per case of EPI detected for the various indications. DESIGN: All FE1 tests performed on children (0-18 years) at a tertiary paediatric hospital in Sydney, Australia between 2010 and 2013 (inclusive) were identified. A retrospective chart audit was performed to identify the indication for testing FE1. The diagnostic yield based on FE1 cut-offs <200 and < 100 µg/g were assessed. RESULTS: The most common indication for testing FE1 was "FTT only" (71/216, 32.9%), however, in this cohort of patients, FE1 was least likely to be positive with only 2 out of the 71 (2.8%) patients returning a positive result. In comparison, CF was the second most common indication for testing (60/216, 27.8%), but nearly half (48.8%) of tests returned a positive result in this cohort. The cost per case detected (FE1 <200 µg/g) reflected the test yield with an average cost per positive test of $262.50 (AUD2015) for FTT with short-gut syndrome and $420.00 (AUD2015) for CF-related indications. CONCLUSION: Our study shows that for patients with isolated failure to thrive, FE1 testing is low yield and costly.

[Clinical nutrition therapy in patients with short bowel syndrome in line with principles of personalized medicine]. / Klinikai táplálásterápia rövidbél-szindrómában a személyre szabott orvoslás elvei szerint.

Home parenteral nutrition administered in selected care centres has been financed in Hungary since January, 2013. The authors discuss diagnostic issues, treatment and nutrition therapy of short bowel syndrome patients in line with the principles of personalised medicine. The most severe form of short bowel syndrome occurs in patients having jejunostomy, whose treatment is discussed separately. The authors give a detailed overview of home parenteral feeding, its possible complications, outcomes and adaptation of the remaining bowel. They describe how their own care centre operates where they administer home parenteral nutrition to 12 patients with short bowel syndrome (5 females and 7 males aged 51.25±14.4 years). The body mass index was 19.07±5.08 kg/m2 and 20.87±3.3 kg/m2, skeletal muscle mass was 25.7±6.3 kg and 26.45±5.38 kg, and body fat mass was 14.25±8.55 kg and 11.77±2.71 kg at the start of home parenteral nutrition and presently, respectively. The underlying conditions of short bowel syndrome were tumours in 4 patients, bowel ischaemia in four patients, surgical complications in three patients, Crohn's disease in one patient, and Crohn's disease plus tumour in one patient.

Clinical, social, and economic impacts of home parenteral nutrition dependence in short bowel syndrome.

Home parenteral nutrition (HPN) provides nourishment and hydration to patients with short bowel syndrome and intestinal failure and is thus a life-sustaining therapy for these patients. However, measures of quality of life (QOL) are lower among the HPN-dependent population than among patients with other intestinal diseases who do not require HPN. Multiple factors contribute to lower QOL in HPN-dependent patients, including fears surrounding the increased risk of HPN-associated adverse events, such as catheter-related complications, parenteral nutrition-associated liver disease, and metabolic bone disease. In addition, HPN-dependent patients report impaired sleep and daytime fatigue because of pump noises, equipment alarms, and nocturia. Psychosocial burdens on families of HPN-dependent patients include decreased social activities, disrupted family relationships and friendships, and depression. These families also face imposing financial constraints, including decreased employment and large out-of-pocket expenses for insurance premiums and nonreimbursed copayments, medications, and supplies. Furthermore, HPN technology and HPN-related complications and sequelae contribute to the rapid overall increase in the costs of healthcare systems. Additionally, family caregivers provide unpaid healthcare services for patients who require HPN, often to the detriment of their own physical and mental well-being. Nonetheless, patients dependent on HPN and their caregivers often demonstrate considerable resilience and are frequently able to normalize their response to illness and disability. Interventions that may improve QOL among HPN-dependent patients and caregivers include patient education, affiliation with support groups, treatment of concomitant symptoms, and pharmacotherapies that decrease HPN requirements.

Economic evaluation in short bowel syndrome (SBS): an algorithm to estimate utility scores for a patient-reported SBS-specific quality of life scale (SBS-QoL™).

PURPOSE: Condition-specific preference-based measures can offer utility data where they would not otherwise be available or where generic measures may lack sensitivity, although they lack comparability across conditions. This study aimed to develop an algorithm for estimating utilities from the short bowel syndrome health-related quality of life scale (SBS-QoL™). METHODS: SBS-QoL™ items were selected based on factor and item performance analysis of a European SBS-QoL™ dataset and consultation with 3 SBS clinical experts. Six-dimension health states were developed using 8 SBS-QoL™ items (2 dimensions combined 2 SBS-QoL™ items). SBS health states were valued by a UK general population sample (N = 250) using the lead-time time trade-off method. Preference weights or 'utility decrements' for each severity level of each dimension were estimated by regression models and used to develop the scoring algorithm. RESULTS: Mean utilities for the SBS health states ranged from -0.46 (worst health state, very much affected on all dimensions) to 0.92 (best health state, not at all affected on all dimensions). The random effects model with maximum likelihood estimation regression had the best predictive ability and lowest root mean squared error and mean absolute error, and was used to develop the scoring algorithm. CONCLUSIONS: The preference-weighted scoring algorithm for the SBS-QoL™ developed is able to estimate a wide range of utility values from patient-level SBS-QoL™ data. This allows estimation of SBS HRQL impact for the purpose of economic evaluation of SBS treatment benefits.

Key issues in addressing the clinical and humanistic burden of short bowel syndrome in the US.

BACKGROUND: The purpose of this analysis was to provide a concise report of the literature on the burden of intestinal failure associated with short bowel syndrome (SBS-IF) in adults, focused on clinical and humanistic issues important to clinicians and payers. SCOPE: A literature search was performed using the National Library of Medicine PubMed database ( http://www.ncbi.nlm.nih.gov/pubmed ) with the search term 'short bowel syndrome' limited to adult populations and English-language reports published from January 1, 1965, to January 18, 2013. Citations were assessed for relevance and excluded articles focused on single case studies, colon fermentation, absorption of medications with PN/IV, surgical technique, mesenteric artery complications/surgery, and transplantation focus. Additional hand searches were performed using the terms 'short bowel syndrome' AND 'cost', and 'home parenteral nutrition' AND 'cost', along with the exclusion criteria described above. FINDINGS: Despite advances in management in recent decades, SBS-IF continues to carry a high burden of morbidity and mortality. In the absence of sufficient intestinal adaptation following resection, many patients remain dependent on long-term parenteral nutrition and/or intravenous fluids (PN/IV). Although potentially life saving, PN/IV is costly, invasive, and associated with numerous complications and deleterious effects on health and quality of life. Surgical interventions, especially intestinal transplantation, are costly and are associated with substantial morbidity and high mortality. New therapies, which show promise in promoting intestinal rehabilitation and reducing dependence on PN/IV therapy, are the subject of active research. CONCLUSIONS: Overall, the available literature suggests that although SBS-IF affects a relatively small population, the clinical and humanistic burden is significant, and there is an unmet need for effective therapeutic options that target the underlying problem of inadequate absorptive capacity of the remaining intestine. Consequently, many patients with SBS-IF remain dependent on long-term PN/IV support, adding to the burden imposed by the underlying disorder.

Interdisciplinary management of infantile short bowel syndrome: resource consumption, growth, and nutrition.

BACKGROUND/PURPOSE: To date, there are hardly any data on the treatment costs of infantile short bowel syndrome (SBS), despite growing interest in evidence-based and cost-effective medicine. Therefore, the aim of the study was to evaluate resource consumption and costs, next to studying nutritional and growth outcomes, in children with SBS who were treated by an interdisciplinary short bowel team. METHODS: Data were collected for 10 children with infantile SBS (

Pediatric short-bowel syndrome: the cost of comprehensive care.

BACKGROUND: Little information is available about the financial charges incurred by patients with short-bowel syndrome (SBS). This is particularly true for pediatric SBS patients who receive some of the most complex medical care. OBJECTIVES: The aims of this study were to determine the total cost of care for these patients and to analyze their utilization of home and hospital-based health care services. DESIGN: This was a retrospective review of the total charges incurred by 41 children with SBS over the past decade, encompassing both inpatient and home-care charges. RESULTS: The mean (+/- SD) total cost of care for pediatric SBS was US$505 250 +/- US$248 398 (corrected for inflation to the year 2005) for the first year of care alone. Inpatient hospitalization accounted for most of these expenses (US$416 818 +/- US$242 689, or 82% of the total), and this was attributable to prolonged requirements for intensive care resources, numerous surgical procedures, and multiple readmissions during the first year of diagnosis. Hospital-based costs steadily declined in subsequent years, but home-care services, in stark contrast, unexpectedly increased every year for the first 5 y of diagnosis-a trend that was highly significant (P < 0.005), reaching US$184 520 +/- US$111 075 for the fifth year of home care. This increasing cost was attributable to increasing complications of parenteral nutrition, especially infectious complications. Although per-patient charges varied widely, the mean total cost of care per child over a 5-y period was US$1 619 851 +/- US$1 028 985. A strong correlation was found between higher charges and infants with <10% of predicted small-bowel length. CONCLUSIONS: This study was the first to calculate the total costs for pediatric SBS patients and to provide an in-depth analysis of these patients' actual utilization of health care services. This information may help guide health care providers and families who have children with SBS. The comprehensive care of pediatric SBS patients costs significantly more than has previously been estimated. Contrary to previous views, home care significantly increases each year after diagnosis.

Economic implications of growth hormone use in patients with short bowel syndrome.

OBJECTIVE: Short bowel syndrome is a rare, life-threatening condition that can result in nutritional malabsorption. Parenteral nutrition provides life-saving support but can lead to complications and affect quality of life. Recombinant human growth hormone, somatropin (rDNA origin), has been shown to significantly reduce dependence on nutritional support (p < 0.05). This study evaluates the economic impact of somatropin use in the management of short bowel syndrome. METHODS: A discrete event simulation (DES) model was developed to estimate the benefits and costs associated with somatropin use. Risks of treatment complications and of disease-related events were modeled in identical patient pairs--one receiving parenteral nutrition alone, the other receiving 4 weeks of somatropin--for 2 years following initiation of treatment. Life expectancy was assumed equivalent. Risk functions were estimated from the literature and one randomized clinical trial. Total and component costs associated with each strategy were determined. The distribution of patients reducing parenteral nutrition need and the final parenteral nutrition frequency were also estimated. Sensitivity analyses were completed for key inputs. Direct medical costs are reported in US 2004 dollars. RESULTS: The model predicted that 96.0% of patients receiving somatropin reduce or eliminate parenteral nutrition within 6 weeks: average use was reduced by 2.8 days and one-third weaned completely. Based on 1.9 L of parenteral nutrition per day, estimated costs were 118,098 dollars in year one and 132,935 dollars in year two. With somatropin, costs dropped to 84,309 dollars in year one--despite the 17,459 dollars cost of somatropin treatment--and 81,250 dollars in year two. Over 2 years savings totaled 85,474 dollars. LIMITATIONS: Insufficient data required that assumptions be made for some inputs. DES is new in pharmacoeconomics and may be perceived as a limitation. CONCLUSIONS: Somatropin use improves quality of life by reducing the need for parenteral nutrition and results in health care cost savings.

Mortality and economics in short bowel syndrome.

The incidence of patients with short-bowel syndrome (SBS) has increased over the years due to progress of intensive care medicine and parenteral nutrition techniques. These techniques have significantly improved the prognosis of neonates, children and adults who have lost major parts of their intestinal tract. Long-term survival is possible and does not depend primarily on the length of the remaining bowel but on complications such as parenteral nutrition-associated cholestasis, recurrent septicaemia, central venous catheter infections, and the motility of the remaining intestine. Thus, the overall related mortality in infants with SBS ranges from 15 to 25%, and in adults from 15 to 47%, depending on the age of the patients, the underlying disease, and the duration on total parenteral nutrition. Home parenteral nutrition (HPN) significantly decreases the complication rate and improves the psychological situation of the patient. Additionally, HPN reduces in-hospital cost significantly. Nevertheless, the annual costs/patient are between $100000 and $150000. The mortality rate of SBS patients on HPN is about 30% after 5 years, which is still lower than the 5-year survival rate of intestinal grafts, and it is about equal to patients' survival after intestinal transplantation. However, the overall costs of a successful intestinal transplantation are already lower after 2 years when compared with the cost of a prolonged HPN programme.

Economic aspects of paediatric home parenteral nutrition.

Children account for 15-20% of home parenteral nutrition programmes. Underlying irreversible intestinal diseases lead to potential indications for intestinal transplantation. Therefore, new controversial issues are timing for referring children for transplantation, and comparison between home parenteral nutrition and transplantation in terms of costs and quality of life.

Short bowel syndrome in patients studied at the National Institute of Pediatrics in mexico. Care, cost and perspectives

Background. Short bowel syndrome (SBS) continues to be one of the most challenging problems in pediatric surgery. Intestinal transplantation (IT) seems to be best form of treatment for this pathology. However, it is thought that the development of an IT programs may be more expensive than the present manner of treatment. Methods. To assess this item, and to identify potential candidates for IT, we reviewed the charts of all the patients with SBS treated at our Institute from 1989 to 1994. Results. Nine patients were identified as carriers of SBS; six with intestinal atresia, two with midgut volvulus and one with post-traumatic mesenteric thrombosis. The small bowel remnants varied from 1 to 80 cm, seven patients had remnants shorter than 30 cm, and the ileocecal valve was resected in three. Results. The overall morbidity and mortality was extremely high; four patients died within the first 3 months postresection and those still alive have had several complications: sepsis; hydroelectrolyte imbalances secondary to loose stools; thrombosis or infection of the catheter; TPN-related cholestasis, and malabsorption syndromes, etc. No patient survived with an intestinal remnant shorter than 15 cm. Of the five survivors, four have a weight/age deficit greater than 40 percent, two have rickets, one still depends on TPN and all, except one, require special enteral diets. Multiple central venous accesses had to be performed in every patient (mean 4.8). They all required multiple readmissions and have spent a considerable part of their lives as inpatients. The mean of the calculated cost per patient was $50,000 USD, while the minimal wage in mexico is $1,616 USD/year (1). conclusions. The shorter the segment of the retained bowel and the longer the survival, the higher the cost. These results may be further improved with the development of IT and, probably, with the same economic burden

Short bowel syndrome in patients studied at the National Institute of Pediatrics in Mexico. Care, cost and perspectives.

BACKGROUND: Short bowel syndrome (SBS) continues to be one of the most challenging problems in pediatric surgery. Intestinal transplantation (IT) seems to be the best form of treatment for this pathology. However, it is thought that the development of an IT program may be more expensive than the present manner of treatment. METHODS: To assess this item, and to identify potential candidates for IT, we reviewed the charts of all the patients with SBS treated at our Institute from 1989 to 1994. RESULT: Nine patients were identified as carriers of SBS; six with intestinal atresia, two with midgut volvulus and one with post-traumatic mesenteric thrombosis. The small bowel remnants varied from 1 to 80 cm, seven patients had remnants shorter than 30 cm, and the ileocecal valve was resected in three. RESULTS: The overall morbidity and mortality was extremely high; four patients died within the first 3 months postresection and those still alive have had several complications: sepsis; hydroelectrolyte imbalances secondary to loose stools; thrombosis or infection of the catheter; TPN-related cholestasis, and malabsorption syndromes, etc. No patient survived with an intestinal remnant shorter than 15 cm. Of the five survivors, four have a weight/age deficit greater than 40%, two have rickets, one still depends on TPN and all, except one, require special enteral diets. Multiple central venous accesses had to be performed in every patient (mean 4.8). They all required multiple readmissions and have spent a considerable part of their lives as inpatients. The mean of the calculated cost per patient was $50,000 USD, while the minimal wage in Mexico is $1,616 USD/year (1). CONCLUSIONS: The shorter the segment of the retained bowel and the longer the survival, the higher the cost. These results may be further improved with the development of IT and, probably, with the same economic burden.