Pediatric post-marketing safety systems in North America: assessment of the current status.

PURPOSE: It is critical to have pediatric post-marketing safety systems that contain enough clinical and epidemiological detail to draw regulatory, public health, and clinical conclusions. The pediatric safety surveillance workshop (PSSW), coordinated by the Food and Drug Administration (FDA), identified these pediatric systems as of 2010. This manuscript aims to update the information from the PSSW and look critically at the systems currently in use. METHODS: We reviewed North American pediatric post-marketing safety systems such as databases, networks, and research consortiums found in peer-reviewed journals and other online sources. We detail clinical examples from three systems that FDA used to assess pediatric medical product safety. RESULTS: Of the 59 systems reviewed for pediatric content, only nine were pediatric-focused and met the inclusion criteria. Brief descriptions are provided for these nine. The strengths and weaknesses of three systems (two of the nine pediatric-focused and one including both children and adults) are illustrated with clinical examples. CONCLUSIONS: Systems reviewed in this manuscript have strengths such as clinical detail, a large enough sample size to capture rare adverse events, and/or a patient denominator internal to the database. Few systems include all of these attributes. Pediatric drug safety would be better informed by utilizing multiple systems to take advantage of their individual characteristics.

Comparative effectiveness of digoxin and propranolol for supraventricular tachycardia in infants.

OBJECTIVES: Supraventricular tachycardia is the most common arrhythmia in infants, and antiarrhythmic medications are frequently used for prophylaxis. The optimal prophylactic antiarrhythmic medication is unknown, and prior randomized trials have been underpowered. We used data from a large clinical registry to compare efficacy and safety of digoxin and propranolol for infant supraventricular tachycardia prophylaxis. We hypothesized that supraventricular tachycardia recurrence is less common on digoxin when compared with propranolol. DESIGN: Retrospective cohort study. SETTING: Pediatrix Medical Group neonatal ICUs. PATIENTS: Infants discharged from 1998 to 2012 with supraventricular tachycardia who were treated with digoxin or propranolol. We excluded infants discharged before completing 2 days of therapy, those with Wolff-Parkinson-White syndrome, structural heart defects (except atrial/ventricular septal defects and patent ductus arteriosus), and those started on multidrug therapy. MEASUREMENTS AND MAIN RESULTS: We used Cox proportional hazards to evaluate supraventricular tachycardia recurrence, defined as need for adenosine or electrical cardioversion while exposed to digoxin versus propranolol, controlling for infant characteristics, inotropic support, supplemental oxygen, and presence of a central line. We identified 342 infants exposed to digoxin and 142 infants exposed to propranolol. The incidence rate of treatment failure was 6.7/1,000 infant-days of exposure to digoxin and 15.4/1,000 infant-days of exposure to propranolol. On multivariable analysis, treatment failure was higher on propranolol when compared with that on digoxin (hazard ratio, 1.97; 95% CI, 1.05-3.71). Hypotension was more frequent during exposure to digoxin versus propranolol (39.4 vs 11.1/1,000 infant-days; p < 0.001). There was no difference in frequency of other clinical adverse events. CONCLUSIONS: Digoxin was associated with fewer episodes of supraventricular tachycardia recurrence but more frequent hypotension in hospitalized infants relative to propranolol.

Innovative clinical trial design for pediatric therapeutics.

Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and 'opportunistic' studies, have addressed some of the historical challenges associated with clinical trials in children.

Adaptation of a postoperative handoff communication process for children with heart disease: a quantitative study.

Handoff communication is a point of vulnerability when valuable patient information can be inaccurate or omitted. An institutional protocol was implemented in 2005 to improve the handoff from the operating room to the intensive care unit after pediatric cardiac surgery. A cross-sectional study of the present process was performed to understand how users adapt a communication intervention over time. Twenty-nine handoff events were observed. Individuals required for the handoff were present at 97% of the events. Content items averaged a 53% reporting rate. Some clinical information not specified in the protocol demonstrated a higher reporting rate, such as echocardiogram results (68%) and vascular access (79%). A mean of 2.3 environmental distractions per minute of communication were noted. Participant-directed adjustments in content reporting suggest that a facilitator in process improvement is user-centered innovation. Future handoff communication interventions should reduce nonessential distractions and incorporate a discussion of the anticipated patient course.

Safety of micafungin in infants: insights into optimal dosing.

INTRODUCTION: Invasive Candida infections are a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Micafungin is a promising therapeutic option for treatment of invasive fungal infections in infants given its safety profile in older children and adults. Understanding micafungin safety in infants is particularly important because antifungals are most often used in premature infants with multiple underlying medical conditions in a critical care setting. AREAS COVERED: This article reviews the literature evaluating the safety profile of micafungin in infants and offers recommendations for optimal dosing for treatment of invasive candidiasis in the NICU setting. The review has been performed using a Medline search in September 2010 for related articles from 1990 to the present with the Mesh related terms 'micafungin' and 'safety' in combination with the free words 'antifungal', 'candidiasis', 'drug toxicity', 'infant, premature' and 'infant, newborn'. EXPERT OPINION: Despite the limitations of the existing literature, we believe micafungin dosing of 10 mg/kg/day for all term and preterm infants is a viable treatment option in the NICU setting for management of invasive candidiasis. Although the number of infants for whom safety data are reported is small, higher doses of micafungin appear safe and well tolerated in this population.