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Introduction: We evaluated the comparative efficacy of 6 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.

Aims: To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings., Methods: Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials' median PFS were also conducted., Results: In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case., Conclusion: Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

Aim: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP)., Methods: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed., Results: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results., Conclusion: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Background: Ebola virus disease (EVD) continues to be a major public health threat globally, particularly in the low-and-middle-income countries (LMICs) of Africa. The social and economic burdens of EVD are substantial and have triggered extensive research into prevention and control. We aim to highlight the impact and economic implications, identify research gaps, and offer recommendations for future economic studies pertaining to EVD., Method: We conducted a comprehensive librarian-led search in PubMed/Medline, Embase, Google Scholar, EconLit and Scopus for economic evaluations of EVD. After study selection and data extraction, findings on the impact and economics of EVD were synthesized using a narrative approach, while identifying gaps, and recommending critical areas for future EVD economic studies., Results: The economic evaluations focused on the burden of illness, vaccine cost-effectiveness, willingness-to-pay for a vaccine, EVD funding, and preparedness costs. The estimated economic impact of the 2014 EVD outbreak in Guinea, Liberia, and Sierra Leone across studies ranged from $30 billion to $50 billion. Facility construction and modification emerged as significant cost drivers for preparedness. The EVD vaccine demonstrated cost-effectiveness in a dynamic transmission model; resulting in an incremental cost-effectiveness ratio of about $96 per additional disability adjusted life year averted. Individuals exhibited greater willingness to be vaccinated if it incurred no personal cost, with a minority willing to pay about $1 for the vaccine., Conclusions: The severe impact of EVD puts pressure on governments and the international community for better resource utilization and re-allocation. Several technical and methodological issues related to economic evaluation of EVD remain to be addressed, especially for LMICs. We recommend conducting cost-of-sequelae and cost-of-distribution analyses in addition to adapting existing economic analytical methods to EVD. Characteristics of the affected regions should be considered to provide evidence-based economic plans and economic-evaluation of mitigations that enhance resource allocation for prevention and treatment.

Aims: To estimate, in the setting of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) for an assumed 1,207 incident US cases in 2024, (1) the cost-efficiency of a toripalimab-gemcitabine-cisplatin regimen compared to a similar pembrolizumab regimen; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens afforded by the accrued savings., Methods: Simulation modeling utilized two cost inputs (wholesale acquisition cost (WAC) at market entry and an ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) and drug administration costs over 1 and 2 years of treatment with treatment rates ranging from 45% to 90%. In the absence of trial data for pembrolizumab-gemcitabine-cisplatin in R/M NPC, it is assumed that such a regimen would be comparable to toripalimab-gemcitabine-cisplatin in efficacy and safety., Results: In the models utilizing the WAC, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 1,207-patient panel, estimated 1-year savings range from $21,733,702 (45% treatment rate) to $43,467,404 (90% rate). Reallocating these savings permits budget-neutral expanded access to an additional 2,359 (45% rate) to 4,717 (90% rate) toripalimab maintenance cycles or to an additional 126 (45% rate) to 252 (90%) full 1-year toripalimab regimens with all agents. Two-year savings range from $42,259,976 (45% rate) to $84,519,952 (90% rate). Reallocating these efficiencies provides expanded access, ranging from an additional 4,586 (45% rate) to 9,172 (90% rate) toripalimab cycles or to an additional 128-257 full 2-year toripalimab regimens. The ex ante ASP model showed similar results., Conclusion: This simulation demonstrates that treatment with toripalimab generates savings that enable budget-neutral funding for up to an additional 252 regimens with toripalimab-gemcitabine-cisplatin for one full year, the equivalent of approximately 21% of the 2024 incident cases of R/M NPC in the US.

Aim: Albumin role as fluid resuscitation in sepsis remains understudied in low- and middle-income countries. This study aimed to evaluate the cost-effectiveness of intravenous (IV) Albumin compared to Crystalloids in sepsis patients using patient-level data in Jordan., Methods: This was a retrospective cohort study of sepsis patients aged 18 or older admitted to intensive care units (ICU) at two major tertiary hospitals during the period 2018-2019. Patients information, type of IV fluid, and clinical outcomes were retrieved from medical records, and charges were retrieved from the billing system. A 90-day partitioned survival model with two health states (alive and dead) was constructed to estimate the survival of sepsis patients receiving either Albumin or Crystalloids as IV fluids for resuscitation. Overall survival was predicted by fitting a Weibull model on the patient-level data from the current study. To further validate the results, and to support the assessment of uncertainty, time-dependent transition probabilities of death at each cycle were estimated and used to construct a state-transition patient-level simulation model with 10,000 microsimulation trials. Adopting the healthcare system perspective, incremental cost-effectiveness ratios(ICERs) of Albumin versus Crystalloids were calculated in terms of the probability to be discharged alive from the ICU. Uncertainty was explored using probabilistic sensitivity analysis., Results: In the partitioned survival model, Albumin was associated with an incremental cost of $1,007 per incremental1% in the probability of being discharged alive from the ICU. In the state-transition patient-level simulation model, ICER was $1,268 per incremental 1% in the probability of being discharged alive. Probabilistic sensitivity analysis showed that Albumin was favored at thresholds >$800 per incremental 1%in the probability of being discharged alive from the ICU., Conclusion: IV Albumin use in sepsis patients might not be cost-effective from the healthcare perspective of Jordan. This has important implications for policymakers to readdress Albumin prescribing practice in sepsis patients.

Introduction: Biologics have shown marked success over the past decades in disease areas as cancer, immunology and diabetes. However, elevated costs of innovative biologic medicines have led to an inequity in accessibility across the world. While 85% of the world's population lives in low- and middle- income countries (LMIC), 80% of the sales of monoclonal antibodies are attributed to Western countries, highlighting the pronounced market imbalance., Areas Covered: This perspective paper draws some analogies as well as differences between biosimilars and generics, aims to address the unmet need for treatment with biologics in LMICs by reviewing possible causes, economic and social, of low access, displaying the disparity between LMICs and HIC, and suggets countermeasures for this unmet medical need in LMICs., Expert Opinion: It is up to all stakeholders to capitalize on the opportunity that biosimilars provide, mostly by committing to transparent collaboration, to make biotherapeutics accessible to all, regardless of region or country of residence.

Introduction: Little is known about the status and the future potential of biosimilars in the Middle East and North Africa (MENA) region., Areas Covered: This perspective provides insights into the current regulatory landscape of some MENA countries, currently available biosimilars, the potential of biosimilars in the next decade, and challenges to overcome., Expert Opinion: Given the economic and demographic heterogeneity across the MENA countries, biosimilars could reduce significant economic unmet needs in these countries. In the next decade, biosimilars may witness higher approval rates and market share over their originators in the MENA countries. We argue that the regulatory bodies in the MENA countries should adopt the new policies of the FDA, the EMA, and the WHO, that aim to ease the biosimilar approval process. These policies are to adopt technology in the process of approval; engage health technology assessment bodies in price assessment; provide educational materials to increase awareness among providers, patients, and payers. Further, MENA countries should upgrade the external-reference pricing systems to more sophisticated ones that consider the heterogeneity in economics and needs.

Background: 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.', Methods: 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., Results: 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., Conclusions: The economic value of knowing BRCA status of all U.S. ROC patients provides short-term and long-term evidence for optimizing treatment.

Background: 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.', Methods: 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., Results: 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., Conclusions: The universal testing for BRCA status of all US women at age 40 provides compelling short-term and long-term economic value.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Aims: 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., Materials and Methods: 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., Results: 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)., Conclusion: This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.

Aims: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

Aim: 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., Methods: 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)., Results: 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., Conclusion: 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.

Background: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19)., Research Design and Methods: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint., Results: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16)., Conclusions: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Background: Talimogene laherparepvec (T-VEC) improves overall survival (OS) in unresectable stage IIIB/C-IV melanoma T-VEC may have synergistic effects with CTLA-4 inhibitors In the absence of a trial comparing T-VEC and ipilimumab (T-VEC + IPI) to T-VEC, we applied a novel indirect comparison method using extrapolated OS curves to estimate OS outcomes in a simulated trial comparing both regimens in stage IIIB/C-IV unresectable melanoma., Research Design and Methods: Two trials with extractable OS curves for a T-VEC versus T-VEC + IPI comparison were identified. Outcomes were adjusted for heterogeneity in prognostic factors using a calculated adjustment factor. T-VEC and adjusted/unadjusted T-VEC+IPI curves were plotted with 95% CIs., Results: Unadjusted indirect OS comparison of T-VEC versus T-VEC + IPI revealed no significant difference up to 15 months. Extrapolation beyond 15 months showed significant survival benefits for T-VEC + IPI over T-VEC, confirmed in adjusted analyses. The expected OS percentage at 48 months is 32.0% (95% CI = 26.6-37.3) for T-VEC, 60.0% (95% CI = 46.2-69.1) for unadjusted, and 81.1% (95% CI = 72.3-85.9) for adjusted T-VEC + IPI., Conclusions: Our novel indirect comparison suggests that T-VEC + IPI may demonstrate a significantly improved OS versus T-VEC alone. Findings may portend a possible role for the addition of T-VEC to advanced melanoma treatment regimens in select patients as salvage therapy.

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.

Aims: 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)., Method: 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., Results: 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., Conclusions: 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.

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.

Background: 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)., Method: 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., Results: 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., Conclusion: 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.

Background: The risk of immune-related(ir)-hypothyroidism in older patients with advanced melanoma treated with anti-CTLA4 or anti-PD1 therapies is poorly understood, especially in the real-world setting. Research design and methods: We identified older patients (≥65 years) diagnosed with advanced melanoma between 2011-2015 and treated with anti-CTLA4 or anti-PD1 agents in the SEER-Medicare database. Applying probability-of-treatment-weighting for confounder adjustment and proportional hazards models, we estimated the risk of ir-hypothyroidism between treatment initiation and up to 90 days from last dose between anti-PD1 and anti-CTLA4 users. Results: Of 210 older patients with advanced melanoma identified, 164 received anti-CTLA4 (ipilimumab) and 46 anti-PD1 agents (11 nivolumab, 35 pembrolizumab). There was no statistically significant difference in ir-hypothyroidism risk between anti-PD1 and anti-CTLA4 users (HR=2.15, 95%CI=0.83-5.53). Pairwise medication comparisons showed a lower risk among ipilimumab versus nivolumab (HR=0.15, 95%CI=0.06-0.40) and pembrolizumab versus nivolumab users (HR=0.13, 95%CI=0.03-0.55). Sensitivity analyses using an all-stages melanoma cohort did not show a difference in ir-hypothyroidism risk between medication classes and individual medications. Conclusions: This retrospective claims data analysis revealed no statistically significant difference in ir-hypothyroidism risk between anti-CTLA4 or anti-PD1 users. However, patients with advanced melanoma treated with ipilimumab or pembrolizumab may have a lower ir-hypothyroidism risk compared to nivolumab users.

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 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.

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 (Q 1 :62.2 kg), median (73.1 kg), third quartile (Q 3 :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 (Q 1 ;10%) to $31,506,804 (Q 3 ;100%) and from trastuzumab-SC monotherapy savings range from $2,071,277 (Q 3 ;10%) to $35,775,475 (Q 1 ;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 (Q 3 ;100%) and over trastuzumab-SC up to $35,322,461 (Q 1 ;100%). Savings from conversion from trastuzumab-IV monotherapy could provide between 3,087 (Q 1 ;10%) and 30,911 (Q 3 ;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 (Q 3 ;10%) and 48,598 (Q 1 ;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 (Q 1 ;10%) to 3,939 (Q 3 ;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 (Q 3 ;10%) to 4,782 (Q 1 ;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.

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.

Aims: In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) from the US payer perspective, (2) simulated how savings enable, on a budget-neutral basis, expanded access to pegfilgrastim-cbqv, and (3) estimated the number-needed-to-convert (NNC) to purchase one additional dose of pegfilgrastim-cbqv., Methods: In a hypothetical panel of 20,000 patients, we modeled cost-savings utilizing: two reference formulations (pre-filled syringe [PFS] and on-body injector [OBI]), three medication cost inputs (average sales price [ASP], wholesale acquisition cost [WAC], and an age-proportionate blended ASP/WAC rate), administration cost for injection (PFS) and device application (OBI), conversion rates of 10-100%, and 1-6 cycles of prophylaxis. Cost-savings were used to estimate additional doses of pegfilgrastim-cbqv that could be purchased and the NNC to purchase one additional dose., Results: Using ASP and 10% conversion from reference OBI to pegfilgrastim-cbqv, savings range from $326,744 (1 cycle) to $2.0M (6 cycles) which could provide 93-556 additional doses of pegfilgrastim-cbqv, respectively; the NNC to purchase one additional dose of pegfilgrastim-cbqv ranges from 21.6 (1 cycle) down to 3.6 patients (6 cycles). The WAC model saves $41.1M per cycle and $246.7M over 6 cycles at 100% conversion from reference PFS which could provide 9,709-58,253 additional pegfilgrastim-cbqv doses; the NNC ranges from 2.1 (1 cycle) to 0.3 (6 cycles). Using the blended ASP/WAC rate, converting 50% from reference OBI to pegfilgrastim-cbqv would save $10.2M per cycle and $60.9M over 6 cycles providing 2,638-15,829 additional doses of pegfilgrastim-cbqv; NNCs are 3.8 (1 cycle) and 0.6 patients (6 cycles)., Conclusions: Converting 20,000 patients from reference to pegfilgrastim-cbqv over 6 cycles can generate savings up to $246.7M, enough to purchase up to 58,253 additional doses of pegfilgrastim-cbqv. This simulation provides economic justification for prophylaxis with biosimilar pegfilgrastim-cbqv.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The second dimension (δ2) estimates prices on the basis of four willingness-to-pay (WTP) thresholds. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: Eight WTP scenarios based on four levels of real gross domestic product per capita (<1GDP/capita, 1 × GDP/capita, 3 × GDP/capita, and >3 × GDP/capita) and two market conditions (monopolistic versus competitive) were assumed. The incremental cost-utility ratio (ICUR) was applied to differently to both markets. In the monopolistic market, assuming no competitors, the cost/QALY ratio for a drug was used; whereas in the competitive market, assuming competitors, the incremental cost-utility ratio (ICUR) was applied. One-way sensitivity analyses were performed and predictive equations were specified to estimate the prices of treatment for the resulting eight WTP scenarios; for which subsequently the average and standard deviation were calculated. A gamma distribution was specified and Monte Carlo Simulation (MCS) was applied to estimate the dimension-specific price based on WTP (DSP WTP ). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) of $14,616 (30-day prescription) was used to estimate the DSP WTP for each contract., Results: The 1-year estimates averaged $4,654 (SD=$6,462) and the MCS yielded a DSP WTP of $4,547 or -68.89% of the 2018 WAC for a 30-day prescription. The 2-year estimates averaged $4,7667 (SD=$6,480) with the MCS generating a DSP WTP of $4,704 or -67.82% of the WAC., Conclusions: We demonstrated that WTP-based methods that include various WTP thresholds and market conditions generate price estimates across these thresholds and market conditions that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The first dimension (δ1) estimates prices on the basis of cost-effectiveness (CEA) and cost-utility analysis (CUA). We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: CEA and CUA were performed using established methods. Probabilistic sensitivity analyses (PSA) were performed to generate cost-effectiveness acceptability curves (CEAC), specifically the PSA incremental cost-effectiveness (PSA ICER) and incremental cost-utility ratio generated CEACs (PSA ICUR). Price of treatment was estimated at three certainty levels (0%, turning point%, 100%). The marketed drug price at turning point was used to estimate prices at 0% and 100% certainty levels, as per PSA ICER and PSA ICUR-generated CEACs. The resulting prices were pooled, inflated, and simulated by Monte Carlo Simulation (MCS) methods to estimate the dimension-specific price based on CEA and CUA (DSP CEA/CUA ). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-years (2019-2021)., Results: Turning points were estimated at the 50% certainty level in both PSA ICER and ICUR-generated CEACS. At these points, the wholesale acquisition cost for osimertinib was $14,616 (30-day prescription); inflated by 0.44% for 1-year and by 0.72% for 2-year contracts. Additional prices at 0% and 100% certainty levels were quantified based on the PSA ICER and ICUR-generated CEACs. The MCS yielded a DSP CEA/CUA of $16,391 for the 1-year contract and a DSP CEA/CUA at $16,677 for the 2-year contract for a 30-day prescription., Conclusions: We demonstrated that conventional CEA and CUA methods generate price estimates at varying levels of certainty that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fifth dimension (δ5) estimates prices on the basis of the risk of efficacy failure of a drug. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: The risk of efficacy failure pricing dimension utilizes a seven-step method: (1) defining risk; (2) extracting data; (3) predicting models; (4) performing Monte Carlo Simulation (MCS) to estimate risk of efficacy failure; 5) estimating ranges for a payback; (6) adjusting for medical inflation; and (7) performing Monte Carlo Simulation (MCS) to estimate the DSP Risk of efficacy failure . A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the risk of efficacy failure for osimertinib in terms of overall and progression-free survival versus standard of care. We used the estimated risk to estimate the price reduction on the wholesale acquisition cost (WAC) for the two hypothetical contracts: a 1-year (2019-2020) and 2-year contract (2019-2021). From this we estimated the DSP Risk of efficacy failure ., Results: Based on the risk of OS and PFS efficacy failure for osimertinib in OS and PFS, in the 1-year contract, the DSP Risk of efficacy failure was estimated at $12,652 (or -13.44% the 2018 WAC) for a 30-day prescription. For the 2-year contract (2019-2021), the DSP Risk of efficacy failure was estimated at $13,019 (or -10.93% the 2018 WAC)., Conclusions: We demonstrated that pricing methods based on risk of efficacy failure methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The six dimensions have been described separately: (δ1) cost-effectiveness analysis and cost-utility analysis-based pricing; (δ2) willingness-to-pay-based pricing; (δ3) reference-based pricing; (δ4) safety-based pricing; (δ5) risk of efficacy failure-based pricing; and (δ6) adherence-based pricing. The final step is to integrate the various dimension-specific pricing estimates into a composite estimate termed the All-Dimensional Price (ADP). We describe the methodology for this integration and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: For better accuracy in estimating the ADP, we used the prices generated from the six dimensions at scenario levels, not at the dimension-specific price (DSP) level. We pooled the price estimates and performed Monte Carlo Simulations (MCS) for the price scenarios generated by the six dimensions. We used the results of the proof-of-concept exercise involving osimertinib in NSCLC with EGFR mutation to estimate the ADP in two hypothetical contracts: 1-year (2019-2020) and 2-year contract (2019-2021)., Results: The average of the 30-day prescription estimates from the six dimensions averaged $10,819 (SD=$8,486) for the 1-year contract and $10,730 (SD=$8,500) for the 2-year contract. MCS yielded for the 1-year contract an ADP of $10,959 (or -25.02% the 2018 WAC price) and an ADP for the 2-year contract was $10,788 (or -26.19% the 2018 WAC price)., Conclusions: We demonstrated that the integration of the prices from the six dimensions of the Six Delta platform and market conditions is feasible and yields multidimensional prices estimates to support outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fourth dimension (δ4) estimates prices on the basis of assessments of the safety of the drug using an ex ante analysis based on clinical trial data. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: The safety-based pricing dimension utilizes a four-step method: 1) pooling adverse events (AE), standardizing, estimating 95%Cis, and adjusting for time; 2) estimating correction factors and corrected probabilities of AEs; 3) estimating the probability of at least one adverse event (AE) occurring and leading to treatment discontinuation; and 4) estimating ranges for payback percentages and performing Monte Carlo Simulation to estimate a DSP Safety . A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the DSP Safety based on the grade 3/4 AEs observed for osimertinib and standard of care. The 2018 wholesale acquisition cost (WAC) of osimertinib at $14,616 for a 30-day prescription was used., Results: AEs3/4 were retrieved from the FLAURA trial. In the 1-year contract, the DSP Safety of osimertinib was estimated at $14,627 (or +0.08% the 2018 WAC) for a 30-day prescription. In the 2-year contract, the DSP Safety of osimertinib was estimated at $14,516 (or -0.68% the 2018 WAC) for a 30-day prescription., Conclusions: We demonstrated that ex ante pricing methods-based paybacks for safety issues leading to treatment discontinuation can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The third dimension (δ3) estimates prices on the basis of international drug price referencing methods. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: The reference-based pricing dimension utilizes a six-step method: (1) selecting foreign countries based on a set of four criteria (drug is available in the foreign country, price information is available in the foreign country, foreign countries are members within the organization for Economic Co-operation and Development, pricing methods in the foreign countries involve value assessment); (2) adjusting for exchange rates; (3) generating reference price (RP) scenarios; (4) adjusting with the medical inflation rate; (5) pooling all generated RP scenarios and calculating average and standard deviation (SD); (6) and Monte Carlo Simulation (MCS) to estimate the dimension-specific DSP Reference . A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021)., Results: The United Kingdom and Canada met the four criteria. For the osimertinib 1-year contract price, the average of eight RP scenarios, adjusted for inflation by 0.44%, was $8,892 (SD = $2,606) for a 30-day prescription. MCS yielded a DSP Reference estimate of $9,395 or -35.72% of the wholesale acquisition cost (WAC) of $14,616. For the 2-year contract, the average, adjusted for inflation by 0.72%, was $8,928 (SD = $2,610). MCS yielded a DSP Reference estimate of $9,442 or -35.40% of the WAC of $14,616., Conclusions: We demonstrated that international price referencing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Aims: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The sixth dimension (δ6) estimates prices on the basis of adherence to the prescribed regimen, whereby manufacturers provide payers with adherence-enhancing programs and whereby payers implement these programs and provide adherence data to the manufacturer. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib., Materials and Methods: We propose two paybacks based on adherence: in-advance (based on clinical trial data) and in-arrear (based on real-world data). The risk of efficacy failure pricing dimension utilizes a 7-step method: 1) defining efficacy endpoints; 2) extracting data; 3) predicting models; 4) estimating in-advance and in-arrear paybacks; 5) suggesting ranges for in-advance and in-arrear paybacks; 6) adjusting for medical inflation; and 7) performing Monte Carlo Simulation (MCS) to estimate the DSP Adherence . A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) for a 30-day prescription was used and inflated as needed. Herein, the DSP Adherence is estimated exclusively in terms of in-advance payback because real-world data about osimertinib are not yet available and thus the in-arrear payback cannot yet be estimated., Results: For the 1-year contract, the average price for osimertinib was $13,798 (SD=$1,265) and the DSP Adherence was $13,785 (or -5.69% of the 2018 WAC) for a 30-day prescription. For the 2-year contract, the average price was $12,555 (SD=$2,847) and the DSP Adherence was $12,582 (or -13.92% of the 2018 WAC)., Conclusions: We demonstrated that adherence-based pricing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting. The proof-of-concept exercise needs to be expanded with the in-arrear pricing method based on real world data to be secured.

Aims: For this economic analysis, we aimed to model: (1) the cost-efficiency of prophylaxis with biosimilar pegfilgrastim-bmez for chemotherapy-induced (febrile) neutropenia (CIN/FN) compared to reference pegfilgrastim, and (2) the expanded access to CIN/FN prophylaxis and anti-neoplastic treatment that could be achieved with biosimilar cost-savings on a budget-neutral basis. Methods: In a hypothetical panel of 20,000 cancer patients receiving CIN/FN prophylaxis and using the average sales price (ASP) for the second quarter of 2019 for reference pegfilgrastim, we: conducted an ex ante simulation from the payer perspective of the cost-savings of 10-100% conversion from reference to biosimilar pegfilgrastim-bmez using drug price discounting ranging from 10-35%; estimated the budget-neutral expanded access to biosimilar pegfilgrastim-bmez enabled by these cost-savings; and estimated the budget-neutral expanded access to anti-neoplastic treatment with pembrolizumab. The simulations were replicated using fourth quarter 2019 wholesale acquisition cost (WAC) for reference pegfilgrastim and biosimilar pegfilgrastim-bmez in a post facto analysis. Results: In ASP simulations, cost-savings of using pegfilgrastim-bmez over reference pegfilgrastim in a 20,000 patient panel range from $1.3 M (at 15% price discount) to $3 M (35%) at 10% conversion rate and from $6.4 M to $14.9 M, respectively, at 50% conversion. These savings could provide prophylaxis with pegfilgrastim-bmez to an additional 352 (15% discount) to 1,076 patients (35%) at 10% conversion or 1,764-5,384, respectively, at 50% conversion. Alternatively, savings could be reallocated for anti-neoplastic treatment with pembrolizumab to 3 (15% discount) to 9 (35%) patients at 10% conversion or 19-45, respectively, at 50% conversion. When utilizing WAC, cost-savings range from $4.6 M (10% conversion) to $23.1 M (50%) which could provide pegfilgrastim-bmez to an additional 1,174 (10% conversion) to 5,873 patients (50%). Conclusions: Prophylaxis with biosimilar pegfilgrastim-bmez increases the value of cancer care by generating significant cost-savings that could be reallocated to provide expanded access to CIN/FN prevention and anti-neoplastic therapy on a budget-neutral basis.

Studies comparing the prognostic role of RUNX1 mutations ( RUNX1 mut ) in acute myeloid leukemia (AML) and acute myeloid leukemia-with myelodysplasia-related changes (AML-MRC) are limited. Our study examines the genetic profile of 118 RUNX1 mut AML patients including 57 AML with RUNX1 mut and 61 AML-MRC with RUNX1 mut and 100 AML, NOS patients with wild type RUNX1 ( RUNX1 wt ). Results revealed that AML-MRC patients with RUNX1 mut had shorter median overall survival (OS) (11 ± 3.3 months) when compared to AML with RUNX1 mut (19 ± 7.1 months) and AML, NOS with RUNX1 wt (not reached) ( p  = .001). The most common concurrent mutations observed in AML-MRC with RUNX1 mut patients were DNMT3A , SRSF2 , ASXL1 , and IDH2 while in AML with RUNX1 mut patients were ASXL1 , SRSF2 , TET2 , IDH2 , and DNMT3A . ASXL1 and TET2 mutations appeared to adversely affect OS in AML-MRC, but not in AML with RUNX1 mut . Concurrent RUNX1/DNMT3A mutations, in contrast had negative impact on OS in AML with RUNX1 mut , but not in AML-MRC with RUNX1 mut .

Objectives : To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors. Methods : The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses. Results : One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I 2  = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I 2  = 87.9%). Conclusion : The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.

Background: Guidelines recommend febrile neutropenia (FN) prophylaxis following myelotoxic chemotherapy with either daily injections of filgrastim (Neupogen ® ) or biosimilar filgrastim-sndz (Zarzio/Zarxio ® ), single-injection pegfilgrastim (Neulasta ® ), or pegfilgrastim administered through an on-body injector (PEG-OBI; Neulasta ® Onpro ® ). PEG-OBI failure rates up to 6.9% have been reported, putting patients at incremental risk for FN and FN-related hospitalization. Our objective was to estimate, from a US payer perspective, the incremental costs of FN hospitalizations and the total incremental costs associated with PEG-OBI prophylaxis at varying device failure rates over assured FN prophylaxis with daily injections of filgrastim or filgrastim-sndz or a single injection of pegfilgrastim. Methods: Cost simulations comparing prophylaxis with PEG-OBI at failure rates of 1-10% versus assured prophylaxis in cycle 1 of chemotherapy were performed for panels of 10,000 patients with lung cancer treated with cyclophosphamide, doxorubicin, and etoposide (1 analysis) or non-Hodgkin lymphoma (NHL) treated with CHOP or CNOP (2 analyses). Daily injection scenarios were 4.3, 5, and 11 injections for lung cancer and 5, 6.5, and 11 for NHL. The analyses are from the US payer perspective. Results: For lung cancer, the total incremental cost of PEG-OBI prophylaxis at varying failure rates and durations ranged from $6,691,969‒$31,765,299 over filgrastim and $18,901,969‒$36,538,299 over filgrastim-sndz. For NHL, in scenario 1, the total incremental costs ranged from $6,794,984‒$30,361,345 over filgrastim and $19,004,984‒$35,911,345 over filgrastim-sndz; in scenario 2, the incremental costs ranged from $7,003,657‒$32,448,067 over filgrastim and $19,213,657‒$37,998,067 over filgrastim-sndz. Conclusions: In this simulation, the incremental costs of FN-related hospitalization due to PEG-OBI failure in cycle 1 compared to assured prophylaxis with reference pegfilgrastim, reference filgrastim, and biosimilar filgrastim-sndz varied depending upon the PEG-OBI failure rate and the alternative G-CSF prophylaxis option. Biosimilar filgrastim-sndz offers the greatest cost-efficiency.