Comparative net cost impact of the utilization of panitumumab versus cetuximab for the treatment of patients with metastatic colorectal cancer in Canada

Objective:

Clinical practice guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens, based on significant clinical benefits in patients with wild-type KRAS. The purpose of the analysis was to compare provincial hospital costs when using panitumumab vs cetuximab with or without irinotecan in this patient population using a Net Impact Analysis (NIA) approach.

Methods:

The NIA determined the total per patient cost of the reimbursed regimens of panitumumab vs cetuximab in British Columbia, Alberta, Manitoba, Ontario, and Québec. Utilization of healthcare resources related to EGFR inhibitor infusions, follow-up monitoring, and treatment of adverse events (AEs) were also included. Healthcare resource use including drugs, medical supplies, laboratory testing, oncology infusion time, and healthcare professionals’ time was obtained through expert consultation and the use was then multiplied by the province-specific cost of each resource. Numerous sensitivity analyses were conducted.

Results:

Based on the dosing regimens in place in each province, the total annual per patient cost of panitumumab ranged from $22,203–$32,600, while the total annual per patient cost of cetuximab treatment varied from $30,321–$40,908. Treatment with panitumumab resulted in lower costs in all cost categories including drug acquisition, infusion preparation/administration, patient monitoring, and AE management. Per patient savings with panitumumab ranged from a low of $3815 in British Columbia to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained cost saving in all scenarios where the savings ranged from $150–$16,006 per patient.

Conclusions:

Treating chemorefractory mCRC patients with panitumumab rather than cetuximab reduced healthcare resource costs. Provincial healthcare savings achieved with the use of panitumumab could potentially be re-allocated to other cancer treatments, although further study would be needed to validate this assumption.     

Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population

Summary

Objective: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective.

Study design: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose).

Results: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1–$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.     

Projecting total costs and health consequences of increasing mt-sDNA utilization for colorectal cancer screening from the payer and integrated delivery network perspectives

Abstract

Aims: To evaluate total costs and health consequences of a colorectal cancer (CRC) screening program with colonoscopy, fecal immunochemical tests (FIT), and expanded use of multitarget stool DNA (mt-sDNA) from the perspectives of Integrated Delivery Networks (IDNs) and payers in the United States.

Materials and methods: We developed a budget impact and cost-consequence model that simulates CRC screening for eligible 50- to 75-year-old adults. A status quo scenario and an increased mt-sDNA scenario were modeled. The status quo includes the current screening mix of colonoscopy (83%), FIT (11%), and mt-sDNA (6%) modalities. The increased mt-sDNA scenario increases mt-sDNA utilization to 28% over 10 years. Costs for both the IDN and the payer perspectives incorporated diagnostic and surveillance colonoscopies, adverse events (AEs), and CRC treatment. The IDN perspective included screening program costs, composed of direct nonmedical (e.g. patient navigation) and indirect (e.g. administration) costs. It was assumed that IDNs do not incur the costs for stool-based screening tests or bowel preparation for colonoscopies.

Results: In a population of one million covered lives, the 10-year incremental cost savings incurred by increasing mt-sDNA utilization was $16.2 M for the IDN and $3.3 M for the payer. The incremental savings per-person-per-month were $0.14 and $0.03 for the IDN and payer, respectively. For both perspectives, increased diagnostic colonoscopy costs were offset by reductions in screening colonoscopies, surveillance colonoscopies, and AEs. Extending screening eligibility to 45- to 75-year-olds slightly decreased the overall cost savings.

Limitations: The natural history of CRC was not simulated; however, many of the utilized parameters were extracted from highly vetted natural history models or published literature. Direct nonmedical and indirect costs for CRC screening programs are applied on a per-person-per modality basis, whereas in reality some of these costs may be fixed.

Conclusions: Increased mt-sDNA utilization leads to fewer colonoscopies, less AEs, and lower overall costs for both IDNs and payers, reducing overall screening program costs and increasing the number of cancers detected while maintaining screening adherence rates over 10 years.     

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States

Background: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF.

Objective: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII.

Methods: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes.

Results: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient.

Conclusions: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.     

Heart rate variability testing: could it change spending for rheumatoid arthritis patients in the United States? An exploratory economic analysis

Background: Autonomic nervous system (ANS) testing with heart rate variability (HRV) has been shown in early research to predict 52-week outcomes in rheumatoid arthritis (RA). HRV testing could be combined with putative ANS biologic pathways to improve treatment response for RA patients. This study explored potential costs and health outcomes of introducing HRV testing into RA treatment, without and with ANS optimization.

Methods: A decision tree exploratory economic model compared HRV testing to standard care in moderate-to-severe biologic-eligible patients over a 10-year time horizon. HRV data was derived from an observational study of RA patients (n?=?33). Patients were stratified into treatment groups based on HRV test scores indicating “low probability of response” and “moderate to high probability of response”. This study explored adding ANS optimization based on HRV score followed by clinically-appropriate treatment. Costs and quality-adjusted life-years (QALYs) for the US population were estimated.

Results: HRV testing in biologic-eligible patients decreased non-effective biologic use, reducing US healthcare costs by $34.6 billion over 10 years with QALYs unchanged. When combined with ANS optimization in biologic-eligible patients, HRV testing could increase costs by $3.6 billion over 10 years but save over 350,000 QALYs. Among all RA patients, HRV testing with ANS optimization could save over $8 billion and over 100,000 QALYs over 10 years, depending on the positive predictive value (PPV) of the HRV test.

Conclusions: The potential economic impact of introducing HRV testing and ANS optimization into RA treatment appears substantial and cost-effective based on the exploratory analysis. Additional rigorous studies are warranted in larger patient samples to better inform decision-making.     

Economic evaluation of a pharmacogenomic multi-gene panel test to optimize anti-hypertension therapy: simulation study

Abstract

Aims: Hypertension is the strongest modifiable risk factor for cardiovascular disease, affecting 80 million individuals in the US and responsible for ～360,000 deaths, at total annual costs of $93.5 billion. Antihypertension therapies guided by single genotypes are clinically more effective and may avert more adverse events than the standard of care of layering anti-hypertensive drug therapies, thus potentially decreasing costs. This study aimed to determine the economic benefits of the implementation of multi-gene panel guided therapies for hypertension from the payer perspective within a 3-year time horizon.

Materials and methods: A simulation analysis was conducted for a panel of 10 million insured patients categorized clinically as untreated, treated but uncontrolled, and treated and controlled over a 3-year treatment period. Inputs included research data; empirical data from a 11-gene panel with known functional, heart, blood vessel, and kidney genotypes; and therapy efficacy and safety estimates from literature. Cost estimates were categorized as related to genetic testing, evaluation and management, medication, or adverse events.

Results: Multi-gene panel guided therapy yielding savings of $6,256,607,500 for evaluation and management, $908,160,000 for medications, and $37,467,508,716 for adverse events, after accounting for incremental genetic testing costs of $2,355,540,000. This represents total 3-year savings of $42,276,736,216, or a 47% reduction, and 3-year savings of $4,228 and annual savings of $1,409 per covered patient.

Conclusions: A precision medicine approach to genetically guided therapy for hypertension patients using a multi-gene panel reduced total 3-year costs by 47%, yielding savings exceeding $42.3 billion in an insured panel of 10 million patients. Importantly, 89% of these savings are generated by averting specific adverse events and, thus, optimizing choice of therapy in function of both safety and efficacy.     

Hospital economic impact from hemostatic matrix usage in cardiac surgery

Objective:

Improved health outcomes can result in economic savings for hospitals and payers. While effectiveness of topical hemostatic agents in cardiac surgery has been demonstrated, evaluations of their economic benefit are limited. This study quantifies the cost consequences to hospitals, based on clinical outcomes, from using a flowable hemostatic matrix vs non-flowable topical hemostatic agents in cardiac surgery.

Research design and methods:

Applying clinical outcomes from a prospective randomized clinical trial, a cost consequence framework was utilized to model the economic impact of comparator groups. From that study, clinical outcomes were obtained and analyzed for a flowable hemostatic matrix (FLOSEAL, Baxter Healthcare Corporation) vs non-flowable topical hemostats (SURGICEL Nu-Knit, Ethicon–Johnson &; Johnson; GELFOAM, Pfizer). Costing analyses focused on the following outcomes: complications, blood transfusions, surgical revisions, and operating room (OR) time. Cardiac surgery costs were analyzed and expressed in 2012 US dollars based on available literature searches and US data. Comparator group variability in cost consequences (i.e., cost savings) was calculated based on annualized impact and scenario testing.

Results:

Results suggest that if a flowable hemostatic matrix (rather than a non-flowable hemostat) was utilized exclusively in 600 mixed cardiac surgeries annually, a hospital could improve patient outcomes by a reduction of 33 major complications, 76 minor complications, 54 surgical revisions, 194 transfusions, and 242?h of OR time. These outcomes correspond to a net annualized cost consequence savings of $5.38 million, with complication avoidance as the largest contributor.

Conclusions:

This cost consequence framework and supportive modeling was used to evaluate the hospital economic impact of outcomes resulting from the usage of various hemostatic agents. These analyses support that cost savings can be achieved from routine use of a flowable hemostatic matrix, rather than a non-flowable topical hemostat, in cardiac surgery.     

The economic burden of brain metastasis among lung cancer patients in the United States

Objective:

Brain metastases among lung cancer patients can impair cognitive and functional ability, complicate care, and reduce survival. This study focuses on the economic burden of brain metastasis in lung cancer—direct healthcare costs to payers and indirect costs to patients, payers, and employers—in the US.

Methods:

Retrospective study using claims data from over 60 self-insured Fortune 500 companies across all US census regions (January 1999–March 2013). Adult, non-elderly lung cancer patients with brain metastasis were evaluated over two study periods: (1) pre-diagnosis (≤30 days prior to first observed lung cancer diagnosis to ≤30 days prior to first-observed brain metastasis diagnosis) and (2) post-diagnosis (≤30 days prior to first observed brain metastasis diagnosis to end of continuous eligibility or observation).

Outcome measures:

Healthcare costs to payers and resource utilization, salary loss to patients, disability payouts for payers, and productivity loss to employers.

Results:

A total of 132 patients were followed for a median of 8.4 and 6.6 months in the pre- and post-diagnosis periods, respectively. At diagnosis of brain metastasis, 21.2% of patients were on leave of absence and 6.1% on long-term disability leave. Substantial differences were observed in the pre- vs post-diagnosis periods. Specifically, patients incurred much greater healthcare utilization in the post-diagnosis period, resulting in $25,579 higher medical costs per-patient-per-6-months (PPP6M). During this period, patients missed significantly more work days, generating an incremental burden of $2853 PPP6M in salary loss for patients, $2557 PPP6M in disability payments for payers, and $4570 PPP6M in productivity loss for employers.

Limitations:

Type of primary lung cancer and extent of brain metastasis could not be assessed in the data. The analysis was also limited to patients with comprehensive disability coverage.

Conclusions:

Development of brain metastasis among lung cancer patients is associated with a substantial economic burden to payers, patients, and employers.     

Cost-impact of cardiac magnetic resonance imaging with Fast-SENC compared to SPECT in the diagnosis of coronary artery disease in the U.S

Aims: The purpose of this study is to assess the economic cost differences and the associated treatment resource changes between the developing coronary artery disease (CAD) diagnostic tool fast strain-encoded cardiac imaging (Fast-SENC) and the current commonly used stress test single-photon emission computed tomography (SPECT).

Materials and methods: A “payer perspective” model was created first, consisting of long-term and short-term components that used a hypothetical cohort of patients of average age (60.8?years) presenting with chest pain and suspected CAD to assess cost-impact. A cost impact model was then built that assessed likely savings from a “hospital perspective” from substituting Fast-SENC for a portion of SPECTs assuming an average number of annual SPECT tests performed in US hospitals.

Results: In the payer model, using Fast-SENC followed by coronary angiography (CA) and percutaneous coronary intervention (PCI) treatment when necessary is less costly than the SPECT method when considering both direct and indirect costs of testing. Expected costs of the Fast-SENC were between $2,510 and $2,632 per correct diagnosis, while expected costs for the SPECT were between $3,157 and $4,078. Fast-SENC reduced false positives by 50% and false negatives by 86%, generating additional cost savings. The hospital model showed total costs per CAD patient visit of $825 for SPECT and $376 for Fast-SENC.

Limitations: Limitations of this study are that clinical data are sourced from other published clinical trials on how CAD diagnostic strategies impact clinical outcome, and that necessary assumptions were made which impact health outcomes.

Conclusion: The lower cost, higher sensitivity and specificity rates, and faster, less burdensome process for detecting CAD patients make Fast-SENC a more capable and economically beneficial stress test than SPECT. The payer model and hospital model demonstrate an alignment between payer and provider economics as Fast-SENC provides monetary savings for patients and resource benefits for hospitals.     

A budget impact analysis for making treatment decisions based on anti-cyclic citrullinated peptide (anti-CCP) testing in rheumatoid arthritis

Abstract

Aim: Given that rheumatoid arthritis (RA) patients with high anti-citrullinated protein antibodies (ACPA) titer values respond well to abatacept, the aim of this study was to estimate the annual budget impact of anti-cyclic citrullinated peptide (anti-CCP) testing and treatment selection based on anti-CCP test results.

Materials and methods: Budget impact analysis was conducted for patients with moderate-to-severe RA on biologic or Janus kinase inhibitor (JAKi) treatment from a hypothetical US commercial payer perspective. The following market scenarios were compared: (1) 90% of target patients receive anti-CCP testing and the results of anti-CCP testing do not impact the treatment selection; (2) 100% of target patients receive anti-CCP testing and the results of anti-CCP testing have an impact on treatment selection such that an increased proportion of patients with high titer of ACPA receive abatacept. A hypothetical assumption was made that the use of abatacept would be increased by 2% in Scenario 2 versus 1. Scenario analyses were conducted by varying the target population and rebate rates.

Results: In a hypothetical health plan with one million insured adults, 2,181 patients would be on a biologic or JAKi treatment for moderate-to-severe RA. In Scenario 1, the anti-CCP test cost was $186,155 and annual treatment cost was $101,854,295, totaling to $102,040,450. In Scenario 2, the anti-CCP test cost increased by $20,684 and treatment cost increased by $160,467, totaling an overall budget increase of $181,151. This was equivalent to a per member per month (PMPM) increase of $0.015. The budget impact results were consistently negligible across the scenario analyses.

Limitations: The analysis only considered testing and medication costs. Some parameters used in the analysis, such as the rebate rates, are not generalizable and health plan-specific.

Conclusions: Testing RA patients to learn their ACPA status and increasing use of abatacept among high-titer ACPA patients result in a small increase in the total budget (<2 cents PMPM).     

Economic burden of sarcoidosis in a commercially-insured population in the United States

Background: Sarcoidosis is a multi-system inflammatory disorder characterized by the presence of non-caseating granulomas in involved organs. Patients with sarcoidosis have a reduced quality-of-life and are at an increased risk for several comorbidities. Little is known about the direct and indirect cost of sarcoidosis following the initial diagnosis.

Aims: To provide an estimate of the healthcare resource utilization (HCRU) and costs borne by commercial payers for sarcoidosis patients in the US.

Methods: Patients with a first diagnosis of sarcoidosis between January 1, 1998 and March 31, 2015 (“index date”) were selected from a de-identified privately-insured administrative claims database. Sarcoidosis patients were required to have continuous health plan enrollment 12 months prior to and following their index dates. Propensity-score (1:1) matching of sarcoidosis patients with non-sarcoidosis controls was carried out based on a logistic regression of baseline characteristics. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched groups over the 12-month period following the index date (“outcome period”).

Results: A total of 7,119 sarcoidosis patients who met the selection criteria were matched with a control. Overall, commercial payers incurred $19,714 in mean total annual healthcare costs per sarcoidosis patient. The principle cost drivers were outpatient visits ($9,050 2015 USD, 46%) and inpatient admissions ($6,398, 32%). Relative to controls, sarcoidosis patients had $5,190 (36%) higher total healthcare costs ($19,714 vs $14,524; p?p?p?Background: Sarcoidosis is a multi-system inflammatory disorder characterized by the presence of non-caseating granulomas in involved organs. Patients with sarcoidosis have a reduced quality-of-life and are at an increased risk for several comorbidities. Little is known about the direct and indirect cost of sarcoidosis following the initial diagnosis.

Aims: To provide an estimate of the healthcare resource utilization (HCRU) and costs borne by commercial payers for sarcoidosis patients in the US.

Methods: Patients with a first diagnosis of sarcoidosis between January 1, 1998 and March 31, 2015 (“index date”) were selected from a de-identified privately-insured administrative claims database. Sarcoidosis patients were required to have continuous health plan enrollment 12 months prior to and following their index dates. Propensity-score (1:1) matching of sarcoidosis patients with non-sarcoidosis controls was carried out based on a logistic regression of baseline characteristics. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched groups over the 12-month period following the index date (“outcome period”).

Results: A total of 7,119 sarcoidosis patients who met the selection criteria were matched with a control. Overall, commercial payers incurred $19,714 in mean total annual healthcare costs per sarcoidosis patient. The principle cost drivers were outpatient visits ($9,050 2015 USD, 46%) and inpatient admissions ($6,398, 32%). Relative to controls, sarcoidosis patients had $5,190 (36%) higher total healthcare costs ($19,714 vs $14,524; p?<?0.001). Sarcoidosis patients also had significantly more work loss days (15.9 vs 11.3; p?<?0.001) and work loss costs ($3,288 vs $2,527; p?<?0.001) than matched controls. Sarcoidosis imposes an estimated total direct medical cost of $1.3–$8.7 billion to commercial payers, and an indirect cost of $0.2–$1.5 billion to commercial payers in work loss.

Conclusions: Sarcoidosis imposes a significant economic burden to payers in the first year following diagnosis.     

Cost-consequence analysis of different active flowable hemostatic matrices in cardiac surgical procedures

Background: A recent retrospective comparative effectiveness study found that use of the FLOSEAL Hemostatic Matrix in cardiac surgery was associated with significantly lower risks of complications, blood transfusions, surgical revisions, and shorter length of surgery than use of SURGIFLO Hemostatic Matrix. These outcome improvements in cardiac surgery procedures may translate to economic savings for hospitals and payers.

Objective: The objective of this study was to estimate the cost-consequence of two flowable hemostatic matrices (FLOSEAL or SURGIFLO) in cardiac surgeries for US hospitals.

Methods: A cost-consequence model was constructed using clinical outcomes from a previously published retrospective comparative effectiveness study of FLOSEAL vs SURGIFLO in adult cardiac surgeries. The model accounted for the reported differences between these products in length of surgery, rates of major and minor complications, surgical revisions, and blood product transfusions. Costs were derived from Healthcare Cost and Utilization Project’s National Inpatient Sample (NIS) 2012 database and converted to 2015?US dollars. Savings were modeled for a hospital performing 245 cardiac surgeries annually, as identified as the average for hospitals in the NIS dataset. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to test model robustness.

Results: The results suggest that if FLOSEAL is utilized in a hospital that performs 245 mixed cardiac surgery procedures annually, 11 major complications, 31 minor complications, nine surgical revisions, 79 blood product transfusions, and 260.3?h of cumulative operating time could be avoided. These improved outcomes correspond to a net annualized saving of $1,532,896. Cost savings remained consistent between $1.3m and $1.8m and between $911k and $2.4m, even after accounting for the uncertainty around clinical and cost inputs, in a one-way and probabilistic sensitivity analysis, respectively.

Conclusions: Outcome differences associated with FLOSEAL vs SURGIFLO that were previously reported in a comparative effectiveness study may result in substantial cost savings for US hospitals.     

The economic burden of depression among adults with rheumatoid arthritis in the United States

Aims: Depression is the most frequent comorbidity reported among patients with rheumatoid arthritis (RA). Comorbid depression negatively impacts RA patients’ health-related quality-of-life, physical function, mental function, mortality, and experience of pain and symptom severity. The objective of this study was to assess healthcare utilization, expenditures, and work productivity among patients with RA with or without depression.

Materials and methods: Data from adult patients who had at least two visits each related to RA and depression over a 1-year period were extracted from the Truven Health MarketScan research databases. Outcomes comprised healthcare resource utilization, work productivity loss, and direct healthcare costs comparing patients with RA with depression (n?=?3,478) vs patients with RA without depression (n?=?43,222).

Results: Patients with RA and depression had a significantly greater relative risk of hospitalization and number of all-cause and RA-related hospitalizations, utilization of emergency services, days spent in the hospital, physician visits, and RA-related surgeries compared with RA patients without depression. Patients with RA and depression had a higher risk of and experienced more events and days of short-term disability compared with patients without depression. The incremental adjusted annual all-cause and RA-related direct costs were $8,488 (95% CI = $6,793–$10,223) and $578 (95% CI = –$98–$1,243), respectively, when comparing patients with RA and depression vs RA only.

Limitations: The current analysis is subject to the known limitations of retrospective studies based on administrative claims data.

Conclusions: This study suggested increased healthcare utilization, work productivity loss, and economic burden among RA patients due to comorbid depression. These findings emphasize the importance of managing depression and including depression as a factor when devising treatment algorithms for patients with RA.     

Cost-efficiency analyses for the US of biosimilar filgrastim-sndz,reference filgrastim,pegfilgrastim, and pegfilgrastim with on-body injector in the prophylaxis of chemotherapy-induced (febrile) neutropenia

Aims: Guidelines recommend prophylaxis with granulocyte colony-stimulating factor for chemotherapy-induced (febrile) neutropenia (CIN/FN) based on regimen myelotoxicity and patient-related risk factors. The aim was to conduct a cost-efficiency analysis for the US of the direct acquisition and administration costs of the recently approved biosimilar filgrastim-sndz (Zarxio EP2006) with reference to filgrastim (Neupogen), pegfilgrastim (Neulasta), and a pegfilgrastim injection device (Neulasta Onpro; hereafter pegfilgrastim-injector) for CIN/FN prophylaxis.

Methods: A cost-efficiency analysis of the prophylaxis of one patient during one chemotherapy cycle under 1–14 days’ time horizon was conducted using the unit dose average selling price (ASP) and Current Procedural Terminology (CPT) codes for subcutaneous prophylactic injection under four scenarios: cost of medication only (COSTMED), patient self-administration (SELFADMIN), healthcare provider (HCP) initiating administration followed by self-administration (HCPSTART), and HCP providing full administration (HCPALL). Two case studies were created to illustrate real-world clinical implications. The analyses were replicated using wholesale acquisition cost (WAC).

Results: Using ASP?+?CPT, cost savings achieved with filgrastim-sndz relative to reference filgrastim ranged from $65 (1?day) to $916 (14 days) across all scenarios. Relative to pegfilgrastim, savings with filgrastim-sndz ranged from $834 (14 days) up to $3,666 (1?day) under the COSTMED, SELFADMIN, and HPOSTART scenarios; and from $284 (14 days) up to $3,666 (1?day) under the HPOALL scenario. Similar to the cost-savings compared to pegfilgrastim, filgrastim-sndz achieved savings relative to pegfilgrastim-injector: from $834 (14 days) to $3,666 (1?day) under the COSTMED scenario, from $859 (14 days) to $3,692 (1?day) under SELFADMIN, from $817 (14 days) to $3,649 (1?day) under HPOSTART, and from $267 (14 days) to $3,649 (1?day) under HPOALL. Cost savings of filgrastim-sndz using WAC?+?CPT were even greater under all scenarios.

Conclusions: Prophylaxis with filgrastim-sndz, a biosimilar filgrastim, was associated consistently with significant cost-savings over prophylaxis with reference filgrastim, pegfilgrastim, and pegfilgrastim-injector, and this across various administration scenarios.     

Economic modeling for the US of the cost-efficiency and associated expanded treatment access of conversion to biosimilar pegfilgrastim-bmez from reference pegfilgrastim

Abstract

Aims: For this economic analysis, we aimed to model: (1) the cost-efficiency of prophylaxis with biosimilar pegfilgrastim-bmez for chemotherapy-induced (febrile) neutropenia (CIN/FN) compared to reference pegfilgrastim, and (2) the expanded access to CIN/FN prophylaxis and anti-neoplastic treatment that could be achieved with biosimilar cost-savings on a budget-neutral basis.

Methods: In a hypothetical panel of 20,000 cancer patients receiving CIN/FN prophylaxis and using the average sales price (ASP) for the second quarter of 2019 for reference pegfilgrastim, we: conducted an ex ante simulation from the payer perspective of the cost-savings of 10–100% conversion from reference to biosimilar pegfilgrastim-bmez using drug price discounting ranging from 10–35%; estimated the budget-neutral expanded access to biosimilar pegfilgrastim-bmez enabled by these cost-savings; and estimated the budget-neutral expanded access to anti-neoplastic treatment with pembrolizumab. The simulations were replicated using fourth quarter 2019 wholesale acquisition cost (WAC) for reference pegfilgrastim and biosimilar pegfilgrastim-bmez in a post facto analysis.

Results: In ASP simulations, cost-savings of using pegfilgrastim-bmez over reference pegfilgrastim in a 20,000 patient panel range from $1.3?M (at 15% price discount) to $3?M (35%) at 10% conversion rate and from $6.4?M to $14.9?M, respectively, at 50% conversion. These savings could provide prophylaxis with pegfilgrastim-bmez to an additional 352 (15% discount) to 1,076 patients (35%) at 10% conversion or 1,764–5,384, respectively, at 50% conversion. Alternatively, savings could be reallocated for anti-neoplastic treatment with pembrolizumab to 3 (15% discount) to 9 (35%) patients at 10% conversion or 19–45, respectively, at 50% conversion. When utilizing WAC, cost-savings range from $4.6?M (10% conversion) to $23.1?M (50%) which could provide pegfilgrastim-bmez to an additional 1,174 (10% conversion) to 5,873 patients (50%).

Conclusions: Prophylaxis with biosimilar pegfilgrastim-bmez increases the value of cancer care by generating significant cost-savings that could be reallocated to provide expanded access to CIN/FN prevention and anti-neoplastic therapy on a budget-neutral basis.     

Annual patient and caregiver burden of oncology clinic visits for granulocyte-colony stimulating factor therapy in the US

Objective:

Prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs) is indicated for chemotherapy patients with a significant risk of febrile neutropenia. This study estimates the annual economic burden on patients and caregivers of clinic visits for prophylactic G-CSF injections in the US.

Methods:

Annual clinic visits for prophylactic G-CSF injections (all cancers) were estimated from national cancer incidence, chemotherapy treatment and G-CSF utilization data, and G-CSF sales and pricing information. Patient travel times, plus time spent in the clinic, were estimated from patient survey responses collected during a large prospective cohort study (the Prospective Study of the Relationship between Chemotherapy Dose Intensity and Mortality in Early-Stage (I–III) Breast Cancer Patients). Economic models were created to estimate travel costs, patient co-pays and the economic value of time spent by patients and caregivers in G-CSF clinic visits.

Results:

Estimated total clinic visits for prophylactic G-CSF injections in the US were 1.713 million for 2015. Mean (SD) travel time per visit was 62 (50) min; mean (SD) time in the clinic was 41 (68) min. Total annual time for travel to and from the clinic, plus time at the clinic, is estimated at 4.9 million hours, with patient and caregiver time valued at $91.8 million ($228 per patient). The estimated cumulative annual travel distance for G-CSF visits is 60.2 million miles, with a total transportation cost of $28.9 million ($72 per patient). Estimated patient co-pays were $61.1 million, ～$36 per visit, $152 per patient. The total yearly economic impact on patients and caregivers is $182 million, ～$450 per patient.

Limitations:

Data to support model parameters were limited. Study estimates are sensitive to the assumptions used.

Conclusions:

The burden of clinic visits for G-CSF therapy is a significant addition to the total economic burden borne by cancer patients and their families.     

Febuxostat in the management of gout: a cost-effectiveness analysis

Objective:

To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout.

Methods:

A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40–80?mg and allopurinol 100–300?mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided.

Results:

Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures.

Conclusions:

Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.     

Derivation of severity index for rheumatoid arthritis and its association with healthcare outcomes

Abstract

Objectives:

To develop a claims-based severity index for rheumatoid arthritis (RA) using the Veterans Health Administration (VHA) database.

Methods:

Adult patients with at least two RA diagnoses 2 months apart were identified between 10/1/2008–09/30/2009. Patients were required to have at least 12 months continuous health plan enrollment before and after the index date (first RA diagnosis date) for an overall study period of 10/1/2007–09/30/2010. A severity index for rheumatoid arthritis (SIFRA, a proprietary algorithm of SIMR, Inc. [STATinMED Research]) was developed by calculating a weighted sum of 34 RA-related indicators assessed by an expert Delphi panel of six rheumatologists, including laboratory, clinical, and functional status, extra-articular manifestations, surgical history, and medications, during a 1-year pre-index period. Separate SIFRA versions were derived for patients with and without laboratory information. Correlations between SIFRA and previously validated claims-based indexes for RA severity (CIRAS), and other traditional comorbidity indexes were calculated during the pre-index period. The relationship between SIFRA and follow-up healthcare outcomes was also examined using histograms.

Results:

The Spearman’s rank correlations between SIFRA and CIRAS were 0.525 for SIFRA without and 0.539 with laboratory data. The correlations between SIFRA and the Charlson Comorbidity Index (CCI) (0.1503 without, 0.1135 with laboratory data), Elixhauser Index (ELIX) (0.105 without, 0.079 with laboratory data), and Chronic Disease Score (CDS) (0.255 without, 0.239 with laboratory data) were low. Histograms showed that patients in the upper tercile of SIFRA incurred $9123 more all-cause and $1326 more RA-related healthcare costs during the 1-year post-index period than patients in the lower tercile. Using SIFRA in combination with CCI, CDS, or ELIX significantly increased the percentage of variation explained in outcomes measures.

Limitations:

Patients in the VHA database may not represent typical RA patients since the database generally contains older, economically disadvantaged men with a high disease burden. Validity of the score is indirectly based on disease activity score 28 (DAS28), which measures disease activity rather than severity.

Conclusions:

SIFRA was found to have moderate correlations with the previously validated CIRAS score, and demonstrated evidence of being a significant determinant of total and RA-related healthcare costs for RA patients. This study suggests that SIFRA could be an important methodological tool to control for severity in RA-related outcomes research. The algorithm can be applied to any claims dataset.     

Economic impact of using fesoterodine for the treatment of overactive bladder with urge urinary incontinence in a vulnerable elderly population in the United States

Objectives:

To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective.

Methods:

A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2–15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI).

Results:

When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization.

Conclusions:

From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.     

Cost-effectiveness of mechanical thrombectomy for acute ischemic stroke: an Australian payer perspective

Aims: The goal of this study was to assess the cost-effectiveness of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) from an Australian payer perspective.

Methods: This study used a Markov model that employed a life-time time horizon, modeling patients from symptom onset of stroke until end of life. Clinical efficacy and safety data were taken from an individual patient level data (IPD) meta-analysis of clinical studies. The treatment effect of MT compared to usual care was measured by changes in modified Rankin Score (mRS). Post-treatment mRS scores were used to determine short- and long-term stroke care costs. Treatment costs were modeled, with health state utility values determined by literature review. All analyses were conducted using Microsoft Excel.

Results: In comparison to usual care, MT is associated with higher costs ($10,666 per patient) and additional quality-adjusted life years (QALYs) (0.8281 per patient), resulting in an incremental cost per QALY of $12,880. Sensitivity analyses demonstrated the reliability of the base case results across a range of assumptions. The higher cost associated with MT is, to an extent, offset by the cost savings resulting from lower stroke care costs due to improved patient outcomes. The life-time cost savings in terms of stroke care costs are estimated to be more than $8,000 per patient for patients who had received MT in combination with usual care.

Limitations: Stroke care costs based on patient disability/functional level were not available and were derived. As a consequence, long-term care costs for patients with poorer outcomes may be under-estimated. Patient outcomes at 90 days were extrapolated to a lifetime horizon, but this approach was supported by long-term evidence on stroke survival.

Conclusions: Mechanical thrombectomy is a cost-effective treatment option for AIS, with clinical benefits translating to short- and long-term cost benefits. This analysis supports rapid update of stroke care pathways to incorporate this therapy as a treatment option.