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The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. Multiple eGFR equations overestimated the drug CL on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Supraphysiological eGFR as high as 380 mL/min/1.73 m2 was obtained using the bedside Schwartz equation for some of the subjects, most of whom are children < 2 years of age with SCR < 0.2 mg/dL. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. When greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of glomerular filtration rate estimation may be necessary. [ABSTRACT FROM AUTHOR]

Exposure-response (E-R) modeling provides a quantitative tool to leverage adult data to support pediatric trial design and drug approval. The pediatric E-R studies submitted to US Food and Drug Administration (FDA) between 2007 and 2018 were surveyed in the context of various types of trial designs supporting drug approval in the pediatric population. The applications of E-R evaluation in pediatric drug development programs are mainly focused on three areas: (i) supporting pediatric extrapolation when the E-R relationships are similar between the pediatric and adult populations; (ii) dose selection to balance the risk-benefit profile based on the change in efficacy and safety response with different exposure levels; and (iii) approval of a new formulation, new dosing regimen, or new route of administration, where E-R evaluation helps quantify the change in clinical response between the old and new strategies. E-R modeling will continue to play an expanded role in pediatric drug development in the future. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical profile of visual impairment (VI) and the effect of low-vision devices (LVD) among patients with primary open-angle glaucoma (POAG). Methodology A retrospective observational study was used. Case records of patients who reported to the low-vision care clinic with POAG were recruited for the study. Glaucoma was defined according to the International Society for Geographical and EO classification. Demographic data, visual acuity (LogMAR), clinical diagnosis, visual fields, occupation, and LVD prescribed were extracted from the records. The visual acuity pre- and post-use of LVD was compared. Visual acuity improvement while using the LVD was noted. Results Of the 200 POAG cases, 20% (n=40) had severe, 15.5% (n=31) had profound (<3/60), 20.5% (n=41) profound (<1/60), and 26.5% (n=53) had total blindness in the VI category. Significant improvement was noted for both distance and near vision (p=0.004 and p=0.000, respectively) for single-vision glasses, and significant improvement (p=0.000) was also noted for patients corrected for both distance and near correction (bifocal/progressive). Patients with severe visual field loss (p=0.004) and with a visual field defect of <10 degrees (p=0.000) both showed a significant improvement in near vision with low-vision rehabilitation. The proportion of patients earning showed improvement following LVD use compared to those who did not have self-earning (60% vs. 40.24%, p=0.0116). Conclusion LVD significantly improved near vision in POAG patients with advanced glaucoma, a visual field defect of less than 10 degrees. To effectively manage POAG patients with low vision, it is vital to understand both the ocular diseases causing VI and the patient's visual requirements and provide timely management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Paramasivan et al.)

Competing Interests: Competing interests: None declared.

A workshop on "Pediatric Formulation Development: Challenges of Today and Strategies for Tomorrow" was organized jointly by the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), the U.S. Food and Drug Administration (FDA) and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Drug Product Pediatric Working Group (PWG). This multi-disciplinary, pediatric focused workshop was held over a two-day period (18-19 Jun 2019) and consisted of participants from industry, regulatory agencies, academia and other organizations from both US and Europe. The workshop consisted of sequential sessions on formulation, analytical, clinical, and regulatory and industry lessons learned and future landscape. Each session began with a series of short framing presentations, followed by facilitated breakout sessions and panel discussion. The formulation session was dedicated to three main topics pertaining to drug product acceptability, excipients in pediatrics and oral administration device considerations. The analytical session discussed key considerations for dosing vehicle selection and analytical strategies for testing of different dosage forms, specifically mini-tablets (multiparticulates). The clinical session highlighted the influence of pediatric pharmacokinetics prediction on formulation design, pediatric drug development strategies and clinical considerations to support pediatric formulation design. The regulatory and industry lessons learned and future landscape session explored the regional differences that exist in regulatory expectations, requirements for pediatric formulation development, and key patient-centric factors to consider when developing novel pediatric formulations. This session also discussed potential collaboration opportunities and tools for pediatric formulation development. This manuscript summarizes the key discussions and outcomes of all the sessions in the workshop with a broadened review and discussion of the topics that were covered., (Copyright © 2021 Elsevier B.V. All rights reserved.)