Modelling the economic impact of recombinant activated Factor VII compared to activated prothrombin-complex concentrate in the home treatment of a mild to moderate bleed in adults with inhibitors to clotting Factors VIII and IX in the UK

Summary

This study estimated the costs and consequences of using recombinant activated Factor VII (rFVIIa; NovoSeven®) at home, compared to activated prothrombin-complex concentrate (aPCC; FEIBA®*) at home, to manage a minor (i.e. mild to moderate) bleeding episode in adults with high titre, high responding inhibitors (>10 BU). The analysis was performed from the perspective of the UK's National Health Service (NHS).

NovoSeven and FEIBA are registered trademarks of Novo Nordisk and Baxter Healthcare, respectively.

Clinical outcomes and resource utilisation attributable to managing a minor bleed were obtained from published literature, supplemented with information about treatment patterns and associated resource utilisation derived from interviews with a panel of 22 consultant haematologists experienced in managing inhibitor patients. Using these data sources a decision tree modelling the management of a minor bleed, initially at home, was constructed. Unit resource costs at 1999/2000 prices were applied to the resource utilisation estimates in the model to estimate the expected NHS cost of managing a minor bleeding episode. Consensus on the probabilities and resource utilisation estimates in the model were reached at a meeting comprising seven panel members.

The expected NHS cost of managing a minor bleeding episode initially treated with rFVIIa or aPCC at home was estimated to be £12,944 and £14,645, respectively. Additionally, the expected time to resolving a minor bleeding episode when initially treated with rFVIIa or aPCC at home was estimated to be 32 hours and 60 hours, respectively. Hence, rFVIIa improves clinical outcome compared to aPCC, but at no additional cost to the NHS, resulting in rFVIIa being the cost-effective treatment. This finding warrants further investigation in a prospective, comparative, randomised, controlled study.     

Systematic literature review of economics analysis on treatment of mild-to-moderate bleeds with aPCC versus rFVIIa

Abstract

Objective:

Two bypassing agents, activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa), have shown similar efficacy and safety in the treatment of bleeding episodes in patients with hemophilia and inhibitors as demonstrated through the only two head-to-head clinical trials. Given the economic burden of bypassing treatment, it is crucial to have a valid estimate of cost effectiveness of alternative treatments. The aims of this study were to conduct a systematic review of published pharmacoeconomic literature on the cost-effectiveness of aPCC versus rFVIIa to treat mild-to-moderate bleeds in patients with hemophilia and inhibitors, with a focus on the model assumptions and their impact on results.

Methods:

An English language search was conducted for original economic studies comparing aPCC and rFVIIa published between 1995 and July 2010. Detailed information on sponsorship, study design, assumptions and their impact on results was collected for each study.

Results:

A total of 11 economic studies were included in the review. Nine studies assessed cost per bleeding episode (eight cost-minimization analysis (CMA) and one cost-effectiveness analysis (CEA)). Two studies were from longitudinal perspective. Studies on cost per bleeding episode were evaluated and systematically compared. All studies were from a third-party payer perspective. Most analyses, except one study, used a similar decision-tree model. The assumptions for all CMA studies were obtained from non-comparable single-armed trials or observational data. All studies were sponsored by the two competing manufacturers of rFVIIa (seven studies) and aPCC (two studies). The crucial parameter assumptions on treatment efficacy and dosing drove their reported findings. Eight of these nine studies favored their sponsor’s product.

Conclusion:

With one exception, published economic studies tend to favor their sponsor’s product primarily by assuming a higher efficacy and lower dosing for the sponsored agent, even though the two existing head-to-head clinical studies do not support superior efficacy for either product.     

Patterns of care and burden of chronic idiopathic thrombocytopenic purpura in Brazil

Aims: Although several therapeutic options are available for chronic immune thrombocytopenic purpura (cITP), little is known about the treatment of cITP in Brazil.

Materials and methods: A multi-center, retrospective chart review, observational study was designed to describe the treatment patterns, clinical burden, resources use, and associated costs for adult patients diagnosed with cITP and treated in public and private institutions in Brazil. Patient charts were screened in reverse chronological order based on their last visit post January 1, 2012. (All costs were calculated using 1.00 USD?=?3.9571 BRL, from February 2016.)

Results: Of 340 patient charts screened, 50 patients were eligible for inclusion in the study. Single-drug therapy (prednisone, dexamethasone, or dapsone) was the most commonly used treatment, followed by combination therapies (azathioprine?+?prednisone, azathioprine?+?prednisone?+?danazol, and prednisone?+?dapsone). Splenectomy was performed in 22% of patients after at least first-line treatment. Platelet count and number of bleeding episodes at diagnosis were 31,561.1/mm³ (SD?=?±26,396.1) and 40 episodes, respectively; in first-line, 92,631.1/mm³ (SD?=?±79,955.3) and 19 episodes, respectively; in second-line, 96,950.0/mm³ (SD?=?±76,476.4) and 17 episodes, respectively. Private system patients had a higher median cost compared to public system patients (USD 17.49/month, range?=?0–2,020.77 vs USD 9.51/month, range?=?0–192.64, respectively).

Limitations: This study does not allow conclusions for causal explanations due to the cohort study design, and treatment patterns represent only the practices of physicians who have agreed to participate in the study.

Conclusions: The data indicate that available therapeutic strategies for second- and third-line therapies appear to be limited.     

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Abstract

Aims: This study aimed to evaluate all-cause economic outcomes, healthcare resource utilization (HRU), and costs in patients with Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) using commercial claims from a large database representing various healthcare settings.

Materials and methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus database was conducted for patients aged 18–64 years with CDI episodes requiring inpatient stay with CDI diagnosis code or an outpatient medical claim for CDI plus a CDI treatment. Index CDI episodes occurred between 1 January 2010 and 30 June 2017, including only those where patients were observable 6 months before and 12 months after the index episode. Each CDI episode was followed by a 14-d claim-free period. rCDI was defined as another CDI episode within an 8-week window following the claim-free period. HRU, all-cause direct medical costs and time to rCDI were calculated over 12 months and stratified by number of rCDI episodes.

Results: A total of 46,571 patients with index CDI were included. Mean time from one CDI episode to the next was approximately 1 month. In the 12-month follow-up period, those with no recurrence had 1.4 inpatient visits per person and those with 3 or more recurrences had 5.8. Most patients with 3 or more recurrences had 2 or more hospital admissions. The mean annual, total all-cause direct medical costs per patient were $71,980 for those with no recurrence and $207,733 for those with 3 or more recurrences.

Limitations: The study included individuals 18–64 years only. A stringent definition of rCDI was used, which may have underestimated the incidence of rCDI.

Conclusions: CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. Timing of recurrences can be predictable, providing a window of opportunity for interventions. Prevention of multiple rCDI appears essential to reduce healthcare costs.     

Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely ill medical patients

SUMMARY

The objective of this study was to assess the cost-effectiveness of prophylaxis for venous thromboembolism (VTE) in acutely ill medical patients using 40 mg enoxaparin od compared with unfractionated heparin (UFH) and placebo. An established decision tree model based on epidemiological data, clinical trials, and a recent meta-analysis was used to evaluate costs and consequences of alternative means of thromboprophylaxis in medical patients. Primary outcome measures were episodes of VTE (deep vein thrombosis or pulmonary embolism) and major bleeding. Secondary effectiveness measures included estimated mortality. In-hospital drug costs and administration time, in conjunction with long-term VTE complications up to 15 years and major bleeding, were considered. Results were estimated for a hypothetical cohort of 100 patients. The expected cost per 100 patients was £9,992 with enoxaparin 40 mg od, £9,972 with UFH 5000 IU bd and £8,781 with no prophylaxis. The expected number of episodes of VTE per 100 patients was 1.2 with enoxaparin 40 mg od, 1.4 with UFH 5000 IU bd and 3.2 with no prophylaxis. The expected number of episodes of major bleeding per 100 patients was 1.7 with enoxaparin 40 mg od, 3.5 with UFH 5000 IU bd and 1.1 with no prophylaxis. The cost-effectiveness ratios for enoxaparin compared to no prophylaxis were £796 per VTE event avoided (taking into account the small increase in bleeding). In acutely ill medical patients, enoxaparin 40 mg od was found to be cost-effective compared with no thromboprophylaxis. Compared to UFH prophylaxis, enoxaparin was found to be cost neutral.     

Treatment experience,burden and unmet needs (TRIBUNE) in MS study: results from Turkey

Abstract

Objective:

To estimate the economic burden of multiple sclerosis (MS) in Turkey, including the relapses and disease severity, and to evaluate the quality-of-life of MS patients.

Methods:

The Treatment Experience, Burden and Unmet Needs (TRIBUNE) study was a multi-national, cross-sectional, retrospective, burden-of-illness survey. Total costs were calculated using unit costs derived from price lists or published literature, where relevant, and inflated to 2011 TL prices.

Results:

A total of 295 MS patients (74% females) were included in the analysis. The population had a mean age of 36 years; 73% had the relapsing–remitting form. Mean Expanded Disability Status Scale (EDSS) score was 2.2. Twenty-two per cent of the MS patients required hospitalization in the past year and spent an average of 29.2 days/year in hospital. These values were 43% and 5.6 days for the outpatients, respectively. Total cost per patient/year was 18,700 TL (Turkish Lira). Total costs for patients with mild, moderate, and severe disability were 15,418 TL, 26,002 TL, and 44,208 TL per patient/year, respectively. The mean EuroQol 5D scores in the same groups were 0.73, 0.52, and 0.05, respectively.

Conclusions:

Multiple sclerosis imposes a significant economic burden on patients and society in Turkey.     

Economic implications of the Total Ischaemic Burden Bisoprolol Study (TIBBS) follow-up

Abstract

Data from the TIBBS follow-up and published costs were combined in an economic analysis of stable angina patients, classified into subgroups defined by number of episodes of transient ischaemia detected on 48-hour ECG (<2, 2 to 6, >6 episodes); response to therapy (100% or non-100% responders); and initial therapy received in the randomised period of TIBBS (bisoprolol or nifedipine). The mean costs per patient over 12 months were: £766, £1481, and £1914 for <2, 2 to 6, and >6 episodes respectively; £1082 and £1938 for 100% responders and non-100% responders respectively; £1372 and £2030 for patients receiving bisoprolol or nifedipine respectively. Higher frequency of ischaemic episodes on ambulant ECG predict increased costs over the following 12 months. Failure to respond to therapy for transient ischaemia may identify patients that have increased costs. Treatment of transient ischaemia with bisoprolol in stable angina patients results in reduced long-term cardiovascular events and decreased total costs in comparison to treatment with nifedipine.     

Cost-effectiveness of quetiapine with lithium or divalproex for maintenance treatment of bipolar I disorder

Abstract

Background: Bipolar I disorder is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. Few studies have investigated the cost-effectiveness of maintenance treatment options. The objective of this analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for maintenance treatment of bipolar disorder.

Methods: The cost-effectiveness of maintenance treatment with QTP in combination with Li or DVP was compared with placebo (PBO) in combination with Li or DVP from a US direct costs perspective using a Markov model. The model simulated a cohort of 1,000 stabilized patients with bipolar I disorder and estimated the quarterly risk in three health states: euthymia, mania, and depression. Efficacy data were derived from two randomized, double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP for up to 2 years. Resource data were obtained from published literature. Direct costs included drug costs, hospitalizations, and physician visits. Outcomes and costs were discounted at 3% and the price reference year was 2007. Endpoints included the number of acute mood episodes, hospitalizations due to an acute mood event, and costs per quality-adjusted life-years. A probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty.

Results: In the base-case analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be robust. In addition, treatment with QTP + Li/DVP was associated with reductions in acute manic episodes (46%), acute depressive episodes (41%), and related hospitalizations (44%) compared with PBO + Li/DVP.

Conclusions: These analyses, based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost-effective maintenance treatment option for patients with bipolar I disorder compared with Li or DVP alone.     

Differences in episode-based care costs for multidetector computed tomographic coronary angiography versus myocardial perfusion imaging for the diagnosis of coronary artery disease

Abstract

Background: Multidetector computed tomography (MDCT) is a novel method for diagnosis and prognosis of coronary artery disease (CAD). The opportunity costs that favour MDCT over other CAD diagnostic methods is currently unknown.

Methods: This study used an episodes of care cost model based on epidemiologic and economic data evaluating individuals without known CAD undergoing MDCT or myocardial perfusion scintigraphy (MPS). It was a multicenter retrospective database review of medical and pharmacy-related claims linked by episodes of care from 2002 to 2005. CAD-related episodes of care costs were examined 1-year downstream for patients after initial MDCT that were matched to patients who underwent MPS.

Results: After adjustment for patient factors, 1-year total CAD-related episodes of care costs for MDCT were 16.4% lower than MPS, by an average of $682 (95% confidence interval $14, $1,350) per patient. While costs per CAD-related episode were similar between MDCT and MPS groups ($4,284 vs. $4,277, p=0.08).

Conclusions: Patients without known CAD who undergo MDCT as an initial diagnostic test, compared to MPS, incurred fewer CAD-related episodes of care and lower overall CAD-related costs.     

Cost of illness associated with Niemann-Pick disease type C in the UK

Abstract

Objective: Niemann-Pick disease type C (NP-C) is a rare and devastating genetic disorder characterised by a range of progressive neurological symptoms, which imposes a burden on patients, family members, the healthcare system and society overall. The objective of this study was to assess direct and indirect costs associated with NP-C in the UK.

Methods: This was a non-interventional, retrospective, cross-sectional cohort study based on responses from patients and/or their carers/guardians recruited from a UK NP-C database. Resource use and direct medical, direct non-medical and indirect costs were evaluated using data collected via postal survey in October 2007, which included a Medical Resource Use questionnaire. Total annual costs per patient were estimated.

Results: In total, 18 Medical Resource Use questionnaires (29% response rate) were received and analysed. The mean total annual cost (SD) of NP-C per patient was £39,168 (£50,315); 46% were direct medical costs, to which home visits and residential care contributed 68% and 15%, respectively. Direct non-medical costs accounted for 24% of the average annual cost per patient, mainly due to specialist education, and indirect costs 30%. If only direct medical costs were considered, the mean annual cost (SD) per patient was reduced to £18,012 (£46,536).

Conclusions: The direct annual per-patient cost of NP-C illness in 2007 appears moderate when compared with other rare and severely disabling diseases. However, cost estimates may be conservative, since findings are limited by a small sample size, low survey response rate and potential recall bias. As demonstrated by this study, a substantial proportion of the cost is shifted from the healthcare system to the patient, family and non-medical providers. These findings highlight the need for treatments that can slow or stop disease progression in NP-C.     

Impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review

Abstract

Objectives:

Gastrointestinal (GI) blood loss is a common medical condition which can have serious morbidity and mortality consequences and may pose an enormous burden on healthcare utilization. The purpose of this study was to conduct a systematic review to evaluate the impact of upper and lower GI blood loss on healthcare utilization and costs.

Methods:

We performed a systematic search of peer-reviewed English articles from MEDLINE published between 1990 and 2010. Articles were limited to studies with patients ≥18 years of age, non-pregnant women, and individuals without anemia of chronic disease, renal disease, cancer, congestive heart failure, HIV, iron-deficiency anemia or blood loss due to trauma or surgery. Two reviewers independently assessed abstract and article relevance.

Results:

Eight retrospective articles were included which used medical records or claims data. Studies analyzed resource utilization related to medical care although none of the studies assessed indirect resource use or costs. All but one study limited assessment of healthcare utilization to hospital use. The mean cost/hospital admission for upper GI blood loss was reported to be in the range $3180–8990 in the US, $2500–3000 in Canada and, in the Netherlands, the mean hospital cost/per blood loss event was €11,900 for a bleeding ulcer and €26,000 for a bleeding and perforated ulcer. Mean cost/ hospital admission for lower GI blood loss was $4800 in Canada, and $40,456 for small bowel bleeding in the US.

Conclusions:

Our findings suggest that the impact of GI blood loss on healthcare costs is substantial but studies are limited. Additional investigations are needed which examine both direct and indirect costs as well as healthcare costs by source of GI blood loss focusing on specific populations in order to target treatment pathways for patients with GI blood loss.     

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States

Aims: Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US.

Methods: Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009–2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; p-values were estimated with bootstrap.

Results: A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age?=?59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS; $1,136), and cardiovascular ($1,036; all p?Limitations: Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment.

Conclusions: The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.     

Healthcare costs associated with skeletal-related events in breast cancer patients with bone metastases

Background:

Patients with bone metastases secondary to breast cancer are pre-disposed to skeletal-related events (SREs), including spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiotherapy to bone (RT).

Objective:

To document current patterns of healthcare utilization and costs of SREs in patients with breast cancer and bone metastases.

Methods:

This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for breast cancer and for bone metastases, and ≥1 claims for an SRE. Unique SRE episodes were identified based on a gap of at least 90 days without an SRE claim, and classified by treatment setting (inpatient or outpatient) and SRE type (SCC, PF, SB, or RT).

Results:

Of 17,266 patients with breast cancer and bone metastases, 9142 (53%) had one or more SRE episodes. Among 5809 patients who met all other criteria, there were 7617 SRE episodes over mean (SD) follow-up of 17.2 (15.2) months. The percentage of episodes that required inpatient treatment ranged from 11% (RT) to 76% (SB). On average, inpatient SCC episodes (n?=?83 episodes) were most costly; while outpatient PF episodes (n?=?552 episodes) were least costly. Of the total SRE costs (mean [SE] $21,072 [$36,462]/episode), 36% were attributable to outpatient RT (n?=?5265 episodes) and 31% to inpatient PF (n?=?838 episodes).

Limitations:

The administrative claims data used in this study may lack sensitivity and specificity for identification of clinical events and may not be generalizable to other populations. Also, for some SRE episode categories, the number of events was small and cost estimates may lack precision.

Conclusion:

In patients with breast cancer and bone metastases, SREs are associated with high costs and hospitalizations.     

Predictors for total hospital and cardiology cost claims among patients with atrial fibrillation initiating dabigatran or acenocoumarol in The Netherlands

Aims: The prevalence of atrial fibrillation (AF) has increased over the past years due to aging of the population, and healthcare costs associated with AF reflect a significant financial burden. The aim of this study was to explore predictors for the real-world AF-related in-hospital costs in patients that recently initiated anticoagulation with acenocoumarol or dabigatran.

Methods: Predictors for claimed total hospital care costs and cardiology costs in AF patients were explored by using hospital financial claims data from propensity score matched patient groups in a large Dutch community hospital. This study analyzed the total dataset (n?=?766) and carried out a secondary analysis for all matched pairs of anticoagulation naïve AF patients (n?=?590) by ordinal regression.

Results: Dabigatran was a predictor for significantly lower cardiology and total hospital care costs (Odds Ratio [OR]?=?0.43, 95% confidence interval (CI)?=?0.33–0.57; and OR?=?0.60, 95% CI?=?0.46–0.79, respectively). Female gender was a predictor for lower total hospital care costs. Predictors for an increase in total hospital care costs were the occurrence of stroke or systemic embolism, major bleeding, and minor bleeding. The costs predictors were comparable when limiting the analysis to patients that were anticoagulation naïve. Age and CHA₂DS₂-VASc were not predictors for either cardiology or total hospital care costs in both analyses.

Conclusion: Dabigatran treatment was as a predictor for lower cardiology costs and lower total hospital care costs in AF patients that initiated oral anticoagulation.