Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. METHODS: Adult patients (18-64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. RESULTS: There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month. CONCLUSIONS: This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

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 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.

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.

From evidence assessments to coverage decisions?: the case example of glinides in Germany.

In Germany, coverage decisions in the statutory health insurance (SHI) system are based on the principles of evidence-based medicine. Recently, an evidence assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) of the oral antidiabetics of the glinide class showed that their long-term benefit is not proven. Accordingly, the responsible Federal Joint Committee (G-BA) decided to exclude glinides from prescription in the SHI system. This was, however, objected to by the Ministry of Health, which is charged with legal supervision. We use this case to illustrate the path from evidence assessments to coverage decisions in Germany against the background of the latest health reform, which has changed the legal requirements for evidence assessments and the ensuing coverage decisions.

Comparing the long-term cost-effectiveness of repaglinide plus metformin versus nateglinide plus metformin in type 2 diabetes patients with inadequate glycaemic control: an application of the CORE Diabetes Model in type 2 diabetes.

OBJECTIVES: As an example application of the CORE Diabetes Model in type 2 diabetes, we simulated the cost-effectiveness of repaglinide/metformin combination therapy versus nateglinide/metformin for treatment of individuals with type 2 diabetes with an inadequate response to sulphonylurea, metformin, or fixed dose glyburide/metformin. METHODS: The CORE Diabetes Model was used to simulate long-term outcomes for a cohort of individuals with type 2 diabetes treated with either repaglinide/metformin or nateglinide/metformin. HbA1c changes for each regimen were taken from a comparative study. At the end of the study, changes in HbA1c from baseline were -1.28% points and -0.67% points for repaglinide/metformin and nateglinide/metformin, respectively. Median final doses were 5.0 mg/day for repaglinide, 360 mg/day for nateglinide and 2000 mg/day metformin in each treatment arm. Costs were calculated as the annual costs for drugs plus costs of complications (US Medicare perspective) over a 30-year period. Life expectancy (LE) and quality-adjusted life expectancy (QALE) were calculated. Outcomes and costs were discounted at 3% annually. RESULTS: With repaglinide/metformin, improved glycaemic control led to projected decreases in complication rates, improvement of LE and QALE by 0.15 and 0.14 years respectively, and total cost savings of 3,662 dollars/person over the 30-year period. Repaglinide/metformin had a 96% probability that the incremental costs per quality-adjusted life year gained would be 20,000 dollars or less, and a 66% probability that repaglinide/metformin would be cost-saving compared to nateglinide/metformin. Sensitivity analyses supported the validity and reliability of the results. CONCLUSIONS: In the health economic context, repaglinide/metformin combination was dominant to nateglinide/metformin. The CORE Diabetes Model is a tool to help third-party reimbursement payers identify treatments for type 2 diabetes that are good value for money.

Modeling the efficiency of reaching a target intermediate end point: a case study in type 2 diabetes in the United States.

OBJECTIVE: The objective of this study was to describe an approach to modeling the efficiency of an intervention by focusing on an established intermediate end point directly. A case study addresses the economic efficiency of obtaining dual glycemic control over time, according to initial choice of treatment. METHODS: From the perspective of a payer in the United States, instead of the usual approach of basing the model on projecting long-term diabetic complications from glycemic control, this model focuses directly on glycemic control. Treatment changes and associated health-care utilization needed to address postprandial glucose. After assigning each of 10000 drug-naïve patients, HbA1c, age, race, and sex based on distributions from a randomized clinical trial, the model applies the efficacy of nateglinide compared to metformin. Sensitivity analyses were carried out for all parameters. Costs are reported in year 2000 US dollars and discounted at 3%. RESULTS: In the base case, starting on nateglinide and increasing the time in dual glycemic control over 3 years by 2.4 months led to savings of US dollars 295 compared to starting on metformin. Savings increased with stricter treatment criteria but decreased if glycemic control was better initially. CONCLUSIONS: This study illustrates the use of an efficiency model that focuses directly on the relevant short-term end point: glycemic control. Starting patients with nateglinide is shown to be an efficient way of obtaining dual glycemic control during the first 3 years of treatment.

Health and economic effects of adding nateglinide to metformin to achieve dual control of glycosylated hemoglobin and postprandial glucose levels in a model of type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus is a common disease whose complications have great costs, both in quality of life and expense of treatment. Improving glycemic control, as measured by monitoring glycosylated hemoglobin (HbA1c) levels, can reduce the rate of such complications. OBJECTIVES: The aims of this study were to estimate the lifetime costs associated with diabetes-related complications in a theoretical population receiving metformin monotherapy and to predict the health and economic effect of improving glycemic control in this theoretical population by combining metformin with nateglinide. METHODS: A pharmacoeconomic model was developed to simulate the long-term (30 years) complication rates (microvascular and macrovascular) of a cohort of patients with type 2 diabetes mellitus. The model simulated each year of life for each patient in a theoretical cohort of 10,000 patients until diabetes-related complications were present or death occurred. The mean accumulated costs (direct medical costs for acute care and subsequent care for diabetes-related complications), mean survival time, and the frequency of each type of complication were estimated. Both effectiveness and cost data were discounted at 3%. Sensitivity analyses were conducted on key model input parameters. RESULTS: Average costs of treating complications in theoretical patients undergoing metformin monotherapy were estimated at $29,565 per patient. Savings of $2,742 were estimated per patient for all complications--particularly, nephropathy ($1,166) and macrovascular disease ($632)--when nateglinide was added. The cost-effectiveness ratio of adding nateglinide to metformin was estimated at $27,131 per undiscounted life-year gained (95% CI, $23,710-$28,577) or $43,024 (95% CI, $37,285-$45,193) per additional discounted life-year gained. In the sensitivity analyses, decreasing HbA1c level at baseline, HbA1c upward drift, and duration of disease improved survival. CONCLUSIONS: Combination therapy with nateglinide and metformin, compared with metformin alone, was predicted to reduce the frequency of complications and, thus, treatment costs in this theoretical model. The major factor in cost savings was fewer complications due to nephropathy. The increased drug treatment costs were expected to be offset by the long-term savings from reducing complication rates.