Qualitative Exploration of the Visual Function Impairments and Health-Related Quality of Life Impacts of Amblyopia in Adult and Pediatric Populations.

Introduction: Amblyopia is a reduction in vision in one or both eyes due to impaired development of the visual pathway. This study explored the experience of amblyopia and treatment from the patient, caregiver, and clinician perspectives.

Methods: A targeted literature review, including a review of social media listening (SML) studies, was conducted.

Efficacy and Safety of Brolucizumab, Aflibercept, and Ranibizumab for the Treatment of Patients with Visual Impairment Due to Diabetic Macular Oedema: A Systematic Review and Network Meta-Analysis.

Introduction: Key clinical guidelines recommend anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for visual impairment due to diabetic macular oedema (DMO). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted comparing the relative efficacy of the anti-VEGF brolucizumab with a focused network of the most relevant comparator dosing regimens approved in countries other than the USA (aflibercept, ranibizumab). The safety and tolerability of brolucizumab were also assessed.

The Amblyopia Quality of Life (AmbQoL): Development and Content Validation of a Novel Health-Related Quality of Life Instrument for Use in Adult and Pediatric Amblyopia Populations.

Introduction: Amblyopia is a neurodevelopmental vision disorder, characterized by poor vision in one or both eyes. Given the lack of existing clinical outcome assessments (COA) considered fit-for-purpose for amblyopia clinical trials, this study developed new COAs to assess amblyopia symptoms and health-related quality of life (HRQoL) impacts in adult and pediatric amblyopia populations that conform with best practice standards and regulatory guidelines.

Methods: Findings from a targeted qualitative literature review informed the development of three versions of the new Amblyopia Quality of Life Questionnaire (AmbQoL): a patient-reported outcome measure (PRO) for individuals aged 13 years and older, a PRO for children aged 9-12 years, and an observer-reported outcome measure (ObsRO) for caregivers of children aged 4-8 years.

A Social Media Listening Study to Understand the Unmet Needs and Quality of Life in Adult and Pediatric Amblyopia Patients.

Introduction: Amblyopia is an important cause of monocular vision impairment worldwide, and it negatively impacts patients' quality of life (QoL). Understanding patients' perspectives may help to optimize treatment outcomes and improve treatment adherence.

Methods: This was a non-interventional, retrospective analysis of social media data available in the public domain posted by patients and caregivers on selected social media channels (Twitter®, forums, blogs, and news) from 12 countries between July 2018 and June 2020.

Machine Learning Methods in Health Economics and Outcomes Research-The PALISADE Checklist: A Good Practices Report of an ISPOR Task Force.

Advances in machine learning (ML) and artificial intelligence offer tremendous potential benefits to patients. Predictive analytics using ML are already widely used in healthcare operations and care delivery, but how can ML be used for health economics and outcomes research (HEOR)? To answer this question, ISPOR established an emerging good practices task force for the application of ML in HEOR. The task force identified 5 methodological areas where ML could enhance HEOR: (1) cohort selection, identifying samples with greater specificity with respect to inclusion criteria; (2) identification of independent predictors and covariates of health outcomes; (3) predictive analytics of health outcomes, including those that are high cost or life threatening; (4) causal inference through methods, such as targeted maximum likelihood estimation or double-debiased estimation-helping to produce reliable evidence more quickly; and (5) application of ML to the development of economic models to reduce structural, parameter, and sampling uncertainty in cost-effectiveness analysis.

Mixture Cure Models in Oncology: A Tutorial and Practical Guidance.

Novel cancer therapies are associated with survival patterns that differ from established therapies, which may include survival curves that plateau after a certain follow-up time point. A fraction of the patient population is then considered statistically cured and subject to the same mortality experience as the cancer-free general population. Mixture cure models have been developed to account for this characteristic.

Cost-effectiveness of obinutuzumab versus rituximab biosimilars for previously untreated follicular lymphoma.

In the randomized phase 3 GALLIUM trial, first-line treatment with obinutuzumab (GA101; G) plus chemotherapy (G + chemo) resulted in superior progression-free survival (PFS) compared with rituximab plus chemotherapy (R + chemo) for patients with follicular lymphoma (FL). G + chemo was found to be cost-effective when compared with R + chemo (incremental cost-effectiveness ratio [ICER] of approximately $2,300 per quality-adjusted life-year [QALY] gained). Two rituximab biosimilars, rituximab-abbs (Ra) and rituximab-pvvr (Rp), have been approved by the FDA for use in this setting.

US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma.

 To evaluate the cost-effectiveness of polatuzumab vedotin (pola) + bendamustine + rituximab (BR) in relapsed/refractory diffuse large B-cell lymphoma based on the GO29365 trial from a US payer's perspective.  A partitioned survival model used progression-free survival and overall survival data from the GO29365 trial. The base case analysis assumed overall survival was informed by progression-free survival; a mixture cure model estimated proportion of long-term survivors.

Semiparametric estimation of the cure fraction in population-based cancer survival analysis.

With rapid development in medical research, the treatment of diseases including cancer has progressed dramatically and those survivors may die from causes other than the one under study, especially among elderly patients. Motivated by the Surveillance, Epidemiology, and End Results (SEER) female breast cancer study, background mortality is incorporated into the mixture cure proportional hazards (MCPH) model to improve the cure fraction estimation in population-based cancer studies. Here, that patients are "cured" is defined as when the mortality rate of the individuals in diseased group returns to the same level as that expected in the general population, where the population level mortality is presented by the mortality table of the United States.

Cost-effectiveness of atezolizumab versus docetaxel and nivolumab in the treatment of non-small cell lung cancer as a second line in France.

To estimate the cost-effectiveness of atezolizumab compared with docetaxel and nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC), as a second-line treatment, in a French setting. A three-state partitioned-survival model was developed (progression-free survival, post-progression survival, death) based on the phase IIIOAK trial on a 10-year time horizon. The comparison between nivolumab and atezolizumab came from a network meta-analysis.

Cost-effectiveness of second-line atezolizumab in Canada for advanced non-small cell lung cancer (NSCLC).

To assess the cost-effectiveness in Canada of atezolizumab compared with docetaxel or nivolumab for the treatment of advanced NSCLC after first-line platinum-doublet chemotherapy. A three-state partitioned-survival model was developed. Clinical inputs were obtained from the phase III OAK trial comparing atezolizumab with docetaxel in patients with advanced NSCLC who progressed after first-line platinum-doublet chemotherapy.

Patient-Reported Outcomes in OAK: A Phase III Study of Atezolizumab Versus Docetaxel in Advanced Non-Small-cell Lung Cancer.

Background: The randomized phase III OAK (a study of atezolizumab compared with docetaxel in participants with locally advanced or metastatic non-small-cell lung cancer [NSCLC] who have failed platinum-containing therapy) trial investigated the anti-programmed cell death ligand 1 (PD-L1) antibody atezolizumab for advanced or metastatic, previously treated, NSCLC. Atezolizumab significantly improved overall survival (OS) compared with docetaxel (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.

Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer.

Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed.

Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1-expressing subgroup.

Enhanced cellular sensitivity from partitioning the integrin receptors into multiple clusters.

Integrins are essential receptors for the development and functioning of multicellular organisms because they mediate cell adhesion and migration, and regulate cell proliferation and apoptosis. In response to cues in the extracellular matrix, they are observed to organize into many clusters. The number and size of such clusters are observed to vary according to the concentration of and affinity for the extracellular ligand.

Analyzing and constraining signaling networks: parameter estimation for the user.

The behavior of most dynamical models not only depends on the wiring but also on the kind and strength of interactions which are reflected in the parameter values of the model. The predictive value of mathematical models therefore critically hinges on the quality of the parameter estimates. Constraining a dynamical model by an appropriate parameterization follows a 3-step process.

Network-of-queues approach to B-cell-receptor affinity discrimination.

The immune system is one of the most complex signal processing machineries in biology. The adaptive immune system, consisting of B and T lymphocytes, is activated in response to a large spectrum of pathogen antigens. B cells recognize and bind the antigen through B-cell receptors (BCRs) and this is fundamental for B-cell activation.

Excitotoxicity downregulates TrkB.FL signaling and upregulates the neuroprotective truncated TrkB receptors in cultured hippocampal and striatal neurons.

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival through activation of TrkB receptors. The trkB gene encodes a full-length receptor tyrosine kinase (TrkB.FL) and its truncated (T1/T2) isoforms.