The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly.

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.

Payer perceptions on the use of patient-reported outcomes in oncology decision making.

BACKGROUND: In oncology, especially with accelerated regulatory approvals and niche populations, US payers appreciate all evidence that can help support formulary decision making, including evidence beyond traditional safety and efficacy data from clinical trials. Research suggests payers incorporate patient-reported outcome (PRO) evidence in their decision making and expect the importance of PRO evidence to grow. Greater understanding on payers' use of PRO information in oncology is needed. OBJECTIVE: To assess US payer perceptions regarding the use of PRO evidence in informing oncology formulary decision making. METHODS: A multidisciplinary steering committee involving a measurement specialist, health economics and outcomes research experts, and payers developed a survey containing single-answer, multiple-answer, and free-response questions. The pilot survey was tested at a mini-advisory board with 5 US payers and revised based on feedback. In February 2020, the survey was distributed to 221 US payers through the AMCP Market Insights program and 10 additional payer panelists who were invited to discuss and contextualize the survey results. Results were presented primarily as frequencies of responses and evaluated by plan size, type of health plan, and geography (regional vs national). Differences in categorical data responses were compared using Pearson chi-square or Fisher exact tests. Two-tailed values are reported and a P value less than or equal to 0.05 was used to indicate statistical significance. RESULTS: Overall, 106 of 231 payers (45.9%) completed the survey; 45.5% represented small plans (< 1 million lives), and 54.5% represented large plans (≥ 1 million lives). Respondents were largely pharmacists (89.9%), with 55.6% of all respondents indicating their job was pharmacy administrator. The majority of payers (60.0% of small health plans and 57.8% of large plans) felt PRO evidence from clinical trials is useful. Similarly, the majority of payers (57.8% of small plans and 51.9% of large plans) felt PRO evidence from real-world studies is useful. Almost half (47.1%) suggested formulary review would be influenced by a lack of PRO evidence from oncology clinical trials either somewhat, much, or a great deal. Most payers (78.2%) thought PRO evidence is useful for providing additional context for safety of oncology therapies. More than one-third of payers (34.3%) valued PRO evidence when comparing 2 similar therapies, and 51.5% felt PRO evidence may help in measuring value for value-based agreements. Panelists indicated PRO evidence can be useful for developing treatment pathways for addressing health-related quality of life, informing provider-patient dialogues, and defining progression-free survival length and quality. CONCLUSIONS: US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models. Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers. DISCLOSURES: Pfizer provided funding for this research, and employees of Pfizer contributed to the development of the survey instrument, were involved in the interpretation of the data, and contributed to the discussion and output as authors. Biskupiak, Oderda, 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. Arondekar, Deal, and Niyazov are employees of Pfizer and own Pfizer stock. Qwek was an employee of Pfizer at the time of this project and owns Pfizer stock.

Payer perceptions on the use of economic models in oncology decision making.

BACKGROUND: To support oncology formulary decisions, especially with accelerated regulatory approvals and niche populations, payers desire data beyond what regulators review. Economic models showing financial impact of treatments may help, but data on payers' use of economic models in oncology are limited. OBJECTIVE: To assess payer perceptions regarding use of economic models in informing oncology formulary decisions. METHODS: A multidisciplinary steering committee involving health economists and payers developed a survey containing singleanswer, multiple-answer, and free-response questions. The pilot survey was tested at a mini-advisory board with 5 US payers and revised based on feedback. In February 2020, the survey was distributed to 221 US payers through the AMCP Market Insights program and 10 additional payer panelists, who were invited to discuss survey results. Results were presented primarily as frequencies of responses and evaluated by plan size, type of health plan, and geography (regional vs national). Differences in categorical data responses were compared using Pearson chi-square or Fisher's exact tests. Two-tailed values were reported and an alpha level of 0.05 or less was used to indicate statistical significance. RESULTS: Overall, 106 of 231 payers completed the survey (45.9%); 45.5% represented small plans (< 1 million lives), and 54.5% represented large plans (≥ 1 million lives). Respondents were largely pharmacists (89.9%), and 55.6% indicated that their job was pharmacy administrator. Payers indicated moderate/most interest in cost-effectiveness models (CEMs; 85.3%) and budget impact models (BIMs; 80.4%). Overall, 51.6% of respondents claimed oncology expertise on their pharmacy and therapeutics committees. Large plans were more likely to have expertise in reviewing oncology economic models than small plans (55.6% vs 31.1%, P = 0.015). The most common reasons for not reviewing economic models included "not available at time of review" (44.1%) and "potential bias" (38.2%). Overall, 43.1% of payers conduct analyses using their own data after reviewing a manufacturer-sponsored economic model. To inform formulary decisions, 62.7% of payers use BIMs and 66.7% use CEMs sometimes, often, or always. When comparing therapies with similar safety/efficacy profiles, 68.6% of payers reported economic models as helpful a moderate amount, a lot, or a great deal. Over one-third of payers (37.3%) were willing to partner with manufacturers on economic models using their plans' data. Payers valued preapproval information, data on total cost of care, and early access to models. Concerns remained regarding model transparency and assumptions. CONCLUSIONS: Most US payers reported interest in using economic models to inform oncology formulary decision making. Opportunities exist to educate payers in assessing economic models, especially among small health plans. Ensuring model availability at launch, transparency in model assumptions, and payer-manufacturer partnership in model development may increase the utility of oncology economic models among US payers. DISCLOSURES: Pfizer provided funding for this research, and Pfizer employees led the development of the survey instrument, were involved in the analysis and interpretation of the data, and contributed to the manuscript as authors. Arondekar and Niyazov are employed by Pfizer. Biskupiak, Oderda, 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.

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

BACKGROUND: 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. OBJECTIVE: To assess US payer perceptions regarding the use and relevance of RWE in informing oncology formulary decisionmaking. METHODS: 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. RESULTS: 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. CONCLUSIONS: RWE providing comparative treatment data, validation of NCCN treatment recommendations, and information on off-label usage are appreciated pre launch with post launch validation. DISCLOSURES: 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.

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

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 MET exon 14 (METex14) 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 METex14 skipping mutation is minimal, and the increased drug costs were partially offset by savings in AEs, and progression-related and terminal care costs.

Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden.

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 patients > 18 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.

Health Care Burden Associated with Outpatient Opioid Use Following Inpatient or Outpatient Surgery.

BACKGROUND: The treatment of postsurgical pain with prescription opioids has been associated with persistent opioid use and increased health care utilization and costs. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (P< 0.001) for opioid users than nonopioid users for commercial insurance (inpatient: $22,209 vs. $14,439; outpatient: $13,897 vs. $8,825), Medicare (inpatient: $31,721 vs. $26,761; outpatient: $24,529 vs. $15,225), and Medicaid (inpatient: $13,512 vs. $9,204; outpatient: $11,975 vs. $8,212). CONCLUSIONS: 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. DISCLOSURES: 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.

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.

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.

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

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.

American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives.

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naïve patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use.

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

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.

Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center.

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.

The Prevalence and Cost of Medicare Beneficiaries Diagnosed and At Risk for Opioid Abuse, Dependence, and Poisoning.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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; P < 0.0001), 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; P < 0.0001), with a mean excess cost of $23,188. CONCLUSIONS: 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. DISCLOSURES: 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 Care & Specialty Pharmacy Annual Meeting 2016; April 19-22, 2016; San Francisco, CA.

Benzodiazepines, Health Care Utilization, and Suicidal Behavior in Veterans With Posttraumatic Stress Disorder.

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.

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.

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.

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.

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.

The potential impact of monitoring disease activity biomarkers on rheumatoid arthritis outcomes and costs.

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.

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

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.