OBJECTIVE: To describe trends in outpatient prescription drug utilization in US children and the changes in major areas of pediatric therapeutic use for the years 2002 through 2010. METHODS: Large prescription databases (the IMS Vector One: National and Total Patient Tracker) were used to examine national drug utilization patterns for the US pediatric population (ages 0–17 years) from 2002 through 2010. RESULTS: In 2010, a total of 263.6 million prescriptions were dispensed to the US pediatric population, 7% lower than in 2002, while prescriptions dispensed to the adult population increased 22% during the same time. Analysis of pediatric drug utilization trends for the top 12 therapeutic areas in 2010 compared with 2002 showed decreases in systemic antibiotics (–14%), allergies (–61%), pain (–14%), depression (–5%), and cough/cold without expectorant (–42%) prescriptions, whereas asthma (14%), attention-deficit/hyperactivity disorder (46%), and contraceptive (93%) prescriptions increased. In 2010, amoxicillin was the most frequently dispensed prescription in infants (aged 0–23 months) and children (aged 2–11 years). Methylphenidate was the top prescription dispensed to adolescents (aged 12–17 years). Off-label use was identified, particularly for lansoprazole; ∼358 000 prescriptions were dispensed in 2010 for infants <1 year old. CONCLUSIONS: Changes in the patterns of pediatric drug utilization were observed from 2002 to 2010. Changes include a decrease in antibiotic use and an increase in attention-deficit/hyperactivity disorder medication use during the examined time. This article provides an overview of pediatric outpatient drug utilization, which could set the stage for further in-depth analyses.

WHAT'S KNOWN ON THIS SUBJECT: Most therapeutic products used in children have not been studied in that population. There is a need for special incentives and market protection (pediatric exclusivity) to compensate drug sponsors for studying these products in children.WHAT THIS STUDY ADDS: Of 189 products studied under pediatric exclusivity, 173 (92%) received new labeling information. Pediatric efficacy was not established for 78 (42%), including 81% of oncology drugs. Probability of demonstrating efficacy was related to therapeutic area and year exclusivity was granted. abstract 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. Pediatrics 2014;134:e512-e518 AUTHORS:

The US Food and Drug Administration's Sentinel System was established in 2009 to use routinely collected electronic health data for improving the national capability to assess post-market medical product safety. Over more than a decade, Sentinel has become an integral part of FDA's surveillance capabilities and has been used to conduct analyses that have contributed to regulatory decisions. FDA's role in the COVID-19 pandemic response has necessitated an expansion and enhancement of Sentinel. Here we describe how the Sentinel System has supported FDA's response to the COVID-19 pandemic. We highlight new capabilities developed, key data generated to date, and lessons learned, particularly with respect to working with inpatient electronic health record data.Early in the pandemic, Sentinel developed a multi-pronged approach to support FDA's anticipated data and analytic needs. It incorporated new data sources, created a rapidly refreshed database, developed protocols to assess the natural history of COVID-19, validated a diagnosis-code based algorithm for identifying patients with COVID-19 in administrative claims data, and coordinated with other national and international initiatives.Sentinel is poised to answer important questions about the natural history of COVID-19 and is positioned to use this information to study the use, safety, and potentially the effectiveness of medical products used for COVID-19 prevention and treatment.

Anecdotal evidence indicates that naloxone prices have risen in recent years, but limited research has examined the magnitude of these increases and potential causes. We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector. We believe that increased demand for naloxone from the opioid epidemic may explain the more gradual price increases for the 0.4 MG single-dose and 4 MG multi-dose products prior to 2012. On the other hand, we believe that the sudden, sustained prices increases occurring for all of the products since 2012 may be the result of a drug shortage for the 0.4 MG single-dose products and the fact that each naloxone product has historically been sold by only a single competitor.

Background The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. Methods Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. Results From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). Conclusions There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing.

Although overall outpatient dispensing of opioid analgesic prescriptions has declined, there may still be overprescribing. Understanding how many opioid analgesic units, primarily tablets, are dispensed with the intention of shorter-vs longer-term use can inform public health interventions. We used pharmacy prescription data to estimate the number of opioid analgesic tablets dispensed annually in the U.S. We studied patterns of new use of opioid analgesics by evaluating how many opioid analgesic prescriptions and tablets were dispensed to patients with no opioid analgesic prescriptions in the previous year. Estimated opioid analgesic tablets dispensed declined from a peak of 17.8 billion in 2012 to 11.1 billion in 2018. Patients newly starting opioid analgesics declined from 47.4 million patients in 2011 to 37.1 million patients in 2017. Approximately 40% fewer tablets were dispensed within a year to patients starting in 2017 (2.4 billion) compared with 2011 (4.0 billion). In 2011, patients with ≥5 opioid analgesic prescriptions within a year were dispensed 2.2 billion tablets (55% of all tablets in our study). This declined by 52% to 1.1 billion tablets (44% of all tablets) in 2017. Tablets dispensed within a year to patients with <5 opioid analgesic prescriptions declined by 26% from 2011 to 2017. Patients with ≥5 prescriptions comprised a small and decreasing proportion of all patients newly starting therapy. However, these patients received almost half of all tablets dispensed within a year to patients in our study, despite a larger decline than tablets dispensed to patients with <5 prescriptions within a year.

Introduction Emerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage. Objective We aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings. Methods We conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA ® ) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017. Results We identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis ( n = 1), biliary dilation with cholangitis ( n = 1), and pericholeductal fibrosis ( n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017. Conclusions We report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01120-9.

PurposeTo assess the prevalence and potential indications of PDE5 inhibitor use among pregnant and reproductive‐age women in the United States.MethodsWe identified women 15 to 50 years with a livebirth from January 2001 through March 2018 in Sentinel Database. We assessed the prevalence of PDE5 inhibitor use prior to and during pregnancy by trimester, identified potential on‐ and off‐label indications using predefined diagnosis codes recorded within 90 days before the estimated last menstrual period through delivery. Separately, we used data from IQVIA's National Prescription Audit and Total Patient Tracker to estimate the dispensed prescriptions for PDE5 inhibitors and the number of patients with PDE5 inhibitor prescriptions.ResultsWe identified approximately 3.3 million pregnancies during 2001 to 2018, 96 of which had PDE5 inhibitor use during pregnancy. Prevalence of PDE5 inhibitor use was 2.61, 0.62, and 0.62 per 100, 000 live‐born pregnancies during the first, second, or third trimesters, respectively. Among women exposed to a PDE5 inhibitor from 90 days before conception to the end of pregnancy, 25.0%, 31.1%, and 15.5% had a diagnosis code for fetal growth restriction, preeclampsia, and pulmonary arterial hypertension. In IQVIA data, an estimated 223, 000 prescriptions from July 2015 through June 2018 and 58, 000 women received prescriptions for PDE5 inhibitors in 2017, of whom approximately 15, 000 (26%) were aged 15 to 50 years.ConclusionWe found a low prevalence of PDE5 inhibitor use in pregnant and reproductive‐age women. Given the very low prevalence of use and the inconsistency of neonatal mortality data across STRIDER centers, the risk to public health is low at present.