Abstract. This article proposes new terminology that distinguishes between different concepts involved in the discussion of the shelf life of pharmaceutical products. Such comprehensive and common language is currently lacking from various guidelines, which confuses implementation and impedes comparisons of different methodologies. The five new terms that are necessary for a coherent discussion of shelf life are: true shelf life, estimated shelf life, supported shelf life, maximum shelf life, and labeled shelf life. These concepts are already in use, but not named as such. The article discusses various levels of "product" on which different stakeholders tend to focus (e.g., a single-dosage unit, a batch, a production process, etc.). The article also highlights a key missing element in the discussion of shelf life-a Quality Statement, which defines the quality standard for all key stakeholders. Arguments are presented that for regulatory and statistical reasons the true product shelf life should be defined in terms of a suitably small quantile (e.g., fifth) of the distribution of batch shelf lives. The choice of quantile translates to an upper bound on the probability that a randomly selected batch will be nonconforming when tested at the storage time defined by the labeled shelf life. For this strategy, a random-batch model is required. This approach, unlike a fixedbatch model, allows estimation of both within-and between-batch variability, and allows inferences to be made about the entire production process. This work was conducted by the Stability Shelf Life Working Group of the Product Quality Research Institute.KEY WORDS: ICH method; quantile for distribution of batch shelf lives; random-batch model; shelf life terminology; stability.

IMPORTANCEIdentifying conditions that could be prioritized for research based on health care system burden is important for developing a research agenda for the care of hospitalized children.However, existing prioritization studies are decades old or do not include data from both pediatric and general hospitals. OBJECTIVE To assess the prevalence, cost, and variation in cost of pediatric hospitalizations at all general and pediatric hospitals in Ontario, Canada, with the aim of identifying conditions that could be prioritized for future research. DESIGN, SETTING, AND PARTICIPANTSThis population-based cross-sectional study used health administrative data from 165 general and pediatric hospitals in Ontario, Canada. Children younger than 18 years with an inpatient hospital encounter between April 1, 2014, and March 31, 2019, were included. MAIN OUTCOMES AND MEASURESCondition-specific prevalence, cost of pediatric hospitalizations, and condition-specific variation in cost per inpatient encounter across hospitals.Variation in cost was evaluated using (1) intraclass correlation coefficient (ICC) and (2) number of outlier hospitals. Costs were adjusted for inflation to 2018 US dollars. RESULTSOverall, 627 314 inpatient hospital encounters (44.8% among children younger than 30 days and 53.0% among boys) at 165 hospitals (157 general and 8 pediatric) costing $3.3 billion were identified. A total of 408 003 hospitalizations (65.0%) and $1.4 billion (43.8%) in total costs occurred at general hospitals. Among the 50 most prevalent and 50 most costly conditions (of 68 total conditions), the top 10 highest-cost conditions accounted for 55.5% of all costs and 48.6% of all encounters. The conditions with highest prevalence and cost included low birth weight (86.

Key Points Question What are the highest-priority unanswered research questions in pediatric hospital medicine from the perspective of young people, parents/caregivers, and health care professionals? Findings This study, which included 2 surveys and a final consensus meeting using nominal group technique, gathered the perspectives of youths, parents/caregivers, and clinicians. The top 10 questions identified focused on the care of special inpatient populations (eg, children with medical complexity), communication, shared decision-making, support strategies, mental health supports, reducing time in the hospital, and supporting Indigenous families. Meaning The findings of this study suggest that the most important research questions in pediatric hospital medicine focus on processes and models of care, communication, and hospitalization outcomes.

Asciminib, a first‐in‐class, Specifically Targeting the Abelson kinase Myristoyl Pocket (STAMP) inhibitor with the potential to overcome resistance to adenosine triphosphate–competitive tyrosine kinase inhibitors, is being investigated in leukemia as monotherapy and in combination with tyrosine kinase inhibitors including imatinib. This phase 1 study in healthy volunteers assessed the pharmacokinetics of asciminib (40 mg single dose) under 2 conditions: when taken with imatinib (steady state; 400 mg once daily) and a low‐fat meal (according to imatinib prescription information), or when taken as single‐agent under different food conditions. Asciminib plus imatinib with a low‐fat meal increased asciminib area under the plasma concentration–time curve from time 0 to infinity and maximum plasma concentration (geometric mean ratios [90% confidence interval], 2.08 [1.93‐2.24] and 1.59 [1.45‐1.75], respectively) compared with asciminib alone under the same food conditions. Asciminib plus food decreased asciminib area under the plasma concentration–time curve from time 0 to infinity compared with asciminib taken under fasted conditions (geometric mean ratios: low‐fat meal, 0.7 [0.631‐0.776]; high‐fat meal, 0.377 [0.341‐0.417]). Asciminib plus imatinib was well tolerated with no new safety signals. Overall, coadministration of asciminib with imatinib and a low‐fat meal results in a moderate increase in asciminib exposure compared with asciminib alone under the same food condition. Food itself decreases asciminib exposure, indicating that single‐agent asciminib should be administered in the fasted state to prevent potential suboptimal exposures.