Recent trends in brand-name and generic drug competition

Objective:

To provide evidence on recent trends in: (1) market exclusivity periods (MEPs, the time between launch of a brand-name drug and its first generic competitor) for new molecular entities (NMEs); (2) the likelihood and timing of patent challenges under Paragraph IV of the Hatch-Waxman Act; and (3) generic drug penetration.

Methods:

IMS Health National Sales Perspectives data were used to calculate MEPs for the 257 NMEs experiencing initial generic entry between January 1995 and September 2012 and the number of generic competitors for 12 months afterwards, by level of annual sales prior to generic entry and time period. The likelihood and timing of Paragraph IV challenge were calculated using data from Abbreviated New Drug Approval (ANDA) approval letters, the FDA website, and public information searches to identify drugs experiencing Paragraph IV filings, and the first filing date.

Results:

For drugs experiencing initial generic entry in 2011–2012, the MEP was 12.6 years for drugs with sales greater than $100 million (in 2008 dollars) in the year prior to generic entry, 12.9 years overall. After generic entry, the brand rapidly lost sales, with average brand unit share of 16% at 1 year; 11% for NMEs with pre-generic entry sales of at least $250 million (in 2008 dollars). Over 80% of NMEs experiencing 2011–2012 initial generic entry had faced at least one Paragraph IV challenge from a generic manufacturer. These challenges were filed relatively early in the brand-name drug life cycle: within 7 years after brand launch, on average.

Limitations:

Analyses, including Paragraph IV calculations, were restricted to NMEs where generic entry had occurred.

Conclusion:

Pharmaceutical competition continues to evolve; while the average MEP below 13 years for 2011–2012 remains consistent with prior research, Paragraph IV challenges are increasingly frequent and occur earlier, and generic share erosion has intensified.     

Cost-effectiveness model of abiraterone plus prednisone,cabazitaxel plus prednisone and enzalutamide for visceral metastatic castration resistant prostate cancer therapy after docetaxel therapy resistance

Abstract

Aims: Among patients diagnosed with prostate cancer, 10–20% will develop castration-resistant prostate cancer (CRPC) within 5?years; for 70%, CRPC will metastasize, mostly to the lungs and/or liver. We performed a cost-effectiveness model comparing abiraterone plus prednisone (ABI?+?PRD), cabazitaxel plus prednisone (CAB?+?PRD) and enzalutamide (ENZ) for visceral metastatic CRPC post-docetaxel therapy resistance.

Methods: A three-state (Progression-Free, Progression, Death) lifetime Markov model was constructed to compare ABI?+?PRD, CAB?+?PRD, and ENZ from a United States healthcare payer perspective (2019?US$; discount rate 3%/yr.). Effectiveness was measured in life-years (LYs) and quality-adjusted life years (QALYs). Inputs included treatment costs, grade III/IV adverse events with incidence ≥5%, physician follow-up, lab and imaging tests. Phase III trial Kaplan-Meier curves were extrapolated to estimate overall survival and Progression-Free transition probabilities. Incremental cost-effectiveness ratios (ICERs) and utility ratios (ICURs), probabilistic sensitivity analyses (PSAs) and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds were estimated.

Results: Models estimated 3-year overall survival rates of 1.3% for patients treated with ABI?+?PRD, 16.2% for CAB?+?PRD, and 13.2% for ENZ. Estimated Progression-Free rates at 1.5?years were 0.51% for ABI?+?PRD, 0.27% for CAB?+?PRD, and 14.47% for ENZ. LYs and QALYs were 1.20 and 0.58 respectively for ABI?+?PRD, 1.48 and 0.56 for CAB?+?PRD, and 1.58 and 0.79 for ENZ. Total treatment costs were: $115,433 for ABI?+?PRD, $85,337 for CAB?+?PRD and $109,213 for ENZ. CAB?+?PRD and ENZ dominated ABI?+?PRD due to higher LYs gained. Incremental QALYs for ENZ vs. CAB?+?PRD were larger than incremental LYs. The ICUR for ENZ was $103,674/QALY compared to CAB?+?PRD.

Conclusions: This analysis found ENZ provided greater LYs and QALYs than both ABI?+?PRD and CAB?+?PRD, at a lower cost than ABI?+?PRD, but at a higher cost compared to CAB?+?PRD. For patients with visceral mCRPC after docetaxel therapy resistance, ENZ was cost-effective 92% of the time with a WTP threshold of $100,000/QALY.     

Economic analysis of bevacizumab,cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC)

Abstract

Objective:

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients.

Methods:

A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources.

Results:

Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab?+?FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab?+?FBC, panitumumab?+?FBC is dominated and cetuximab?+?FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab?+?FBC had ～100%, ～100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively.

Conclusion:

For first-line treatment of KRAS-WT mCRC, bevacizumab?+?FBC is associated with substantially lower costs as compared to panitumumab?+?FBC or cetuximab?+?FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.     

Cost-effectiveness of daclatasvir plus sofosbuvir-based regimen for treatment of hepatitis C virus genotype 3 infection in Canada

Objective:

New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV?+?SOF) and sofosbuvir plus ribavirin (SOF?+?RBV), from a Canadian health-system perspective.

Methods:

A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0–F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis.

Results:

In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV?+?SOF (12.37) and SOF?+?RBV (12.48) compared to that of pINF?+?RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV?+?SOF ($170,371) and SOF?+?RBV ($194,776) vs pINF?+?RBV regimen ($90,905). Compared to pINF?+?RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV?+?SOF and SOF?+?RBV, respectively. In treatment-experienced patients, DCV?+?SOF regimen dominated the SOF?+?RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV?+?SOF regimen was cost saving in treatment-experienced patients.

Conclusion:

Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.     

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.     

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US

Abstract

Aims: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US.

Materials and methods: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab?+?chemotherapy (carboplatin/cisplatin?+?pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab?+?chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1)?≥?50%.

Results: In the full non-squamous population, pembrolizumab?+?chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1?≥?50% and 1–49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1?<?1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1?≥?50%, 1–49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1?≥?50% patients, representing current standard of care, pembrolizumab?+?chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY.

Limitations and conclusions: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab?+?chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.     

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States

Background: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients.

Aim: This study evaluated the cost-effectiveness of DCV?+?SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer.

Methods: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted.

Results: DCV?+?SOF was associated with lower costs and better effectiveness than SOF?+?RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV?+?SOF was less costly, but also slightly less effective than SOF?+?RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV?+?SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF?+?RBV.

Conclusion: DCV?+?SOF is a dominant option compared with SOF?+?RBV in the US for the overall GT 3 HCV patient population.     

Cost-effectiveness of risk stratification for preventing type 2 diabetes using a multi-marker diabetes risk score

Abstract

Background:

Personalized medicine requires diagnostic tests that stratify patients into distinct groups that may differentially benefit from targeted treatment approaches. This study compared the costs and benefits of two approaches for identifying those at high risk of developing type 2 diabetes for entry into a diabetes prevention program. The first approach identified high risk patients using impaired fasting glucose (IFG). The second approach used the PreDx Diabetes Risk Score (DRS) to further stratify IFG patients into high-risk and moderate-risk groups.

Methods:

A Markov model was developed to simulate the incidence and disease progression of diabetes and consequent costs and quality-adjusted life expectancy (QALY), comparing alternative approaches for identifying high-risk patients. We modeled direct medical costs, including the costs of the stratification testing, over a 10-year time horizon from a US payer perspective.

Results:

Stratification of IFG patients by the DRS method leads to improved identification and prevention among those at highest risk. At 5 years, the number needed to treat (NNT) in the IFG-only approach was 39 patients to prevent one case of diabetes compared to an NNT of 15 in the IFG?+?DRS approach. When compared to IFG alone, the IFG?+?DRS approach results in an incremental cost-effectiveness ratio (ICER) of $17,100/QALY gained at 5 years and would become cost saving in 10 years. In contrast and as compared to no stratification, the IFG-only approach would produce an ICER of $235,500/QALY gained at 5 years and $94,600/QALY gained at 10 years. The study findings are limited by the generalizability of the DRS validation study and uncertainty regarding the long-term effectiveness of diabetes prevention.

Conclusions:

The analysis indicates that the cost-effectiveness of diabetes prevention can be improved by better identification of patients at highest risk for diabetes using the DRS.     

Societal burden of cluster headache in the United States: a descriptive economic analysis

Aim: To estimate direct and indirect costs in patients with a diagnosis of cluster headache in the US.

Methods: Adult patients (18–64 years of age) enrolled in the Marketscan Commercial and Medicare Databases with ≥2 non-diagnostic outpatient (≥30 days apart between the two outpatient claims) or ≥1 inpatient diagnoses of cluster headache (ICD-9-CM code 339.00, 339.01, or 339.02) between January 1, 2009 and June 30, 2014, were included in the analyses. Patients had ≥6 months of continuous enrollment with medical and pharmacy coverage before and after the index date (first cluster headache diagnosis). Three outcomes were evaluated: (1) healthcare resource utilization, (2) direct healthcare costs, and (3) indirect costs associated with work days lost due to absenteeism and short-term disability. Direct costs included costs of all-cause and cluster headache-related outpatient, inpatient hospitalization, surgery, and pharmacy claims. Indirect costs were based on an average daily wage, which was estimated from the 2014?US Bureau of Labor Statistics and inflated to 2015 dollars.

Results: There were 9,328 patients with cluster headache claims included in the analysis. Cluster headache-related total direct costs (mean [standard deviation]) were $3,132 [$13,396] per patient per year (PPPY), accounting for 17.8% of the all-cause total direct cost. Cluster headache-related inpatient hospitalizations ($1,604) and pharmacy ($809) together ($2,413) contributed over 75% of the cluster headache-related direct healthcare cost. There were three sub-groups of patients with claims associated with indirect costs that included absenteeism, short-term disability, and absenteeism?+?short-term disability. Indirect costs PPPY were $4,928 [$4,860] for absenteeism, $803 [$2,621] for short-term disability, and $3,374 [$3,198] for absenteeism?+?disability.

Conclusion: Patients with cluster headache have high healthcare costs that are associated with inpatient admissions and pharmacy fulfillments, and high indirect costs associated with absenteeism and short-term disability.     

The budget impact of using enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg to prevent recurrent cardiovascular events

Objective: Aspirin (acetylsalicylic acid; ASA) is commonly used for secondary prevention of cardiovascular (CV) events, but may be associated with gastrointestinal (GI) adverse events, which can reduce adherence. Use of ASA co-therapy with proton pump inhibitors in patients at risk may be suboptimal. PA32540 (Yosprala?) is a coordinated-delivery tablet combining EC-ASA 325?mg and immediate-release omeprazole 40?mg. The objective of this flexible budget impact model was to project the financial consequences of introducing PA32540 325?mg/40?mg to prevent recurrent CV events, while reducing ASA-associated GI events in US adults.

Methods: A Markov Model was employed to estimate health state transitions associated with ASA 75–325?mg, ASA 75–325?mg?+?generic delayed-release omeprazole 40?mg, PA32540, or clopidogrel 75?mg to prevent recurrent CV events. Health states included ulcers, GI bleeding, CV events, and death. Model inputs included demographics, treatment dosages, treatment costs, adverse GI and CV events, and premature death. Data from peer-reviewed literature and censuses enabled appropriate allocation of CV and GI disease prevalence and mortality. The PA32540 non-adherence rate was conservatively set at 20%. PA32540 market share was set to 50%.

Results: The model projected annual savings of $81.0 million to $190.9 million within 1–5 years after PA32540 introduction to the plan, which included 134,558 members at risk for recurrent CV events. These values translate into savings of $602 (year 5) to $1,419 (year 1) per patient per year, and $81 (year 5) to $191 (year 1) per member per year. These values were robust to variations in parameters under a deterministic sensitivity analysis.

Conclusion: PA32540 use to prevent recurrent CV events was associated with cost reductions in each year examined with the model. From a health plan perspective, PA32540 is likely to have a net overall effect, resulting in significant cost savings.     

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.     

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States

Abstract

Objective:

To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV?+?r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy.

Methods:

A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts.

Limitations:

The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV?+?r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained <$50,000/QALY when these values were varied in sensitivity analyses.

Results:

ATV?+?r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs ($275,986 vs. 269,160). ATR?+?r patients had lower rates of AIDS (19.08 vs. 20.05 cases/1,000 patient-years), OIs (0.44 vs. 0.52), diarrhea (1.27 vs. 6.26), and CHD events (5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25). ATV?+?r added 0.26 QALYs at a cost of $6826, for $26,421/QALY.

Conclusions:

By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV?+?r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (<$50,000/QALY) compared with LPV/r.     

Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer

Background: Nab-paclitaxel plus gemcitabine (NAB-P?+?GEM) and FOLFIRINOX have shown superior efficacy over gemcitabine (GEM) in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDA). Although the incremental clinical benefits are modest, both treatments represent significant advances in the treatment of a high-mortality cancer. In this independent economic evaluation for the US, the aim was to estimate the comparative cost-utility and cost-effectiveness of these three regimens from the payer perspective.

Methods: In the absence of a direct treatment comparison in a single clinical trial, the Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. A Markov model evaluated life years (LY) and quality-adjusted life years (QALY) gained with NAB-P?+?GEM and FOLFIRINOX over GEM, expressed as incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). All costs and outcomes were discounted at 3%/year. The impact of parameter uncertainty on the model was assessed by probabilistic sensitivity analyses.

Results: NAB-P?+?GEM was associated with differentials of +0.180 LY and +0.127 QALY gained over GEM at an incremental total cost of $25,965; yielding an ICER of $144,096/LY and ICUR of $204,369/QALY gained. FOLFIRINOX was associated with differentials of +0.368 LY and +0.249 QALY gained over GEM at an incremental total cost of $93,045; yielding an ICER of $253,162/LY and ICUR of $372,813/QALY gained. In indirect comparison, the overall survival hazard ratio (OS HR) for NAB-P?+?GEM vs FOLFIRINOX was 0.79 (95%CI?=?0.59–1.05), indicating no superiority in OS of either regimen. FOLFIRINOX had an ICER of $358,067/LY and an ICUR of $547,480/QALY gained over NAB-P?+?GEM. Tornado diagrams identified variation in the OS HR, but no other parameters, to impact the NAB-P?+?GEM and FOLFIRINOX ICURs.

Conclusions: In the absence of a statistically significant difference in OS between NAB-P?+?GEM and FOLFIRINOX, this US analysis indicates that the greater economic benefit in terms of cost-savings and incremental cost-effectiveness and cost-utility ratios favors NAB-P?+?GEM over FOLFIRINOX.     

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US

Aims: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G?+?B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G?+?B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective.

Materials and methods: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial’s refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty.

Results: G?+?B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR?=?0.61–1.87); the incremental total cost was $58,100 (95% CR?=?$54,500–$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G?+?B was cost-effective at the $100,000 per QALY threshold.

Limitations and conclusions: This US-based analysis suggests that treatment with G?+?B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.     

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma

Objective: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A?+?AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A?+?AVD from a US healthcare payer perspective.

Methods: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1.

Results: The ICER for A?+?AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure.

Conclusion: The ICER for A?+?AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A?+?AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Trial registration: ClinicalTrials.gov identifier: NCT01712490.     

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism

Background:

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin?+?VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin?+?VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin?+?VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.

Methods:

A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin?+?VKA in adult patients treated for acute DVT or PE. All patients entered the model in the ‘on-treatment’ state upon commencement of oral rivaroxaban or enoxaparin?+?VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.

Results:

Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin?+?VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model’s results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin?+?VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin?+?VKA approximately 76% of the time.

Limitations:

The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. ‘Real-world’ applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.

Conclusion:

Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.     

Cost–consequence analysis of a hemostatic matrix alone or in combination for spine surgery patients

Background: A five-year retrospective database analysis comparing the use of Floseal¹ flowable topical hemostat alone (F) and in combination with gelatin/thrombin (F?+?G/T) to achieve hemostasis and control surgical bleeding showed higher resource utilization for F?+?G/T cases relative to F matched pairs during spinal surgery. Lower resource use in the F group was characterized by shorter hospital length of stay and surgical time as well as fewer blood transfusions and less hemostat agent used per surgery.

Objective: To evaluate the cost–consequence of using F compared to F?+?G/T in minor, major and severe spinal surgery from the US hospital perspective.

Methods: A cost–consequence model was developed using the US hospital perspective. Model inputs include clinical inputs from the literature, cost inputs (hemostatic matrices, blood product transfusion, hospital stay and operating room time) from the literature, and an analysis of annual spine surgery volume (minor, major and severe) using the 2012 National Inpatient Sample (NIS) database. Costs are reported in 2017?US dollars. One-way and probabilistic sensitivity analyses address sources of variability in the results.

Results: A medium-volume hospital (130 spine surgeries per year) using F versus F?+?G/T for spine surgeries is expected to require 85 less hours of surgical time, 58 fewer hospital days and 7 fewer blood transfusions in addition to hemostat volume savings (F: 1?mL, thrombin: 1994?mL). The cost savings associated with the hospital resources for a medium-volume hospital are expected to be $317,959 (surgical hours?=?$154,746, hospital days?=?$125,237, blood transfusions?=?$19,023, hemostatic agents?=?$18,953) or $2445 per spine surgery.

Conclusions: The use of F versus F?+?G/T could lead to annual cost savings for US hospitals performing a low to high volume of spinal surgeries per year.     

Infusion administration billing for vedolizumab and infliximab in inflammatory bowel disease

Abstract

Aims: Increasing use of biologics has led to interest in treatment components with potential for cost savings. This study was aimed at comparing administration times and associated costs of infliximab and vedolizumab infusions for inflammatory bowel disease (IBD).

Materials and methods: This study used claims data from the Symphony Health Integrated Dataverse to identify IBD patients using infliximab or vedolizumab between 20 May 2014 and 29 February 2016. Use of Current Procedural Terminology administration codes was evaluated and costs calculated using the 2016 Center for Medicare and Medicaid Services Physician Fee Schedule. Assessments included infusion times, associated costs, productivity loss using average wage estimates from the United States Bureau of Labor Statistics, and home infusion adoption.

Results: A total of 10,051 infliximab and 3114 vedolizumab patients with first-hour claims were identified; 52.0% were female and 64.5% had Crohn’s disease. There were 48,377 infliximab first-hour claims (mean 4.8 infusions per patient); 46,462 (96.0%) had a second-hour claim. In comparison, there were 14,717 vedolizumab claims (mean 4.7 infusions per patient), with only 411 (2.8%) second-hour claims, resulting in vedolizumab cost savings of approximately $1.27 million. The difference in second-hour infusions resulted in 46,051 additional hours of productivity loss with infliximab, and lost wages averaging $1.18 million (range $0.68–$1.77 million).

Limitations: Administration costs were inferred as charge costs and not directly assessed. Productivity loss assessed time spent on infusion only, and included a small proportion of patients beyond working age.

Conclusions: Second-hour infusion billing was significantly lower with vedolizumab than with infliximab, corresponding to cost savings and reduced productivity loss.