Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy-Induced Nausea and Vomiting.

Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unnecessary clinical trials, improve efficiency, and increase the likelihood of success in obtaining a pediatric indication. The acceptability of the use of extrapolation depends on a series of evidence-based assumptions regarding the similarity of disease, response to intervention, and exposure-response relationships between adult and pediatric patients.

Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure-Response.

Objectives: Food and Drug Administration approval of proton-pump inhibitors for infantile gastroesophageal reflux disease has been limited by intrapatient variability in the clinical assessment of gastroesophageal reflux disease. For children 1 to 17 years old, extrapolating efficacy from adults for IV esomeprazole was accepted. The oral formulation was previously approved in children.

Exposure-Response of Palonosetron for Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients.

Objectives: Extrapolation of efficacy from adult populations to pediatrics may be appropriate if it is reasonable to assume that the 2 populations have similar disease progression and response to intervention. When full extrapolation of efficacy is deemed appropriate, the pediatric dose can be determined by "matching" exposure to a drug with that observed in adult patients. This approach has been used in certain therapeutic areas to alleviate the burden of pediatric clinical trials.

Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction.

The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered.

Well-defined and reliable clinical outcome assessments for pediatric Crohn disease: a critical need for drug development.

Objectives: The aim of the present study was to identify areas for further development of clinical outcome assessment (COA) in pediatric Crohn disease (CD).

Methods: The study analyzed the measurement properties of all existing COA tools for pediatric CD in literature and published registration trials of approved drugs for pediatric CD based on criteria described in Food and Drug Administration guidance for patient-reported outcome (PRO) development.

Results: The Pediatric Crohn's Disease Activity Index (PCDAI) and its derivatives (abbreviated, short, modified, and weighted PCDAIs) were reviewed.

Proceedings From FDA/A.S.P.E.N. Public Workshop: Clinical Trial Design for Intravenous Fat Emulsion Products, October 29, 2013.

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited.

Steps toward harmonization for clinical development of medicines in pediatric ulcerative colitis-a global scientific discussion, part 2: data extrapolation, trial design, and pharmacokinetics.

Objectives: To facilitate global drug development, the International Pediatric Inflammatory Bowel Disease Working Group (i-IBD Working Group) discussed data extrapolation, trial design, and pharmacokinetic (PK) considerations for drugs intended to treat pediatric ulcerative colitis (UC), and considered possible approaches toward harmonized drug development.

Methods: Representatives from the US Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan convened monthly to explore existing regulatory approaches, reviewed the results of a literature search, and provided perspectives on pediatric UC drug development based on the available medical literature.

Results: Although pediatric UC, when compared with UC in adults, has a similar disease progression and response to intervention, the similarity of the exposure-response relation has not been adequately established.

Steps toward harmonization for clinical development of medicines in pediatric ulcerative colitis-a global scientific discussion, part 1: efficacy endpoints and disease outcome assessments.

Objectives: There is a pressing need for drug development in pediatric ulcerative colitis (UC). Lack of scientific consensus on efficacy endpoints and disease outcome assessments presents a hurdle for global drug development in pediatric UC. Scientists from 4 regulatory agencies convened an International Inflammatory Bowel Disease Working Group (i-IBD Working Group) to harmonize present thinking about various aspects of drug development in pediatric UC globally.

Proton pump inhibitor use in infants: FDA reviewer experience.

The Food and Drug Administration has completed its review of 4 clinical trials evaluating the use of proton pump inhibitors (PPIs) in infants (ages 1 month to <12 months) for the treatment of gastroesophageal reflux disease (GERD). An Advisory Committee meeting was held in November 2010 to discuss the potential reasons why PPI use in these trials failed to show a benefit in infants with GERD, and directions for future study. The present review summarizes the findings from the clinical trials.

Research challenges in central nervous system manifestations of inborn errors of metabolism.

The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants.

Evolution of clinical trials for irritable bowel syndrome: issues in end points and study design.

Irritable bowel syndrome (IBS) involves a broad range of physiological and psychological alterations that may affect brain-gut dysregulation, gut function, visceral perception, and mucosal integrity and function. Despite advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis, a reliable biologic marker of IBS has yet to be identified. IBS diagnosis and status depend entirely on an assessment of IBS signs and symptoms.

Workshop on imaging science development for cancer prevention and preemption.

The concept of intraepithelial neoplasm (IEN) as a near-obligate precursor of cancers has generated opportunities to examine drug or device intervention strategies that may reverse or retard the sometimes lengthy process of carcinogenesis. Chemopreventive agents with high therapeutic indices, well-monitored for efficacy and safety, are greatly needed, as is development of less invasive or minimally disruptive visualization and assessment methods to safely screen nominally healthy but at-risk patients, often for extended periods of time and at repeated intervals. Imaging devices, alone or in combination with anticancer drugs, may also provide novel interventions to treat or prevent precancer.

Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients.

The objective of this study was to characterize the pharmacokinetics (PK) of intravenous busulfan in pediatric patients and provide dosing recommendations. Twenty-four pediatric patients were treated with intravenous busulfan, 1.0 or 0.

Evaluation of health-related quality-of-life measures in oncology drug product applications: issues and concerns.

Health-related quality-of-life outcomes as reported by patients are valuable data and ideally should be critical to evaluating clinical benefit. The unblinded or open-label designs commonly adapted in oncology trials have the potential to introduce selection bias, reporting bias, and analyses bias. In this paper, issues surrounding use of patient reported outcomes to evaluate oncology drug products, including definition of hypothesis, study design, analysis, and interpretation of patient reported outcome data, are reported.

FDA drug approval summaries: oxaliplatin.

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration.

U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid.

The purpose of this report is to summarize information on drugs recently approved by the U.S. Food and Drug Administration.

Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors.

Purpose: Imatinib mesylate (Gleevec; Novartis, East Hanover, NJ)is a receptor tyrosine kinase inhibitor approved previously in 2001 by the United States Food and Drug Administration for the treatment of chronic myelogenous leukemia in blast crisis, accelerated phase, or in chronic phase after failure of IFN-alpha therapy. We review herein the clinical profile of this drug and the regulatory review leading to the approval of a supplemental New Drug Application for the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors (GISTs).

Experimental Design: We discuss the efficacy and side effects of imatinib mesylate in a Phase II trial of 147 patients with metastatic and/or unresectable malignant GISTs, the basis for marketing approval, and postmarketing commitments by the drug's manufacturer.

Syntheses of the sulfoconjugated isomers of norepinephrine and dopamine, controlled by HPLC with ultraviolet detection.

The physiological significance of sulfoconjugated catecholamines and their involvement in clinical disorders, e.g. hypertension and Parkinsonism, is poorly investigated.