Most drug labels do not contain dosing recommendations for a significant portion of real-world patients for whom the drug is prescribed. Current label recommendations predominately reflect the population studied in pivotal trials that typically exclude patients who are very young or old, emaciated or morbidly obese, pregnant, or have multiple characteristics likely to influence dosing. As a result, physicians may need to guess the correct dose and regimen for these patients. It is now feasible to provide dose and regimen recommendations for these patients by integrating available scientific knowledge and by utilizing or modifying current regulatory agency-industry practices. The purpose of this commentary is to explore several factors that should be considered in creating a process that will provide more effective, safe, and timely drug dosing recommendations for most, if not all, patients. These factors include the availability of real-world data, development of predictive models, experience with the US Food and Drug Administration (FDA)'s pediatric exclusivity program, development of clinical decision software, funding mechanisms like the Prescription Drug Users Fee Act (PDUFA), and harmonization of global regulatory policies. From an examination of these factors, we recommend a relatively simple, efficient expansion of current practices designed to predict, confirm, and continuously improve drug dosing for more patients. We believe implementing these recommendations will benefit patients, payers, industry, and regulatory agencies. Today clinicians may have to guess the drug dosing regimen if the patient is a neonate, very old, morbidly obese, emaciated, or has any number of other factors (e.g., unusual genotype, renal failure, and/or taking an interacting drug). It has been estimated that clinicians treating neonate patients may face this dilemma five times daily. 1 Relatively recent regulatory changes have provided a scientific and clinical basis for dosing pediatric patients for many new drugs. 2 Yet, drug dosing is still guesswork for clinicians treating the many patients who are not well-represented in clinical trials upon which the regulatory approved label is primarily based. Current labels typically fall between one of two patient drug dosing extremes where either each patient's dose is titrated to a biomarker (e.g., plasma glucose, cholesterol, or drug concentration), or one dosing regimen is approved for all adult patients without adequately understanding the limits based on age, size, organ function, genetics, or drug interactions. At market approval, the new drug labelled dosing regimen usually reflects the dosing scheme used in the phase III pivotal studies, upon which the regulatory approval decision was based with additional dosing adjustments for pharmacokinetic (PK) and/or pharmacodynamic (PD) reasons. Dosing adjustment characteristics are either quantitative or directional (e.g., increase/decrease dose) and univariate (one factor, not combinations of factors). Although more recent legislation ...

Introduction In March and April 2020 of the COVID-19 pandemic, site clinical practice guidelines were implemented for prone positioning of awake, alert, spontaneously breathing suspected COVID-19 patients in hypoxic respiratory distress. The purpose of this pandemic disaster practice improvement project was to measure changes in pulse oximetry associated with prone positioning on awake, alert, spontaneously breathing non-intubated adult acute respiratory distress, or ARDS, patients with COVID-19 infection. Methods A retrospective chart review of ED COVID-19 positive patients from 3/30/2020 to 4/30/2020 was conducted for patients with a room air pulse oximetry < 90% and a pre-prone position pulse oximetry ≤ 94% who tolerated prone positioning for at least 30 minutes. The primary outcome was change in pulse oximetry associated with prone positioning, measured on room air, with supplemental oxygen, and approximately 30 minutes after initiating prone positioning. Median differences were compared with the Wilcoxon signed-rank test. Results Of the 440 COVID-19 patients, 31 met inclusion criteria. Median pulse oximetry increased as 83% (IQR= 75%-86%) on room air, 90% (IQR=89%-93%) with supplemental oxygen, and 96% (IQR=94%-98%) with prone positioning (x.xx, p<.001). 45% (N=14) were intubated during their hospital stay and 26% (N=8) of the included patients died. Conclusion In awake, alert, and spontaneously breathing patients with COVID-19, an initially low pulse oximetry reading improved with prone positioning. Future studies are needed to determine the association of prone positioning with subsequent endotracheal intubation and mortality.

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