Post-infusion Costs Associated with Idecabtagene Vicleucel Treatment for Patients with Relapsed/Refractory Multiple Myeloma in the KarMMa Trial.

INTRODUCTION: Patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM) have poor outcomes with substantial healthcare costs. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, showed deep, durable responses in patients with RRMM in the pivotal phase 2 KarMMa trial (NCT03361748). Healthcare resource utilization (HCRU) and costs were estimated for ide-cel-treated patients in the KarMMa trial. METHODS: Post-infusion costs were estimated based on HCRU data, including facility care, diagnostics, medications, and procedures. Length of stay (LOS) was extracted for inpatient and intensive care unit (ICU) care. All patients had a 14-day post-infusion inpatient stay per trial protocol. Analyses were conducted for patients treated in the United States (US), who received the ide-cel target dose of 450 × 106 CAR + T cells and assuming a 7-day inpatient stay. RESULTS: Overall, 128 patients received ide-cel and were included in this analysis. Mean age was 60 years, 59% were men, and 81% were white. Mean total LOS was 23.9 days. Total estimated costs over 24 months post-infusion were US$115,614 per patient, driven by facility costs (75%; $86,385). Most costs were incurred in the first month (58%; $67,259). The scenario analysis assuming a 7-day inpatient stay showed estimated 24-month costs of $92,294. For the 54 (42%) patients who received ide-cel high dose, total costs over 24 months were $113,298 per patient. CONCLUSIONS: Extrapolation of costs based on HCRU data from patients receiving single-infusion of ide-cel in the KarMMa trial showed substantially reduced HCRU and costs over 2 years after initial treatment. Most costs were incurred during the first month after ide-cel infusion, likely attributable to the 14-day inpatient stay required by the trial protocol. These findings suggest a nominal, incremental monthly cost of care immediately after treatment, which may be lower in routine clinical practice.

Chronic Myeloid Leukemia: Part I-Real-World Treatment Patterns, Healthcare Resource Utilization, and Associated Costs in Later Lines of Therapy in the United States.

Background: Despite advances in tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia in chronic phase (CML-CP), a sizeable proportion of patients with CML-CP remains refractory or intolerant to these agents. Objectives: Treatment patterns, healthcare resource utilization (HRU), and costs were evaluated among patients with CML who received third or later lines of therapy (3L+), a clinical population that has not been previously well-studied, with unmet treatment needs as TKI therapy has repeatedly failed. Methods: Adult patients with CML who received 3L+ were identified in the IBM® MarketScan® Databases (January 1, 2001-June 30, 2019) and the SEER-Medicare-linked database (January 1, 2006-December 31, 2016). Treatment patterns were observed from CML diagnosis. HRU and direct healthcare costs (payer's perspective, 2019 USD) were measured in a 3L+ setting. Results: Among 296 commercially insured patients with 3L+ (median age, 58.5 years; female, 49.7%), the median duration of first-line (1L), second-line (2L), and 3L therapy was 8.5, 4.2, and 8.3 months, respectively. The annual incidence rate during 3L+ was 3.4 for inpatient days, 30.8 for days with outpatient services, and 1.2 for emergency department visits. Mean per-patient-per-month (PPPM) total healthcare costs (pharmacy + medical costs) were $18 784 in 3L+, $15 206 in 3L, and $19 546 in 4L, with inpatient costs driving most of the difference between 3L and 4L (mean [3L] = $2528 PPPM, mean [4L] = $6847 PPPM). Among 53 Medicare-insured patients with 3L+ (median age, 72.0 years; female, 39.6%), the median duration of 1L, 2L, and 3L therapy was 9.7, 5.0, and 7.0 months, respectively. During 3L+, the annual incidence rate was 10.3 for inpatient days, 61.9 for days with outpatient services, and 1.5 for emergency department visits. Mean PPPM total healthcare costs were $14 311 in 3L+, $15 100 in 3L, and $16 062 in 4L. Discussion: Patients with CML receiving 3L+ rapidly cycled through multiple lines. Costs increased from 3L to 4L; in commercially insured patients, inpatient costs were responsible for most of the cost increase between 3L and 4L, underlying these patients' continued need for care. Conclusions: These findings support the need for better treatment options in patients with CML undergoing later lines of therapy.

Eltrombopag treatment of patients with secondary immune thrombocytopenia: retrospective EHR analysis.

Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.

Cost-minimization analysis comparing eltrombopag vs romiplostim for adults with chronic immune thrombocytopenia.

BACKGROUND: Promacta (eltrombopag; EPAG) and Nplate (romiplostim; ROMI) have not been compared in head-to-head trials for treatment of chronic immune thrombocytopenia (cITP); however, indirect treatment comparisons have indicated similar efficacy and safety outcomes, and the drugs are generally accepted as therapeutic alternatives. OBJECTIVE: To determine which of the 2 therapies would result in the lowest overall cost from a US health plan perspective, under the assumption of equivalent clinical efficacy and safety. METHODS: A cost-minimization model was developed in Microsoft Excel. The model incorporated only costs that differ between the treatments, including drug acquisition, administration, and monitoring costs, over a 52-week horizon. Average dosing for EPAG and ROMI was taken from the long-term EXTEND trial and from a published metaanalysis of 14 clinical trials, respectively. ROMI is injectable and EPAG is oral, so only ROMI had administration costs. The model assumed patients used 25 mg EPAG tablets and the 250 µg vial size of ROMI. ROMI wastage was included in drug acquisition costs by rounding up average dose to the nearest whole vial. Monitoring requirements were determined from US prescribing information, with platelet monitoring assumed equal, and hepatic panel testing every 4 weeks for EPAG. The model was adjustable to commercial, Medicare, and Medicaid plan perspectives, with optional inclusion of drug wastage, monitoring, or administration costs. RESULTS: The base case used a commercial plan perspective, with average dosing of 51.5 mg/day for EPAG and 4.20 µg/kg/week for ROMI. The analysis found a cost difference per treated patient of $64,770 in favor of EPAG on an annual basis. Breakdown by unique costs for EPAG included drug-acquisition cost of $123,135 and monitoring cost of $705. Breakdown by unique costs for ROMI included drug-acquisition cost of $183,234, with wastage of $63,179 and administration cost of $5,377. Based on a hypothetical commercial plan with 1 million members and an estimated 11 patients with cITP receiving ROMI, potential annual savings for switching all patients from ROMI to EPAG is $712,473 or $0.06 per member per month. EPAG remained the less costly option for all plan types and assumptions. A sensitivity analysis found that the result was most sensitive to drug pricing and wastage inputs. CONCLUSIONS: Because of lower drug-acquisition costs (including drug wastage) and administration costs, treatment of cITP with EPAG is associated with a lower net cost per patient than ROMI. DISCLOSURES: This study was funded by Novartis Pharmaceuticals Corporation. Proudman, Lucas, and Nellesen are employees of Analysis Group, Inc., which received funding from Novartis Pharmaceuticals Corporation to conduct this study. Patwardhan was employed by Novartis Pharmaceuticals Corporation at the time of this study; Allen is an employee of Novartis. This research was presented as an e-poster at the AMCP 2020 Virtual, April 2020.

Real-world PD-L1 testing and distribution of PD-L1 tumor expression by immunohistochemistry assay type among patients with metastatic non-small cell lung cancer in the United States.

BACKGROUND: The anti-programmed death receptor-1 (anti-PD-1) pembrolizumab is approved as first-line monotherapy for metastatic non-small cell lung cancer (mNSCLC) with PD-ligand 1 (PD-L1) tumor expression ≥50%. Most studies comparing PD-L1 results by immunohistochemistry (IHC) assay type have been conducted by prespecified and, in most cases, highly experienced, trained pathologists; however, knowledge is limited regarding the current use and concordance of PD-L1 assays in the real-world clinical setting. Our aim was to study the distribution of PD-L1 tumor expression by IHC assay type among patients with mNSCLC in US oncology practices. METHODS: This retrospective observational study utilized de-identified, longitudinal data from a large US electronic medical record database. Eligible patients were adults (≥18 years) with histologically/cytologically confirmed initial diagnosis of metastatic or recurrent NSCLC from October 2015 through December 2017. We determined PD-L1 testing trends and distribution of PD-L1 tumor expression (percentage of tumor cells staining for PD-L1) by IHC assay type. RESULTS: The 12,574 eligible patients (mean age, 69 years) included 6,620 (53%) men and 86% with positive smoking history. Of 4,868 evaluable tests, 3,799 (78%), 195 (4%), 165 (3%), and 709 (15%) used the Agilent 22C3 pharmDx, Agilent 28-8 pharmDx, Ventana PD-L1 (SP142) Assay, and laboratory-developed tests (LDTs, including SP263), respectively. The percentages of tests scoring PD-L1 tumor expression of ≥50% were 33%, 32%, 10%, and 23%, respectively. Measured PD-L1 tumor expression varied across the four assay types (χ2 p < 0.001) and across three assay types excluding SP142 (p < 0.001), with no significant difference between 22C3 and 28-8 assays (p = 0.96). The PD-L1 testing rate increased from 18% in the fourth quarter of 2015 to 71% in the fourth quarter of 2017. CONCLUSIONS: In the real-world clinical setting, we observed that measured PD-L1 tumor expression is concordant using the 22C3 and 28-8 assays; however, the SP142 assay and LDTs appear discordant and could underestimate high PD-L1 positivity. Further study is needed to evaluate the association between PD-L1 tumor expression and response to therapy.

Epidemiology and treatment patterns of epithelial ovarian cancer.

INTRODUCTION: While ovarian cancer (OC) is relatively rare, it remains one of the most fatal cancers. Lack of robust screening methods for eOC lead to detection of most cases at advanced stages, and most patients relapse following initial treatment. Areas covered: This review summarizes epidemiology and treatment patterns of epithelial ovarian cancer (eOC). MEDLINE, EMBASE, conference proceedings, and the Cochrane Library were searched using key terms and Medical Subject Headings for ovarian cancer, treatment patterns, and epidemiology to identify articles published from 2005-2015. Expert commentary: To improve early detection, future studies should focus on the identification of biomarkers that can detect asymptomatic disease. Following diagnosis and eventual relapse, response to first-line platinum appears to guide physicians' choice of subsequent therapies, but we do not understand what patients ultimately receive or its relationship to categories of response to first-line platinum. Improved understanding of later-line treatment patterns, by initial response to platinum, could correlate with overall outcomes among relapsed patients and promote development of more effective treatment guidelines. Novel treatment approaches, such as immunotherapies, would fulfill a need for an effective strategy against advanced stages of OC that results in fewer toxic side effects.

Modeling The Economic Burden Of Adult Vaccine-Preventable Diseases In The United States.

Vaccines save thousands of lives in the United States every year, but many adults remain unvaccinated. Low rates of vaccine uptake lead to costs to individuals and society in terms of deaths and disabilities, which are avoidable, and they create economic losses from doctor visits, hospitalizations, and lost income. To identify the magnitude of this problem, we calculated the current economic burden that is attributable to vaccine-preventable diseases among US adults. We estimated the total remaining economic burden at approximately $9 billion (plausibility range: $4.7-$15.2 billion) in a single year, 2015, from vaccine-preventable diseases related to ten vaccines recommended for adults ages nineteen and older. Unvaccinated individuals are responsible for almost 80 percent, or $7.1 billion, of the financial burden. These results not only indicate the potential economic benefit of increasing adult immunization uptake but also highlight the value of vaccines. Policies should focus on minimizing the negative externalities or spillover effects from the choice not to be vaccinated, while preserving patient autonomy.

Intervention research to enhance community pharmacists' cognitive services: a systematic review.

BACKGROUND: Positive impact of community pharmacists' cognitive pharmaceutical services (CPS) is well documented. However, community pharmacists have been slow to expand CPS roles. This systematic review explores how community pharmacy intervention research can help inform efforts to expand cognitive pharmaceutical service delivery. OBJECTIVES: To: 1) identify community pharmacy CPS intervention studies that report data on pharmacist behaviors, either as a final study outcome itself or as a fidelity measure in patient outcome studies, and 2) describe the state of this research to help frame future research agendas. METHODS: Empirical articles examining improvement or expansion of community pharmacist cognitive services published through December 2010 were searched using various search engines, bibliography searches and authors' libraries. Studies were included if they: 1) reported findings on pharmacist behaviors during cognitive service delivery, 2) employed a minimum of pre-post design or two study arms for pharmacists/pharmacies, and 3) were in community-based pharmacies. RESULTS: A total of 50 studies evaluated impact of community pharmacy based CPS delivery; however, only 21 included a pharmacist behavior outcome measure as a final outcome or as a fidelity measure. The majority (14 out of 21) of studies used a randomized controlled trial design. Nearly half (10 of 21) addressed asthma or tobacco cessation. Limited details were provided about interventions to prepare pharmacists for CPS delivery. The most frequent measures of pharmacist behavior were patient surveys and observation of pharmacists' behavior by secret shoppers; electronic data sets were rarely used. CONCLUSIONS: There is a need for well-designed intervention research that evaluates how interventions impact on pharmacist cognitive service behavior. Positive findings from this review reinforce that planned interventions have the potential to improve and expand pharmacist cognitive service delivery; however, more detail is needed in study publications for this potential to be fully realized.

Consumer perceptions of the sale of tobacco products in pharmacies and grocery stores among U.S. adults.

BACKGROUND: Pharmacy-based tobacco sales are a rapidly increasing segment of the U.S. retail tobacco market. Growing evidence links easy access to tobacco retail outlets such as pharmacies to increased tobacco use. This mixed-mode survey was the first to employ a nationally representative sample of consumers (n = 3057) to explore their opinions on sale of tobacco products in pharmacies and grocery stores. RESULTS: The majority reported that sale of tobacco products should be either 'allowed if products hidden from view' (29.9%, 25.6%) or 'not allowed at all' (24.0%, 31.3%) in grocery stores and pharmacies, respectively. Significantly fewer smokers, compared to non-smokers, reported agreement on point-of-sale restrictions on sales of tobacco products (grocery stores: 27.1% vs. 59.6%, p < .01; pharmacy: 32.8% vs. 62.0%, p < .01). Opinions also varied significantly by demographic characteristics and factors such as presence of a child in the household and urban/rural location of residence. CONCLUSIONS: Overall, a majority of consumers surveyed either supported banning sales of tobacco in grocery stores and pharmacies or allowing sales only if the products are hidden from direct view. Both policy changes would represent a departure from the status quo. Consistent with the views of practicing pharmacists and professional pharmacy organizations, consumers are also largely supportive of more restrictive policies.

Effectiveness of intervention to implement tobacco cessation counseling in community chain pharmacies.

OBJECTIVES: To test the feasibility of implementing ask-advise-refer (AAR) tobacco cessation counseling approach in community chain pharmacies serving low socioeconomic areas and to assess the effectiveness of a multimodal intervention on short-term implementation of AAR. DESIGN: Randomized controlled trial. SETTING: South-central Wisconsin from July 2008 through March 2009. PARTICIPANTS: Pharmacists and technicians from 16 community chain pharmacies. INTERVENTION: Training to implement AAR, workflow integration recommendations, tobacco cessation poster to create awareness, and a support visit. MAIN OUTCOME MEASURES: Number of pharmacy patrons asked about tobacco use, number of tobacco users advised to quit, number of tobacco users enrolled in the quit line, and number of quit line cards given. RESULTS: As hypothesized, the multimodal intervention significantly predicted the number of patrons asked to quit (estimate 4.84, incidence rate ratio 127.2, P < 0.001), number of tobacco users advised to quit (2.12, 8.33, P < 0.01), number of tobacco users enrolled in the quit line (2.31, 10.13, P < 0.001), and number of quit line cards given (1.04, 2.82, P < 0.05). CONCLUSION: This trial demonstrates the feasibility of implementing AAR in routine community pharmacy practice. This trial also supports the short-term effectiveness of the multimodal intervention in facilitating AAR in partnership with other public health systems. More research is needed to evaluate the generalizability, effectiveness, and sustainability of AAR, including factors influencing adoption and the impact on cessation.

A national mass media smoking cessation campaign: effects by race/ethnicity and education.

PURPOSE: To assess the effectiveness of a large-scale, national smoking cessation media campaign, the EX campaign, across racial/ethnic and educational subgroups. DESIGN: A longitudinal random-digit-dial panel study conducted prior to and 6 months following the national launch of the campaign. SETTING: The sample was drawn from eight designated media markets in the United States. SUBJECTS: The baseline survey was conducted on 5616 current smokers, aged 18 to 49 years, and 4067 (73% follow-up response rate) were resurveyed at the 6-month follow-up. MEASURES: The primary independent variable is confirmed awareness of the campaign advertising, and the outcome variables are follow-up cessation-related cognitions index score and quit attempts. ANALYSIS: Multivariable logistic and linear regression analyses were conducted within racial/ethnic and educational strata to assess the strength of association between confirmed awareness of campaign advertising and cessation-related outcomes. RESULTS: Confirmed awareness of campaign advertising increased favorable cessation-related cognitions among Hispanics and quit attempts among non-Hispanic blacks, and increased favorable cessation-related cognitions and quit attempts among smokers with less than a high school education. CONCLUSIONS: These results suggest that the EX campaign may be effective in promoting cessation-related cognitions and behaviors among minority and disadvantaged smokers who experience a disproportionate burden of tobacco-related illness and mortality.

Tobacco users' perceptions of a brief tobacco cessation intervention in community pharmacies.

OBJECTIVE: To explore factors affecting tobacco users' perceived appropriateness of a brief and proactive tobacco cessation counseling program, ask, advise, and refer (AAR), at community pharmacies. DESIGN: Inductive thematic analysis. SETTING: Southern Wisconsin during fall 2008. PATIENTS: 24 tobacco users who had recently received brief and proactive tobacco cessation counseling at a community pharmacy. INTERVENTION: Semistructured telephone interviews conducted by primary author. MAIN OUTCOME MEASURES: Perceptions of a brief and proactive tobacco cessation counseling program conducted at community pharmacies. RESULTS: In conducting the thematic analysis, eight distinct themes were identified. Display of information and resources at pharmacies for use by tobacco users as needed was identified as the most predominant theme and was found to be most helpful by many respondents. Other themes identified in decreasing order of prevalence were: tobacco users' perceptions of the role of pharmacists in health care, tobacco users' belief that smoking could interact with a current medication or health condition, tobacco users' sensitivity toward their tobacco use behavior or being told what to do, nonconfrontational and friendly approach of pharmacists, tobacco users' readiness to quit at the time of AAR counseling, tobacco user initiation of tobacco use discussion, and tobacco users' belief that tobacco use is bad. CONCLUSION: Overall, this qualitative investigation suggests that several factors might influence tobacco users' perceived appropriateness of AAR counseling at community pharmacies. AAR might be well received by tobacco users and pharmacy patrons as long as it is done in a professional and respectful manner.

Ask, advise and refer: hypothesis generation to promote a brief tobacco-cessation intervention in community pharmacies.

OBJECTIVES: A preliminary qualitative study was conducted to identify key facilitators and barriers for pharmacists' adoption of a brief tobacco-cessation protocol, Ask-Advise-Refer (AAR). METHODS: Ten community pharmacists were interviewed using semi-structured, face-to-face interviews with open-ended questions. Purposive and saturation sampling techniques were applied to identify participants and determine sample size respectively. Interviews were audio-recorded and transcribed. Using thematic analysis, two reviewers independently coded all transcripts to identify prominent themes. Appropriate measures were taken to ensure study rigor and validity. KEY FINDINGS: All facilitators and barriers identified were grouped into nine distinct themes. Pharmacists' fear of negative patient reaction was the most prominent barrier to initiating tobacco-cessation discussions with patients. Other themes identified in decreasing order of prevalence were pharmacists perceiving a rationale for initiating tobacco cessation, pharmacy environment, pharmacists' perception of/prior knowledge of patients' willingness to discuss tobacco cessation/to quit, patient initiation of tobacco-cessation or worsening-health discussion, pharmacists' perceptions of AAR characteristics, length of pharmacist-patient relationship/rapport with patients, low expectations of pharmacy patrons and pharmacists' communication ability. CONCLUSIONS: This study highlights the potential fear among pharmacists about negative reactions from patients in response to initiating tobacco cessation discussions. Based on the results of this study it is hypothesized that the following strategies would facilitate adoption of AAR: (1) train pharmacists to initiate cessation discussions; (2) initially target discussions with patients who have a disease or medication adversely affected by tobacco use; (3) encourage patient enquiry about pharmacy cessation services through visual cues; and (4) help pharmacists set up a workflow system compatible with the AAR protocol.

Fed-batch cultivation of Wautersia eutropha.

Batch kinetics of polyhydroxybutyrate (PHB) synthesis in a bioreactor under controlled conditions of pH and dissolved oxygen gave a biomass of 14 g l(-1) with a PHB concentration of 6.1 g l(-1) in 60 h. The data of the batch kinetics was used to develop a mathematical model, which was then extrapolated to fed-batch by incorporating the dilution due to substrate feeding. Offline computer simulation of the fed-batch model was done to develop the nutrient feeding strategies in the fed-batch cultivation. Fed-batch strategies with constant feeding of only nitrogen and constant feeding of both nitrogen and fructose were tried. Constant feeding strategy for nitrogen and fructose gave a better PHB production rate of 0.56 g h(-1) over the value obtained in batch cultivation (PHB production rate - 0.4 g h(-1)).