Background
Treatment options for patients with platinum‐refractory, recurrent, metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and prognosis is poor. The recent CheckMate 141 ...clinical trial demonstrated that nivolumab, an anti‐programmed cell death protein 1 monoclonal antibody, was efficacious in extending the median overall survival (OS) in this patient population compared with standard therapies. We conducted a cost‐effectiveness analysis to determine whether nivolumab is a cost‐effective treatment in this patient population and examined various subgroups to determine for which, if any, the treatment is more cost‐effective.
Materials and Methods
We implemented a state transition model for HNSCC with a patient cohort who had tumor progression 6 months after the last dose of platinum‐containing chemotherapy and compared the cost‐effectiveness of nivolumab with docetaxel. Treatment effect estimates and adverse event rates were obtained from CheckMate 141. Costs, utilities, and other model inputs were gathered from published sources. We used a Canadian perspective, a 5‐year time horizon, and a 1.5% discount rate for the analysis.
Results
Nivolumab extended mean OS by 4 months compared with docetaxel and resulted in fewer treatment‐related adverse events, producing an incremental effectiveness of 0.13 quality‐adjusted life years (QALY). The incremental cost of treatment with nivolumab was $18,823. At a willingness‐to‐pay threshold of $100,000/QALY, nivolumab was not a cost‐effective treatment option for r/m HNSCC, with an incremental cost‐effectiveness ratio of $144,744/QALY. Nivolumab would be cost‐effective if its price was reduced by 20%. Our subgroup analysis seemed to indicate that nivolumab might be cost‐effective for tumors with expression of programmed death‐ligand 1 >5%.
Conclusion
We conclude that although nivolumab offers clinical benefit for the treatment of r/m HNSCC over current regimens, it is not cost‐effective based on its list price. We have also established a value‐based price estimate for nivolumab to be cost‐effective in this patient population. Further study is required to draw a definitive conclusion on biomarkers for cost‐effectiveness.
Implications for Practice
In health care settings in which cost considerations are a constraint on choice of therapy, patient selection should be carefully considered to maintain efficiency in the system. Until a biomarker for response to therapy is identified for nivolumab, this medication is unlikely to be cost‐effective for most patients with recurrent, metastatic head and neck squamous cell carcinoma.
Although nivolumab has shown clinical efficacy in platinum efractory recurrent metastatic head and neck squamous cell carcinoma, its value is less clear given the high price of the drug. This article discusses the cost‐effectiveness of nivolumab compared with docetaxel at the current listed price in Canada and considers whether there are any patient subgroups for whom nivolumab could be cost‐effective.
Questions remain about the long-term health impacts of the 1991 Gulf War on its veterans.
To measure psychological disorders in Australian Gulf War veterans and a military comparison group and to ...explore any association with exposure to Gulf War-related psychological stressors.
Prevalences of DSM-IV psychological disorders were measured using the Composite International Diagnostic Interview. Gulf War-related psychological stressors were measured using a service experience questionnaire.
A total of 31% of male Gulf War veterans and 21% of the comparison group met criteria for a DSM-IV disorder first present in the post-Gulf War period. The veterans were at greater risk of developing post-Gulf War anxiety disorders including post-traumatic stress disorder, affective disorders and substance use disorders. The prevalence of such disorders remained elevated a decade after deployment. The findings can be explained partly as a 'war-deployment effect'. There was a strong dose-response relationship between psychological disorders and number of reported Gulf War-related psychological stressors.
Service in the 1991 Gulf War is associated with increased risk of psychological disorders and these are related to stressful experiences.
We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of ...the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.
Background
Chimeric antigen receptor (CAR) T-cell therapy is a novel cell therapy for treating non-Hodgkin lymphoma. The development of CAR T-cell therapy has transformed oncology treatment by ...offering a potential cure. However, due to the high cost of these therapies, and the large number of eligible patients, decision makers are faced with difficult funding decisions. Our objective was to assess the cost-effectiveness of tisagenlecleucel for adults with relapsed/refractory diffuse large B-cell lymphoma in Canada using updated survival data from the recent JULIET trial.
Methods
We developed an individual-simulated discrete event simulation model to assess the costs and quality-adjusted life-years (QALY) of tisagenlecleucel compared with salvage chemotherapy. Survival estimates were obtained from a published clinical trial and retrospective analysis. If patients remained progression free for 5 y, they were assumed to be in long-term remission. Costing and utility data were obtained from reports and published sources. A Canadian health care payer perspective was used, and outcomes were modeled over a lifetime horizon. Costs and outcomes were discounted at 1.5% annually, with costs reported in 2021 Canadian dollars. A probabilistic analysis was used, and model parameters were varied in 1-way sensitivity analyses and scenario analyses.
Results
After we incorporated the latest clinical evidence, tisagenlecleucel led to an additional cost of $503,417 and additional effectiveness of 2.48 QALYs, with an incremental cost-effectiveness ratio of $202,991 compared with salvage chemotherapy. At a willingness-to-pay threshold of $100,000/QALY, tisagenlecleucel had a 0% likelihood of being cost-effective.
Conclusions
At the current drug price, tisagenlecleucel was not found to be a cost-effective option. These results heavily depend on assumptions regarding long-term survival and the price of CAR T. Real-world evidence is needed to reduce uncertainty.
Highlights
For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.
These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.
Three independent modeling methods—a nutrient-phytoplankton–zooplankton (NPZ) model (NEMURO), a food web model (Ecopath/Ecosim), and a bioenergetics model for pink salmon (
Oncorhynchus ...gorbuscha)—were linked to examine the relationship between seasonal zooplankton dynamics and annual food web productive potential for Pacific salmon feeding and growing in the Alaskan subarctic gyre ecosystem. The linked approach shows the importance of seasonal and ontogenetic prey switching for zooplanktivorous pink salmon, and illustrates the critical role played by lipid-rich forage species, especially the gonatid squid
Berryteuthis anonychus, in connecting zooplankton to upper trophic level production in the subarctic North Pacific. The results highlight the need to uncover natural mechanisms responsible for accelerated late winter and early spring growth of salmon, especially with respect to climate change and zooplankton bloom timing. Our results indicate that the best match between modeled and observed high-seas pink salmon growth requires the inclusion of two factors into bioenergetics models: (1) decreasing energetic foraging costs for salmon as zooplankton are concentrated by the spring shallowing of pelagic mixed-layer depth and (2) the ontogenetic switch of salmon diets from zooplankton to squid. Finally, we varied the timing and input levels of coastal salmon production to examine effects of density-dependent coastal processes on ocean feeding; coastal processes that place relatively minor limitations on salmon growth may delay the seasonal timing of ontogenetic diet shifts and thus have a magnified effect on overall salmon growth rates.
We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely polarized 3 GeV electrons from unpolarized protons at Q2=0.15, 0.25 (GeV/c)2. The results are inconsistent ...with calculations solely using the elastic nucleon intermediate state and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A(n) provides a direct probe of the imaginary component of the 2gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.
Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, with a uniformly poor prognosis. The tumor microenvironment is composed of both supportive cellular substrates and exogenous ...factors. We hypothesize that exogenous factors secreted by brain tumor initiating cells (BTICs) could predispose normal neural precursor cells (NPCs) to transformation. When NPCs are grown in GBM-conditioned media, and designated as “tumor-conditioned NPCs” (tcNPCs), they become highly proliferative and exhibit increased stem cell self-renewal, or the unique ability of stem cells to asymmetrically generate another stem cell and a daughter cell. tcNPCs also show an increased transcript level of stem cell markers such as CD133 and ALDH and growth factor receptors such as VEGFR1, VEGFR2, EGFR and PDGFRα. Media analysis by ELISA of GBM-conditioned media reveals an elevated secretion of growth factors such as EGF, VEGF and PDGF-AA when compared to normal neural stem cell-conditioned media. We also demonstrate that tcNPCs require prolonged or continuous exposure to the GBM secretome in vitro to retain GBM BTIC characteristics. Our in vivo studies reveal that tcNPCs are unable to form tumors, confirming that irreversible transformation events may require sustained or prolonged presence of the GBM secretome. Analysis of GBM-conditioned media by mass spectrometry reveals the presence of secreted proteins Chitinase-3-like 1 (CHI3L1) and H2A histone family member H2AX. Collectively, our data suggest that GBM-secreted factors are capable of transiently altering normal NPCs, although for retention of the transformed phenotype, sustained or prolonged secretome exposure or additional transformation events are likely necessary.
In Canada, chimeric antigen receptor (CAR) T-cell therapy was recommended for funding for the treatment of select hematological cancers. Canadian hospitals have limited experience and capacity in ...administrating this therapy. We conducted a qualitative interview-based study with stakeholders in Canada. Questions were asked related to the development, administration, implementation and logistical planning of CAR T-cell therapy. Results were summarized into four main themes: (i) novel; (ii) patient characteristics and the delivery of care; (iii) processes from "bench-to-bedside"; and (iv) the future state, including both challenges and recommendations to ensure sustainability. Valuable perspectives from stakeholders highlight some of the unique challenges to implementing a highly personalized and expensive-to-deliver therapy.
This study examines psychological stressors reported by Australian Navy Gulf War veterans in relation to the 1991 Gulf War and other military service. Using a 44‐item questionnaire, veterans reported ...few direct‐combat encounters during the Gulf War; however, they reported many other stressful experiences, including fear of death and perceived threat of attack, more frequently in relation to the Gulf War than other military service. Reporting of stressful experiences was associated with younger age, lower rank, and deployment at the height of the conflict. These experiences may partly explain increased rates of psychological disorders previously demonstrated in this Navy veteran population. Findings highlight the importance of documenting war experiences in close proximity to deployment, and developing war exposure instruments which include naval activities and which reflect stressors other than those related to direct combat.
The development of chimeric antigen receptor (CAR) T cells has transformed oncology treatment, with the potential to cure certain cancers. Although shown to be effective in selected populations and ...studies, CAR T-cell technology requires considerable health care resources, which may lead to additional wait times to access this type of treatment in future. The objective of our study was to estimate the potential impact of increasing wait times on CAR T-cell therapy effectiveness compared with standard chemotherapy for patients with relapsed/refractory diffuse large B-cell lymphoma.
A health system-level discrete event simulation model was developed to project the potential impact of wait times on CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma. Waiting queues and health states related to treatment and clinical progression were implemented. Using data from the literature, we evaluated nine scenarios of using CAR T-cell therapy with wait times ranging from 1 to 9 months. The outcome of interest was 1-year all-cause mortality.
Increasing the wait time of receiving CAR T-cell therapy from 1 to 9 months increased the predicted 1-year mortality rate from 36.1% to 76.3%. Baseline 1-year mortality was 34.0% in patients receiving CAR T-cell therapy with no wait times and 75.1% in patients treated with chemotherapy. This resulted in an increased relative mortality rate of 6.2% to 124.5% over a 1- to 9-month wait time compared with no wait time.
We found that modest delays in CAR T-cell therapy significantly hinder its effectiveness. Because CAR T-cell therapy offers a potential cure, it is expected that the uptake rate will be substantially increased once the therapy is regularly funded by a health care system. Wait times may be prolonged if system resource availability does not match the demand. Strategies must be developed to minimize the impact of delays and reduce complications during waiting.
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