Medical devices and the pediatric population - a head-to-toe approach.

Introduction: This review uses a head-to-toe approach, a standardized approach similar to the format used by clinicians during the physical examination, to highlight important differences between children, adolescents and adults. The assessment of a pediatric patient is significantly different from an adult and the heterogeneity of the pediatric population requires knowledge of the inter- and intra-subpopulation differences in growth and development for all organ systems. Areas covered: A search of the English medical literature (PubMed and EMBASE) resulted in identification and review of articles that reported medical device use in the pediatric population based on specific organ systems. The review highlights unique considerations for the pediatric population with respect to growth and development as well as important physiologic and maturational differences between children and adults pertaining to the use of medical devices. Expert opinion: Children have unique medical device needs; adult devices are often adapted or configured to address these unmet needs. It is important that clinicians, and those who manufacture and design medical devices for the pediatric population, have a heightened awareness of the varied pediatric subpopulations (neonates to adolescents) with respect to growth and development, and the adjustments needed to ensure safe and effective use of devices for their unique needs.

FDA Safety Reviews on Drugs, Biologics, and Vaccines: 2007-2013.

BACKGROUND AND OBJECTIVES: In 2002, Congress mandated that the US Food and Drug Administration (FDA) monitor postmarketing pediatric adverse events and present safety reports to the FDA's Pediatric Advisory Committee (PAC). These safety reviews play a critical role in the postmarketing surveillance and identification of pediatric safety issues. This article follows a previous review ending in 2007 and summarizes 6 years of recent pediatric safety reporting, recommendations by the PAC, and actions by the FDA, including labeling changes. METHODS: An analysis of the FDA's PAC safety reviews performed from November 2007 through September 2013 was conducted. PAC recommendations for subsequent labeling changes, future studies, or other safety issues were reviewed. RESULTS: There were 6930 serious adverse event reports in 181 reviews. These findings resulted in 33 (18%) recommended labeling changes, and 21 (64%) of these changes were adopted. For 10 products, information was added to the Warning and Precautions section of the label. The PAC also discussed or recommended additional studies for certain products. CONCLUSIONS: This article highlights the importance of the FDA's ongoing pediatric postmarketing safety reviews of regulated products, advice from the PAC, and FDA actions in the best interest of pediatric patients. This mandated process facilitates detection of safety concerns that may not be identified in prelicensure clinical trials. It continues to identify critical safety concerns, including unlabeled adverse events, frequent off-label use, product misuse, and secondary exposures in children.

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.

Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports.

Background. Ewing sarcoma family of tumors (ESFT) are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS) was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT.

Pediatric use of insulin pump technology: a retrospective study of adverse events in children ages 1-12 years.

BACKGROUND: Growing technological improvements in insulin pump design have increased the use of these devices in young children. To better understand the types of infusion pump-related problems and associated adverse events in this age group, we performed a comprehensive evaluation of pump-related adverse event reports received by the U.S. Food and Drug Administration (FDA) for children ages 1-12 years. METHODS: A query was conducted of FDA's Manufacturer and User Facility Device Experience database from January 1, 1996, through December 31, 2009, in children ages 1-12 years involving insulin pumps. Report narratives were individually reviewed for age, gender, and seriousness of outcomes. Device or patient problems and potential contributory factors were assessed. RESULTS: Over the past 14 years, 1774 (7%) of all insulin pump adverse event reports were identified in children ages 1-12. Of these reports, 777 (43%) resulted in hospitalization. In hospitalized cases (n = 614), diabetic ketoacidosis and/or hyperglycemia were the predominant patient problems, and in other cases (n = 98), hypoglycemia was evident. There were 106 emergency room visits, 19 cases requiring paramedic attention, and five deaths. The majority of reports indicated that the devices were not returned to the manufacturer, and root causes were not always confirmed. CONCLUSIONS: Younger children with diabetes deserve careful consideration of the risk and benefit of insulin pump technology. Studies are needed to better understand pediatric safety issues and to identify the root cause of adverse events. Problems related to patient education, device misuse, and malfunctions were found, highlighting the need to strengthen user training for children and their caregivers.

Emergency department visits for medical device-associated adverse events among children.

OBJECTIVES: The purposes of this study were to provide national estimates of emergency department (ED) visits for medical device-associated adverse events (MDAEs) in the pediatric population and to characterize these events further. METHODS: ED medical record reports from the National Electronic Injury Surveillance System All Injury Program database from January 1, 2004, through December 21, 2005, were reviewed. MDAEs among pediatric patients were identified, and data were abstracted. National estimates for pediatric MDAEs were determined according to medical specialty, device category and class, injury diagnosis, and patient characteristics and outcome. RESULTS: The total estimated number of pediatric MDAEs during the 24-month period was 144,799 (95% confidence interval: 113,051-183,903), involving devices from 13 medical specialties. Contact lenses accounted for most MDAEs (23%), followed by hypodermic needles (8%). The distribution of MDAEs according to medical specialty varied according to age subgroup. The most-prevalent types of injuries included contusions/abrasions, foreign-body intrusions, punctures, lacerations, and infections. The most-frequently affected body parts were the eyeball, pubic region, finger, face, and ear. The majority of pediatric MDAEs involved class II (moderate-risk) devices. The incidence of pediatric MDAEs decreased with increasing age from early to late childhood and then spiked after 10 years of age. More girls than boys were affected at older ages (16-21 years) and more boys than girls at younger ages (< or =10 years). Hospitalizations were more likely to involve invasive or implanted devices. CONCLUSIONS: This study provides national estimates of pediatric MDAEs resulting in ED visits and highlights the need to develop interventions to prevent pediatric device-related injuries.

Device safety and effectiveness in the pediatric population: a US FDA perspective.

The US FDA recognizes that there are many challenges to ensuring that medical devices are used responsibly and safely in the pediatric population. Education plays a key role, and manufacturers and healthcare providers must be informed of medical device issues unique to the pediatric population. Healthcare workers and device manufacturers must recognize that adverse events may differ between the adult and pediatric population and among pediatric subpopulations. Risk mitigation may also differ, and heightened awareness will reduce the potential for adverse events and promote the safe use of medical devices in children.

Pediatric drug surveillance and the Food and Drug Administration's adverse event reporting system: an overview of reports, 2003-2007.

PURPOSE: Our objective was to examine the numbers and characteristics of US pediatric adverse events (AEs) reported to the Food and Drug Administration (FDA)'s adverse event reporting system (AERS) for 5 years following implementation of the Best Pharmaceuticals for Children Act (BPCA) in 2002. METHODS: We analyzed reports in AERS received by FDA from January 1, 2003 to January 1, 2008 for overall numbers, age, gender, and seriousness of outcome in children and adults. Pediatric and adult age groups (<2, 2-10, 11-17, 18-50, and >50 years of age) were further evaluated for most frequently reported suspect drug classes and AEs. RESULTS: Seventy-two percent of 815 267 crude count reports had specified age information. Six percent of the total reports with age information reported age <18 years. Numbers of AEs being reported for children have remained steady, while those for adults have increased. The proportion of serious AEs reported was similar for pediatrics as compared to adults. Frequently reported suspect drug classes noted in pediatric age groups that were not observed in adults included anticonvulsants, attention deficit hyperactivity disorder (ADHD), anti-acne, and respiratory medications. CONCLUSIONS: This overview highlights the need for strengthening the passive drug surveillance system from a pediatric perspective, as well as investing in more active surveillance systems. Drug safety initiatives to better capture risk information in order to balance the risk/benefit of drug use in children.

Adolescent use of insulin and patient-controlled analgesia pump technology: a 10-year Food and Drug Administration retrospective study of adverse events.

OBJECTIVES: From January 1, 2005, through December 31, 2005, the Food and Drug Administration received 5 adolescent death reports associated with the use of insulin pumps, raising concerns about use of this device in this age group. To understand better the types of infusion pump-related problems in adolescents, we performed a comprehensive evaluation of insulin and patient-controlled analgesic pump-related adverse events reported for adolescents that were received by the Food and Drug Administration from 1996 to 2005. METHODS: A search for medical device adverse event reports from January 1, 1996 through December 31, 2005, involving insulin pumps or patient-controlled analgesic pumps used by patients who were aged 12 to 21 years was conducted in the Food and Drug Administration's Manufacturer and User Facility Device Experience Database. Reports were reviewed for demographic characteristics, type of adverse event, and patient morbidity, and potential contributory factors were classified from narratives in the reports. RESULTS: A total of 1674 reports were identified: 1594 for insulin pumps and 53 for patient-controlled analgesic pumps. In reports of insulin pump events, there were 13 reported deaths, 2 reports that indicated possible suicide attempts, and several additional reports indicating severe hypoglycemic or hyperglycemic events that seemed to be device-related. A total of 102 (6.4%) insulin-pump reports highlighted factors that may have contributed to the adverse event, including problems associated with compliance, education, sports-related activities, and dropping or damaging the pump. Eighty-two percent of cases involving the insulin pump resulted in hospitalization. Half of the reports involving patient-controlled analgesic pumps indicated that the patient received an excess of medication; tampering and noncompliance were evident in some cases. CONCLUSIONS: Adolescents are a special population who deserve careful consideration of risk and benefit for use of device technology. Studies need to further identify safety problems in this age group.

Breast implant surveillance reports to the U.S. Food and Drug Administration: maternal-child health problems.

There is continuing concern that women who receive breast implants may be at increased risk for adverse reproductive outcomes or experience problems with breastfeeding. It is unknown whether exposure to biomaterials in breast implants may have teratogenic effects or leach into breast milk causing postnatalproblems. We studied the Food and Drug Administration (FDA) experience by analyzing a case series of adverse event reports received and entered into the FDA's Manufacturer and User Facility Device Experience (MAUDE) database or the Device Experience Network (DEN) database by December 31, 2002 regarding women with breast implants. Reports were critically reviewed for lactation difficulties, reproductive problems (spontaneous abortion, delayed conception) and medical conditions among offspring, including neonatal, infant, and childhood diseases and congenital defects that were attributed to implants. We identified 339 reports that described maternal-child adverse events. Nearly half of these reports (46%) described actual problems with breastfeeding or expressed concern that implants would be unsafe or interfere with breastfeeding. Forty-four percent of reports (n=149) described either nonspecific or specific signs, symptoms, or illnesses in children. An additional 3.5% of reports (n=12) detailed a congenital anomaly believed by the reporter to be caused by breast implants.

Appendectomy during childhood and adolescence and the subsequent risk of cancer in Sweden.

OBJECTIVE: Researchers have speculated that surgical excision of lymphoid tissue, such as appendectomy, early in life might confer an increased risk of cancer. In this study, we determined the risks of cancer for people who had appendectomy performed during childhood. METHODS: We studied the risk of cancer in a large Swedish cohort of children who had appendectomy performed during the period of 1965-1993. Standardized incidence ratios (SIRs) were computed using age-, gender-, and period-specific incidence rates derived from the entire Swedish population as comparison. Hospital discharge diagnosis data were used to examine cancer risks by categories of surgery, medical conditions, and type of appendicitis. The average length of follow-up was 11.2 years. RESULTS: We found no excess overall cancer risk but noted a significant excess for stomach cancer (SIR: 2.45; 95% confidence interval [CI]: 1.1-4.8) and a borderline increase of non-Hodgkin's lymphoma (NHL; SIR: 1.55; 95% CI: 1.0-2.3). The elevated risks for both cancers were only evident 15 or more years after appendectomy (stomach cancer, SIR: 3.82; 95% CI: 1.7-7.5; NHL, SIR: 2.49; 95% CI: 1.4-4.2). CONCLUSIONS: It is reassuring that there was no overall increase of cancer several years after childhood appendectomy. Increased risks for NHL and stomach cancer, occurring 15 or more years after appendectomy, were based on small absolute numbers of excess cancers. As 95% of the subjects were younger than 40 years at exit, this cohort requires continuing follow-up and monitoring.