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Introduction: We evaluated the comparative efficacy of six later-line (≥3) therapies for metastatic colorectal cancer (mCRC) over placebo. We applied a novel statistical method of reconstructing pseudo-patient-level data (pseudo-IPD) to inform a network meta-analysis of survival curves that considers shape in addition to scale parameters. Methods: A literature search yielded 10 phase II/III trials. We digitized all survival curves and applied a novel method incorporating curve coordinates, patients-at-risk, and events reported to generate pseudo-IPD. Using fitted random effects lognormal distributions, we estimated the survival proportions and HRs (95CrI) of progression-free (PFS) and overall survival (OS) over 12 months of follow-up. Results: Compared to placebo, in ascending order, 12-month OS HRs were 0.50 (95% CrI = 0.35, 0.69; PFS = 0.11 (95% CrI = 0.06, 0.14)) for TAS+bevacizumab; 0.71 (95% CrI = 0.51, 0.97; PFS = 0.26 (95% CrI = 0.16, 0.41)) for regorafenib; 0.75 (95% CrI = 0.61, 0.91; (PFS = 0.24 (95% CrI = 0.17, 0.31)) for TAS-102; 0.80 (95% CrI = 0.79, 0.90; PFS = 0.18 (95% CrI = 0.13, 0.24)) for fruquintinib; 0.83 (95% CrI = 0.50, 0.99; PFS = 0.42 (95% CrI = 0.20, 0.75)) for atezolizumab+cobimetinib; and 1.03 (95% CrI = 0.55, 1.65; PFS = 0.67 (95% CrI = 0.29, 1.01)) for atezolizumab. Conclusion: In this independent NMA of survival data, all later-line mCRC therapies but atezolizumab monotherapy exhibited superiority in 12-month PFS and OS over placebo. TAS+bevacizumab emerged as the most dominant option and may be the preferred choice, with fruquintinib, regorafenib, and TAS-102 monotherapy showing statistically significant but lower PFS and OS benefits. Registration: PROSPERO: CRD42022371953 [ABSTRACT FROM AUTHOR]

Objectives: Optimal postpartum care promotes healthcare utilization and outcomes. This qualitative study investigated the experiences and perceived needs for postpartum care among women in rural communities in Arizona, United States. Methods: We conducted in-depth interviews with thirty childbearing women and analyzed the transcripts using reflexive thematic analysis to gauge their experiences, needs, and factors affecting postpartum healthcare utilization. Results: Experiences during childbirth and multiple structural factors, including transportation, childcare services, financial constraints, and social support, played crucial roles in postpartum care utilization for childbearing people in rural communities. Access to comprehensive health information and community-level support systems were perceived as critical for optimizing postpartum care and utilization. Conclusions for Practice: This study provides valuable insights for policymakers, healthcare providers, and community stakeholders in enhancing postpartum care services for individuals in rural communities in the United States. Significance: What is already known on this subject: Centering postpartum policies and interventions to particular population groups necessitates a comprehensive and nuanced understanding of priority needs. What this study adds: This study sheds light on the distinct experiences and challenges influencing postpartum experiences and healthcare utilization among childbearing individuals in rural communities in the United States. [ABSTRACT FROM AUTHOR]

Purpose: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. Methods: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. Results: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. Conclusions: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

Background: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons. Objective: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis. Methods: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making. Results: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots. Conclusion: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS). [ABSTRACT FROM AUTHOR]

This article provides an overview of important trends in health economics and outcomes research (HEOR) for 2024. It highlights key topics such as the need for alternate metrics of benefit and harm in health economics, patient preference research, the use of real-world evidence in healthcare decision-making, equity in healthcare distribution, challenges in low- and middle-income countries, the economics of prevention, and the evaluation of medications for rare conditions. The article emphasizes the need for research and innovation to address these trends and improve healthcare outcomes globally. The text also discusses the uncertainty surrounding the cost-effectiveness of orphan drugs and explores outcomes-based contracting as a potential approach to pharmaceutical pricing and reimbursement. It provides insights into what makes a high-quality HEOR paper, including the importance of clinical context and the challenges of securing useful peer review. The authors of the text are experts in the field of HEOR with extensive experience and knowledge in their respective areas of expertise. [Extracted from the article]

Background: The combinations of BRAF + MEK inhibitors—encorafenib (ENC) + binimetinib (BIN), cobimetinib (COB) + vemurafenib (VEM), and dabrafenib (DAB) + trametinib (TRA)—are recommended for the treatment of BRAF-mutated advanced melanoma. Objective: To assess the cost-effectiveness and cost-utility of ENC + BIN versus COB + VEM versus DAB + TRA from a US payer perspective. Methods: A Markov model was constructed to simulate a hypothetical cohort over a time horizon of 10 years. The overall survival (OS) and progression-free survival (PFS) curves were independently digitized from a randomized controlled trial for ENC + BIN and fitted using R software. Published and indirectly estimated hazard ratios were used to fit OS and PFS curves for COB + VEM and DAB + TRA. Costs, life-year gains, and quality-adjusted life years (QALYs) associated with the 3 treatment combinations were estimated. A base case analysis and probabilistic sensitivity analysis (PSA) were conducted to estimate the incremental cost-utility ratio (ICUR). A discount rate of 3.5% was applied on cost and outcomes. Results: The ENC + BIN versus COB + VEM comparison was associated with an ICUR of $656 233 per QALY gained. The ENC + BIN versus DAB + TRA comparison was associated with an ICUR of $3 135 269 per QALY gained. The DAB + TRA combination dominated COB + VEM. The base case analysis estimates were confirmed by the PSA estimates. ENC + BIN was the most cost-effective combination at a high willingness-to-pay (WTP) threshold of $573 000 per QALY and $1.5 million/QALY when compared to COB + VEM and DAB + TRA, respectively. Conclusion and Relevance: Given current prices and acceptable WTP thresholds, our study suggests that DAB + TRA is the optimum treatment. In this study, ENC + BIN was cost-effective only at a very high WTP per QALY threshold. [ABSTRACT FROM AUTHOR]

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions. [ABSTRACT FROM AUTHOR]

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management. [ABSTRACT FROM AUTHOR]

Background: Coronavirus 2019 (COVID-19) patients are at risk of thrombosis. Literature that compares the effectiveness of enoxaparin to unfractionated heparin (UFH) in COVID-19 patients is scarce. Objective: We aimed to evaluate the effectiveness and safety of enoxaparin compared with UFH when used at their standard/intermediate dosing in COVID-19 patients. Methods: This was a retrospective study conducted at a large COVID-19 center located in Eastern Province, Saudi Arabia. Confirmed COVID-19 cases (≥18 years old) admitted between January and December 2020 were randomly screened for inclusion. Exclusion criteria were patients receiving therapeutic anticoagulation, on chronic anticoagulation, had active bleeding, a platelet count <25 × 109/L, or an incomplete electronic file. The primary endpoint was the occurrence of any thrombotic event (pulmonary embolism, deep venous thrombosis, stroke, or myocardial infarction) or mortality. Secondary endpoints were major or minor bleeding. We applied inverse propensity score weighting (IPTW) with survival analysis to analyze the primary endpoint. Logistic regression was used for the secondary endpoint. Results: A total of 980 patients were included (enoxaparin, n = 470 and UFH, n = 510) with a mean age (±SD) of 47.7 (± 12.3) for the enoxaparin arm and 52 (±13.9) for the UFH arm. There was a statistically significant difference in the primary endpoint with an adjusted hazard ratio (aHR) of 0.46 (95%CI: 0.22 to 0.96, P = 0.039) in favor of the enoxaparin arm. There was no statistically significant difference in major or minor bleeding rates between the two arms. Conclusion and Relevance: When compared with UFH, enoxaparin was associated with a significant reduction in thrombotic events or mortality among COVID-19 patients. The results need confirmation from randomized controlled trials. [ABSTRACT FROM AUTHOR]

We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing BRCA information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)'with BRCA information' and (2)'without BRCA information.' We also estimated the expected value of perfect information. The incremental NMB (INMB) quantified the monetized benefit per person of knowing BRCA status. The net-monetized-value of knowing BRCA information was estimated by multiplying the INMB with the eligible population. The INMBs of knowing BRCA information were $43,357 (payer) and $43,487 (society). in payer and societal perspectives, respectively. Escalated to the eligible patients in 2020, knowing BRCA status resulted in net monetized lifetime value of $1.7 billion (payer and society) for the 2020 cohort; and yielded accumulated net-monetized-value of $28.0 billion (payer) and $28.1 billion (society) over 16 yearly cohorts of eligible PCa patients. The economic value of knowing BRCA status for all low-risk localized PCa patients in the US provides short-term and long-term evidence for BRCA testing to screen early and optimize treatment. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information for recurrent ovarian cancer (ROC) patients in a given year and the cumulative savings of yearly hypothetical cohort testing over 16 years. We compared two strategies: (1) 'with BRCA information' and (2) 'without BRCA information.' Incremental NMB (INMB) was calculated as the average net monetized benefit of knowing BRCA status. The net monetized value (cumulative INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible ROC patients in year 2020 and extended for potential ROC patients over 16 yearly hypothetical cohorts of ROC patients Knowing BRCA information for ROC patients provided an additional monetized value of $3,528 in (payer) and $3,194 (society). Escalated to all ROC patients in the U.S. and future incidence ROC estimates, knowing BRCA information resulted in a lifetime cumulative INMB of $35.6 million (payer) and $32.2 million (society) for the 2020 cohort; and yielded an accumulated value of $97.3 million (payer) and $88.0 million (society) over 16 yearly hypothetical cohorts of ROC patients The economic value of knowing BRCA status of all U.S. ROC patients provides short-term and long-term evidence for optimizing treatment [ABSTRACT FROM AUTHOR]

This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information by universal genetic testing of all US women without breast cancer turning 40 in a given year, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1) 'with BRCA information' and (2) 'without BRCA information.' Incremental NMB (INMB) was calculated as the monetized benefit per person of knowing BRCA status. The net monetized value (cumulated INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible population or the year 2020 cohort of US women age 40 and extended for a total of 16 yearly cohorts. Universal testing of the female population at the age of 40 in a given year provided aan INMB of $663/person (payer) and $1,006/person (society).Escalated to the U.S. population of women age 40 , knowing BRCA status resulted in lifetime cumulated INMB of $1.3 billion (payer) and $2.0 billion (society) for the 2020 cohort; and yielded accumulated monetized value of $18.3 billion (payer) and $27.6 billion (society) over 16 yearly cohorts of 40-year-old women. The universal testing for BRCA status of all US women at age 40 provides compelling short-term and long-term economic value. [ABSTRACT FROM AUTHOR]

To assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer. A 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients' access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD). Rixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima. Rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access. [ABSTRACT FROM AUTHOR]

To evaluate the cost-effectiveness of standard-of-care treatment (SoC) to SoC in combination with omalizumab (OML + Soc) in patients with severe asthma using real-world prospective clinical data from four major medical centers in Turkey. Between February 2018 and November 2019, a total of 206 patients with severe asthma, including 126 of whom were in the OML + SoC group and 80 in the SoC group, were followed for 12 months to evaluate their asthma status and quality of life. Cost data for this patient-level economic evaluation were sourced from the MEDULA database of the hospitals and expressed in Turkish Lira (₺). Efficacy data were obtained by means of Turkish versions of the Asthma Control Test for asthma status, the 5-level EQ-5D-5L version (EQ-5D-5L), and the Asthma Quality of Life Scale for quality of life. A Markov model with 2-week cycles was specified, comparing costs and treatment effects of SoC vs. OML + SoC over a lifetime from the Turkish payer perspective. Per-patient costs were ₺23,607.08 in the SoC arm and ₺425,329.81 in the OML + Soc arm, for a difference of ₺401,722.74. Life years (LY) and quality-adjusted life years (QALY) were 13.60 and 10.08, respectively, in the SoC group; and 21.26 and 13.35, respectively, in the OML + SoC group, for differences of 7.66 LYs and 3.27 QALYs. This yielded an incremental cost-effectiveness ratio of an additional ₺52,427.04 to gain 1 LY and an incremental cost-utility ratio of an incremental ₺122,675.57 to gain 1 QALY; the latter being below the ₺156,948 willingness-to-pay threshold for Turkey referenced by WHO. One-way and multivariate sensitivity analyses confirmed the base-case results. Whereas most economic evaluations are based on aggregate data, this independent cost-effectiveness analysis using prospective real-world patient-level data suggests that omalizumab in combination with standard of care is cost-effective for severe asthma from the Turkish public payer perspective. What is the context? Severe asthma, a subset of difficult-to-treat asthma, refers to asthma that cannot be controlled despite adherence to optimized maximal therapy and treatment of contributing factors, or asthma that worsens when high-dose therapy is reduced. Omalizumab is the first biologic therapy approved for the treatment of allergic asthma. Its main role is to prevent the release of various inflammation factors that cause severe asthma episodes. Cost-effectiveness analysis is an economic method of determining how much more a new and better treatment costs relative to the current treatment in terms of how many life years (LY) and how many quality-adjusted life years (QALY) are gained with the new treatment. Cost-effectiveness results tell us how much more money is needed over the cost of the current treatment to achieve one additional LY, regardless of the quality of life, or one additional LY with good quality of life. No cost-effectiveness data obtained from actual clinical patient data are available for Turkey. What is new? Our study found that the addition of omalizumab to the current standard of care for severe asthma increases costs but also increases life years and quality-adjusted life years. The additional cost was less than what the World Health Organization assumes is reasonable for Turkey. This study used actual clinical patient data and noted that asthma patients in the omalizumab group used fewer health services, had a better clinical course, had a better quality of life, and lived longer with their disease under control. What is the impact? In severe asthmatic patients, adding omalizumab to standard-of-care, while more costly, yields better outcomes and is therefore cost-effective. The cost-effectiveness estimates fall within the margins of being cost-responsible. The Turkish public payer should strongly consider making omalizumab available to all eligible patients. This will enable working-age patients to work, and contribute to their families, while also strengthening the Turkish economy. [ABSTRACT FROM AUTHOR]

This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment. Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio). This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care. [ABSTRACT FROM AUTHOR]

Melanoma in Black patients carries a poor prognosis. Due to its rarity, melanoma in this population has not been well characterized. This study evaluates survival predictors in Black patients with melanoma. This was a retrospective cohort study of Black patients with cutaneous melanoma from the National Cancer Database 2004–2018. Of the 2464 cases, melanoma was more common among females than males (57.1% vs. 42.9%, p <.001). Median Breslow depth was 1.8 mm (interquartile range 0.4–4.4). Lower extremities were the most common location (52.8%), followed by upper extremities (13.1%) along with otherwise specified/overlapping/other (13.1%), then by trunk (11.8%), and lastly head and neck (9.2%). Stage at diagnosis was I (30.7%), II (27.5%), III (24.1%), and IV (17.7%). Ulceration was observed in 41.4% of lesions. Acral lentiginous melanoma (ALM) was the most common specific histologic subtype (20.3%), followed by superficial spreading melanoma (9.4%). After adjusting for confounders, higher stages and primary site on the head and neck were the strongest independent predictors of worse overall survival. Melanoma in Black patients is most likely to appear on the lower extremities. A large portion (41.8%) presented with stage III or IV disease. ALM was the most common specific histologic subtype. [ABSTRACT FROM AUTHOR]

Objective: This article reviews current evidence for the approved anti-CD38 monoclonal antibodies, isatuximab and daratumumab, for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM) and the implications for pharmacists. Data sources: We conducted a literature search on PubMed/Medline and other sources using the drug names and the terms CD38, multiple myeloma, and pharmacists. Data summary: Monoclonal antibodies targeting the CD38 transmembrane glycoprotein offer a promising treatment approach for patients with RRMM. Isatuximab and daratumumab bind to different epitopes on CD38. In this review, we describe the similarities and differences in their mechanism of action, regulatory labeling, and the current guidelines for isatuximab and daratumumab use in RRMM. We review the current evidence for the efficacy and safety of these agents in combination with pomalidomide or carfilzomib and dexamethasone from the landmark phase 3 clinical trials that led to their approval. We discuss key differences in the eligibility criteria between the clinical trials, and differences in dosing, administration, available formulations, and pre- and post-infusion medications for the two agents. We outline recent data from pharmacoeconomic analyses comparing the cost-effectiveness of isatuximab-based regimens with that of daratumumab-based regimens. A brief overview of other anti-CD38 agents in the pipeline for the treatment of patients with RRMM is presented. Conclusions: Given that pharmacists play an integral role in driving cost-effective use of drugs without compromising efficacy and safety for the end user, educating pharmacists on the key differences between isatuximab and daratumumab can guide the selection of the appropriate anti-CD38 antibody. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

Aim: To determine the incidence of chemotherapy-induced febrile neutropenia (FN) and related outcomes after same-day pegfilgrastim in lung cancer. Materials & methods: This single-center, retrospective study evaluated electronic health records of patients with lung cancer treated between 2013-2018. The main end points were incidence of FN and grade 3/4 neutropenia after the first and across all chemotherapy cycles. Results: A total of 114 patients received same-day pegfilgrastim in 384 cycles. The incidence of FN and grade 3/4 neutropenia was 2.3 and 25% after the first chemotherapy cycle and 1.6 and 10.4% across all cycles, respectively. Conclusion: Same-day prophylactic pegfilgrastim in patients with lung cancer may be a suitable option, owing to its low incidence of FN and related outcomes. [ABSTRACT FROM AUTHOR]

Background: Endoscopically visualized spine surgery has become an essential tool that aids in identifying and treating anatomical spine pathologies that are not well demonstrated by traditional advanced imaging, including MRI. These pathologies may be visualized during endoscopic lumbar decompression (ELD) and categorized into primary pain generators (PPG). Identifying these PPGs provides crucial information for a successful outcome with ELD and forms the basis for our proposed personalized spine care protocol (SpineScreen). Methods: a prospective study of 412 patients from 7 endoscopic practices consisting of 207 (50.2%) males and 205 (49.8%) females with an average age of 63.67 years and an average follow-up of 69.27 months was performed to compare the durability of targeted ELD based on validated primary pain generators versus image-based open lumbar laminectomy, and minimally invasive lumbar transforaminal interbody fusion (TLIF) using Kaplan-Meier median survival calculations. The serial time was determined as the interval between index surgery and when patients were censored for additional interventional and surgical treatments for low back-related symptoms. A control group was recruited from patients referred for a surgical consultation but declined interventional and surgical treatment and continued on medical care. Control group patients were censored when they crossed over into any surgical or interventional treatment group. Results: of the 412 study patients, 206 underwent ELD (50.0%), 61 laminectomy (14.8%), and 78 (18.9%) TLIF. There were 67 patients in the control group (16.3% of 412 patients). The most common surgical levels were L4/5 (41.3%), L5/S1 (25.0%), and L4-S1 (16.3%). At two-year f/u, excellent and good Macnab outcomes were reported by 346 of the 412 study patients (84.0%). The VAS leg pain score reduction was 4.250 ± 1.691 (p < 0.001). No other treatment during the available follow-up was required in 60.7% (125/206) of the ELD, 39.9% (31/78) of the TLIF, and 19.7% (12/61 of the laminectomy patients. In control patients, only 15 of the 67 (22.4%) control patients continued with conservative care until final follow-up, all of which had fair and poor functional Macnab outcomes. In patients with Excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients (p < 0.001). The overall survival time in control patients was eight months with a standard error of 0.942, a lower boundary of 6.154, and an upper boundary of 9.846 months. In patients with excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients versus control patients at seven months (p < 0.001). The most common new-onset symptom for censoring was dysesthesia ELD (9.4%; 20/206), axial back pain in TLIF (25.6%;20/78), and recurrent pain in laminectomy (65.6%; 40/61) patients (p < 0.001). Transforaminal epidural steroid injections were tried in 11.7% (24/206) of ELD, 23.1% (18/78) of TLIF, and 36.1% (22/61) of the laminectomy patients. The secondary fusion rate among ELD patients was 8.8% (18/206). Among TLIF patients, the most common additional treatments were revision fusion (19.2%; 15/78) and multilevel rhizotomy (10.3%; 8/78). Common follow-up procedures in laminectomy patients included revision laminectomy (16.4%; 10/61), revision ELD (11.5%; 7/61), and multilevel rhizotomy (11.5%; 7/61). Control patients crossed over into ELD (13.4%), TLIF (13.4%), laminectomy (10.4%) and interventional treatment (40.3%) arms at high rates. Most control patients treated with spinal injections (55.5%) had excellent and good functional outcomes versus 40.7% with fair and poor (3.7%), respectively. The control patients (93.3%) who remained in medical management without surgery or interventional care (14/67) had the worst functional outcomes and were rated as fair and poor. Conclusions: clinical outcomes were more favorable with lumbar surgeries than with non-surgical control groups. Of the control patients, the crossover rate into interventional and surgical care was 40.3% and 37.2%, respectively. There are longer symptom-free intervals after targeted ELD than with TLIF or laminectomy. Additional intervention and surgical treatments are more often needed to manage new-onset postoperative symptoms in TLIF- and laminectomy compared to ELD patients. Few ELD patients will require fusion in the future. Considering the rising cost of surgical spine care, we offer SpineScreen as a simplified and less costly alternative to traditional image-based care models by focusing on primary pain generators rather than image-based criteria derived from the preoperative lumbar MRI scan. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

The author discusses a study by M. F. Qian and colleagues, published in the issue on a claims database analysis of treatment related and total healthcare costs in patients with metastatic melanoma treated with either nivolumab, pembrolizumab, ipilimumab-plus-nivolumab, or BRAF/MEK inhibitor regimens. Topics include proportion of patients treated with molecularly targeted BRAF/MEK inhibitors and market share correction in pembrolizumab's rise and nivolumab's decline in market share.

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2+ (HER2+ BC) patients, varying treatment duration (one-six cycles) and conversion rates (10-100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients. [ABSTRACT FROM AUTHOR]

Proliferating hematopoietic stem and progenitor cells (HSPCs) are susceptible to chemotherapy-induced damage, resulting in myelosuppressive adverse events (AEs) such as neutropenia, anemia, and thrombocytopenia that are associated with high health care costs and decreased quality of life (QoL). In this study, a trial-based cost-effectiveness analysis was performed to help assess the economic impact of administering trilaciclib, a myeloprotective therapy that protects multilineage HSPCs from chemotherapy-induced damage, prior to standard first-line chemotherapy, using data from a pivotal Phase II study of trilaciclib in the setting of extensive-stage small cell lung cancer (ES-SCLC, NCT03041311). The aim of this study was to assess the cost-effectiveness of administering trilaciclib prior to chemotherapy versus chemotherapy alone among patients with ES-SCLC from a United States payer perspective. Data on the rate and frequency of myelosuppressive AEs and health utility were derived from the pivotal study of trilaciclib. Costs of managing myelosuppressive AEs and costs of chemotherapy treatment were sourced from published literature. Outcomes included the number of myelosuppressive AEs, costs (in 2021 US dollars), quality-adjusted life-years (QALYs), incremental cost, incremental QALY, and an incremental cost-effectiveness ratio. Administering trilaciclib prior to chemotherapy was associated with a reduction in neutropenia (82%), febrile neutropenia (75%), anemia (43%), and thrombocytopenia (96%) compared with chemotherapy alone. Additionally, trilaciclib prior to chemotherapy was cost-saving compared with chemotherapy alone ($99,919 vs $118,759, respectively) and associated with QALY improvement (0.150 vs 0.145, respectively). Probabilistic sensitivity analyses showed 58% of iterations projecting cost savings and QALY improvement with trilaciclib. The findings suggest that the use of trilaciclib prior to first-line chemotherapy in patients with ES-SCLC can be cost-beneficial owing to fewer myelosuppressive AEs and lower costs, together with a favorable QoL profile. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate how medical purchasing power parities (mPPP) may harmonize economic evaluations from different jurisdictions and enable comparisons across jurisdictions.Methods: We describe the use of mPPPs and illustrate this with an example of economic evaluations of nab-paclitaxel with gemcitabine (Nab-P + Gem) versus gemcitabine monotherapy in the setting of metastatic pancreatic cancer. Following a literature search, we extracted data from cost-effectiveness studies on these treatments performed in various countries. mPPPs from the Organization for Economic Co-operation and Development were used to convert reported costs in the jurisdiction of origins to US dollars for the most current year using two possible pathways: (1) reported costs first adjusted by mPPP then adjusted by exchange index; and (2) reported costs first adjusted by exchange index then adjusted by mPPP.Results: Despite many of the pharmaco-economic evaluations sharing similar assumptions and inputs, even after mPPP conversion, residual heterogeneity was attributable to perspectives, discount rate, outcomes, and costs, among others; including in studies conducted in the same jurisdiction.Conclusion: Despite the methodological challenges and heterogeneity within and across jurisdictions, we demonstrated that mPPP offers a way to compare economic evaluations across jurisdictions. [ABSTRACT FROM AUTHOR]

Aim: Polatuzumab vedotin-bendamustin-rituximab (PBR) and tafasitamab-lenalidomide (Tafa-L) were approved recently for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in autologous stem cell transplant (ASCT) ineligible patients. We performed an industry-independent pharmacoeconomic evaluation of both regimens over a 5-year (y) time horizon (US payer perspective; 2020 USD).Methods: Survival curves, treatment costs, and utility values were applied in a three-state Markov model (progression-free survival (PFS), post-progression survival (PPS), death) to estimate the incremental follow-up (ICER) and cost-utility ratios (ICUR). A novel metric of the incremental cost per 1% gain in the probability of achieving objective response (OR), PFS, and OS were estimated.Results: Five-year Tafa-L costs ($470,119) exceeded PBR's ($249,217) by $220,902 with incremental gains of 0.71 life-years (LY) and 0.32 quality-adjusted life-years (QALY); yielding ICER of $310,041/LYg and ICUR of $694,241/QALYg. Tafa-L had favorable PFS and OS rates over PBR with adjusted differences of +19.2 and +34.1%, respectively at trial follow-up (∼2 years), with corresponding 5 years differences in survival of +7.8% in PFS and +21.4% in OS. The incremental cost per 1% gain in the probability of achieving OR, PFS and OS at follow-up were $8,479, $6,359, and $3,583; and $28,321 and $10,323 for PFS and OS at 5 years.Conclusion: The sustained Tafa-L treatment demonstrated better survival outcomes than 6-cycle PBR though at a greater cost. The incremental costs to gain a 1% improvement in 2 and 5 years survival outcomes with Tafa-L over PBR were modest, underscoring the longer-term benefit of Tafa-L over PBR in patients ineligible for or opting out of ASCT. [ABSTRACT FROM AUTHOR]

With the increasing occurrence of infectious diseases in lower-and-middle-income countries (LMICs), emergency preparedness is essential for rapid response and mitigation. Economic evaluations of mitigation technologies and strategies have been recommended for inclusion in emergency preparedness plans. We aimed to perform an economic evaluation using dynamic transition modeling of ebola virus disease (EVD) vaccination in a hypothetical community of 1,000 persons in the Democratic Republic of Congo (DRC). Using a modified SEIR (Susceptible, Exposed, Infectious, Recovered, with Death added [SEIR-D]) model that accounted for death and epidemiological data from an EVD outbreak in the DRC, we modeled the transmission of EVD in a hypothetical population of 1,000. With our model, we estimated the cost-effectiveness of an EVD vaccine and an EVD vaccination intervention. The results showed vaccinating 50% of the population at risk prevented 670 cases, 538 deaths, and 22,022 disability-adjusted life years (DALYs). The vaccine was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of $95.63 per DALY averted. We also determined the minimum required vaccination coverage for cost-effectiveness to be 40%. Sensitivity analysis showed our model to be fairly robust, assuring relatively consistent results even with variations in such input parameters as cost of screening, as well as transmission, infection, incubation, and case fatality rates. EVD vaccination in our hypothetical population was found to be cost-effective from the payer perspective. Our model presents an efficient and reliable approach for conducting economic evaluations of infectious disease interventions as part of an emergency preparedness plan. Infectious diseases affect lower-and-middle-income (LMIC) countries, with their limited resources, disproportionately more. This is certainly the case for ebola virus disease (EVD), a rare, severe, and mostly fatal disease. Vaccination is now available, but whether it is cost-effective remains an open question. We evaluated its cost-effectiveness by modeling the spread of EVD in a hypothetical population of 1000 persons. Using data from an EVD outbreak in the Democratic Republic of Congo (DRC), we estimated how many of persons susceptible to infection were exposed to the virus, became infected, recovered, or died. We did so for two scenarios: vaccinating versus not vaccinating enough people to achieve herd immunity. We assumed vaccinating 50% of the people and estimated how many infections, deaths, and disability-adjusted life years (DALY; the loss of the equivalent of a year of full health) would be prevented by vaccination. Our cost-effectiveness metric was the incremental cost of preventing one DALY. The outcomes of vaccination offset the additional costs. Vaccinating 50% of the population of 1000 cost an additional $2,081,358 but prevented 670 infections, 538 deaths, and 22022 DALYs. Preventing one DALY cost $95.63. This is very cost-effective as it is less than the gross domestic product (GDP) per capita for the DRC of $556.81. Vaccination below 40% of the population was less cost-effective, was most cost-effective at the herd immunity threshold of 45.3%, beyond which there were diminishing returns. Summarized, vaccination against EVD is clinically very effective and certainly worth the additional cost. [ABSTRACT FROM AUTHOR]

Aims: To investigate the cost-efficiency and budget-neutral expanded access of biosimilar intravenous trastuzumab-dkst versus reference intravenous (trastuzumab-IV) and subcutaneous trastuzumab (trastuzumab-SC) (with/without pertuzumab) in metastatic breast cancer (MBC). Methods: Economic simulation modeling in a panel of 1,000 MBC patients to estimate: 1) cost-savings by conversion from trastuzumab-IV or trastuzumab-SC to trastuzumab-dkst at 10-100% conversion rates in 3 weight groups: first quartile (Q1:62.2 kg), median (73.1 kg), third quartile (Q3:88.6 kg), and 2) budget-neutral expanded access to trastuzumab-dkst from cost-savings. Results: In monotherapy, conversion (%) from trastuzumab-IV generates one-year cost-savings from $2,272,189 (Q1;10%) to $31,506,804 (Q3;100%) and from trastuzumab-SC monotherapy savings range from $2,071,277 (Q3;10%) to $35,775,475 (Q1;100%). In combination with pertuzumab, trastuzumabdkst is cost-efficient in all patient weights with one-year savings over trastuzumab-IV up to $32,662,714 (Q3;100%) and over trastuzumab-SC up to $35,322,461 (Q1;100%). Savings from conversion from trastuzumab-IV monotherapy could provide between 3,087 (Q1;10%) and 30,911 (Q3;100%) additional trastuzumab-dkst doses--enough to treat 58 to 583 patients for one year. Conversion from trastuzumab-SC monotherapy could provide between 1,559 (Q3;10%) and 48,598 (Q1;100%) additional trastuzumab-dkst doses or 38 to 918 additional one-year treatments with trastuzumab-dkst. In combination with pertuzumab, conversion from trastuzumab-IV could provide from 311 (Q1;10%) to 3,939 (Q3;100%) maintenance doses (pertuzumabþtrastuzumab-dkst) or 17 to 210 additional one-year regimens (all agents). Savings from conversion from trastuzumab-SC could expand access to 226 (Q3;10%) to 4,782 (Q1;100%) additional maintenance doses or 12 to 254 one-year regimens. Conclusions: This first cost-efficiency and expanded access study of biosimilar therapeutic cancer agents shows that trastuzumab-dkst is cost-efficient over trastuzumab-IV and trastuzumab-SC across all patient weights in both monotherapy and combination with pertuzumab and paclitaxel. These cost savings could provide more patients with trastuzumab-dkst treatment on a budget-neutral basis. [ABSTRACT FROM AUTHOR]

Aims: Therapeutic guidelines recommend prophylaxis against chemotherapy-induced (febrile) neutropenia (CIN/FN). Pegfilgrastim (Neulasta), biosimilar pegfilgrastim-jmdb (Fulphila), and pegfilgrastim with on-body injector (OBI; Neulasta Onpro) are options for CIN/FN prophylaxis. We aimed to simulate the cost-savings and budget-neutral expanded access to CIN/FN prophylaxis or anticancer treatment achieved through conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and to evaluate the economic impact of FN-related hospitalization costs due to pegfilgrastim-OBI failure. Methods: Cost-savings from conversion from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb were simulated in a panel of 15,000 patients with cancer from the US payer perspective. The primary analyses included conversion rates of 10% to 100%. Adjusted analyses also considered OBI device failure rates of 1% to 7% and associated costs of FN-related hospitalization. Simulations of budget-neutral expanded access to prophylaxis with pegfilgrastim-jmdb or to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL) were also performed. Results: In a 15,000-patient panel, conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings ranging from $481,259 (10% conversion) to $4,812,585 (100% conversion) in a single cycle. Over 6 cycles at 100% conversion, savings were $28,857,510 and could provide 9,191 additional doses of pegfilgrastim-jmdb or 4,463 cycles of R-CHOP to patients with DLBCL. Adjusted for OBI failure, cost-savings over 6 cycles ranged from $2,935,565 (10% conversion; pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (100% conversion; 7% failure). These cost-savings could provide 943 doses of pegfilgrastim-jmdb or 454 doses of R-CHOP (10% conversion; 1% pegfilgrastim-OBI failure) or provide 10,261 doses of pegfilgrastim-jmdb or 4,982 cycles of R-CHOP (100% conversion; 7% failure). Conclusion: Conversion from pegfilgrastim to pegfilgrastim-jmdb is associated with significant costsavings which increase markedly when also accounting for pegfilgrastim-OBI failure and associated FNrelated hospitalizations. These general and failure-related cost-savings could be allocated on a budgetneutral basis to provide more patients with additional CIN/FN prophylaxis or antineoplastic treatment. [ABSTRACT FROM AUTHOR]

Aim: To estimate the cost-savings from conversion to biosimilar pegfilgrastim-cbqv that can be reallocated to provide budget-neutral expanded access to FOLFIRINOX in patients with metastatic pancreatic cancer. Methods: Simulation modeling in a panel of 2500 FOLFIRINOX-treated patients, using varying treatment duration (1-12 cycles) and conversion rates (10-100%), to estimate cost-savings and additional FOLFIRINOX treatment that could be budget neutral. Results: In a 2500-patient panel at 100% conversion, savings of US$6,907.41 per converted patient over 12 cycles of prophylaxis translate to US$17.3 million and could provide 72,273 additional FOLFIRINOX doses or 6023 full 6-month regimens. Conclusion: Conversion to biosimilar CIN/FN prophylaxis can generate significant cost-savings and provide budget-neutral expanded access to FOLFIRINOX treatment for patients with metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]

In this population-based study, we used the SEER database (1985–2015) to examine survival outcomes in chronic lymphocytic leukemia (CLL) patients followed up to the era of advanced treatments including targeted therapies. Data were extracted for patients 15 years or older with a primary diagnosis of CLL. A period analysis was performed to estimate 5- and 10-year relative survival rates for patients diagnosed during different calendar periods from 1985 to 2015. A mixture cure model was used to examine long-term survivors' proportions among patients diagnosed in 1985–2015 and for two cohorts diagnosed in 2000–2003, followed up to 2012 and 2004–2007, and followed up to 2015. Cox proportional hazard modeling was used for the two cohorts to estimate hazard ratios (HRs) of death adjusted for gender and age. The 5-year and 10-year age-adjusted relative survival rate ranged between 73.7 and 89.4% and from 51.6% to "not reached," respectively, for calendar periods of 1985–1989 to 2010–2014. The long-term survivor proportions varied by age and gender from 0 to 59%. The HRs (95%CI) for the 2004–2007 cohort in comparison to the 2000–2003 cohort were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.0.67), 0.68 (0.54–0.85), and 0.83 (0.68–1.02) for the age categories of 45–54, 55–64, 65–74, 75–84, and ≥ 85 years, respectively. Overall, relative survival improved significantly for CLL patients diagnosed between 1985 and 2015. These improvements were markedly better following the introduction of targeted therapies. [ABSTRACT FROM AUTHOR]

Aim: To compare the incidence of febrile neutropenia and related outcomes of prophylactic same-day versus next-day pegfilgrastim/pegfilgrastim-cbqv in patients with lymphoma receiving cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone (CHOP)-like chemotherapy. Methods: Retrospective, real-world, single-institution study. Results: 93 patients received 460 cycles of CHOP-like chemotherapy. The incidence of febrile neutropenia and grade 3/4 chemotherapy-induced neutropenia was 5 and 16.5%, respectively. In 401 cycles pegfilgrastim was administered same-day versus 12 cycles next-day. Febrile neutropenia occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. Conclusion: Pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To examine the outcomes associated with granulocyte colony stimulating factors (G-CSFs) administered as primary versus secondary prophylaxis in setting of bendamustine plus rituximab (BR) regimens. Methods: Eighty-five patients who underwent treatment for non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) with BR at the University of Arizona Cancer Center from November 2013 to June 2019 were evaluated through retrospective chart review. Patients were stratified into two groups: those who were given G-CSF for primary prophylaxis (n = 47) and for secondary prophylaxis (n = 38). G-CSF-included filgrastim or pegfilgrastim. The primary endpoints were incidence of febrile neutropenia and grade 3 or 4 neutropenia. Results: Same-day G-CSF compared with next-day G-CSF was the most common G-CSF dosing method utilized in primary and secondary prophylaxis (94% and 100%), respectively. Primary and secondary prophylaxis groups were similar on baseline characteristics (p > 0.05); the primary outcome of FN (p > 0.05); all secondary outcomes (p > 0.05) except for a higher frequency of dose delays in secondary (40%) vs primary prophylaxis patients (13%; p = 0.01), and mean absolute neutrophil counts (ANC) in cycles 1 through 5. With higher ANC levels observed during all cycles in the primary prophylaxis group compared with secondary prophylaxis. Conclusions: In this single-center retrospective study, BR-treated lymphoma and CLL patients receiving primary versus secondary with G-CSF showed similar outcomes except, notably, for chemotherapy dose delays that may put secondary patients at risk for poor treatment outcomes. Further research is needed to evaluate the impact of primary versus secondary prophylaxis on treatment outcomes. [ABSTRACT FROM AUTHOR]

Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April–August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan–Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. Overall, median time to discharge was 10 days (95%CI = 9–10) in the favipiravir arm versus 15 days (95%CI = 14–16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56–2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04–0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73–3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99–7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum. [ABSTRACT FROM AUTHOR]

This study examined whether (a) cancer patients in two cohorts reported greater subjective cognitive impairment (SCI) in prevalence and severity than noncancer healthy controls; and (b) selected psychoneurological factors (fatigue, stress, and sleep disturbance) contribute to such differences. Data from 60 prechemotherapy cancer patients, 81 active-chemotherapy cancer patients, and 116 noncancer healthy controls were analyzed using hierarchical regressions. The prevalence rate of SCI was higher in the prechemotherapy cancer cohort (41.6%) and in the active-chemotherapy cancer cohort (46.9%) than in healthy controls (21.5%; p <.001). SCI severity was also higher in two cancer cohorts than noncancer controls (p <.001). The two cancer cohorts were similar to each other in severity and prevalence of SCI. The two cancer cohorts experienced higher fatigue, stress, and sleep disturbance than healthy controls. After controlling for psychoneurological factors, however, the two cancer cohorts did not differ from healthy controls in experiencing SCI in prevalence and severity. Psychoneurological factors may be a major determinant of the higher prevalence and severity of SCI in cancer patients. [ABSTRACT FROM AUTHOR]

Objective: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. Methods: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. Results: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Conclusion: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF. [ABSTRACT FROM AUTHOR]

Seven prospective real-world studies conducted in general practices in Belgium of antihypertensive treatment with valsartan-centric regimens were pooled to examine similarities and differences in determinants of blood pressure (BP) values (mmHg) and BP control rates between female and male patients. Pooled analysis of a total evaluable sample of 17,044 patients, including 8273 (48.5%) women and 8771 men (51.5%) treated over approximately 90 days with valsartan-centric regimens in second or later line. Hierarchical linear and logistic regressions were applied to identify patient- and physician-related determinants of BP outcomes and a potential physician class effect. Reductions in BP (mmHg) over 90 days were similar for women and men, and so were changes in BP control rates. Approximately a quarter of the variance in 90 day BP values was attributable to a physician class effect. Both gender groups shared some patient- and physician-related determinants of BP outcomes, though often varying in degree of influence. Analyses also revealed gender-specific determinants. Among others, modifiable/manageable patient-related determinants included BP at hypertension diagnosis (proxy for time of diagnosis), risk factors, antihypertensive treatment and adherence; while among the physician-related determinants clinical experience in hypertension treatment was modifiable/manageable. Valsartan-centric treatment regimens are associated with significant reductions in BP level and improvement in BP control in both women and men. The determinants revealed in modeling provide guidance to clinicians in the common and differential management of hypertension in female and male patients. [ABSTRACT FROM AUTHOR]

Objective Macrolide antibiotics are among the most commonly used antibiotics; the association of macrolide antibiotics exposure with sensorineural hearing loss (SNHL) has been hypothesized. A systematic search was conducted in PubMed, EMBASE and Cochrane Library from inception to 15 July 2019 to identify studies used macrolide antibiotics for any indication. The results were reported as odds ratio (OR) with 95% confidence interval (CI) using random-effects model to derive the association of macrolide antibiotics exposure with SNHL. The objective of this meta-analysis was to estimate the association of macrolide antibiotics exposure and SNHL from up-to-date evidence. Key findings: Nine studies met the inclusion criteria. There was no statistically significant association between macrolide antibiotics exposure and SNHL; the OR was 1.20 (95% CI: 0.96 to 1.49). No significant association was found with any of the subgroup meta-analyses. Summary Whilst the frequency of SNHL was higher with macrolide antibiotics exposure compared with controls, overall, no association was found between macrolide antibiotics and SNHL. [ABSTRACT FROM AUTHOR]

To investigate the cost-efficiency and budget-neutral expanded access of biosimilar intravenous trastuzumab-dkst versus reference intravenous (trastuzumab-IV) and subcutaneous trastuzumab (trastuzumab-SC) (with/without pertuzumab) in metastatic breast cancer (MBC). Economic simulation modeling in a panel of 1,000 MBC patients to estimate: 1) cost-savings by conversion from trastuzumab-IV or trastuzumab-SC to trastuzumab-dkst at 10-100% conversion rates in 3 weight groups: first quartile (Q1:62.2 kg), median (73.1 kg), third quartile (Q3:88.6 kg), and 2) budget-neutral expanded access to trastuzumab-dkst from cost-savings. In monotherapy, conversion (%) from trastuzumab-IV generates one-year cost-savings from $2,272,189 (Q1;10%) to $31,506,804 (Q3;100%) and from trastuzumab-SC monotherapy savings range from $2,071,277 (Q3;10%) to $35,775,475 (Q1;100%). In combination with pertuzumab, trastuzumab-dkst is cost-efficient in all patient weights with one-year savings over trastuzumab-IV up to $32,662,714 (Q3;100%) and over trastuzumab-SC up to $35,322,461 (Q1;100%). Savings from conversion from trastuzumab-IV monotherapy could provide between 3,087 (Q1;10%) and 30,911 (Q3;100%) additional trastuzumab-dkst doses—enough to treat 58 to 583 patients for one year. Conversion from trastuzumab-SC monotherapy could provide between 1,559 (Q3;10%) and 48,598 (Q1;100%) additional trastuzumab-dkst doses or 38 to 918 additional one-year treatments with trastuzumab-dkst. In combination with pertuzumab, conversion from trastuzumab-IV could provide from 311 (Q1;10%) to 3,939 (Q3;100%) maintenance doses (pertuzumab + trastuzumab-dkst) or 17 to 210 additional one-year regimens (all agents). Savings from conversion from trastuzumab-SC could expand access to 226 (Q3;10%) to 4,782 (Q1;100%) additional maintenance doses or 12 to 254 one-year regimens. This first cost-efficiency and expanded access study of biosimilar therapeutic cancer agents shows that trastuzumab-dkst is cost-efficient over trastuzumab-IV and trastuzumab-SC across all patient weights in both monotherapy and combination with pertuzumab and paclitaxel. These cost savings could provide more patients with trastuzumab-dkst treatment on a budget-neutral basis. [ABSTRACT FROM AUTHOR]

Therapeutic guidelines recommend prophylaxis against chemotherapy-induced (febrile) neutropenia (CIN/FN). Pegfilgrastim (Neulasta), biosimilar pegfilgrastim-jmdb (Fulphila), and pegfilgrastim with on-body injector (OBI; Neulasta Onpro) are options for CIN/FN prophylaxis. We aimed to simulate the cost-savings and budget-neutral expanded access to CIN/FN prophylaxis or anticancer treatment achieved through conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and to evaluate the economic impact of FN-related hospitalization costs due to pegfilgrastim-OBI failure. Cost-savings from conversion from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb were simulated in a panel of 15,000 patients with cancer from the US payer perspective. The primary analyses included conversion rates of 10% to 100%. Adjusted analyses also considered OBI device failure rates of 1% to 7% and associated costs of FN-related hospitalization. Simulations of budget-neutral expanded access to prophylaxis with pegfilgrastim-jmdb or to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL) were also performed. In a 15,000-patient panel, conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings ranging from $481,259 (10% conversion) to $4,812,585 (100% conversion) in a single cycle. Over 6 cycles at 100% conversion, savings were $28,857,510 and could provide 9,191 additional doses of pegfilgrastim-jmdb or 4,463 cycles of R-CHOP to patients with DLBCL. Adjusted for OBI failure, cost-savings over 6 cycles ranged from $2,935,565 (10% conversion; pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (100% conversion; 7% failure). These cost-savings could provide 943 doses of pegfilgrastim-jmdb or 454 doses of R-CHOP (10% conversion; 1% pegfilgrastim-OBI failure) or provide 10,261 doses of pegfilgrastim-jmdb or 4,982 cycles of R-CHOP (100% conversion; 7% failure). Conversion from pegfilgrastim to pegfilgrastim-jmdb is associated with significant cost-savings which increase markedly when also accounting for pegfilgrastim-OBI failure and associated FN-related hospitalizations. These general and failure-related cost-savings could be allocated on a budget-neutral basis to provide more patients with additional CIN/FN prophylaxis or antineoplastic treatment. [ABSTRACT FROM AUTHOR]

Background: Severe asthma affects 5–10% of the 350 million people with asthma worldwide. Findings from the authors' previous meta-analysis supported omalizumab use as an adjuvant treatment for severe allergic asthma. The publication of fourteen new articles necessitates an update of the meta-analysis. Objective: To evaluate the 'real-world' effectiveness of omalizumab in the treatment of acute allergic asthma in adults by calculating pooled effects estimates from data in published articles. Methods: Articles on omalizumab effectiveness in 'real-world' settings were identified. Effect sizes, including point estimates of the proportion of patients who met a given criteria, mean improvements relative to baseline, and change in the proportion of patients requiring oral corticosteroids compared to baseline were extracted. Meta-analysis of proportions was conducted to pool effect sizes based on proportions. Standardized mean differences (Hedges' g) were calculated from means and standard deviations. Relative risk was calculated from changes in proportions. Variability within and between studies was evaluated. Results: Omalizumab increases the percentage of individuals rated 'good' or 'excellent' on the Global Evaluation of Treatment Effectiveness Scale. Omalizumab also improves respiratory function, quality-of-life, and asthma control while reducing medication usage, exacerbations, hospitalizations, and adverse events. Conclusion: 'Real-world' evidence continues to support the use of omalizumab as adjuvant treatment for severe allergic asthma. [ABSTRACT FROM AUTHOR]