Paediatric Drug Development in China: Current Status and Future Prospects.

For more than two decades, regulatory agencies throughout the world released guidelines, rules and laws to stimulate and assist in paediatric drug development. In 2014, the National Health and Family Planning Commission (now known as the National Health Commission, NHC) and five other departments in China jointly issued 'Several Opinions on Safeguarding Medication for Children', after which several policies and regulations were issued to implement the priority review and approval of paediatric medicinal products and support the development of new drugs, including new dosage forms and strengths, for children. A total of 172 special medicinal products for children were approved from 2018 to 2022. Since 2016, the NHC, together with relevant administrative departments, has formulated and issued four paediatric drug lists containing 129 medicinal products to encourage research and development. At present, approximately 25 of these drugs (at exactly the same dosage forms and strengths as on the lists) have been approved for marketing, including antitumour drugs and immunomodulators, nervous system drugs, drugs for mental disorders and drugs for rare diseases. In this review, we analysed the regulations issued for promoting paediatric drug development in China, including the priority review and approval system, technical guidelines, data protection and financial support policies and general profiles of paediatric drug approval, clinical trials and the addition of information for children in the labels of marketed medicinal products. Finally, we discussed the challenges and possible strategies in the research and development of paediatric drugs in China.

Pediatric Support for Children Eligible for Legal Humanitarian Relief.

Many children in immigrant families may qualify for legal protection-for themselves if unaccompanied, or as a derivative on parents' claims-on humanitarian grounds related to persecution or forced migration. Pediatric providers can offer a spectrum of multidirectional medical-legal supports to increase access to medical-legal services and support children who are undocumented or in mixed-status families. These activities can include providing trusted information, incorporating screening for health-related social needs, establishing networks for multidirectional referrals, and providing letters of support for legal protection. To expand workforce capacity for medical-legal services related to immigration, pediatric providers can also receive training to conduct specialized, trauma-informed forensic evaluations and can advocate at individual, local, state, federal, and global levels to address factors leading to persecution and forced migration while supporting individuals who may be eligible for legal protection. [Pediatr Ann. 2024;53(5):e183-e188.].

Bridging the Knowledge Gap: A Toolkit on Reproductive Rights for Pediatric Surgeons in the Post-Dobbs Era.

BACKGROUND: The ripple effect of the Supreme Court ruling in Dobbs v. Jackson Women's Health Organization has impacted physicians and patients across numerous medical specialties. In pediatric surgery, the patient population ranges from fetus to the pregnant patient. There is a gap in the knowledge of pediatric surgeons regarding abortion laws and access. This project aims to bridge the gap by creating access to reliable resources which may be used to optimize patient care and support physicians. METHODS: We collaborated with the Reproductive Health Coalition, co-founded by the American Medical Women's Association and Doctors for America, to curate a list of resources beneficial to pediatric surgeons. RESULTS: We created a web-based toolkit with the purpose of providing easily accessible and reliable information on reproductive rights in the United States. We identified up-to-date resources on state-by-state abortion laws, legal resources, patient-centered information on obtaining abortion care, and resources for physicians interested in getting involved in advocacy. CONCLUSION: Pediatric surgery rests at a critical juncture with respect to reproductive rights in the United States. Our toolkit enables users to understand the current climate and identify next steps to advocate for patients and physicians amidst a formidable legal environment. LEVEL OF EVIDENCE: Level V.

Off-Label Prescription of COVID-19 Vaccines in Children: Clinical, Ethical, and Legal Issues.

The US Food and Drug Administration (FDA) approval of the biologics license application for the Pfizer-BioNTech coronavirus disease 2019 vaccine (Comirnaty) on August 23, 2021, opened the door to the off-label vaccination of children younger than the age range currently covered by either the biologics license application (16 years old and older) or the emergency use authorization (12 to 15 years old). Although prescribing medications at doses, for conditions, or in populations other than those approved by the FDA is generally legal and is common in pediatrics, the FDA, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics have recommended against off-label prescription of the coronavirus disease 2019 vaccine. Several commentaries consider a case in which parents ask their child's pediatrician to prescribe the vaccine for their 11-year-old with special health care needs before approval or authorization in her age group. The first commentary considers the potential benefits and risks to the patient, as well as to the family, the provider, and society, emphasizing the unknown risks in younger patients and the need for adequate informed consent. The second commentary describes an algorithm and principles for evaluating off-label prescribing and argues that the current benefits of prescribing Comirnaty off label to children <12 do not outweigh the risks. The third commentary addresses ethical and legal issues, ultimately calling on federal agencies to remove legal barriers to making the vaccine available to children in age groups that currently lack authorization.

Quantification of US Food and Drug Administration Premarket Approval Statements for High-Risk Medical Devices With Pediatric Age Indications.

Importance: Medical device companies submit premarket approval (PMA) statements to the US Food and Drug Administration (FDA) for approval of the highest-risk class of devices. Devices indicated for the pediatric population that use the PMA pathway have not been well characterized or analyzed. Objective: To identify and characterize high-risk devices with pediatric age indications derived from PMA statements. Design, Setting, and Participants: In this cross-sectional study of PMA statements, those statements containing the words indicated or intended for medical devices listed in the FDA PMA database as of February 2020 were retrieved. Age indications were manually annotated in these approval statements via PubAnnotation. Based on the PMA identification from the PMA statements, device metadata including product codes, regulation numbers, advisory panels, and approval dates were queried. Main Outcomes and Measures: The main outcome was discernment of the distribution of devices indicated for the pediatric population (neonate, infant, child, and adolescent). Secondary measures included outlining the clinical specialties, device types, and lag time between the initial approval date and the first date of an approval statement with a pediatric indication for generic device categories. Results: A total of 297 documents for 149 unique devices were analyzed. Based on the manual age annotations, 102 devices with a pediatric indication, 10 with a neonate age indication, 32 with an infant age indication, 60 with a child age indication, and 94 with an adolescent age indication were identified. For indications for patients from age 17 to 18 years, the number of devices available nearly doubled from 42 devices to 81 devices. Although more than half of the surveyed devices had a pediatric age indication, many were available only for a limited range of the pediatric population (age 18-21 years). For indications for patients from age 0 to 17 years, the mean (SD) number of clinical specialties at each age was 7.27 (1.4), and 12 clinical specialties were represented from ages 18 to 21 years. Conclusions and Relevance: In this cross-sectional study on device PMA statements, a gap was identified in both quantity and diversity of high-risk devices indicated for the pediatric population. Because the current scarcity of pediatric devices may limit therapeutic possibilities for children, this study represents a step toward quantifying this scarcity and identifying clinical specialties with the greatest need for pediatric device innovation and may help inform future device development efforts.

Analysis of lawsuits related to diagnostic errors from point-of-care ultrasound in internal medicine, paediatrics, family medicine and critical care in the USA.

PURPOSE: The purpose of this study is to identify the extent of diagnostic error lawsuits related to point-of-care ultrasound (POCUS) in internal medicine, paediatrics, family medicine and critical care, of which little is known. METHODS: We conducted a retrospective review of the Westlaw legal database for indexed state and federal lawsuits involving the diagnostic use of POCUS in internal medicine, paediatrics, family medicine and critical care. Retrieved cases were reviewed independently by three physicians to identify cases relevant to our study objective. A lawyer secondarily reviewed any cases with discrepancies between the three reviewers. RESULTS: Our search criteria returned 131 total cases. Ultrasound was mentioned in relation to the lawsuit claim in 70 of the cases returned. In these cases, the majority were formal ultrasounds performed and reviewed by the radiology department, echocardiography studies performed by cardiologists or obstetrical ultrasounds. There were no cases of internal medicine, paediatrics, family medicine or critical care physicians being subjected to adverse legal action for their diagnostic use of POCUS. CONCLUSION: Our results suggest that concerns regarding the potential for lawsuits related to POCUS in the fields of internal medicine, paediatrics, family medicine and critical care are not substantiated by indexed state and federal filed lawsuits.

"The Hopkins Mongol Case": The Dawn of the Bioethics Movement.

One of the earliest controversies in the modern history of bioethics was known at the time as "the Hopkins Mongol case," involving an infant with Trisomy 21 and duodenal atresia whose parents declined to consent to surgery. Fluids and feeding were withheld, and the infant died of dehydration after 15 days. The child's short life had a profound impact on the author's career and that of several others and ultimately led to changes in the care of children and adults with disabilities and the way difficult end-of-life decisions are made in US hospitals today. It also contributed to the growth of the modern bioethics movement and scholarship focused on pediatric bioethics issues.

First pediatric organ donation after circulatory determination of death in Singapore: Facing challenges in the absence of a local practice guideline.

Pediatric organ donation represents only a low proportion of overall organ donation in many parts of world, unable to match the needs for pediatric organ transplantation. Pediatric organ donation after circulatory determination of death (DCD) is increasingly explored in pediatric transplantation, as it increases the availability of organ grafts. A 6-year-old Caucasian boy with a history of arteriovenous malformation presented with a catastrophic intracranial bleed, resulting in severe brainstem dysfunction despite maximal medical and surgical measures. He did not fulfill the criteria for brain death, which must be met for pediatric organ donation in Singapore. Due to parental request, his organs were donated after withdrawal of life support and determination of death by circulatory criteria. Pediatric organ DCD poses many challenges in the pediatric population, especially in the absence of a local practice guideline. We present the first case of a pediatric organ DCD that has occurred in Singapore. Further work is needed, particularly in establishing a national policy for pediatric organ DCD and increasing overall awareness and acceptance toward pediatric organ donations.

Pediatric Trials for Cancer Therapies With Targets Potentially Relevant to Pediatric Cancers.

The Research to Accelerate Cures and Equity (RACE) for Children Act was enacted in 2017 to authorize the US Food and Drug Administration (FDA) to require pediatric studies for new cancer drugs that have a molecular target relevant to the growth or progression of a pediatric cancer. To assess the possible scope of this new policy, we examined all 78 adult cancer drugs approved by the FDA from 2007 to 2017. Only 17 (21.8%) drugs received any pediatric labeling information. Based on the FDA's Pediatric Molecular Target List, we found that the RACE Act could have increased the proportion of cancer drugs potentially subject to pediatric study requirements from 0% to 78.2%. However, the actual effect of the legislation will depend on how often regulators require pediatric trials and on timely completion of such trials.

National child death review statutory and operational guidance: Key concepts for practising paediatricians.

In October 2018, National Health Service England published new operational guidance for reviewing child deaths, which covers all children who die less than 18 years of age regardless of the cause of death. The Guidance is for all healthcare professionals caring for children as well as senior leaders who commission, provide or regulate children's services. It does not aim to be prescriptive but instead sets out a framework of expectations that intends to be flexible and proportionate. Its essential building blocks will be familiar to practising paediatricians: notification, investigation, review and reporting. It should be regarded as a key pillar in the hospital's governance program.

Pediatric drug development in China: Reforms and challenges.

In China, child and adolescent pediatricians often face challenges in treating children with the appropriate medications. Within the last 8 years, the Chinese government has already initiated a series of policies to promote development of age-appropriate medicines for children. In this study,we introduced the current status of pediatric drugs, obstacles for pediatric drugs development and regulatory reforms in China. The lack of label information in drugs for children, inadequacy of age-appropriate dosage forms and strengths, and shortage of pediatric drugs are some of the problems commonly faced. There exists neither mandatory requirements nor enough financial drivers for development of pediatric medicines. Though some progress in terms of pediatric drugs development as well as distribution have been made by Chinese government over past years, further efforts are necessary to improve availability of pediatric medications.

Electronic Communication of the Health Record and Information With Pediatric Patients and Their Guardians.

Communication of health data has evolved rapidly with the widespread adoption of electronic health records (EHRs) and communication technology. What used to be sent to patients via paper mail, fax, or e-mail may now be accessed by patients via their EHRs, and patients may also communicate securely with their medical team via certified technology. Although EHR technologies have great potential, their most effective applications and uses for communication between pediatric and adolescent patients, guardians, and medical teams has not been realized. There are wide variations in available technologies, guiding policies, and practices; some physicians and patients are successful in using certified tools but others are forced to limit their patients' access to e-health data and associated communication altogether. In general, pediatric and adolescent patients are less likely than adult patients to have electronic access and the ability to exchange health data. There are several reasons for these limitations, including inconsistent standards and recommendations regarding the recommended age for independent access, lack of routine EHR support for the ability to filter or proxy such access, and conflicting laws about patients' and physicians' rights to access EHRs and ability to communicate electronically. Effective, safe electronic exchange of health data requires active collaboration between physicians, patients, policy makers, and health information technology vendors. This policy statement addresses current best practices for these stakeholders and delineates the continued gaps and how to address them.