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BACKGROUND: In oncology, especially with accelerated regulatory approvals and niche populations, US payers appreciate all evidence that can help support formulary decision making, including evidenc...

Aim: HTX-011 (ZYNRELEF™) is an extended-release, dual-acting local anesthetic containing bupivacaine and meloxicam. In bunionectomy and herniorrhaphy studies, HTX-011 resulted in less postoperative pain and less opioid consumption versus bupivacaine HCl. Here we evaluate HTX-011 in patients aged ≥65 years. Materials & methods: Patients received placebo, bupivacaine HCl or HTX-011 following surgery. End points included pain intensity, total opioid consumption, opioid-free patients and safety. Results: HTX-011-treated patients reported lower postoperative pain through 72 h versus bupivacaine HCl and placebo. Elderly patients administered HTX-011 used fewer opioids versus bupivacaine HCl, and a greater proportion remained opioid-free through 72 h. HTX-011 was well tolerated with a safety profile similar to bupivacaine HCl and placebo. Conclusion: HTX-011 maintained effectiveness and was well tolerated in elderly patients. Clinical Trial registration numbers: NCT03295721 and NCT03237481

BACKGROUND: To support oncology formulary decisions, especially with accelerated regulatory approvals and niche populations, payers desire data beyond what regulators review. Economic models showin...

The treatment of postsurgical pain with prescription opioids has been associated with persistent opioid use and increased health care utilization and costs.To compare the health care burden between opioid-naive adult patients who were prescribed opioids after a major surgery and opioidnaive adult patients who were not prescribed opioids.Administrative claims data from the IBM Watson Health MarketScan Research Databases for 2010-2016 were used. Opioid-naive adult patients who underwent major inpatient or outpatient surgery and who had at least 1 year of continuous enrollment before and after the index surgery date were eligible for inclusion. Cohorts were defined based on an opioid pharmacy claim between 7 days before index surgery and 1 year after index surgery (opioid use during surgery and inpatient use were not available). To ensure an opioid-naive population, patients with opioid claims between 365 and 8 days before surgery were excluded. Acute medical outcomes, opioid utilization, health care utilization, and costs were measured during the post-index period (index surgery hospitalization and day of index outpatient surgery not included). Predicted costs were estimated from multivariable log-linked gamma-generalized linear models.The final sample consisted of 1,174,905 opioid-naive patients with an inpatient surgery (73% commercial, 20% Medicare, 7% Medicaid) and 2,930,216 opioid-naive patients with an outpatient surgery (74% commercial, 23% Medicare, and 3% Medicaid). Opioid use after discharge was common among all 3 payer types but was less common among Medicare patients (63% inpatient/43% outpatient) than patients with commercial (80% inpatient/75% outpatient) or Medicaid insurance (86% inpatient/81% outpatient). Across all 3 payers, opioid users were younger, were more likely to be female, and had a higher preoperative comorbidity burden than nonopioid users. In unadjusted analyses, opioid users tended to have more hospitalizations, emergency department visits, and pharmacy claims. Adjusted predicted 1-year post-period total health care costs were significantly higher (Filling an outpatient opioid prescription (vs. no opioid prescription) in the 1 year after inpatient or outpatient surgery was associated with increased health care utilization and costs across all payers.Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Brummett is a paid consultant for Heron Therapeutics and Recro Pharma and reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holding a patent for peripheral perineural dexmedetomidine. Oderda is a paid consultant for Heron Therapeutics. Pawasauskas is a paid consultant to Heron Therapeutics and Mallinckrodt Pharmaceuticals. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Portions of this work were presented as a poster at the AMCP Managed Care and Specialty Pharmacy Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

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.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.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.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.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.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.

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

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.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.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.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.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.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.

Reliance on prescription opioids to manage pain has been associated with increases in diversion, overdose, and addiction. Prevalence of misuse and abuse has been shown to be higher among government-insured populations than commercially insured populations. However, the prevalence and costs of misuse/abuse among the Medicare fee-for-service (FFS) population has not been studied.To (a) determine the prevalence and costs of prescription opioid misuse/abuse and (b) evaluate the prevalence and costs associated with those identified as at risk for opioid misuse/abuse in Medicare FFS beneficiaries.This retrospective case-control study used Medicare claims data for the calendar years of 2010 and 2011 and included Medicare beneficiaries aged at least 18 years. The index date was the date of first diagnosed misuse/abuse or at risk for abuse and had to occur between July 1, 2010, and June 30, 2011, and beneficiaries had to have at least 6 months continuous eligibility before and after the index date. Matching (1:1) was used for comparing opioid misusers/abusers with nonabuser controls, as well as comparing patients at risk for opioid abuse with controls not at risk for abuse. Controls were matched to cases by gender, age, disability, and geographic region. The index date of the control patient was set equal to the index date of the matched case.Prevalence of misuse/abuse in the Medicare FFS population was 13.1 per 1,000 persons, with the majority among patients receiving Medicare based on disability (76.2%). The prevalence of at risk for misuse/abuse was 117.4 per 1,000 persons. Approximately half of the Medicare FFS patients used an opioid. Overall total annual unadjusted mean costs of health care resources were significantly greater for abusers than for matched controls ($46,194 vs. $21,964; P0.0001), with a mean annual excess cost of $24,230. The overall total adjusted 6-month post-index mean costs of health care resources for abusers was significantly greater than that of matched controls ($33,942 vs. $10,754; P0.0001), with a mean excess cost of $23,188.The prevalence of diagnosed abuse among Medicare FFS population (13.1 per 1,000 persons) was higher than other payer groups studied using similar ICD-9-CM codes, and the majority of abuse was among those receiving Medicare based on disability (76.2%). The prevalence of at-risk abuse was 9 times higher than the prevalence of diagnosed abuse. As with other studies, health care resource utilization and costs were significantly greater for diagnosed abuse than matched controls.This study was sponsored by Pfizer. Roland is a Pfizer employee and stockholder and was involved in all aspects of the study as part of a mid-career fellowship in pharmacoeconomics with the University of Utah. Ye and Stevens are employees of University of Utah, and Oderda was an employee of University of Utah, which received financial support from Pfizer in connection with the development of this manuscript. Oderda also reports consulting fees from Pfizer, Trevena, and Pacira, unrelated to this study. The results of this study were presented at the Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, FL, and the AMCP Managed CareSpecialty Pharmacy Annual Meeting 2016; April 19-22, 2016; San Francisco, CA.

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.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.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.In the US, ribociclib plus letrozole represents a cost-saving first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.

Rheumatoid arthritis (RA) management requires monitoring of disease activity to determine course of treatment. Global assessments are used in clinical practice to determine RA disease activity. Monitoring disease activity via biomarkers may also help providers optimize biologic and nonbiologic drug use while decreasing overall drug spend by delaying use of expensive biologic therapies. By testing multiple biologic domains at the same time, a multibiomarker disease activity test may have utility in RA patient management, through improved intra- and inter-rater reliability. This report provides a comprehensive review of studies of objective measures, single biomarkers and multibiomarker disease activity tests as disease activity measures to decrease uncertainty in treatment decisions, and of biomarkers’ potential impact on economic and clinical outcomes of treatment choices.

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

Enhanced recovery pathways have quickly become part of the standard of care for patients undergoing elective surgery, especially in North America and Europe. One of the central tenets of this multidisciplinary approach is the use of multimodal analgesia with opioid-sparing and even opioid-free anesthesia and analgesia. However, the current state is a historically high use of opioids for both appropriate and inappropriate reasons, and patients with chronic opioid use before their surgery represent a common, often difficult-to-manage population for the enhanced recovery providers and health care team at large. Furthermore, limited evidence and few proven successful protocols exist to guide providers caring for these at-risk patients throughout their elective surgical experience. Therefore, the fourth Perioperative Quality Initiative brought together an international team of multidisciplinary experts, including anesthesiologists, nurse anesthetists, surgeons, pain specialists, neurologists, nurses, and other experts with the objective of providing consensus recommendations. Specifically, the goal of this consensus document is to minimize opioid-related complications by providing expert-based consensus recommendations that reflect the strength of the medical evidence regarding: (1) the definition, categorization, and risk stratification of patients receiving opioids before surgery; (2) optimal perioperative treatment strategies for patients receiving preoperative opioids; and (3) optimal discharge and continuity of care management practices for patients receiving opioids preoperatively. The overarching theme of this document is to provide health care providers with guidance to reduce potentially avoidable opioid-related complications including opioid dependence (both physical and behavioral), disability, and death. Enhanced recovery programs attempt to incorporate best practices into pathways of care. By presenting the available evidence for perioperative management of patients on opioids, this consensus panel hopes to encourage further development of pathways specific to this high-risk group to mitigate the often unintentional iatrogenic and untoward effects of opioids and to improve perioperative outcomes.

Supplemental Digital Content is available in the text., New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients’ and providers’ perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Objective To evaluate the relationships between benzodiazepine use and (1) health care utilization and (2) suicide risk in veterans diagnosed with posttraumatic stress disorder (PTSD). Methods This propensity-matched retrospective cohort study included veterans diagnosed with 1 ICD-9 code for PTSD who were active users of the Veterans Affairs health care system between January 1, 2001, and December 31, 2014. Exposure included at least 1 thirty-day prescription of a benzodiazepine within 1 year following PTSD diagnosis among patients with no recent history of benzodiazepine use. The primary outcomes were health care utilization and suicidal behavior. Results A total of 242,493 of 1,134,201 eligible veterans were included in the propensity-matched cohort, 80,831 (7.13%) of whom were prescribed benzodiazepines. Veterans with PTSD who received benzodiazepines had significantly more hospitalizations (incident rate ratio [IRR] = 1.27; 95% CI, 1.10-1.47) and emergency department (IRR = 1.16; 95% CI, 1.13-1.20), general outpatient (IRR = 1.19; 95% CI, 1.16-1.21), outpatient mental health (IRR = 1.49; 95% CI, 1.41-1.57), and total mental health (IRR = 1.37; 95% CI, 1.34-1.40) visits. Benzodiazepine users had a significantly greater risk of death due to suicide (hazard ratio [HR] = 2.74; 95% CI, 2.40-3.13) and were significantly more likely to have medically documented suicide attempts (HR = 1.85; 95% CI, 1.65-2.08) and suicidal ideation (HR = 1.57; 95% CI, 1.48-1.67). Conclusions Benzodiazepine users had higher rates of health care utilization and were more likely to attempt and complete suicide than patients without benzodiazepine exposure. This study strengthens the empirical evidence against the use of benzodiazepines in veterans with PTSD. Prescribers should weigh the benefits and risks-especially the almost 3-fold increase in suicide risk-when prescribing benzodiazepines in these patients.

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.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.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.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.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).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.

Painful diabetic neuropathy (PDN) affects nearly half of patients with diabetes. The objective of this study was to compare the cost-effectiveness of starting patients with PDN on pregabalin (PRE), duloxetine (DUL), gabapentin (GABA), or desipramine (DES) over a 10-year time horizon from the perspective of third-party payers in the United States. A Markov model was used to compare the costs (2013 $US) and effectiveness (quality-adjusted life-years [QALYs]) of first-line PDN treatments in 10,000 patients using microsimulation. Costs and QALYs were discounted at 3% annually. Probabilities and utilities were derived from the published literature. Costs were average wholesale price for drugs and national estimates for office visits and hospitalizations. One-way and probabilistic (PSA) sensitivity analyses were used to examine parameter uncertainty. Starting with PRE was dominated by DUL as DUL cost less and was more effective. Starting with GABA was extendedly dominated by a combination of DES and DUL. DES and DUL cost $23,468 and $25,979, while yielding 3.05 and 3.16 QALYs, respectively. The incremental cost-effectiveness ratio for DUL compared with DES was $22,867/QALY gained. One-way sensitivity analysis showed that the model was most sensitive to the adherence threshold and utility for mild pain. PSA showed that, at a willingness-to-pay (WTP) of $50,000/QALY, DUL was the most cost-effective option in 56.3% of the simulations, DES in 29.2%, GABA in 14.4%, and PRE in 0.1%. Starting with DUL is the most cost-effective option for PDN when WTP is greater than $22,867/QALY. Decision makers may consider starting with DUL for PDN patients.

A 2009 systematic review found that the total cost of prescription opioid abuse in 2001 in the United States was approximately $8.6 billion and medical expenses were estimated to be $15,884 for opioid abusers and $1,830 for nonabusers. A search was conducted for English publications on the cost of prescription opioid abuse and misuse from 2009 to 2014. The initial literature search identified 5,412 citations. Title and abstract review selected 59 for further review. The final review process resulted in 16 publications for inclusion that examined cost from the payer perspective. Mean costs to the payer for abusers were $23,000–$25,000 per year and excess costs approximately $15,000 per patient. Three papers were identified that presented societal costs, including direct and indirect costs such as criminal justice costs and costs associated with lost productivity. The strongest evidence suggests that societal cost is in excess of $50 billion per year in the United States. Prescription opioid abuse and misuse is a common and important problem throughout the world that has significant associated societal costs and excess medical costs.

This retrospective study utilized a large, national hospital database to assess the impact of opioid-related adverse events (ORADE) on patient outcomes following selected surgical procedures known to require postoperative pain control.Outcomes of patients with administratively documented ORADE were compared to those without. Multivariate regression determined differences in hospital costs; length of stay (LOS); odds of individuals being an outlier in total cost and LOS; and having a 30-day all-cause readmission.Among 319,898 surgeries of interest, 12.2% of patients experienced an ORADE. Patients had higher adjusted mean costs ($22,077 [95% CI 21,823-22,333] vs. $17,370 [95% CI 17,238-17,503]; p0.0001) and greater LOS (7.6 [95% CI 7.5-7.6] vs. 4.2 days [95% CI 4.2-4.2]; p0.0001). Adjusted odds of being a total cost and LOS outlier were 2.8 (95% CI 2.7-2.8) and 3.2 (95% CI 3.1-3.3) times greater in the ORADE group. These patients were more likely to be readmitted (OR 1.06, 95% CI 1.02-1.09).Patients exhibiting a documented ORADE had greater overall costs, longer hospitalizations, and increased likelihood for readmission. These results highlight the economic impact associated with opioid use for postsurgical pain management.

This study compared patient characteristics and health care costs between newly treated diabetic painful neuropathy (DPN) patients receiving mono- pharmacotherapy and those receiving combination pharmacotherapy. A retrospective cohort was developed through Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2) database. Patients included were ≥18 years on the date of first DPN prescription: tricyclic antidepressant, opioids, duloxetine, gabapentin, pregabalin, or lidocaine. The authors conducted a simple proportional hazards model comparing times to discontinuation, switch, or addon. Multiple logistic regression was used to identify predictors of combination pharmacotherapy. There were 7145 patients on mono-pharmacotherapy and 421 patients on combination pharmacotherapy. Patients receiving combination pharmacotherapy were 130% more likely to discontinue their medications than patients receiving mono-pharmacotherapy. Female patients and those with7 comorbidities were more likely to be started with combination pharmacotherapy. Elderly patients were less likely to be started with combination pharmacotherapy. The total cost of care difference between mono- and combination pharmacotherapy was not statistically significant (P = .66); therefore, newly treated DPN patients should add on another medication sooner than 30 days when considering combination pharmacotherapy. All first-line medications have similar efficacy; for this reason, cost should be considered in the treatment decision.

The study objective was to assess methodological quality of opioid conversion systematic reviews. The electronic databases PubMed, EMBASE, and Scopus were used to identify the systematic reviews from the earliest available date until April 2012. Studies were not restricted based on type of opioid, country, or languages. Methodological quality was evaluated using the "Assessment of Multiple Systematic Reviews (AMSTAR)." A total of 2772 articles were found from which five met inclusions criteria. No review mentioned about the duplicate study selection and data extraction. Two reviews included a list of studies that were excluded studies. One study did not provided information on the characteristics of primary studies that were included. Of the three reviews that evaluated the quality of primary studies, two used the quality of included studies in formulating conclusions. Only two reviews provided information about conflicts of interest. Of the five included systematic reviews, three reached a moderate score; two had poor quality. Specific recommendations to improve methodological quality would include performing the data selection and extraction in duplicate, listing or showing the flowchart of studies that were included and excluded along with the reasons, including the main studies data illustrating tables, and including an assessment of the quality of the primary included studies.

Pain and depression are major reasons for pharmacotherapy, making the relationship between these two complaints important in defining optimal pharmacotherapy for both. Although the association between the two has been documented in the literature, most of the available work only focused on specific disease group or patients with certain type of pain. Whether the association exists for the general population is still an unsettled issue. The goal of this study was to examine the association between pain and depression and explore the some determinants of depression using national representative survey data for the general population in the United States. This work employed data from Medical Expenditure Panel Survey (MEPS) 2009, with people older than 18 were included in the study. Ordered logistic regression and generalized ordered logistic regression were performed while incorporating complex survey features. Estimation results suggested that depression and physical pain were positively associated. In addition, individuals with better perceived health, older age, male gender, higher family income, and employed were less depressed. Divorced or separated marital status was associated with higher depression level. This work fills the gap in the literature by using nationally representative survey data set to examine the association between physical pain and depression. Levels of physical pain and many socioeconomic factors were found significantly associated with depression.

This paper reviews the economic evaluation literature on pharmacotherapy for migraine and identifies important trends and gaps in the literature. Given the tremendous economic burden of migraine and the availability of various therapies for migraine treatment, economic evaluation of alternative therapies plays a critical role in identifying the most cost-effective therapy to optimize health care resource allocation and clinical decisions. Particularly, physicians and clinical administrators are expected to take an active role in resource allocation decisions at the clinical level. Thus, it is important for them to be familiar with the economic evaluation in migraine pain management, and most importantly, methodologies of economic analyses and the associated shortcomings of published estimates. In this paper, the methodological characteristics of these studies are examined and their results are compared and interpreted. Alternative treatment and health outcome measures are defined and data sources described while methods for assessing the direct and indirect costs are explored. Directions for future research are identified and discussed.

Background: Recent changes in national reimbursement policies expand the ability of pharmacists to seek reimbursement for cognitive services. The quality of pharmacist-provided cognitive services has, until now, remained unassessed. Pharmacists should demonstrate the quality and value of their work to ensure the continued and expanded acceptance of reimbursement for their services. A preliminary step in assessing quality is to compare agreement between pharmacists for basic problem identification. Objective: To quantify agreement between pharmacist reviewers for problem identification among Utah Medicaid recipients. Methods: Five pharmacists retrospectively reviewed drug regimens, patient characteristics, diagnosis codes, and procedures for 80 Medicaid patients in September 2008 and identified drug-related problems (DRPs) in 15 predetermined categories. Data for each patient were reviewed twice, and each combination of 2 pharmacists reviewed the same 8 patients' information. We calculated a reliability coefficient to compare the number of DRPs identified and used prevalence and bias adjusted κ (PABAK) to determine interrater reliability for the presence of a specific DRP. Results: Of the 15 DRPs categorized by pharmacist reviewers, 1 (untreated indications) had a PABAK coefficient of 0.20, indicating a relatively low level of agreement between reviewers. All other DRP categories had good to excellent agreement, with PABAK coefficients ranging between 0.43 and 0.98. Conclusions: Pharmacist reviewers exhibited less variability in DRP identification or categorization than had been expected for most categories. This work supports the conclusion that pharmacists in our center provide a basic and necessary level of quality for problem assessment. Future work is needed to document the impact of this quality on patient outcomes.

To determine in an eligible Utah Medicaid population (1) medical and drug costs associated with treating uterine fibroids (UFs) and (2) the cost and incidence of hysterectomy complications.Medical and drug cost analyses were based on data from 897 premenopausal patients with UFs included in the Utah Medicaid database from 1996 to 2004. UF-related medical and pharmacy costs were determined from first diagnosis of UFs until a related procedure or until estimated menopause. Outcomes for patients treated with a procedure (hysterectomy, myomectomy, or embolization), medication, and watchful waiting (no procedure, no UF-related drug) were compared. When determining hysterectomy complication rates for the population of women in the Medicaid database, a total of 1,323 pre- or postmenopausal patients with UFs were included.Overall, 20% of patients were treated with medication, 33% with a procedure, and 47% with watchful waiting. Mean total UF costs were: $11,996 (procedure), $2,703 (medication), and $2,118 (watchful waiting). Mean eligibility months were 8.8, 28.8, and 14.1, respectively. Costs/eligible month were: $1,358 (procedure), $151 (watchful waiting), and $94 (medication). The mean hysterectomy cost was $12,107.Treatment for UFs is expensive with a mean cost of $5,504 per study patient. The highest costs are seen in patients receiving procedures, which can lead to complications; 15% in this study. Costs for watchful waiting are similar to costs in patients receiving UF-related drugs. Consideration should be given to using non-surgical therapies for the treatment of UFs before procedures are performed.

Purpose The effects of i.v. acetaminophen on adverse events, hospital length of stay (LOS), and overall hospital costs for total hip or knee replacements were evaluated. Methods We conducted a matched-pairs analysis of adult inpatients who underwent elective total hip arthroplasty or total knee arthroplasty in hospitals participating in the Premier Healthcare Alliance from January 1, 2011, to November 30, 2012. Each case who received i.v. acetaminophen on the day of surgery was matched to a control who did not receive i.v. acetaminophen within the same hospital. Treatment groups were analyzed for differences in the rate of adverse effects, LOS, and hospital resource utilization. Results A total of 22,146 cases and controls were similar in terms of age, race, sex, marital status, insurance status, and preoperative comorbidities. Overall adverse events were significantly lower with i.v. acetaminophen (24.3%) than with controls (26.3%, p < 0.001), numerically less frequent in all subgroups, and significantly less frequent for renal, infectious, and miscellaneous adverse events (all p < 0.05). I.V. acetaminophen was also associated with a shorter LOS, with 1 out of 11 patients discharged one day earlier ( p < 0.001) and lower average hospital costs: $16,381 for cases compared with $16,927 for controls ( p < 0.001). Cost savings estimated by structural equation modeling of $547 per patient were due to $325 from direct effects and $222 from indirect effects, the latter mediated through adverse events and reduced LOS. Conclusion In this retrospective cohort study of case-matched patients who underwent total hip or knee replacement surgery, multimodal analgesia with i.v. acetaminophen was associated with improved clinical outcomes in terms of fewer adverse events, shortened LOS, and reduced total hospital resources compared with patients who did not receive i.v. acetaminophen

Study Objectives. To determine the incidence of heparin-induc ed thrombocytopenia (HIT) in patients admitted to a medical service who were given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) to prevent venous thromboembolism, the incremental cost of developing HIT, and the cost consequences of using LMWH to prevent venous thromboembolism in medical patients. Design. Retrospective analysis with a nested case-control. Setting. University-affiliated tertiary-care hospital. Patients. A total of 10,121 adult medical patients admitted between August 1, 2000, and November 2, 2004, received UFH or LMWH to prevent venous thromboembolism during their admission. From these, patients with immune-mediated HIT were identified and served as case patients, and 3‐5 matched control patients were identified for each case patient. Measurements and Main Results. The development of HIT was determined for patients who received LMWH and for patients who received UFH. Costs were compared between the patients with HIT and the matched control patients. The cost of using LMWH to prevent venous thromboembolism was compared with the cost of using UFH. In patients receiving UFH and those receiving LMWH, the incidence of HIT was 0.51% (43/8420) and 0.084% (1/1189), respectively (p=0.037), with an overall incidence of 0.43% (44/10,121). Admissions that included development of HIT incurred an average cost of $56,364 compared with $15,231 (p

BACKGROUND: Despite numerous reports of state Medicaid drug utilization review (DUR) programs, little data are available about the prevalence of drugrelated problems (DRPs) in Medicaid patients. A university-based, pharmacist-run DUR program for high utilizers was created as an alternative to imposition of a statutory limit of 7 medications per month in the Utah Medicaid program in 2002. The DUR program was designed to suggest ways that high-utilizing patients could decrease their total number of medications to 7 or fewer prior to imposition of the 7-medication limit at some time in the future. OBJECTIVE: To describe the experience in 1 Medicaid DUR program and to report the prevalence of DRPs and cost-saving opportunities (CSOs) among a population of Medicaid recipients who were high utilizers of prescription drugs. METHODS: DRPs were identified by 5 clinical pharmacists employed by the Drug Regimen Review Center (DRRC) in Salt Lake City. The purpose of the center was to provide drug therapy review services for a select number of Utah Medicaid recipients (200-300 per month) who exceeded a 7-medication limit during the calendar years 2003 and 2004. RESULTS: Out of 391,890 eligible Medicaid recipients, 242,411 (62%) received at least 1 medication, and 16,958 (4.3%) exceeded the 7-medication limit during the review period. Of those exceeding the limit, the DRRC reviewed a total of 3,706 (21.9%) patients, representing the highest utilizers by volume of medication. The prevalence of DRPs considered clinically important in the review cohort was 79.7% of patients, including therapeutic duplications in 54.6% of patients, dose form optimization in 29.7%, and inappropriate uncoordinated care in 25.3%. The average pharmacy cost per month for patients with at least 1 DRP was $1,081; by contrast, the average pharmacy cost per month for all other patients receiving at least 1 prescription was $91. CONCLUSIONS: Approximately 4% of Medicaid recipients exceeded the 7-medication monthly limit. Among the 22% highest utilizers in this group, 48% of nursing home residents and 87% of ambulatory recipients had at least 1 DRP, or an overall rate of 80% of high-use Medicaid recipients or as much as 3.2% of the Medicaid population.

The objective of this study was to examine the relationship of work loss associated with gastro- the relationship of work loss associated with gastro- the relationship of work loss associated with gastro-esophageal reflux disease (GERD) and peptic ulcer disease (GERD) and peptic ulcer disease (PUD) in a large population of employed individuals in the United States (US) and quantify the individuals in the United States (US) and quantify the economic impact of these diseases to the employer.A proprietary database that contained work place absence, disability and workers' compensation data in addition to prescription drug and medical claims was used to answer the objectives. Employees with a medical claim with an ICD-9 code for GERD or PUD were identified from 1 January 1997 to 31 December 2000. A cohort of controls was identified for the same time period using the method of frequency matching on age, gender, industry type, occupational status, and employment status. Work absence rates and health care costs were compared between the groups after adjusting for demo graphic, and employment differences using analysis of covariance models.There were significantly lower (p0.05) prescription, and outpatient costs in the controls compared to the disease groups, although the eta-square values were very low. The mean work absence attributed to sick days was 2.8 (+/- 2.3) for controls, 3.4 (+/- 2.5) for GERD, 3.2 (+/- 2.6) for PUD, and 3.2 (+/- 2.3) days for GERD + PUD. For work loss, a significantly higher (p0.05) rate of adjusted all-cause absenteeism and sickness-related absenteeism were observed between the disease groups versus the controls. In particular, controls had an average of 1.2 to 1.6 days and 0.4 to 0.6 lower all-cause and sickness-related absenteeism compared to the disease groups. The incremental economic impact projected to a hypothetical employed population was estimated to be $3441 for GERD, $1374 for PUD, and $4803 for GERD + PUD per employee per year compared to employees without these diseases.Direct medical cost and work absence in employees with GERD, PUD and GERD + PUD represent a significant burden to employees and employers.

Many underserved patients in Utah lack insurance coverage for health care and prescription drugs but are provided medical care in community health centers (CHCs). Before June 2000, comprehensive pharmacy services were not provided to these patients at a Utah CHC. As part of a Health Resources and Services Administration grant, a collaborative agreement between the University of Utah College of Pharmacy and Utah CHCs was established so that a faculty clinician who is a certified diabetes educator (CDE) could provide diabetes education and care to underserved patients. The College of Pharmacy faculty clinician (pharmacist CDE) collaborated with physicians and midlevel practitioners to provide diabetes education and care for 176 patients. In addition to initial diabetes education, the pharmacist CDE provided continuing disease management by providing information and feedback to patients and recommendations to providers. The pharmacist CDE conducted continuing chart reviews to track certain parameters, such as laboratory test results for hemoglobin A 1c (A1C) and lipid levels, and blood pressure. Patients were followed for 1-3 years. The same outcome data were also collected for 176 patients with diabetes mellitus in another CHC clinic to provide a comparison group. Total cholesterol, low-density lipoprotein cholesterol, A1C, and triglyceride levels declined significantly from baseline at both sites. However, more patients who were provided care by the pharmacist CDE reached the American Diabetes Association A1C target goal of below 7%.

DAVID C. YOUNG, PHARM.D., is Clinical Pharmacist, Intermountain Cystic Fibrosis Adult Center (ICFAC), Salt Lake City, UT, and Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Utah (UU), Salt Lake City. KRISTIN BLEYL, R.N., is Clinical Coordinator and TERESA CLARK, R.R.T., is Respiratory Therapist, ICFAC. GARY ODERDA, PHARM.D., M.P.H., is Director, Pharmacotherapy Outcomes Research Center, and Professor, Department of Pharmacy Practice, College of Pharmacy, UU. THEODORE G. LIOU, M.D., is Director, ICFAC; Assistant Professor Increasing pneumococcal vaccination rates among adults with cystic fibrosis

Cost-of-illness studies measure the overall economic impact of a disease on society. Such studies are important in setting public health priorities and for economic evaluation of new treatments. These studies should take the societal perspective and include both direct and indirect costs. Often indirect costs exceed direct costs. Comparison of cost-of-illness studies from different countries is difficult because of differences in population, currency, the way health care is provided, and other social and political factors.

To assess the incidence and economic impact of postoperative ileus (POI) following laparotomy (open) and laparoscopic procedures for colectomies and cholecystectomies in patients receiving postoperative pain management with opioids.Using the Premier research database, we retrospectively identified adult inpatients discharged between 2008 and 2010 receiving postsurgical opioids following laparotomy and laparoscopic colectomy and cholecystectomy. POI was identified through ICD-9 diagnosis codes and postsurgical morphine equivalent dose (MED) determined.A total of 138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more frequently in colectomy than cholecystectomy and more often when performed by laparotomy. Ileus patients receiving opioids had an increased length of stay (LOS) ranging from 4.8 to 5.7 days, total cost from $9945 to $13,055 and 30 day all-cause readmission rate of 2.3 to 5.3% higher compared to patients without ileus. Patients with ileus received significantly greater MED than those without (median: 285 vs. 95 mg, p 0.0001) and were twice as likely to have POI. MED above the median in ileus patients was associated with an increase in LOS (3.8 to 7.1 days), total cost ($8458 to $19,562), and readmission in laparoscopic surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients undergoing open procedures regardless of MED.Use of opioids in patients who develop ileus following abdominal surgeries is associated with prolonged hospitalization, greater costs, and increased readmissions. Furthermore, higher doses of opioids are associated with higher incidence of POI. Limitations are related to the retrospective design and the use of administrative data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore underestimated in our study. Assessment of pre-existing disease and preoperative pain management was not assessed. Despite these limitations, strategies to reduce opioid consumption may improve healthcare outcomes and reduce the associated economic impact.

This paper introduces a new series in the Journal that will address Outcomes Research and Pharmacoeconomics in Pain & Palliative Care. The goal of the series is to provide an overview of the field of outcomes research that will be geared to clinicians, and to review the outcomes literature in the area of Pain and Palliative Care. This paper defines the common types of outcomes research that are relevant to pain and symptom control. There are a lot of misconceptions about the field including some who look at outcomes research as not really science and not adding to our knowledge about drugs and drug use. To the contrary, outcomes research is a powerful tool, but like many others it has limitations and it is important to understand both what outcomes research is, and what it isn't.

Objective: Providing care to patients with comorbid medical problems may result in complicated, multiple drug therapy regimens, increasing the risk of clinically meaningful drug–drug interactions (DDIs). The purpose of this article is to describe the prevalence of DDIs and provide examples on how to identify and intervene on DDIs. Methods: We described DDI data from the Utah Drug Regimen Review Center, where adult Medicaid patients were reviewed by pharmacists from 2005 to 2009. Patients were selected by the number of prescriptions filled per month (>7) or having a high RxRisk score. Summary: A total of 8860 patients were reviewed, and 16.6% had at least 1 clinically meaningful DDI. Patients with DDIs were slightly younger (mean age 45.2 vs 48.2), more likely to be female (75.0% vs 68.9%), and had more prescriptions per month (13.4 vs 12.5) compared to patients without ( P < .001). Pharmacodynamic DDIs were more prevalent (80.2%) than pharmacokinetic. Pharmacodynamic DDIs mainly occurred with drugs used to treat psychiatric/seizure/sleep disorders (69.4%) and pain/migraine (56.6%). Pharmacokinetic DDIs mainly occurred with drugs used to treat psychiatric/seizure/sleep disorders (53.2%), cardiovascular diseases (46.3%), and infectious diseases (29.6%). Conclusions: Clinically meaningful DDIs are common in patients with complex medication regimens. A systematic approach for identifying DDIs, determining clinical significance, formulating patient-specific recommendations, and communicating recommendations is important in pharmacy practice.

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.

The majority of patients who undergo surgery will require drug therapy for the management of acute postsurgical pain. Effective control of acute postsurgical pain is essential for the patient not only in the short term but also in the long term to prevent the development of chronic pain, which can occur if early acute pain is prolonged. Currently, opioid analgesics are widely used for the management of acute postsurgical pain. Although opioids provide effective postsurgical pain relief, their use is associated with a number of risks, including the development of opioid-related adverse drug events (ORADEs). This review investigates the prevalence of opioid use in the postsurgical setting, the incidence of ORADEs, and the impact of these ORADEs on patient outcomes, length of stay, and costs after common surgeries. According to a national analysis of ORADE incidence, almost 20% of patients treated with opioids experienced an ORADE, with the most common being gastrointestinal effects, central nervous system effects, pruritus, or urinary retention. Studies show that the risk of developing an ORADE is higher in patients receiving higher doses of opioids and in patients undergoing orthopedic or gynecologic surgery compared with patients undergoing general surgery. Elderly patients and those with comorbidities (e.g., obesity, sleep apnea, respiratory disease, urinary disorders) may be particularly vulnerable to ORADE development. Both hospital costs and length of stay are increased in patients with an ORADE versus those without an ORADE. Strategies to reduce the use of opioids after surgery are likely to result in positive outcomes by reducing the incidence of ORADEs and, as a result, reducing treatment costs associated with surgery and improving patient care.

BACKGROUND: Faced with competition from other drugs and therapies, drug manufacturers may be able to use comparative effectiveness research (CER) to help reduce barriers to a new drug’s adoption and integration into formularies. But few examples exist to show how CER can be used effectively and whether the data can make a difference. OBJECTIVES: To examine how CER can help strengthen a new drug’s entry into the market and integration into formularies, and how ongoing CER might be valuable as a drug is implemented in the real world. SUMMARY: A roundtable of 9 representatives from health plans, including formulary decision makers, evaluated how CER in phase 3 development of a new drug can add to the drug’s strength of evidence, helping decision makers understand how and where to integrate that drug into a formulary. The round table participants viewed, as a case study, the development of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist for adults with type 2 diabetes that was approved by the FDA in January 2010. With this drug, CER was incorporated into an extensive type 2 diabetes clinical development program, comparing how the drug worked in comparison with other established therapies. Although there are many antidiabetic drugs available for use, patients with type 2 diabetes often need additional agents. The FDA approved liraglutide with the conclusion that benefits of the drug outweighed potential risks but noted the association with pancreatitis in humans and animal data that showed rare medullary thyroid cancer associated with liraglutide. Roundtable participants agreed that while prelaunch CER can be valuable, ongoing real-world research is also important for confirming expected results, identifying additional uses and indications and managing risks. The participants also suggested opportunities for additional CER studies and made recommendations for manufacturers. CONCLUSIONS: Roundtable thought leaders agreed that well-planned trial designs incorporating CER result in high-quality evidence that may provide sufficient data to support adoption of a new therapy onto the formulary. When more real-world data become available and confirm the phase 3 clinical trial results, decision makers may be able to use the results to change the drug’s position and either lessen or extend its use.

BACKGROUND: In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. OBJECTIVES: To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ’s 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). SUMMARY: As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections.

Study objectives: To investigate the ability of a supranormal dose of N -acetylcysteine to overcome the effects of activated charcoal on N -acetylcysteine bioavailability and to determine the effects of activated charcoal on serum acetaminophen levels. Design, setting, and participants: Ten healthy adult volunteers participated in a controlled cross-over experiment. During phase I (control), subjects ingested 3 g acetaminophen, followed one hour later by the normal loading dose of N -acetylcysteine (140 mg/kg). During phase II (charcoal), subjects ingested 3 g acetaminophen, followed one hour later by 60 g activated charcoal and a supranormal loading dose of N -acetylcysteine (235 mg/kg). Main outcome measures: Serum levels of N -acetylcysteine were measured every 30 minutes for six hours. A serum acetaminophen level was measured at four hours. Results: The area under the curve for N -acetylcysteine was significantly higher for phase II than phase I ( P t -test). Peak N -acetylcysteine and time to peak were not significantly different. The four-hour serum acetaminophen level was significantly lower for phase II than phase I ( P t -test). Diarrhea occurred during both phases, but N -acetylcysteine was otherwise well tolerated. Conclusion: These results suggest that activated charcoal can be used safely for victims of acetaminophen overdose. A beneficial effect in preventing acetaminophen absorption can be expected if it is given within one hour after ingestion. If N -acetylcysteine is needed because of a toxic serum acetaminophen level, bioavailability can be ensured by increasing the N -acetylcysteine loading dose from 140 mg/kg to 235 mg/kg.

This analysis of 25,368 occupational and 7,565 environmental exposure cases characterizes the occupational and environmental exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System. Compared with other poisonings, occupational and environmental exposures were predominantly inhalation exposures rather than ingestions, were more often subacute or chronic, and demonstrated greater morbidity, mortality, and increased use of health care resources. As regional poison centers evolve to fill a critical information void in the management and assessment of environmental and occupational exposures, the American Association of Poison Control Centers Toxic Exposure Surveillance System provides an important, untapped passive surveillance mechanism.

According to the Bylaws of the American Association of Colleges of Pharmacy (AACP), the Academic Affairs Committee shall consider the intellectual, social, and personal aspects of pharmaceutical education. It is expected to identify practices, procedures, and guidelines that will aid faculties in developing students to their maximum potential. It will also be concerned with curriculum analysis, development, and evaluation beginning with the pre-professional level and extending through professional and graduate education. The Committee shall seek to identify issues and problems affecting the administrative and financial aspects of member institutions. The Academic Affairs Committee shall extend its attention beyond intra-institutional matters of colleges of pharmacy to include interdisciplinary concerns with the communities of higher education and especially with those elements concerned with health education. Consistent with a theme of exploring the way in which AACP might foster organizational improvement and success among its institutional members, President Jeffrey Baldwin charged the 2009-10 AACP Academic Affairs Standing Committee to consider the outcomes of the 2009 AACP Curricular Change Summit and the recommendations contained in the 5 background white papers. (1-5) The Committee was charged to synthesize recommendations for AACP and its member institutions with regard to curricular issues that need further development, study or implementation. The Committee reviewed and discussed some of the key outcomes from the AACP Curricular Change Summit. Summit participants were asked to identify the 1 or 2 key outcomes that each graduate should possess upon graduation. The Summit participants concluded that the most essential components were critical thinking and problem solving skills. Another of the major findings from the September 2009 AACP Curricular Change Summit was that the generation of students currently entering undergraduate education and trickling into colleges/ schools of pharmacy learn differently from previous student cohorts. Summit participants suggested that it is not as much what is being taught that is the issue with this generation of learners, but rather the manner in which it is taught; specifically the way critical thinking and problem solving skills are learned. The Changing Learner The ability to educate students is an increasingly complicated task that is impacted by a number of factors including the changing learner. It has become apparent that today's students communicate and may even learn in ways unlike previous generations. (6) These students are more comfortable with technology, having used computers, played videogames, and utilized other interactive technologies throughout most of their lives. They are more adept than previous generations at multi-tasking with media and technology; they listen to music, talk or text and use the computer simultaneously. (7) Some categorize these students as the Net generation, while others refer to them as the Millennial generation. (8) This group, typically born between 1982 and 1991, is the first generation to be raised with Internet availability. (8) Prensky refers to these learners as digital natives, as they are "native speakers" of the digital language of computers and the Internet. (7) Computers, the Internet, online resources, and the desire for instantaneous access are fundamental to these students' lives. (8) They are constantly connected and in communication with others through the use of email, social network sites, instant messages (IM), and text messages. (9) Socialization is very important to this new generation of learners. They are especially attracted to activities that include interaction with their peer group. (6) They like to learn and work in teams, however, their interaction need not be face-to-face. For them, technologies such as email, blogs, and online social networking sites can be just as effective as face-to-face interaction. …

This study determined the associations between opioid abuse, dependence, and poisonings on costs and comorbidities in the Medicaid population. Medicaid patients in the Medicaid Analytic eXtract (MAX) files from 2002 to 2003 with 12 months of continuous eligibility, ageor=12 years, and with an opioid abuse/dependence-related diagnosis, including opioid abuse, dependence, or poisoning, in 2002 (index date) were matched 3:1 to Medicaid patients with no such diagnosis (controls). Medical costs by claim type incurred 12 months post index date were compared as was the prevalence of select comorbidities. The authors conducted a two-step multivariate regression analysis adjusted for patient characteristics that could influence cost outcomes. Opioid abuse/dependence prevalence was 8.7 per 1000 in 2002-2003. A total of 50,162 patients with abuse or dependence-related diagnoses were matched to 150,486 control patients. Total costs were significantly higher for the abuse/dependence patients ($14,537) than matched controls ($8,663) (P.001). When controlling for baseline characteristics, adjusted costs continued to be higher for abuse/dependence patients ($23,556 versus $8,436; P.001). A total of 83.7% of abuse/dependence patients and 51.6% of controls hador=1 of the predefined comorbidities. Other substance abuse (odds ratio [OR] 9.4), hepatitis A, B, or C (OR 8.8), and poisonings (OR 8.5) were highly associated with a diagnoses for opioid abuse or dependence (P.001). Medicaid opioid abuse/dependence patients had more comorbidities and higher medical costs in 2002-2003 than Medicaid control patients. Successful interventions to prevent opioid abuse and manage comorbidities could help to reduce costs associated with opioid abuse in the Medicaid population.

The predictive value of initial clinical evaluation in the management of alkaline corrosive ingestion remains unclear. This multicenter study was designed to determine if specific clinical signs and symptoms following ingestion of alkaline corrosives could predict significant esophageal injury. Alkaline corrosives were defined by a pH greater than or equal to 12. Signs and symptoms previously suggested as predictive of significant esophageal injury were documented on a standardized data form. Esophagoscopy reports were reviewed blinded to initial symptoms. Three hundred thirty-six alkaline-corrosive ingestions were analyzed. The mean number of symptoms reported in patients who did not have esophagoscopy was 1.2, in patients who had esophagoscopy was 3.0, and in patients that had visualized second or third degree esophageal burns was 4.8. Of 88 patients who had esophagoscopy, 63 (72%) had both the esophagoscopy report and initial symptom assessment available. Esophagoscopy was positive, defined as second or third degree esophageal burns, in 18 of 63 cases (29%). All patients with significant burns were symptomatic. No single or group of initially reported signs and symptoms could identify all patients with potentially serious esophageal burns.

Background Maintaining quality of care while managing limited healthcare resources is an ongoing challenge in healthcare. The objective of this study was to evaluate how the impact of drug management programs is reported in the literature and to identify potentially existing quality standards. Methods This analysis relates to the published research on the impact of drug management on economic, clinical, or humanistic outcomes in managed care, indemnity insurance, VA, or Medicaid in the USA published between 1996 and 2007. Included articles were systematically analyzed for study objective, study endpoints, and drug management type. They were further categorized by drug management tool, primary objective, and study endpoints. Results None of the 76 included publications assessed the overall quality of drug management tools. The impact of 9 different drug management tools used alone or in combination was studied in pharmacy claims, medical claims, electronic medical records or survey data from either patient, plan or provider perspective using an average of 2.1 of 11 possible endpoints. A total of 68% of the studies reported the impact on plan focused endpoints, while the clinical, the patient or the provider perspective were studied to a much lower degree (45%, 42% and 12% of the studies). Health outcomes were only accounted for in 9.2% of the studies. Conclusion Comprehensive assessment of quality considering plan, patient and clinical outcomes is not yet applied. There is no defined quality standard. Benchmarks including health outcomes should be determined and used to improve the overall clinical and economic effectiveness of drug management programs.

Study objective: To determine the absorption rate of a supratherapeuticdose of acetaminophen elixir and compare the effect of activated charcoal (AC) given at different time intervals on preventing acetaminophen absorption. Design: Randomized, nonblinded, crossover controlled study. Setting: A certified regional poison control center. Participants: Ten healthy, adult male volunteers from 21 to 39 years old. Interventions: Each subject received 5 g acetaminophen (elixir) on fouroccasions: a control phase plus 30 g of AC administered 15, 30, or 120 minutes after acetaminophen. Serum acetaminophen levels were obtained during the control phase only, and 24-hour urine collections were obtained during all four phases. Measurements and main results: The highest serum acetaminophen levels were measured 1.4 ± 0.52 hours after ingestion, and absorption was 97% complete by a mean of 2.05 hours. The administration of AC at 15, 30, and 120 minutes after acetaminophen reduced urinary recovery of acetaminophen and metabolites by 48%, 44%, and 33%, respectively. Conclusion: AC significantly reduces urinary recovery but not absorption of acetaminophen when administered two hours after acetaminophen elixir.

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)

To evaluate prior analyses that quantify how drug management programs impact health plans and patients with respect to those analyses' effectiveness in measuring program quality.We examined 77 US studies from 1996 to 2007 that evaluated the respective drug management programs of managed care, indemnity insurance, Veterans Health Administration, and Medicaid health plans. Our review included those studies that assessed the ways in which specific drug management tools and the drug management program overall impacted economic, clinical, and/or humanistic outcomes.The 77 studies included in our review used 11 types of outcome end points. A total of 52 studies (68%) incorporated an economic end point; of these, 35 (68%) reported economic data only and did not address clinical or humanistic outcomes. Overall, 33 (43%) evaluated clinical or humanistic end points; of these, 17 (52%) also reported on an economic end point.Although the number of studies evaluating drug management programs has trended upward, only a handful have integrated economic, clinical, and/or humanistic outcomes when assessing the effects these programs have on health plans and patients. The efforts of these researchers to assess the overall quality of drug management programs have fallen short. To ensure that drug management tools have a desired effect on outcomes and medical costs, measures used to evaluate drug management programs must be improved.

To characterize healthcare costs associated with antipsychotic polypharmacy and to investigate predictors of high-cost patients.A retrospective cohort study using Medicaid claims data from California, Nebraska, Oregon, Utah, and Wyoming evaluated 55 383 fee-for-service patients with antipsychotic prescriptions between 1998 and 2002. Polypharmacy was defined as initiating multiple antipsychotic drugs or concomitant antipsychotic therapy (or=60 days). Healthcare costs (drug and non-drug) were summed for 365 days following index antipsychotic claim. Adjusted mean costs were compared to antipsychotic monotherapy. Logistic regression was performed to identify predictors of high-cost patients (top quintile) with regard to patient age, gender, race/ethnicity, mental disorders, hospitalization, index antipsychotic, concomitant psychotropic drugs, and polypharmacy.The average annual prevalence of antipsychotic polypharmacy was 6%. 70-80% of total healthcare expenditures for polypharmacy patients were drug-related. Polypharmacy was associated with significantly higher drug expenditures ($1716-2079) in the year following drug initiation than monotherapy even after adjusting for case mix and index antipsychotic (p0.05). Differences in non-drug expenditures versus monotherapy were smaller and varied by state ranging from a $77 increase in California (p0.001) to a $211 savings in Utah (p = 0.02). In California, polypharmacy alone (OR = 2.69; 95% CI: 2.30-3.16) or in combination with concomitant psychotropics (OR = 6.26; 95% CI: 5.51-7.11) was associated with greater likelihood of being a high-cost patient than monotherapy.Cost savings from limiting antipsychotic polypharmacy could be significant. Caution must be taken in ensuring reductions in polypharmacy do not lead to unintended consequences or shift care to more costly alternatives. Study limitations, including the known shortcomings of claims data and differences across state Medicaid programs, should be considered when interpreting the results of this or any multi-state study.

Purpose This study presents corrected rates and probability (risk) estimates of experiencing a hysterectomy and of selected conditions commonly treated with hysterectomy. Methods Analyses are based on hysterectomy prevalence data from the Behavior Risk Factor Surveillance Survey (calendar years 2000–2006), hysterectomy incidence data from the National Hospital Discharge Survey (2001–2005), and population estimates from the U.S. Census Bureau (2001–2005). The correction involved removing those women without a uterus from the denominator in the rate calculation. Results Corrected hysterectomy incidence rates per 1000 women were greater than the uncorrected rates for women ages 18–44 years (6.0 vs. 5.0), 45–64 years (10.4 vs. 7.1), and 65 years and older (4.9 vs. 2.6). Correcting the rates had a comparatively larger impact in the South. Incidence rates of selected conditions associated with the female reproductive system were greater after correction for hysterectomy prevalence. For example, corrected compared with uncorrected rates of uterine fibroids per 1000 women were 2.9 vs. 2.7 for ages 18–44 and 5.0 vs. 3.4 for ages 45–64. The uncorrected and corrected 10-year risk of being diagnosed with uterine fibroids among women aged 50 who have not previously had fibroids is 3.87 (1 in 26) and 4.54 (1 in 22), respectively. Conclusions The correction method employed produces greater incidence and age-conditional-risk estimates of hysterectomy and of conditions commonly treated with hysterectomy. Corrected rates and age-conditional risk estimates may allow women with intact uteri to better assess their probability of undergoing a hysterectomy and certain other conditions of the reproductive system.