New clinical information and physician prescribing: How do pediatric labeling changes affect prescribing to children?

Our study examines how physician prescribing responds to new scientific information added to drug labels. We focus on a series of label changes with new information about the effects of drugs in children. The information arose in response to a 1997 policy, pediatric exclusivity, which gave drug sponsors a 6-month exclusivity extension for conducting additional pediatric studies of already marketed drugs. The information from these studies was expected to improve pediatric prescribing by promoting appropriate use and by reducing inappropriate off-label prescribing. However, there has been little study about the actual effects of these labeling changes on physician prescribing behavior. We use a difference-in-differences strategy to examine how pediatric prescriptions respond to different types of labeling changes. Our results show that most label changes lead to reductions in prescribing to children. We find that the largest drop in prescribing occurs when the label indicates a drug is not effective for children. The evidence suggests that the labeling changes alleviated physician uncertainty about prescribing drugs to children and reduced some inappropriate off-label use.

Paediatric cardiovascular clinical trials: an analysis of ClinicalTrials.gov and the Food and Drug Administration Pediatric Drug Labeling Database.

Recent regulatory initiatives in the United States of America and Europe have transformed the paediatric clinical trials landscape by significantly increasing capital investment and paediatric trial volume. The purpose of this manuscript was to review the impact of these initiatives on the paediatric cardiovascular trials landscape when compared with other paediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major paediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field.

Pediatric exclusivity: evolving legislation and novel complexities within pediatric therapeutic development.

OBJECTIVE: To review the successes and omissions of the Food and Drug Administration (FDA) pediatric exclusivity incentive. DATA SOURCES: Pediatric drug development receives less attention and funding than drug development targeting adults resulting in fewer appropriately labeled pediatric drugs. Newly introduced legislation aims to correct this deficit using market exclusivity incentives. Under the Food and Drug Administration Modernization Act (FDAMA, 1997), the FDA established the exclusivity principle. This legislation was renewed and amended in 2007 under Food and Drug Administration Amendments Act (FDAAA) allowing drug companies to receive a 6-month patent extension for initiating clinical investigation in pediatric populations. Fostering improved knowledge in pediatric indications and dosing is the motivating force behind this program. STUDY SELECTION AND DATA EXTRACTION: We examined drugs granted exclusivity through FDA published database as well as relevant drug labeling and postmarket safety studies. Our examination shows that studies conducted in support of patent protection are often not designed to meet current pediatric needs. CONCLUSION: Amendments to FDAAA are needed to ensure that studies approved for exclusivity strive to meet the following requirements: relevant pediatric clinical indication ; disease addressed should represent a significant disease burden to the appropriate population; important age ranges should be covered; studies should not be allowed when a safety signal is identified prior to initiation of the study; and trials where endpoints are successfully achieved providing considerable contribution to pediatric dosing knowledge or result in labeling changes may gain an additional incentive.

Who cares about a label? The effect of pediatric labeling changes on prescription drug utilization.

Off-label drug use is common, particularly in pediatric populations. In response, legislation requires and/or provides financial incentives for drug manufacturers to perform pediatric clinical trials. Using New Hampshire's all-payer claims database, we examine the impact of subsequent changes to drug labeling on pediatric drug utilization. To separate changes in utilization induced by labeling changes from other temporal factors, we estimate difference-in-differences models that compare utilization trends for pediatric patients to those of adults. We estimate that establishing safety and efficacy increases a drug's market share by (a statistically significant) 2.8 percentage points, whereas failure to do so decreases a drug's market share by (a statistically insignificant) 0.9 percentage points. We then interpret these estimates within the context of public and market incentives to conduct pediatric clinical trials.

Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy.

BACKGROUND: Besides vaccines and otitis media medicines, most products prescribed for children have not been studied in the pediatric population. To remedy this, Congress enacted legislation in 1997, known as pediatric exclusivity (PE), which provides 6 months of additional market protection to drug sponsors in exchange for studying their products in children. METHODS: We reviewed requests for pediatric studies and subsequent labeling for drugs granted PE from 1998 through 2012. Regression analysis estimates the probability of demonstrating efficacy in PE trials. Variables include therapeutic group, year of exclusivity, product sales, initiation process, and small disease population. RESULTS: From 1998 through 2012, the US Food and Drug Administration issued 401 pediatric study requests. For 189 drugs, studies were completed and granted exclusivity. A total of 173 drugs (92%) received new pediatric labeling, with 108 (57%) receiving a new or expanded pediatric indication. Three drugs had non-efficacy trials. Efficacy was not established for 78 drugs. Oncology, cardiovascular, and endocrine drugs were less likely to demonstrate efficacy (P < .01) compared with gastrointestinal and pain/anesthesia drugs. Drugs studied later in the program were less likely to demonstrate efficacy (P < .05). Sales, initiation process, and small disease population were not significant predictors. CONCLUSIONS: Most drugs (173; 92%) granted exclusivity added pediatric information to their labeling as a result of PE, with 108 (57%) receiving a new or expanded pediatric indication. Therapeutic area and year of exclusivity influenced the likelihood of obtaining a pediatric indication. Positive and negative outcomes continue to inform the construct of future pediatric trials.

Comparison of the regulation of pediatric drugs research and development at home and abroad / 国际药学研究杂志

The problem of pediatric drugs has been the challenges facing the world. The two most important issues are the lack of appropriate drug dosage forms for children and the safety and effectiveness data of drug use in children. How to encourage produc?tion enterprises to produce drug varieties,specifications and dosage forms suitable for children use,guide drug manufacturers to ob?tain drug use data are the most important work for pediatric drugs.Based on the literature home and abroad,we analyze the regulatory policies for the research and development(RD)and application of pediatric drugs in the USA,EU and Japan,which have made great efforts to encourage enterprises to conduct pediatric research. Their successful experiences are summarized and can be used as refer?ence for the establishment of the policies adaptive to the situation of China for the RD of pediatric drugs.

Comparison of the regulation of pediatric drugs research and development at home and abroad / 国际药学研究杂志

The problem of pediatric drugs has been the challenges facing the world. The two most important issues are the lack of appropriate drug dosage forms for children and the safety and effectiveness data of drug use in children. How to encourage production enterprises to produce drug varieties, specifications and dosage forms suitable for children use, guide drug manufacturers to obtain drug use data are the most important work for pediatric drugs.Based on the literature home and abroad, we analyze the regulatory policies for the research and development(RD) and application of pediatric drugs in the USA, EU and Japan, which have made great efforts to encourage enterprises to conduct pediatric research. Their successful experiences are summarized and can be used as reference for the establishment of the policies adaptive to the situation of China for the RD of pediatric drugs.