Publications by authors named "Joseph Biskupiak"

42 Publications

Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials.

J Manag Care Spec Pharm 2021 Oct;27(10):1367-1375

Department of Pharmacotherapy, University of Utah, Salt Lake City.

Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.
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http://dx.doi.org/10.18553/jmcp.2021.27.10.1367DOI Listing
October 2021

Payer perceptions of the use of real-world evidence in oncology-based decision making.

J Manag Care Spec Pharm 2021 Aug;27(8):1096-1105

Pfizer, Inc.

Randomized controlled trials (RCTs), the gold standard of safety and efficacy evidence, are conducted in select patients that may not mirror real-world populations. As a result, healthcare decision makers may have limited information when making formulary decisions, especially in oncology, given accelerated regulatory approvals and niche patient populations. Real-world evidence (RWE) studies may help address these knowledge gaps and help inform oncology formulary decision making. To assess US payer perceptions regarding the use and relevance of RWE in informing oncology formulary decisionmaking. A national survey containing single-answer, multiple-answer, and free-response questions evaluated 4 key areas: (1) the value of RWE, (2) barriers to RWE, (3) sources of RWE, and (4) use of RWE in outcomes-based contracting. The survey was distributed to 221 US payers through the Academy of Managed Care Pharmacy (AMCP) Market Insights program in February 2020. Ten additional respondents were invited to discuss the survey results. The survey results were presented primarily as frequencies of responses and were evaluated by the respondent's plan size, type, and geography (regional vs national). Differences in responses for categorical data were compared using a Pearson Chi-Square or a Fisher's Exact test. Two-tailed values are reported and a level of ≤ 0.05 was used to indicate statistical significance. The national survey had a 45.9% response rate, with 106 payers responding. Most were from managed care organizations (MCOs; 47.5%) and pharmacy benefit managers (PBMs; 37.4%), with 54.5% from large plans (≥ 1 million lives) and 45.5% from small plans (< 1 million lives). Respondents were largely pharmacists (89.9%), with 55.6% overall indicating their job was a pharmacy administrator. Most (84.9%) used RWE to inform formulary decisions in oncology to support comparative effectiveness in the absence of head-to-head clinical trials (4.1 on a scale of 1 = Not At All Useful to 5 = Extremely Useful) and validation of National Comprehensive Cancer Network (NCCN) recommendations (4.0). Almost half (41.5%) used RWE results to inform off-label usage decisions. Payers valued RWE pre-launch to inform formulary and contracting decisions and desired real-world comparative effectiveness data post-launch to validate coverage decisions. However, the majority of payers (54.7%) did not conduct their own real-world studies. Commonly considered RWE sources included claims data (79.2%), medical records (68.9%), prospective cohort studies (60.4%), patient registries (36.8%), and patient outcome surveys (33.0%). Barriers to conducting internal RWE studies included the lack of resources and personnel, analytic capabilities, appropriate in-house data, and perceived value in conducting analyses. Payers expressed interest in using outcomes-based contracting in oncology; few have direct experience, and operationalizing through value measurement is challenging. RWE providing comparative treatment data, validation of NCCN treatment recommendations, and information on off-label usage are appreciated pre launch with post launch validation. Pfizer provided funding for this research, and employees of Pfizer led the development of the survey and contributed to the manuscript as authors. Arondekar and Niyazov are employees of Pfizer; Oderda, Biskupiak, and Brixner are managers of Millcreek Outcomes Group and were paid as consultants on this project. Burgoyne was a consultant for Pfizer on this project. Malone was paid by Millcreek Outcomes as a consultant on this project.
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http://dx.doi.org/10.18553/jmcp.2021.27.8.1096DOI Listing
August 2021

Comparative Safety and Efficacy of Therapeutic Options in Resectable and Advanced/Metastatic Pancreatic Cancer: A Systematic Review and Indirect Comparison.

Oncol Res Treat 2021 27;44(9):476-484. Epub 2021 Jul 27.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

Objectives: FOLFIRINOX, gemcitabine/nab-paclitaxel (gem-nab/P), and gemcitabine-capecitabine (gem-cap) demonstrated superiority over gemcitabine monotherapy for pancreatic cancer (PC). It is still unclear which chemotherapy regimen is the most optimal. This study aimed to conduct a systematic review (SR) and indirect comparison to compare safety and efficacy of FOLFIRINOX versus gem-nab/P and gem-cap in PC.

Methods: An SR was conducted in several databases from inception to November 2020. RCTs investigating resectable or advanced PC were included. Primary outcomes including overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and grade 3/4 adverse events (AEs) were pooled using a random effects model. Indirect comparisons were done to compare FOLFIRINOX versus gem-cap and gem-nab/P. Heterogeneity was evaluated using Cochran's Q test and I2 statistics.

Results: Nine studies were identified involving 6,564 patients. Indirect comparisons showed FOLFIRINOX had significantly better OS (resectable: HR 0.78 [0.61-0.99]; advanced: HR 0.71 [0.60-0.85]) and RFS/DFS/PFS (resectable: HR 0.67 [0.55-0.82]; advanced: HR 0.65 [0.57-0.74]) compared to gem-cap as well as OS (resectable: HR 0.78 [0.61-1.00]; advanced: HR 0.73 [0.54-0.98]) and DFS/PFS (resectable: HR 0.66 [0.53-0.82]; advanced: HR 0.64 [0.49-0.83]) compared to gem-nab/P. FOLFIRINOX increased grade 3/4 AE risk compared to gem-cap and gem-nab/P.

Conclusions: FOLFIRINOX is associated with significant survival benefits compared to gem-nab/P and gem-cap. However, it is important to consider the increased grade 3/4 AE risk associated with FOLFIRINOX.
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http://dx.doi.org/10.1159/000517409DOI Listing
October 2021

Statin use and mortality in rheumatoid arthritis: an incident user cohort study.

J Manag Care Spec Pharm 2021 Mar;27(3):296-305

College of Pharmacy, University of Utah, Salt Lake City.

Patients with rheumatoid arthritis (RA) have higher rates of mortality attributed to the inflammatory nature and the associated burden of cardiovascular complications. Previous research indicates that treatment with statin therapy may play a role in reducing the mortality rate of RA patients, but similar evidence in U.S. patients is lacking. To assess the association between statin use and overall mortality among RA patients in the United States. A population-based study of RA patients with incident statin use was conducted. Patients aged ≥ 18 years with a diagnosis of RA between January 2007 and December 2015 were included and reviewed for the use of statin medication. Time stratified propensity score matching was used to adequately balance the comparison groups. Logistic regression and Cox proportional hazard models were used to estimate the association. 19,614 people fulfilled the inclusion criteria for the study out of which 2,089 were statin users. There were 1,883 statin users that were matched to 1,883 statin nonusers. Baseline characteristics were well balanced across the 2 groups after matching. The hazards ratio for all-cause mortality in patients with RA for statin users was 0.72 (95% CI = 0.56-0.91; = 0.008) compared with statin nonusers. Compared with no use of statins, current statin use is associated with 28% lower risk of mortality in RA patients. Decision makers and providers should consider and support integration of these results into the current clinical guidelines for delivering quality health care to RA patients. No outside funding supported this study. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript.
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http://dx.doi.org/10.18553/jmcp.2021.27.3.296DOI Listing
March 2021

Estimation of healthcare-related charges in women with BRCA mutations and breast cancer.

BMC Health Serv Res 2021 Jan 13;21(1):58. Epub 2021 Jan 13.

Department of Pharmacotherapy, Outcomes Research Center, University of Utah, Salt Lake City, USA.

Background: Breast cancer costs were estimated at $16.5 billion in 2010 and were higher than other cancer costs. There are limited studies on breast cancer charges and costs by BRCA mutations and receptor status. We examined overall health care and breast cancer-related charges by BRCA status (BRCAm vs. BRCAwt), receptor status (HER2+ vs. HER2-), and treatment setting (neoadjuvant vs. adjuvant).

Methods: Retrospective cohort study of charge data from 1995-2014 in an academic medical center. Facilities, physician, pharmacy, and diagnosis-related charges were presented as mean and median charges with standard deviation (SD) and interquartile ranges (25%-75%). Wilcoxon rank-sum test was used to assess statistically significant differences in charges between comparators.

Results: Total median breast-cancer related charges were $65,414 for BRCAm and $54,635 for BRCAwt (p=0.19); however all-cause charges were higher for BRCAm patients ($145,066 vs. $119,119, p<0.001). HER2+ status was associated with higher median breast cancer charges ($152,159 vs. $44,087, p<0.0001) that was driven by the charges for biological agents. Patients initially seen in the neoadjuvant setting had higher mean breast cancer charges than in the adjuvant setting ($117,922 vs. $80,061, p<0.0001).

Conclusion: BRCA mutation status was not associated with higher breast cancer charges but HER2+ status had significantly higher charges, due to charges for biological agents. Patients who initially received neoadjuvant treatment had significantly higher overall treatment charges than adjuvant therapy patients. With the advent of novel therapies for BRCAm, the economic impact of these treatments will be important to consider relative to their survival benefits.
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http://dx.doi.org/10.1186/s12913-020-06038-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805040PMC
January 2021

Budget impact of capmatinib for adults with metastatic non-small cell lung cancer harboring a exon 14 skipping mutation in the United States.

J Med Econ 2021 Jan-Dec;24(1):131-139

Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA.

Aims: To estimate the budget impact of adding capmatinib, the first FDA approved MET inhibitor, to a US commercial or Medicare health plan for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation that leads to exon 14 (ex14) skipping.

Methods: Target population size was estimated using published epidemiology data. Clinical data were obtained from the GEOMETRY mono-1 capmatinib trial and published trials. Treatments in the market mix included crizotinib, pembrolizumab, ramucirumab, and chemotherapy. Uptake of capmatinib and testing rates were based on market research. All costs (drug acquisition and administration, pre-progression, progression, terminal care, adverse event, and testing) were estimated based on public sources (2020 USD).

Results: The number of patients eligible for capmatinib in the first three years was estimated to be 2-3 in a hypothetical 1 million member commercial plan and 34-44 in a hypothetical 1 million member Medicare plan each year. The estimated total budget impact ranged from $9,695 to $67,725 for a commercial plan and $141,350 to $985,695 for Medicare. With capmatinib included, a marginal per member per month budget impact was estimated (commercial: $0.0008 to $0.0056; Medicare: $0.0118 to $0.0821). Capmatinib inclusion resulted in lower medical costs (commercial: -$0.0003 to -$0.0007; Medicare: -$0.0037 to -$0.0106), partially offsetting increased drug costs ($0.0011 to $0.0064; $0.0154 to $0.0928, respectively), and were primarily driven by reductions in progression and terminal care costs (-$0.0003 to -$0.0009; -$0.0037 to -$0.0125, respectively). The results were most sensitive to capmatinib market share, capmatinib price, and treatment duration.

Limitations: Certain assumptions were applied to the model to account for inputs with limited evidence.

Conclusions: The estimated budget impact of including capmatinib for mNSCLC with a ex14 skipping mutation is minimal, and the increased drug costs were partially offset by savings in AEs, and progression-related and terminal care costs.
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http://dx.doi.org/10.1080/13696998.2020.1867470DOI Listing
September 2021

BRCA testing and outcomes in women with breast cancer.

Breast Cancer Res Treat 2021 Apr 3;186(3):839-850. Epub 2021 Jan 3.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Main Purpose: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer.

Research Question: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?"

Methods: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status.

Results: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients.

Conclusions: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.
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http://dx.doi.org/10.1007/s10549-020-06038-xDOI Listing
April 2021

Trends in outpatient emergency department visits during the COVID-19 pandemic at a large, urban, academic hospital system.

Am J Emerg Med 2021 Feb 9;40:20-26. Epub 2020 Dec 9.

Department of Health Policy & Management, School of Public Health, Texas A&M University, College Station, TX, United States of America.

Background: The coronavirus disease 2019 (COVID-19) pandemic has critically affected healthcare delivery in the United States. Little is known on its impact on the utilization of emergency department (ED) services, particularly for conditions that might be medically urgent. The objective of this study was to explore trends in the number of outpatient (treat and release) ED visits during the COVID-19 pandemic.

Methods: We conducted a cross-sectional, retrospective study of outpatient emergency department visits from January 1, 2019 to August 31, 2020 using data from a large, urban, academic hospital system in Utah. Using weekly counts and trend analyses, we explored changes in overall ED visits, by patients' area of residence, by medical urgency, and by specific medical conditions.

Results: While outpatient ED visits were higher (+6.0%) in the first trimester of 2020 relative to the same period in 2019, the overall volume between January and August of 2020 was lower (-8.1%) than in 2019. The largest decrease occurred in April 2020 (-30.4%), followed by the May to August period (-12.8%). The largest declines were observed for visits by out-of-state residents, visits classified as non-emergent, primary care treatable or preventable, and for patients diagnosed with hypertension, diabetes, headaches and migraines, mood and personality disorders, fluid and electrolyte disorders, and abdominal pain. Outpatient ED visits for emergent conditions, such as palpitations and tachycardia, open wounds, syncope and collapse remained relatively unchanged, while lower respiratory disease-related visits were 67.5% higher in 2020 relative to 2019, particularly from March to April 2020. However, almost all types of outpatient ED visits bounced back after May 2020.

Conclusions: Overall outpatient ED visits declined from mid-March to August 2020, particularly for non-medically urgent conditions which can be treated in other more appropriate care settings. Our findings also have implications for insurers, policymakers, and other stakeholders seeking to assist patients in choosing more appropriate setting for their care during and after the pandemic.
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http://dx.doi.org/10.1016/j.ajem.2020.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725055PMC
February 2021

Tetrodotoxin-Sensitive Neuronal-Type Na Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation.

J Am Heart Assoc 2020 06 29;9(11):e015119. Epub 2020 May 29.

Dorothy M. Davis Heart and Lung Research Institute College of Medicine The Ohio State University Wexner Medical Center Columbus OH.

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca-dependent nature of both of these pathologies, AF often responds to Na channel blockers. We investigated how targeting interdependent Na/Ca dysregulation might prevent focal activity and control AF. Methods and Results We studied AF in 2 models of Ca-dependent disorders, a murine model of catecholaminergic polymorphic ventricular tachycardia and a canine model of chronic tachypacing-induced heart failure. Imaging studies revealed close association of neuronal-type Na channels (nNa) with ryanodine receptors and Na/Ca exchanger. Catecholamine stimulation induced cellular and in vivo atrial arrhythmias in wild-type mice only during pharmacological augmentation of nNa activity. In contrast, catecholamine stimulation alone was sufficient to elicit atrial arrhythmias in catecholaminergic polymorphic ventricular tachycardia mice and failing canine atria. Importantly, these were abolished by acute nNa inhibition (tetrodotoxin or riluzole) implicating Na/Ca dysregulation in AF. These findings were then tested in 2 nonrandomized retrospective cohorts: an amyotrophic lateral sclerosis clinic and an academic medical center. Riluzole-treated patients adjusted for baseline characteristics evidenced significantly lower incidence of arrhythmias including new-onset AF, supporting the preclinical results. Conclusions These data suggest that nNas mediate Na-Ca crosstalk within nanodomains containing Ca release machinery and, thereby, contribute to AF triggers. Disruption of this mechanism by nNa inhibition can effectively prevent AF arising from diverse causes.
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http://dx.doi.org/10.1161/JAHA.119.015119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429002PMC
June 2020

Clinical and economic analysis of patients with acute myeloid leukemia by FLT3 status and midostaurin use at a Comprehensive Cancer Center.

Leuk Res 2019 12 24;87:106262. Epub 2019 Oct 24.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, UT, United States; Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN, United States. Electronic address:

Introduction: Identification of cytogenetic and molecular abnormalities has become vital for the appropriate treatment of acute myeloid leukemia (AML). One of the most common molecular alterations in AML is the constitutive activation by internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3).

Methods: This observational, retrospective, cohort study at the Huntsman Cancer Institute (HCI) had two time periods: 1) a historical pre-midostaurin time period which consisted of the FLT3 mutated (FLT3m) and FLT3 wild type (FLT3wt) cohorts from January 1, 2007, to December 31, 2016, and 2) a post-midostaurin cohort which consisted of the FLT3 mutated midostaurin-user cohort (early mido) from May 01, 2017 to December 31, 2018.

Results: In total, 39 patients were included in the FLT3m cohort, 61 in the FLT3wt cohort, and seven in the early mido cohort. FLT3m patients spent fewer days in the hospital during the first consolidation regimen and received fewer consolidation cycles compared to FLT3wt patients. Overall survival (OS) was similar between FLT3m and FLT3wt patients. For patients without hematopoietic stem cell transplant, OS was significantly shorter for FLT3m patients compared to FLT3wt patients. Mean AML related inpatient charges and physician charges for FLT3m patients were significantly higher than FLT3wt patients.

Conclusion: The FLT3 mutation is historically associated with a shorter time to transplant and increased total health care charges. More information is needed to evaluate the real-world treatment strategies for FLT3-mutated patients in the presence of FLT3 inhibitors and the impact of these treatment strategies on clinical and economic outcomes.
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http://dx.doi.org/10.1016/j.leukres.2019.106262DOI Listing
December 2019

Quantification of Economic Impact of Drug Wastage in Oral Oncology Medications: Comparison of 3 Methods Using Palbociclib and Ribociclib in Advanced or Metastatic Breast Cancer.

J Manag Care Spec Pharm 2019 Aug;25(8):859-866

2Novartis Pharmaceuticals, East Hanover, New Jersey.

Background: Discarding unused drugs after dose changes or discontinuation can significantly affect pharmacy budgets. This is especially concerning for expensive oncology agents. However, few economic studies account for drug wastage, providing an inaccurate estimate of a drug's actual economic cost, cost-effectiveness, and value.

Objectives: To (a) compare the economic impact of drug wastage between ribociclib and palbociclib-clinically similar oral medications for metastatic breast cancer-using 3 approaches (Markov model, pharmacy acquisition cost model, and a retrospective claims analysis) and (b) compare the modeling results with a published estimate of drug wastage for palbociclib from a claims analysis.

Methods: A Markov model and a pharmacy acquisitions cost model were developed to evaluate the economic impact of dose reductions for ribociclib and palbociclib over a 1-year time period. Data inputs were pharmacy costs (RED BOOK wholesale acquisition cost) and proportion of patients experiencing dose reductions from either ribociclib randomized clinical trials (MONALEESA-2, -3, or -7) or real-world observational data (Symphony Health retrospective claims analysis). The latter constituted the third approach for quantifying drug wastage. The economic impact of dose reductions for ribociclib and palbociclib in postmenopausal women with previously untreated HR-positive/HER2-negative advanced breast cancer was assessed. Drug wastage was defined as drug doses that could not be used by a patient following a dose reduction. The cost of drug wastage was defined as the cost associated with an unused drug resulting from a dose reduction. The predicted results from the 2 models were compared with a previously published claims analysis that estimated the effect of treatment costs and drug wastage for palbociclib based on the observed dosing patterns from the Symphony Health Solutions database.

Results: In the Markov model, relative to ribociclib, palbociclib users experienced drug wastage of $112,382 total, or $1,124 per treated patient, per year due to dose changes. In the pharmacy acquisition cost model, relative to ribociclib, palbociclib usage was associated with an increased cost of $7,196 per patient per year (based on a mid-cycle dose reduction) comprising dosing-based cost differences and drug wastage cost for palbociclib of $3,727. The previously published claims analysis found that palbociclib users experiencing a dose reduction had drug wastage costs of $5,471 per patient.

Conclusions: In both models, dose reductions for ribociclib patients resulted in no wastage, since unused tablets could be administered in subsequent cycles, while dose reductions for palbociclib resulted in drug wastage and increased costs. The results from both models were consistent with previously published results from the claims analysis, demonstrating drug wastage costs for palbociclib.

Disclosures: This study received financial support from Novartis Pharmaceuticals, which has products approved for treatment of breast cancer. Tang was employed by Novartis during this study; Zacker and Dalal are employed by Novartis and own company stock. Biskupiak, Brixner, and Oderda received payment from Novartis for this study. Brixner serves as a consultant for Millcreek Outcomes Group and also declares consulting fees from Abbvie, AstraZeneca, Abbott, Becton Dickinson, and Xcenda, unrelated to this study.
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http://dx.doi.org/10.18553/jmcp.2019.25.8.859DOI Listing
August 2019

The Challenge of Variable Costs in Decisions Based on Cost-Effectiveness Evidence: A Case Study for Brodalumab.

Am Health Drug Benefits 2019 Feb;12(1):22-26

Professor of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Payers often consider cost-effectiveness studies for new drugs when making decisions on coverage, formulary position, and budgets; however, cost-effectiveness studies are often calculated using estimated pricing before a drug's launch. If the drug's price changes on or after launch, or if rebate programs are initiated, cost-effectiveness studies need to be updated to prevent payers from making decisions using inaccurate value assumptions, which can lead to unexpected financial impacts and potentially delay patient access to drugs.

Objective: To evaluate how lower at-launch drug pricing versus initial estimated pricing affects cost-effectiveness ratios and potentially influences treatment decisions, using the case study of brodalumab, a biologic drug indicated for the treatment of moderate-to-severe plaque psoriasis.

Methods: We compared the estimated cost-effectiveness of brodalumab, which was published in a December 2016 Institute for Clinical and Economic Review (ICER) report based on estimated pricing, with the drug's cost-effectiveness based on its actual pricing after its approval.

Discussion: The 2016 ICER report on the cost-effectiveness of targeted immunomodulators indicated for the treatment of moderate-to-severe plaque psoriasis, brodalumab's price was estimated to be $4267 by averaging the cost of its likely competitors. Brodalumab's effectiveness as a treatment for moderate-to-severe plaque psoriasis is high in clinical trials, but its estimated cost placed it as the fourth most cost-effective targeted immunomodulatory drug in the ICER report. On its approval in February 2017, brodalumab's newly estimated base price was $3900, based on its prelaunch price. Calculations using this base price placed brodalumab as the most cost-effective option among targeted immunomodulators in this setting. At the time this current article was written, brodalumab's cost was $3500, making it even more cost-effective.

Conclusion: Because payers, providers, and patients are all concerned with achieving better outcomes for the often painful and disfiguring disease of plaque psoriasis, while controlling costs, updating cost-effectiveness data when new pricing information becomes available may reveal significant cost differences to help stakeholders make better decisions about their population's healthcare outcomes and costs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404800PMC
February 2019

Preapproval Information Exchange: Perspectives of U.S. Population Health Decision Makers on Preferences for Early Engagement with Investigational Therapies.

J Manag Care Spec Pharm 2019 Feb;25(2):164-173

1 University of Utah College of Pharmacy, Salt Lake City, and Millcreek Outcomes Group, Salt Lake City, Utah.

Background: Preapproval information exchange (PIE) is the communication of clinical and health care economic information (HCEI) on therapies in development between U.S. population health decision makers (PHDMs) and drug manufacturers before regulatory approval. Early access to HCEI can help PHDMs plan budgets, inform formulary coverage decisions, and accelerate policy development to improve patient access to innovative health technologies. While recent FDA guidelines and proposed legislation aim to clarify definitions and execution of PIE, the level of U.S. PHDMs' awareness and preferences for early engagement with investigational therapies is unclear.

Objectives: To (a) assess U.S. PHDMs' current knowledge and perceptions of PIE and (b) identify their preferences for PIE, in order to shape future development of related guidelines and policy.

Methods: An expert panel of 5 U.S. PHDMs representing national and regional payers from integrated health plans, pharmacy benefit management, and specialty pharmacy organizations participated in a 2-round modified Delphi process. A targeted literature review of PIE was used to develop a web-based survey administered to the panel. Survey responses were grouped by consensus, with ≥ 80% agreement or disagreement as the threshold in round 1. In round 2, content experts moderated an inperson meeting where panelists deliberated and then revoted on round 1 nonconsensus topics.

Results: In the round 1 survey, the panelists reached consensus on 35 of 54 (65%) multiple-choice questions. In the round 2 face-to-face discussion, 19 nonconsensus questions were debated. One question was removed due to duplication, and consensus was achieved on 16 additional questions, with 2 items of nonconsensus remaining. Overall, consensus was achieved on 51 of 53 topics (96%). There was full consensus by the panelists that PIE should encompass new molecular entities and new indications of marketed therapies. Panelists completely agreed on the need for a legislative "safe harbor" for PIE. Four of five panelists reported that the value of PIE was high to PHDMs, and they expressed a strong preference for peer-to-peer conversations with manufacturers' medical or outcomes liaisons for PIE. The main topic of nonconsensus was the optimal timing of PIE.

Conclusions: This panel of U.S. PHDMs achieved consensus on the value of PIE to proactively budget, make informed formulary decisions, and develop pharmaceutical policy to facilitate patient access to new therapies. The PHDM panel's preferences for PIE should be considered in legislative discussions and planning for future PIE by PHDMs and manufacturers. The full contribution of PIE to improving the U.S. health system can best be realized under a safe harbor that allows U.S. PHDM and manufacturer experts to engage in robust scientific and economic discourse. Additional research and broad stakeholder engagement is needed to advance the development of formal U.S. PIE guidelines.

Disclosures: This study was funded by GlaxoSmithKline (GSK). Brixner, Oderda, and Biskupiak are principals of Millcreek Outcomes Group, a consultancy that received funding from GSK to conduct this study. Marciniak and Woodward are employees of GSK and own stock in GSK. Seifter was employed by GSK at the time of this study. Neumann served as external health policy advisor for this study and has consulted or served on advisory boards with Merck, Bayer, Pacira, Novo Nordisk, Amgen, Abbvie, Boston Health Economics, Vertex, Precision Health Economics, the Congressional Budget Office, CEA Registry Sponsors, Axovant, Veritech, Janssen, Parateck, Avexis, GSK, Celegene, Bluebird, Roche, Sage, Sarepta, Biogen, and Ipsen. Neumann also reports grants from Amgen, Lundbeck, Gates, NPC, Alzheimer's Association, and NIH.
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http://dx.doi.org/10.18553/jmcp.2019.25.2.164DOI Listing
February 2019

The effect of a prescription order requirement for pharmacist-administered vaccination on herpes zoster vaccination rates.

Vaccine 2019 01 15;37(4):631-636. Epub 2018 Dec 15.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA. Electronic address:

Objective: To determine the effect of a prescription order requirement for pharmacist-administered zoster vaccination on zoster vaccination in adults aged 60+.

Methods: A 50-state law review of statutes and regulations regarding pharmacists' ability to administer the zoster vaccine with/without a prescription order was performed. States were classified as prescription order required or not required as of January 1, 2014. Data on adults aged 60+ were obtained from the 2014 Behavioral Risk Factor Surveillance System (BRFSS). Chi-square tests and multilevel logistic regression models with and without propensity scores methods were used.

Results: Of the 50 states, 39 and the District of Columbia did not require a prescription order. After propensity score matching, zoster vaccination rates for adults ages 60 and older were significantly higher in states that did not require a prescription order (23.0% vs 21.1%, p = 0.0022). The propensity score-matched multilevel logistic regression model for adults aged 60+ found modestly higher odds of HZ vaccination for states that removed the prescription order requirement (OR 1.17, 95% CI 1.01-1.35). Similar estimates were found across other methodologies employed and age strata, although statistical significance varied.

Conclusions: Prescription order requirements are associated with HZ vaccination rates. By removing a prescription order requirement, states may be able to promote increases in HZ vaccination in adults aged 60+.
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http://dx.doi.org/10.1016/j.vaccine.2018.12.003DOI Listing
January 2019

Budget impact of including ribociclib in combination with letrozole on US payer formulary: first-line treatment of post-menopausal women with HR+/HER2- advanced or metastatic breast cancer.

Curr Med Res Opin 2018 12 17;34(12):2143-2150. Epub 2018 Aug 17.

d Novartis , East Hanover , NJ , USA.

Objectives: The combination of a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor with the aromatase inhibitor letrozole is a safe and effective alternative to letrozole monotherapy for first-line hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study evaluates the budget impact of using the CDK 4/6 inhibitor ribociclib plus letrozole as a first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer, from a United States (US) payer perspective.

Methods: A cohort-based budget impact model was used to calculate the incremental cost of introducing ribociclib plus letrozole over three years for the target population. The analysis compared two scenarios: treatment options excluding or including ribociclib plus letrozole. Market shares were derived from market research and the assumption was the introduction of ribociclib plus letrozole would only displace existing CDK-based therapies. Treatment duration was based on the median time to treatment discontinuation or median progression-free survival for first-line treatment, and on clinical trial data for second- and third-line treatment. Acquisition costs were based on wholesale acquisition costs and considered co-payment. Costs for drug administration and monitoring, subsequent therapy, and relevant adverse events were included.

Results: Of 1 million insured members, 263 were eligible for CDK 4/6 inhibitor treatment. Cumulative total savings with ribociclib plus letrozole were $3.01M over three years, corresponding to a cumulative incremental cost saving of $318.11 per member treated per month.

Conclusions: In the US, ribociclib plus letrozole represents a cost-saving first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.
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http://dx.doi.org/10.1080/03007995.2018.1503484DOI Listing
December 2018

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective.

J Manag Care Spec Pharm 2018 Jun;24(6):514-523

4 Novartis, East Hanover, New Jersey.

Background: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated. Cost-effectiveness studies are required to inform payers and clinical decision makers on the money value of combination treatment in clinical practice.

Objective: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer from a U.S. private third-party payer perspective.

Methods: A partitioned survival model including 3 health states (progression free, with either overall response or stable disease; progressed disease; and death) simulated lifetime costs and outcomes over a 40-year lifetime horizon with a 1-month cycle length. Clinical efficacy data (PFS and overall survival [OS]) were derived from a phase III trial of ribociclib plus letrozole (MONALEESA-2; NCT01958021), a phase II trial of palbociclib plus letrozole (PALOMA-1; NCT00721409), and a Bayesian network meta-analysis. Health care costs included drug acquisition and monitoring, disease management, subsequent therapies, and serious drug-related adverse events. Effectiveness was measured in life-years, derived from survival projections, and in quality-adjusted life-years (QALYs), calculated from time spent in each state combined with health-state utility values. A one-way deterministic sensitivity analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis.

Results: Ribociclib plus letrozole was dominant versus palbociclib plus letrozole, with a cost saving of $43,037 and a gain of 0.086 QALYs. Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY of 0.689, equating to an incremental cost-effectiveness ratio of $210,369 per QALY. Key model drivers included OS HRs for palbociclib plus letrozole versus letrozole and for ribociclib plus letrozole versus letrozole, the PFS HR for palbociclib plus letrozole versus letrozole, PD health-state costs, utility of response, and cost discount rate. The probabilities that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained were 1.6%, 6.3%, and 50.5%, respectively.

Conclusions: In the United States, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Ribociclib plus letrozole is also cost-effective versus letrozole monotherapy at willingness-to-pay thresholds greater than $198,000 per QALY (for probabilistic analysis).

Disclosures: Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.
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http://dx.doi.org/10.18553/jmcp.2018.24.6.514DOI Listing
June 2018

Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients.

J Opioid Manag 2017 Sep/Oct;13(5):291-301

Pfizer Inc., Durham, North Carolina.

Objectives: To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population.

Design: A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/or abuse-related events, opioid discontinuation, and switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated.

Results: Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223-1,410 and associated costs ranged from $20-$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions.

Conclusions: A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.
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http://dx.doi.org/10.5055/jom.2017.0398DOI Listing
April 2018

Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.

J Am Coll Cardiol 2017 Sep;70(11):1311-1321

CARMA Center, Division of Cardiovascular Medicine, School of Medicine, University of Utah, Salt Lake City, Utah. Electronic address:

Background: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF.

Objectives: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF.

Methods: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk.

Results: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98).

Conclusions: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA.
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http://dx.doi.org/10.1016/j.jacc.2017.07.758DOI Listing
September 2017

Effect of Inpatient Dobutamine versus Milrinone on Out-of-Hospital Mortality in Patients with Acute Decompensated Heart Failure.

Pharmacotherapy 2017 Jun;37(6):662-672

Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, Utah.

Study Objective: To determine the effect of dobutamine versus milrinone on out-of-hospital mortality in the treatment of patients with acute decompensated heart failure (ADHF).

Design: Propensity score weighted retrospective cohort study with mortality as the primary outcome.

Setting: An academic health care system.

Patients: Five hundred adult patients with a prior history of heart failure who survived a hospitalization for ADHF that included treatment with dobutamine or milrinone between January 1, 2006, and April 30, 2014.

Measurements And Main Results: ADHF events were defined as a hospitalization with receipt of an intravenous loop diuretic or a brain-type natriuretic peptide (BNP) value greater than 400 pg/ml during the hospitalization. Patients were followed until death or 180 days from hospital discharge. Risk ratios (RRs) for mortality associated with dobutamine compared with milrinone were calculated at 15, 30, and 180 days postdischarge using Poisson regression with robust error variance. Mean age was 62.7 years, 65.4% were male, and 48.2% had a mean left ventricular ejection fraction (LVEF) of 40% or lower. Overall, 55 (18%) of dobutamine-treated versus 23 (12%) of milrinone-treated patients died during follow-up (RR 1.27, 95% confidence interval [CI] 0.76-2.13, p=0.360). For death from cardiovascular causes, the RR for dobutamine was 1.49 (95% CI 0.79-2.82, p=0.214). For death from worsening heart failure, the RR for dobutamine was 2.55 (95% CI 1.07-6.10, p=0.035). A trend toward significance was observed at day 15 after discharge for all mortality analyses (all p values < 0.10).

Conclusions: Dobutamine was associated with higher short-term out-of-hospital mortality compared with milrinone in patients with ADHF. These results replicate and extend prior associations with mortality and should be confirmed in a prospective study.
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http://dx.doi.org/10.1002/phar.1939DOI Listing
June 2017

Prognostic Implications of Left Ventricular Scar Determined by Late Gadolinium Enhanced Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

Am J Cardiol 2016 10 18;118(7):991-7. Epub 2016 Jul 18.

Division of Cardiovascular Medicine, University of Utah, Salt Lake City, Utah; Comprehensive Arrhythmia Research & Management Center, Salt Lake City, Utah. Electronic address:

Left ventricular (LV) scar identified by late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) is associated with adverse outcomes in coronary artery disease and cardiomyopathies. We sought to determine the prognostic significance of LV-LGE in atrial fibrillation (AF). We studied 778 consecutive patients referred for radiofrequency ablation of AF who underwent CMR. Patients with coronary artery disease, previous myocardial infarction, or hypertrophic or dilated cardiomyopathy were excluded. The end points of interest were major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke/transient ischemic attack. Of the 754 patients who met the inclusion criteria, 60% were men with an average age of 64 years. Most (87%) had a normal LV ejection fraction of ≥55%. LV-LGE was found in 46 patients (6%). There were 32 MACCE over the mean follow-up period of 55 months. The MACCE rate was higher for patients with LV-LGE (13.0% vs 3.7%; p = 0.002). In multivariate analysis, CHA2DS2-VASc score (hazard ratio [HR] 1.36, 95% CI 1.05 to 1.76), the presence of LV-LGE (HR 3.21, 95% CI 1.31 to 7.88), and the LV-LGE extent (HR 1.43, 95% CI 1.15 to 1.78) were independent predictors of MACCE. In addition, the presence of LV-LGE was an independent predictor for ischemic stroke/transient ischemic attack (HR 3.61, 95% CI 1.18 to 11.01) after adjusting for CHA2DS2-VASc score. In conclusion, the presence and extent of LV scar identified by LGE-CMR were independent predictors of MACCE in patients with AF.
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http://dx.doi.org/10.1016/j.amjcard.2016.06.054DOI Listing
October 2016

Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States.

J Clin Lipidol 2016 Jan-Feb;10(1):63-71.e1-3. Epub 2015 Sep 25.

Global Health Economics, Amgen Inc., Thousand Oaks, CA, USA.

Background: Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk.

Objective: To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients.

Methods: Patients included were aged ≥ 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post-index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post-index. Descriptive statistics were used to report results.

Results: There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post-index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C ≥ 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C ≥ 100 mg/dL. At 1 year post-index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event.

Conclusion: There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk.
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http://dx.doi.org/10.1016/j.jacl.2015.09.008DOI Listing
November 2016

Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center.

Pharmacotherapy 2016 Feb 3;36(2):174-86. Epub 2016 Feb 3.

Amgen Inc., Thousand Oaks, California.

Study Objective: To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting.

Design: Retrospective analysis.

Data Source: Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System.

Patients: A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower.

Measurements And Main Results: The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received β-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of β-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a β-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (β-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases.

Conclusion: This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities.
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http://dx.doi.org/10.1002/phar.1701DOI Listing
February 2016

Oral anticoagulant discontinuation in patients with nonvalvular atrial fibrillation.

Am J Manag Care 2016 01 1;22(1):e1-8. Epub 2016 Jan 1.

University of Utah College of Pharmacy, L.S. Skaggs Pharmacy Institute, 30 South 2000 East, Rm 4962, Salt Lake City, UT 84112. E-mail:

Objectives: To identify factors associated with all-cause discontinuation (patient discontinued on their own or physician discontinuation) of oral anticoagulants (OACs) among nonvalvular atrial fibrillation (NVAF) patients.

Study Design: Retrospective cohort study.

Methods: We analyzed the MarketScan claims database from October 2009 to July 2012. Adult patients were eligible if they newly initiated an OAC in the study period, had an atrial fibrillation diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 427.31 or 472.32), and had at least 6 months of continuous enrollment after OAC initiation. Multivariable Cox proportional hazards regression was used to assess factors associated with discontinuation. Adjusted hazard ratios (HRs) and 95% CIs were reported.

Results: Among 12,129 eligible patients, 8143 (67.1%) initiated warfarin and 3986 (32.9%) initiated direct oral anticoagulants (DOACs). Overall, 47.3% of patients independently discontinued during follow-up (mean number of days of follow-up = 416.6 [SD ± 141.7]) with mean time to discontinuation of 120 days (SD ± 114.7). Patients significantly less likely to discontinue included those taking DOACs versus warfarin (HR, 0.91; 95% CI, 0.86-0.97), older patients (≥65 years vs 18 to 34 years) (HR, 0.32; 95% CI, 0.24-0.43), those with diabetes (HR, 0.84; 95% CI, 0.77-0.90), those with prior stroke/transient ischemic attack (HR, 0.65; 95% CI, 0.56-0.75), those with prior pulmonary embolism (HR, 0.71; 95% CI, 0.58-0.88), and those with congestive heart failure (HR, 0.80; 95% CI, 0.74-0.87). Patients with prior bleeding events were significantly more likely to independently discontinue (HR, 1.20; 95% CI, 1.08-1.34).

Conclusions: The risk of independent discontinuation of OAC treatment among NVAF patients was high. Patients on DOACs compared with warfarin and those with several comorbid conditions had significantly lower risk of discontinuation, while those with prior bleeding were more likely to discontinue.
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January 2016

Cost of palliative external beam radiotherapy (EBRT) use for bone metastases secondary to prostate cancer.

J Community Support Oncol 2015 Mar;13(3):95-103

Amgen Inc, Thousand Oaks, California, USA.

Background: Evaluations of the costs of palliative external beam radiation therapy (EBRT) for treatment of bone metastases are limited.

Objective: To summarize EBRT lifetime care patterns in deceased men with metastatic prostate cancer treated in a cancer hospital in the United States.

Methods: A retrospective review of electronic health records identified deceased adult prostate cancer (ICD-9 185.xx) patients with bone metastases (ICD-9 198.5) and who were treated for bone pain and metastasis management with EBRT between January 1, 1995 and December 17, 2012. Common Procedural Terminology codes were used to identify all EBRT episodes (total billed EBRT services; initial and final evaluation) to calculate length of EBRT treatments and per episode costs (2011 US$). Bootstrapping approximated the 95% confidence interval for final cost estimates.

Results: 176 men were identified; 19 (10.8%) had bone metastases in >1 site. Eighty-nine men (50.6%) received >1 EBRT episode (range, 1-6; median, 2), with first episode length ranging from 1-44 calendar days (mean, 13.4; SD, 8.4) at a mean cost of $7,084 (SD, $4,028). About 70% of costs were attributable to hospital charges and 30% to physician charges.

Limitations: Small sample size limits broad applicability to large populations of men with prostate cancer.

Conclusion: Care costs for EBRT constitute one of many costs that should be taken into account when planning for palliative care of prostate cancer and bone metastasis.
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http://dx.doi.org/10.12788/jcso.0115DOI Listing
March 2015

Research to real-world application: experts weigh in on the underuse of anticoagulants.

Am J Manag Care 2014 Dec;20(14 Suppl):s312-8

Although numerous studies have shown that anticoagulants can reduce the risk of stroke and thromboembolic events in patients with nonvalvular atrial fibrillation, they are underprescribed in the clinical setting. While standardized risk scoring assessments are recommended in treatment guidelines to determine when anticoagulant use may be appropriate, they are not widely used in the real-world clinical setting. Many factors contribute to anticoagulant underuse, including patient characteristics and comorbidities. Reluctance to prescribe an anticoagulant may also stem from concerns about bleeding or other perceived risks. In addition, physicians may be discouraged from prescribing anticoagulant therapy, particularly warfarin, if follow-up care and monitoring is potentially unfeasible. Patient fears of treatment and lack of access to the healthcare system also contribute to underuse. Increased awareness and education, medical therapy management programs, better care coordination, and improvements in monitoring and follow-up programs may help to increase the use of anticoagulant therapies in appropriate patients.
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December 2014

Cost implications of formulary decisions on oral anticoagulants in nonvalvular atrial fibrillation.

J Manag Care Pharm 2013 Nov-Dec;19(9):789-98

Pharmacotherapy Outcomes Research Center, University of Utah, 30 South 2000 East, 4th Floor, L.S. Skaggs Pharmacy Institute, Salt Lake City, UT 84112, USA.

Background: Nonvalvular atrial fibrillation (AF) is a major public health issue. The major complication of AF is an increased risk of stroke. Warfarin, long used for stroke prophylaxis in AF patients, has a narrow therapeutic window and numerous food and drug interactions necessitating regular laboratory monitoring. New oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban) may meet the need for predictable anticoagulation with fixed, unmonitored dosing.

Objective: To review costs of monitoring, bleeding, and stroke in AF patients to analyze costs of anticoagulants for stroke prophylaxis in AF patients.

Methods: A literature search on the costs of treating AF used PubMed/MEDLINE databases (to April 2012) focusing on studies in the United States. Key words or MeSH terms were used, such as "observational studies," "oral anticoagulants," "warfarin," "cost of bleeding," "cost of stroke," and "cost of INR monitoring."

Results: The literature focused mainly on short-term, in-hospital expenditures and less on long-term care costs. Annual overall costs per patient for treating AF in the United States ranged from $18,454 to $38,270. Annual incremental costs of treating AF ranged from $8,705 to $16,311. Annual inpatient costs ranged from $7,841 to $22,582 per patient. Annual costs of anticoagulation monitoring ranged from $291 to $943 per patient. Intracranial hemorrhage and major gastrointestinal bleeding with oral anticoagulants were uncommon but expensive: 1-year costs ranged from $7,584 to $193,804. Annual direct costs of stroke in AF patients ranged from $23,143 to $37,620 (incremental cost of $7,824 to $8,232 vs. AF patients without stroke).

Conclusions: AF-associated direct costs are high and can be broken into costs of warfarin monitoring and direct costs of managing consequences of anticoagulant therapy-stroke and bleeding.
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http://dx.doi.org/10.18553/jmcp.2013.19.9.789DOI Listing
June 2014

Application of electronic medical record data for health outcomes research: a review of recent literature.

Expert Rev Pharmacoecon Outcomes Res 2013 Apr;13(2):191-200

Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA.

Electronic medical records (EMRs) have become a common source of data for outcomes research. This review discusses trends in EMR data use for outcomes research as well as strengths and limitations, and likely future developments to help optimize value and use of EMR data for outcomes research. EMR-based studies reporting treatment outcomes published between 2007 and 2012 were predominantly from the USA and Europe. There has been a substantial increase in the number of EMR-based outcomes studies published from 2007-2008 (n = 28) to 2010-2011 (n = 55). Many studies evaluated biometric and laboratory test outcomes in common chronic conditions. However, researchers are expanding the scope of evaluated diseases and outcomes using advanced techniques, such as natural language processing and linking EMRs to other patient-level data to overcome issues with missing data or data that cannot be accessed using standard queries. These advances will help to expand the scope and sophistication of outcomes research in the coming years.
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http://dx.doi.org/10.1586/erp.13.7DOI Listing
April 2013

Cost effectiveness of liposomal doxorubicin vs. paclitaxel for the treatment of advanced AIDS-Kaposi's sarcoma.

J Med Econ 2013 1;16(5):606-13. Epub 2013 Mar 1.

University of Utah, Pharmacotherapy Outcomes Research Center, Salt Lake City, UT 84108, USA.

Objective: Epidemic Kaposi's sarcoma (KS) is one of the most common acquired immune deficiency syndrome (AIDS) defining malignancies, a disease with stigmatized clinical features that characterizes the diagnosis of AIDS. This study aims to perform a cost-effectiveness analysis between liposomal doxorubicin and paclitaxel in treating AIDS-KS.

Methods: A 21 week decision tree analysis was created using a hospital perspective to compare treatment patterns with liposomal doxorubicin and paclitaxel. All costs were calculated in 2011 US dollars and obtained from an academic treatment center. Acquisition costs were obtained from public estimates using wholesale acquisition cost (WAC). Effectiveness was estimated based on a Phase 3 study of liposomal doxorubicin and paclitaxel (Von-Roenn et al.). Adverse events (AEs) associated with treatment and not the disease were included in the analysis. One-way sensitivity analysis was performed to test the robustness of the results.

Results: Cost minimization analysis showed that treatment with liposomal doxorubicin was $18,125 whereas paclitaxel costs $12,347. After accounting for response rate, the results showed that liposomal doxorubicin costs $39,403 versus $21,661 for paclitaxel. This study has some limitations. Clinical data were derived from different clinical trials. In addition, many assumptions were made.

Conclusion: Paclitaxel is dominant due to its lower acquisition cost and high response rate. Acquisition cost of liposomal doxorubicin and paclitaxel are significantly different. After accounting for all the factors that contribute to cost and response rate, paclitaxel is more cost effective than liposomal doxorubicin.
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http://dx.doi.org/10.3111/13696998.2013.777347DOI Listing
November 2013

Characterization of clinical course and usual care patterns in female metastatic breast cancer patients treated with zoledronic acid.

Breast 2013 Aug 23;22(4):495-503. Epub 2012 Oct 23.

Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, University of Utah, 421 Wakara Way, Suite 208, Salt Lake City, UT 84108, USA.

Purpose: To describe usual care received by women with bony metastatic breast cancer (ICD-9: 174.xx and 198.5) treated in a United States specialty cancer hospital, an Electronic Medical Record (EMR)-based retrospective review identified 111 deceased female breast cancer patients ≥18 years of age treated with zoledronic acid (ZOL).

Results: Baseline symptoms included bone pain/fracture (58.6%), breathing difficulties (24.3%), or mental status changes (11.7%). ZOL was started at/after metastatic diagnosis for 75.7% of women (N = 84), with average administration of 15.9 months (median 11.3). Nearly 20% required reduced ZOL doses, most (54.5%) due to impaired renal function; 61.3% discontinued ZOL due to patient death/disease progression. Adverse events were reported in 10.8%, while 0.9% (N = 1) had a documented osteonecrosis of the jaw.

Conclusions: Initiation of palliative care should be considered early in patients with a history of metastatic breast cancer who report bone pain or other skeletal-related events.
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http://dx.doi.org/10.1016/j.breast.2012.09.012DOI Listing
August 2013

Implementing CER: what will it take?

J Manag Care Pharm 2012 Jun;18(5 Supp A):S19-29

University of Utah, College of Pharmacy, Dept. of Pharmacotherapy, 421 Wakara Way, Salt Lake City, UT 84108, USA.

Background: Comparative effectiveness research (CER) is undeniably changing how drugs are developed, launched, priced, and reimbursed in the United States. But most organizations are still evaluating what CER can do for them and how and when they can utilize the data. A roundtable of stakeholders, including formulary decision makers, evaluated CER's possible effects on managed care organizations (MCOs) and what it may take to fully integrate CER into decision making.

Objectives: To examine the role of CER in current formulary decision making, compare CER to modeling, discuss ways CER may be used in the future, and describe CER funding sources.

Summary: While decision makers from different types of organizations, such as pharmacy benefit management (PBM) companies and MCOs, may have varying definitions and expectations of CER, most thought leaders from a roundtable of stakeholders, including formulary decision makers, see value in CER's ability to enhance their formulary decision making. Formulary decision makers may be able to use CER to better inform their coverage decisions in areas such as benefit design, contracting, conditional reimbursement, pay for performance, and other alternative pricing arrangements. Real-world CER will require improvement in the health information technology infrastructure to better capture value-related information. The federal government is viewed as a key driver and funding source behind CER, especially for infrastructure and methods development, while industry will adapt the clinical development and create increasing CER evidence. CER then needs to be applied to determining value (or cost efficacy).

Conclusions: It is expected that CER will continue to grow as a valuable component of formulary decision making. Future integration of CER into formulary decision making will require federal government and academic leadership, improvements in the health information technology infrastructure, ongoing funding, and improved and more consistent methodologies.
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http://dx.doi.org/10.18553/jmcp.2012.18.s5-a.S19DOI Listing
June 2012
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