Determining the right dose for drugs used to treat neonates is critically important. Neonates have significant differences in physiology affecting drug absorption, distribution, metabolism, and elimination that makes extrapolating dosages from adults and older children inappropriate. In spite of recent legislative efforts requiring drug studies in this population, most drugs given to neonates remain insufficiently studied. Many ethical and logistical concerns make designing studies in this age group difficult. Fortunately, specialized analytical techniques, such as the use of dried blood spots, scavenged sampling, population pharmacokinetics analyses, and sparse sampling, have helped investigators better define doses that maximize efficacy and safety. Through the use of these methods, successful clinical trials have resulted in recent changes to drug dosing in this population.
IMPORTANCE: The increasing prevalence of pediatric chronic disease has resulted in increased exposure to long-term drug therapy in children. The duration of recently completed drug trials that support approval for drug therapy in children with chronic diseases has not been systematically evaluated. Such information is a vital first step in forming safety pharmacovigilance strategies for drugs used for long-term therapy in children. OBJECTIVE: To characterize the duration of clinical trials submitted to the US Food and Drug Administration (FDA) for pediatric drug approvals, with a focus on drugs used for long-term therapy. DESIGN AND SETTING: A review was performed of all safety and efficacy clinical trials conducted under the Best Pharmaceuticals for Children Act or the Pediatric Review Equity Act and submitted to the FDA from September 1, 2007, to December 31, 2014, to support the approval of drugs frequently used for long-term therapy in children. Statistical analysis was performed from July 1, 2015, to December 31, 2017. MAIN OUTCOMES AND MEASURES: Maximum duration of trials submitted to support FDA approval of drugs for children. RESULTS: A total of 306 trials supporting 86 drugs intended for long-term use in children were eligible for the primary analysis. The drugs most commonly evaluated were for treatment of neurologic (25 [29%]), pulmonary (16 [19%]), and anti-infective (14 [16%]) indications. The median maximum trial duration by drug was 44 weeks (minimum, 1.1 week; maximum, 364 weeks). For nearly two-thirds of the drugs (52 [61%]), the maximum trial duration was less than 52 weeks. For 10 of the drugs (12%), the maximum trial duration was 3 years or more. Maximum duration of trials did not vary by therapeutic category, minimum age of enrollment, calendar year, or legislative mandate. CONCLUSIONS AND RELEVANCE: Pediatric clinical trials designed to sufficiently investigate drug safety and efficacy to support FDA approval are of relatively limited duration. Given the potential long-term exposure of ...
Objective This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. Study Design In this retrospective database study, we included all ELBW infants who were 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. Results A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). Conclusions Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP. ; National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) ; U.S. government ; National Institute of Child Health and Human Development ; NIH ; National Center for Advancing Translational Sciences of the NIH ; U.S. Food and Drug Administration ; Cempra Pharmaceuticals ; Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA ; Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA ; KK Womens & Childrens Hosp, Childrens Intens Care Unit, Singapore, Singapore ; Univ Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, Brazil ; Univ N Carolina, Dept Pediat, Chapel Hill, NC USA ; MEDNAX Inc, Pediat Med Grp, Jacksonville, FL USA ; Univ Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, Brazil ; NIH: UL1TR001117 ; U.S. government: HHSN267200700051C ; National Institute of Child Health and Human Development: K23HD068497 ; National Institute of Child Health and Human Development: HHSN275201000003I ; National Institute of Child Health and Human Development: 1R01-HD081044-01 ; National Center for Advancing Translational Sciences of the NIH: UL1TR001117 ; U.S. Food and Drug Administration: 1R18-FD005292-01 ; Cempra Pharmaceuticals: HHS0100201300009C ; Web of Science
Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.
Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials.
