Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC).

Objectives: To evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world.

Methods: A US-based electronic health record-derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021, and September 30, 2022, and docetaxel between January 1, 2019, and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up.

Strategies for Accelerated Drug Development: An Industry Perspective Based on an IQ Consortium Survey of CMC Considerations.

Over the past decade, there has been an increase in accelerated drug development with successful regulatory approval that has provided rapid access of novel medicines to patients world-wide. This has created the opportunity for the pharmaceutical industry to continuously improve the process of quickly bringing new medicines to patients with unmet medical needs. This can be accomplished through sharing the learnings and advancements in drug development, enhancing regulatory interactions, and collaborating with academics on developing the underlying science to reduce drug development timelines.

Points to consider regarding the use and implementation of virtual controls in nonclinical general toxicology studies.

The replacement of a proportion of concurrent controls by virtual controls in nonclinical safety studies has gained traction over the last few years. This is supported by foundational work, encouraged by regulators, and aligned with societal expectations regarding the use of animals in research. This paper provides an overview of the points to consider for any institution on the verge of implementing this concept, with emphasis given on database creation, risks, and discipline-specific perspectives.

Silver nanoparticles in electrochemical immunosensing and the emergence of silver-gold galvanic exchange detection.

Nanoparticle-based electrochemical immunosensors demonstrate high sensitivity toward biomarker detection due to the large surface area of the nanoparticles and their ability to amplify the signal of the target molecule. Additionally, they have a fast response time, relatively lower cost, and can be easily miniaturized for point-of-care applications. Among noble metals, silver nanoparticles (AgNPs) have been extensively used in electrochemical sensors due to their unique properties, such as catalytic activity and excellent electrical conductivity.

Real-world outcomes among patients with metastatic colorectal cancer treated first line with a bevacizumab biosimilar (bevacizumab-awwb).

Background: Bevacizumab-awwb (MVASI) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation.

Real-world outcomes in patients with KRAS G12C-mutated advanced non-small cell lung cancer treated with docetaxel in second-line or beyond.

Introduction: The KRAS G12C mutation has recently become a druggable target in non-small cell lung cancer (NSCLC). In this observational study, we present real-world clinicopathological characteristics, treatment patterns, and survival outcomes data in patients with KRAS mutation-positive advanced NSCLC (aNSCLC), including those with KRAS G12C and KRAS non-G12C mutations, who received docetaxel as standard-of-care treatment in the second-line and beyond (2L+).

Methods: US-based electronic health record-derived de-identified databases were used to assess clinicopathological characteristics and outcomes in adult aNSCLC patients with KRAS mutations treated with 2L+ docetaxel between January 1, 2011, and March 31, 2021.

Impact of Sotorasib on the Pharmacokinetics and Pharmacodynamics of Metformin, a MATE1/2K Substrate, in Healthy Subjects.

Background And Objective: The objectives of this study were to evaluate the effect of sotorasib on metformin pharmacokinetics and pharmacodynamics and the effect of metformin on sotorasib pharmacokinetics in healthy subjects. Sotorasib is an oral, small molecule inhibitor of the Kirsten rat sarcoma oncogene homolog (KRAS) G12C mutant protein (KRASG12C) protein approved by the U.S.

ordinalbayes: Fitting Ordinal Bayesian Regression Models to High-Dimensional Data Using R.

The stage of cancer is a discrete ordinal response that indicates the aggressiveness of disease and is often used by physicians to determine the type and intensity of treatment to be administered. For example, the FIGO stage in cervical cancer is based on the size and depth of the tumor as well as the level of spread. It may be of clinical relevance to identify molecular features from high-throughput genomic assays that are associated with the stage of cervical cancer to elucidate pathways related to tumor aggressiveness, identify improved molecular features that may be useful for staging, and identify therapeutic targets.

Establishing content validity for the migraine Global Impression Item (mGI-I) assessment: a modified single-item migraine symptom severity questionnaire.

Objective: To establish content validity of a single-item, migraine-specific symptom severity questionnaire for completion by migraine patients, key family members (KFMs) of migraine patients, and Healthcare Professionals (HCPs) who treat migraine patients.

Background: Migraine is a common disabling primary headache disorder with high prevalence and significant socioeconomic burden and personal impacts. There is a need for a global assessment of migraine symptom severity to evaluate potential new therapies from multiple perspectives.

Extrapolation as a Default Strategy in Pediatric Drug Development.

Pediatric drug development lags adult development by about 8 years (Mulugeta et al. in Pediatr Clin 64(6):1185-1196, 2017). In such context, many incentives, regulations, and innovative techniques have been proposed to address the disparity for pediatric patients.

Migraine Characteristics, Comorbidities, Healthcare Resource Utilization, and Associated Costs of Early Users of Erenumab in the USA: A Retrospective Cohort Study Using Administrative Claims Data.

Introduction: Erenumab is indicated for migraine preventive treatment in adults. The objective of this study was to provide descriptive information on real-world use of erenumab including patient profile and treatment patterns.

Methods: We completed a retrospective review of US data (through May 2019) from the IBM MarketScan Early View Databases, identifying adult patients newly treated with erenumab with a migraine claim in the year prior to first erenumab claim (index) and at least 1 year of continuous pre-index medical and pharmacy insurance coverage, to assess pre- and post-erenumab migraine characteristics, comorbidities, healthcare resource utilization, and associated costs.

A proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing.

Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate the abundance of off-target proteins.

Design and Analysis of a Biosimilar Bridging Study with a Prediction Interval-Based Consistency Test.

The development of biosimilars has substantially increased in recent years. A biosimilar is a biological product which is highly similar to a licensed biological product (reference product), with no clinically meaningful differences between the proposed biosimilar and the reference product. A bridging study is a viable strategy to bring an approved biosimilar product from the original region(s) to new regions or countries.

Duration of short-acting granulocyte colony-stimulating factor for primary prophylaxis and risk of neutropenia-related hospitalization in older patients with cancer.

Purpose: Evaluate the relationship between duration of primary prophylactic short-acting granulocyte colony-stimulating factor (PP-sG-CSF) and risk of neutropenia-related hospitalization (NRH) in older patients receiving myelosuppressive chemotherapy.

Methods: Using the Medicare claims database, we conducted a nested case-control study in a cohort of patients aged ≥66 years with breast, colorectal, lung, ovarian, or prostate cancer, or non-Hodgkin lymphoma who initiated a first cycle of any myelosuppressive chemotherapy January 1, 2008-September 30, 2016, and received PP-sG-CSF. We matched up to four controls to each NRH case by age, cancer type, regimen febrile neutropenia (FN) risk category, and year using incidence density sampling.

Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients: estimates from Swedish population-based registry data.

Aims: Clinical studies have demonstrated the efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. Our objective was to examine statin titration patterns and the association between titration patterns and subsequent CV events in very high-risk patients.

Methods And Results: Using Swedish national population-based registry data, we identified 192 435 patients with very high risk of atherosclerotic CV disease initiated on moderate-intensity statin therapy between 2006 and 2013.

Design and analysis of bridging studies with prior probabilities on the null and alternative hypotheses.

The pharmaceutical industry and regulatory agencies are increasingly interested in conducting bridging studies in order to bring an approved drug product from the original region (eg, United States or European Union) to a new region (eg, Asian-Pacific countries). In this article, we provide a new methodology for the design and analysis of bridging studies by assuming prior knowledge on how the null and alternative hypotheses in the original, foreign study are related to the null and alternative hypotheses in the bridging study and setting the type I error for the bridging study according to the strength of the foreign-study evidence. The new methodology accounts for randomness in the foreign-study evidence and controls the average type I error of the bridging study over all possibilities of the foreign-study evidence.

Characterization of Subvisible Particles in Biotherapeutic Prefilled Syringes: The Role of Polysorbate and Protein on the Formation of Silicone Oil and Protein Subvisible Particles After Drop Shock.

Subvisible particles (SbVPs) are a critical quality attribute for biotherapeutics. Particle content in prefilled syringes (PFSs) of a biotherapeutic can include protein particles and silicone oil particles (SiOP). Here, a real-world protein therapeutic PFS shows that although polysorbate is effective in preventing protein particle formation, it also leads to the formation of SiOP.

Chemi-Net: A Molecular Graph Convolutional Network for Accurate Drug Property Prediction.

Absorption, distribution, metabolism, and excretion (ADME) studies are critical for drug discovery. Conventionally, these tasks, together with other chemical property predictions, rely on domain-specific feature descriptors, or fingerprints. Following the recent success of neural networks, we developed Chemi-Net, a completely data-driven, domain knowledge-free, deep learning method for ADME property prediction.

Therapeutic protein purity and fragmented species characterization by capillary electrophoresis sodium dodecyl sulfate using systematic hybrid cleavage and forced degradation.

Positive identification of capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) electropherogram peaks provides information to understand protein molecular characteristics at the structural level. It is critical in the design of a robust assay that can accurately resolve, differentiate, and quantify all therapeutic protein components including fragmented species, which are considered as product related impurities. However, direct identification of the impurity peaks observed in CE-SDS is a challenging and oftentimes an ambiguous task.

Correction to: A Multi‑Center, Open‑Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Healthy Females.

The authors would like to correct the error in the publication of the original article. The correction detail is given below.

A Multi-Center, Open-Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Healthy Females.

Background: Erenumab is a human anti-calcitonin gene-related peptide monoclonal antibody developed for migraine prevention. Migraine predominately affects women of childbearing age; thus, it is important to determine potential drug-drug interactions between a common oral contraceptive and drugs used to treat migraine.

Objectives: We sought to evaluate potential drug-drug interactions between erenumab and a common oral contraceptive.

Methods to account for uncertainties in exposure assessment in studies of environmental exposures.

Background: Accurate exposure estimation in environmental epidemiological studies is crucial for health risk assessment. Failure to account for uncertainties in exposure estimation could lead to biased results in exposure-response analyses. Assessment of the effects of uncertainties in exposure estimation on risk estimates received a lot of attention in radiation epidemiology and in several studies of diet and air pollution.

Mortality by a proxy performance status as defined by a claims-based measure for disability status in older patients with newly diagnosed multiple myeloma in the United States.

Objectives: We applied a claims-based definition of disability status as a proxy for performance status (PS) and examined associations between PS and mortality in a population-based cohort of older US adults with multiple myeloma (MM).

Materials And Methods: We identified older (≥66 years) Medicare beneficiaries diagnosed with MM January 1, 2008-December 31, 2011, who began first-line therapy in the study period (through December 31, 2012). We estimated predicted probability of poor PS for each patient at initiation of each line up to fourth-line therapy, classified as poor (predicted probability ≥0.