Pediatric Drug Use Research Articles

Off‑label and unapproved pediatric drug utilization: A meta‑analysis.

Despite legislative enforcement on authorized drugs, off-label and unapproved pediatric drug use is prevalent. The present study aimed to assess the global prevalence of off-label and unlicensed prescriptions among hospitalized children via meta-analysis. A comprehensive examination of articles published between 1990 and 2023 from the PubMed, Scopus, Excerpta Medica Database, Web of Science and Google Scholar databases was conducted. Key word-based advanced searches were executed using the aforementioned databases. A total of 45 studies that reported the prescriptions of off-label and unlicensed drugs to pediatric patients were included. The global prevalence of off-label and unlicensed drug prescriptions to children in pediatrics or neonatal departments was 56%. Patient sample sizes varied from 40-13,426, with a range of 240-8,891 total prescriptions issued. Of the 45 studies examined, 22 studies originated from Europe, 13 from Asia, 3 from South America, 3 from Africa, and 2 each from North America and Australia. Africa had the highest prevalence rate at 66%, followed by Asia, South America, North America, Australia and Europe. The present meta-analysis demonstrated that the prevalence of off-label and unlicensed drug prescriptions given to pediatric patients was notably high and geographically diverse. Therefore, drug authorities should standardize pediatric prescription practices in future.

The implementation of the guideline for the management of pediatric off-label use of drugs in China: a cross-sectional study.

Previously, we developed the Guidelines for the Management of Pediatric Off-Label Use of Drugs in China in addressing the need for standardization of pediatric off-label drug use. As the implementation of recommendations in Guidelines among healthcare professionals is weak, it is important to identify barriers to guideline implementation for developing appropriate strategies for specific settings and target groups. This study aimed to assess the difficulty and urgency in implementing the recommendations in the Guideline, identifying the factors affecting the implementation of these recommendations to realize the clinical translation of the Guideline. A cross-sectional study was conducted from March 1 to June 17, 2022. Pediatricians, pharmacists, and health managers from all 31 mainland Chinese provinces were involved. The electronic questionnaires were distributed nationwide by The Clinical Pharmacology Group of the Pediatric Society of the Chinese Medical Association and the National Clinical Research Center for Child Health. Data analysis, including frequency, percentages, averages, and standard deviations was performed using Microsoft Excel 16.54. Chi-squared tests, multi-factor logistic regression, and linear regression were analyzed in SPSS 23.0. A Sankey diagram was constructed using R software. A total of 869 valid questionnaires were collected from 491 participating organizations. More than half of the recommendations were implemented, and 12 recommendations were implemented more in tertiary hospitals than in secondary hospitals. The mean urgency scores of all 21 recommendations were over 5. The mean difficulty scores of all 21 recommendations were over 4. The percentage of the most urgent was 44.33%, and the least urgent was 1.45%. The most difficult portion was 12.03%, and the least difficult was 5.74%. Factors impacting the urgency and difficulty of guideline implementation were different, with common influences including the position, education level of clinicians and hospital level. The recommendations in the Guideline for the Management of Pediatric Off-Label Use of Drugs are considered highly urgent for implementation in China. Nevertheless, the study revealed challenges in applying all 21 recommendations within clinical practice. The key factors affecting implementation include the position, education, experience, and hospital level of healthcare professionals. It is recommended to facilitate implementing the recommendations by sharing experience across various hospital levels, starting from high-level hospitals and extending to primary healthcare settings. Moreover, adjustments to the professional structure within hospitals are needed to enhance the management of off-label drug use in pediatric patients.

Pediatric Pharmacology for the Primary Care Provider: Advances and Limitations.

Despite >1 in 5 children taking prescription drugs in the United States, off-label drug use is common. To increase the study of drugs in children, regulatory bodies have enacted legislation to incentivize and require pediatric drug studies. As a result of this legislation, novel trial approaches, and an increase in personnel with pediatric expertise, there have been numerous advancements in pediatric drug development. With this review, we aim to highlight developments in pediatric pharmacology over the past 6 years for the most common disease processes that may be treated pharmacologically by the pediatric primary care provider. Using information extracted from label changes between 2018 and 2023, the published literature, and Clinicaltrials.gov, we discuss advances across multiple therapeutic areas relevant to the pediatric primary care provider, including asthma, obesity and related disorders, mental health disorders, infections, and dermatologic conditions. We highlight instances in which new drugs have been developed on the basis of a deeper mechanistic understanding of illness and instances in which labels have been expanded in older drugs on the basis of newly available data. We then consider additional factors that affect pediatric drug use, including cost and nonpharmacologic therapies. Although there is work to be done, efforts focused on pediatric-specific drug development will increase the availability of evidence-based, labeled guidance for commonly prescribed drugs and improve outcomes through the safe and effective use of drugs in children.

Considerable paediatric drug dispensing - A nationwide study of more than 2 million Swedish children.

The aim of the nationwide study was to describe paediatric drug utilisation in Sweden. Drug prescriptions dispensed to all children aged 0-17 years in 2019 were analysed using data from the Swedish National Prescribed Drug Register. We retrieved data on 2 180 508 unique children. Nearly 4.6 million prescriptions were dispensed to children aged 0-17 years, and 52% of these were to boys. Just under half of the children (47%) were dispensed at least one drug: 48% of girls and 45% of boys (p < 0.01). More than a third (34%) were dispensed three or more different drugs during 2019. The number of dispensed prescriptions per 1000 children was higher in boys than girls up to 12 years of age (p < 0.01), and the opposite trend was observed from 13 years and above, even when we excluded contraceptives (p < 0.01). The most common therapeutic areas were drugs for the respiratory tract (25%), namely antihistamines, antiasthmatics and cough medication. These were followed by psychoanaleptics and melatonin for the nervous system (19%) and dermatologicals (16%), namely cortisone creams and emollients. Paediatric drug use was common, and a considerable proportion of children were dispensed multiple drugs.

Paediatric off-label use of drugs in Gansu, China: a multicentre cross-sectional study

ObjectiveTo examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors.DesignThe prevalence of off-label prescriptions in paediatrics was evaluated according to...

Barriers and facilitators to guideline for the management of pediatric off-label use of drugs in China: a qualitative descriptive study

BackgroundDespite being a global public health concern, there is a research gap in analyzing implementation strategies for managing off-label drug use in children. This study aims to understand professional health managers’ perspectives on implementing the Guideline in hospitals and determine the Guideline’s implementation facilitators and barriers.MethodsPediatric directors, pharmacy directors, and medical department directors from secondary and tertiary hospitals across the country were recruited for online interviews. The interviews were performed between June 27 and August 25, 2022. The Consolidated Framework for Implementation Research (CFIR) was adopted for data collection, data analysis, and findings interpretation to implement interventions across healthcare settings.ResultsIndividual interviews were conducted with 28 healthcare professionals from all over the Chinese mainland. Key stakeholders in implementing the Guideline for the Management of Pediatric Off-Label Use of Drugs in China (2021) were interviewed to identify 57 influencing factors, including 27 facilitators, 29 barriers, and one neutral factor, based on the CFIR framework. The study revealed the complexity of the factors influencing managing children’s off-label medication use. A lack of policy incentives was the key obstacle in external settings. The communication barrier between pharmacists and physicians was the most critical internal barrier.ConclusionTo our knowledge, this study significantly reduces the implementation gap in managing children’s off-label drug use. We provided a reference for the standardized management of children’s off-label use of drugs.

Influence of national centralized drug procurement policy on the use of antibiotics in pediatric inpatients

ObjectiveTo explore the safety and efficacy of centrally procured antimicrobial drugs in the pediatric population, the impact of centrally procured policies on pediatric antimicrobial drug use and drug costs, and to make recommendations for hospitals to balance better the relationship between centralized procurement policies and antimicrobial drug management. MethodsThe data on the use of antimicrobial drugs and adverse reactions reported by inpatients in our hospital for half a year before and after centralized drug procurement were collected. Changes in the intensity, structure and utilization rate of antibacterial drugs, incidence of adverse reactions and drug costs, average length of stay, cure rate and improvement rate of patients before and after centralized procurement were compared. An electronic questionnaire survey was conducted on the cognition of clinical medical staff on the use of antibacterial drugs before and after centralized drug procurement. Results1. Centralized antibacterial drugs are widely used in our hospital, and there is no obvious difference in safety and effectiveness from non-centralized drugs. 2. The centralized procurement policy significantly reduces antimicrobial drug costs but increases non-antimicrobial drug costs. 3. The intensity and utilization rate of antimicrobial drugs has stayed the same after the centralized procurement policy, but the drug structure changed. ConclusionThere is still some prejudice among medical professionals and the public towards centralized antibacterial drugs, and positive guidance should be strengthened. The implementation of the centralized procurement policy needs corresponding management measures to ensure the rational use of antimicrobial drugs in clinic.

Are pediatrics taking the prescribed tablet dosage form? Practices of off-label tablet modification in pediatric wards: A prospective observational study

Tablet manipulation (modification) is a practice where the licensed tablet product is customized into reduced fractions of doses or changed into dispersions using solvents because of suitable dose for paediatrics and neonates are frequently unavailable. As a result, unlicensed dosage form frequently used after manipulation, outside what is approved by drug regulatory authorities. ObjectiveTo assess the practice of off-label tablet manipulation in pediatric and neonatal wards at selected public hospitals in Ethiopia. MethodsA prospective, direct observational approach was used to investigate the frequency, nature and appropriateness of tablet manipulations in neonatal and pediatrics patients of two public hospitals of Ethiopia from April 12, to June 30, 2021. ResultsDuring the study period a total of 303 tablet manipulations were observed. Two hundred nine (69%) of tablets were dispensed to pediatric patients to be taken after split into lower strengths. The remaining nighty four (31%) tablets were manipulated into dispersion using 0.9% normal saline as a main solvent. Interestingly, 48 (15.8%) of tablet manipulations into dispersions involved practically insoluble drugs whose manipulation may probably affect their bioavailability. In 12.5% (12/94) dispersion manipulations, large undissolved fractions were observed during administration through naso-gastric tubes. The most commonly manipulated tablets were drugs for central nervous system (n = 135, 44.6%) followed by cardiovascular drugs (n = 85, 28%). Conclusionsand recommendations: The study revealed the off-label use of tablets for pediatrics age groups is very common in Ethiopia. Evidence-based guidelines for tablet manipulations should be practiced to improve the safety of paediatric drug use. As for policy implication, this study concurs with previous scientific recommendations that manufacturers introduce a wide range of dosage forms to reduce the need for manipulations.

The Pediatric Pharmacy Association and Members Threaded Through a Career and the Impact on Pediatric Drug Development.

The Pediatric Pharmacy Association and Members Threaded Through a Career and the Impact on Pediatric Drug Development.

Guideline for the management of pediatric off-label use of drugs in China (2021)

BackgroundThe "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance.MethodsWe established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk–benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009).ResultsWe developed the first guideline for the management of pediatric off-label use of drugs in China.ConclusionsThe guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Analysis on off-label use of drugs in pediatric guidelines and consensus published by Chinese authors

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.

How paediatric drug development and use could benefit from OMICs: A c4c expert group white paper.

The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good-quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis-generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages.

Utilization of biotechnological drugs in rare diseases requiring the use of off-label drugs in children in Turkey

Background/aim Pediatric patients, especially those with rare diseases, represent a population that has a high tendency towards off-label drug use (OLDU) and needs a more careful practice of pharmacotherapy than in adults. We aimed to investigate biotechnological drug use in children with rare diseases requiring OLDU.Materials and methods This retrospective study examined all single-diagnosed OLDU applications (n = 5792) for 4992 children (<18-year) in Turkey. Applications of rare diseases were selected, and their descriptive characteristics were examined, including demographic features of patients, biotechnological drug utilization status, and disease categories. The off-label statuses of the drugs at the end of 2020 were also examined.Results In total, 77.7% (n = 4501) of OLDU applications were made for rare diseases. Biotechnological drug use was higher in rare disease applications than in nonrare diseases (37.9% vs. 19.2%, respectively; p < 0.0001). Canakinumab was the top applied biotechnological drug (73.2%). Compared to that in small-molecule drugs, the mean age of patients was higher in biotechnological drug-containing applications (8.1 ± 5.3 vs. 9.7 ± 4.9, respectively; p < 0.0001). Biotechnological drug use was higher in nonneoplastic rare diseases (40.3%) than in neoplastic rare diseases (26.4%), (p < 0.0001). At the end of 2020, the approval status of the off-label indications covered in 2016 was significantly higher for rare (24.4%) vs. nonrare (5.2%, p < 0.0001) diseases and for biotechnological (32.3%) vs. small-molecule (13.9%, p < 0.0001) drugs. In total, 87.7% of the drugs would have to be still used in the off-label setting at the end of 2020.Conclusion It was seen that more than three-quarters of the pediatric OLDU applications are for rare diseases, and the need for biotechnological OLDU in this group is almost 2-fold of small-molecule drug use. While further projected findings imply a higher approval tendency for rare diseases and biotechnological drugs, there seems to be more room for improvement for pediatric drug use.

The Revolution in Pediatric Drug Development and Drug Use: Therapeutic Orphans No More.

This lecture was given by Dr. Burckart in association with presentation of the 2014 Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics, which is selected by the Pediatric Pharmacy Association. Multiple factors make conducting drug studies in the pediatric population difficult, resulting in a historic lack of information surrounding safe and efficacious drug dosing in children. The paradigm in pediatric drug development has shifted from normal science being that children are therapeutic orphans in the drug development system, to a model drift caused by pediatric legislation, to a model crisis caused by failed pediatric drug development trials, to finally a model revolution that includes pediatric patients routinely in drug development. Major regulatory actions and the accumulation of scientific evidence has created an environment where clinicians can expect properly labeled drug usage information for the pediatric population.

A computational method to quantitatively measure pediatric drug safety using electronic medical records

BackgroundDrug safety in children is a major concern; however, there is still a lack of methods for quantitatively measuring, let alone to improving, drug safety in children under different clinical conditions. To assess pediatric drug safety under different clinical conditions, a computational method based on Electronic Medical Record (EMR) datasets was proposed.MethodsIn this study, a computational method was designed to extract the significant drug-diagnosis associations (based on a Bonferroni-adjusted hypergeometric P-value < 0.05) among drug and diagnosis co-occurrence in EMR datasets. This allows for differences between pediatric and adult drug use to be compared based on different EMR datasets. The drug-diagnosis associations were further used to generate drug clusters under specific clinical conditions using unsupervised clustering. A 5-layer quantitative pediatric drug safety level was proposed based on the drug safety statement of the pediatric labeling of each drug. Therefore, the drug safety levels under different pediatric clinical conditions were calculated. Two EMR datasets from a 1900-bed children’s hospital and a 2000-bed general hospital were used to test this method.ResultsThe comparison between the children’s hospital and the general hospital showed unique features of pediatric drug use and identified the drug treatment gap between children and adults. In total, 591 drugs were used in the children’s hospital; 18 drug clusters that were associated with certain clinical conditions were generated based on our method; and the quantitative drug safety levels of each drug cluster (under different clinical conditions) were calculated, analyzed, and visualized.ConclusionWith this method, quantitative drug safety levels under certain clinical conditions in pediatric patients can be evaluated and compared. If there are longitudinal data, improvements can also be measured. This method has the potential to be used in many population-level, health data-based drug safety studies.

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data.

Children constitute a special population for off-label drug use (OLDU), yet limited drug-focused data exist regarding pediatric OLDU in clinical practice. This study aimed to investigate pediatric OLDU practice and compare it with pediatric drug utilization patterns of routine prescribing data. This cross-sectional study examined all approved pediatric OLDU applications, compared with electronic prescription data on national Prescription Information System of Turkish Medicines and Medical Devices Agency in 2015. OLDU applications and prescriptions were analyzed for demographic characteristics, healthcare/socioeconomic indices as well as details of drugs and diagnoses. We found 7,896 OLDU applications and 7,029,512 prescriptions for the pediatric population in 2015. OLDU applications and prescriptions were mostly practiced for `2-11-year-old` children (52.7% vs. 63.4%, respectively; p < 0.01). OLDU applications and prescriptions were detected to have a positive correlation with socio-economic development index (r = 0.45, p < 0.0001 and r: 0.40, p = 0.0002; respectively) and the physician density (r = 0.66, p < 0.0001 and r: 0.43, p < 0.0001; respectively). In addition, OLDU was also positively correlated with the number of hospital beds per province (r = 0.39, p = 0.0003). Antineoplastic/immunomodulating agents were the most commonly applied drug category in OLDU (47.0%), compared with respiratory system drugs (36.6%) in routine prescribing. Eculizumab (6.5%), mycophenolate (5.6%), and canakinumab (4.4%) were the top drugs used as off-label. OLDU applications and routine prescription data revealed the most frequent diagnosis as `I27-other pulmonary heart diseases` (7.4%) and `J06-acute upper respiratory infections` (12.6%), respectively. This is the first nationwide study to show indication- and drug-centered aspects of pediatric OLDU and prescribing practice. Though OLDU applications is overall consistent with routine clinical practice in terms of demographics and institutional capacity, substantial variations exist regarding main drug classes and diseases. Our findings are expected to shed light on interventions focused on improving `indicated` pediatric use of drugs currently applied as off-label.

Incidence of diagnosed pediatric anxiety disorders and use of prescription drugs: a nation-wide registry study.

The aim of this study was to calculate time trends in incidence of diagnosed anxiety disorders, including obsessive-compulsive disorder, and post-traumatic stress disorder, and to examine changes in use of prescribed drugs in the Norwegian pediatric population. Furthermore, we aimed to investigate whether comorbid mental disorders are associated with the use of prescribed drugs. Nation-wide registries with data from 2008 to 2015 were used, covering diagnostic data from primary health care [the Norwegian database for the control and reimbursement of health expenses (KUHR)] and secondary health care [the Norwegian Patient registry (NPR)], and data on prescribed drugs [the Norwegian prescription database, (NorPD)]. Data from the two latter were linked. During the period 2010-2015, 19,154 children and adolescents (61% girls) received a first diagnosis of anxiety disorders in primary care. The corresponding number from secondary care was 17,115 (61% girls). The incidence of diagnosed anxiety disorders increased over time, especially in girls, with an overall raise of ~ 2 per 1000 children across 2010-2015. Anti-anxiety drugs were used by < 12% of diagnosed children and < 25% of diagnosed adolescents, mainly by those with several contacts with the specialist health care system. There was no strong indications of an increase over time. Of other drugs, the most frequently prescribed were hypnotics and psychostimulants. Psychiatric comorbidity (33-55%) contributed to the use of drugs, including anti-anxiety drugs. The incidence of diagnosed anxiety disorders increased from 2010 to 2015, but the percentage using anti-anxiety drugs was stable. Drug use appears to be in line with the Norwegian guidelines.

Current practice and awareness of pediatric off-label drug use in Shanghai, China -a questionnaire-based study

BackgroundOff-label drug use is widespread in pediatric drug treatment, and the implementation of guidelines on this topic remains challenging. The objective of this study was to evaluate current practice and awareness of healthcare professionals towards pediatric off-label drug use, as well as the barriers to guideline implementation among pediatric healthcare professionals in Shanghai, China.MethodsA validated questionnaire was issued to representatives of pediatricians, pharmacists, nurses and administrators from hospitals with pediatric qualification in Shanghai.ResultsA total of 679 completed questionnaires from 69 hospitals were included in the analysis. Nearly half (47.9%) of the pediatricians acknowledged that they had prescribed off-label drugs. Most (88.4%) of the pharmacists acknowledged that they had dispensed off-label medicines. The main reason for off-label prescribing was the lack of pediatric dosage information. The most common category of off-label prescribing in children was dosage. Nearly half (42.0%) of the participating hospitals had developed internal protocols for off-label drug use. However, approximately half of the respondents reported that they did not adhere to the guidance and that it had barriers to implementation. Most respondents (84.5%) declared that they were familiar with the term “off-label drug use”. However, the awareness rate of the Chinese Expert Consensus of Pediatric Off-Label Drug Use was low (45.7%). More than half (55.4%) of the respondents declared that they did not adhere to the process proposed in the consensus and that barriers existed for its utilization.ConclusionsPediatric off-label drug use is widespread in Shanghai, China, and barriers exist to the implementation of the guideline. A legally recognized national guideline with a broad scope of application for off-label drug use is urgently needed; at the same time, more education and training on off-label drug use should be provided to targeted healthcare professionals.

Pediatric off-label use of psychotropic drugs approved for adult use in Japan in the light of approval information regarding pediatric patients in the United States: a study of a pharmacy prescription database.

Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan. This study sought to clarify pediatric patients' off-label use of psychotropics approved only for adults in Japan. This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016. Seven psychotropic drugs were examined. For each drug, we calculated the proportion of patients aged < 16years or who were under the approved age limit set in the United States out of all patients. The maximum daily dose of each drug within the study period was plotted by age. Data of 45,715 patients (female: 26,799, male: 18,916) with 331,920 prescriptions were examined in this study. For each drug, the proportion of pediatric patients aged < 16years ranged from 0.15 to 1.1%, while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%. Olanzapine had the highest reported proportion. No drugs other than olanzapine were taken under the approved age limit in the United States. We identified the pediatric off-label use of psychotropics that were limited to adult use in Japan. The results indicated the possibility of referring to international guidelines or evidence in clinical practice, but these factors do not discount the existing problems with off-label use. More clinical trials within the pediatric population in Japan are needed to address the issue of off-label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.

Comparing drug effectiveness in children: A systematic review.

The purpose of the study is to assess the current state of the art in pediatric comparative effectiveness research, potential gaps, and areas for improvement. Relevant articles from inception to February 2015 were retrieved from Embase and Medline. We sequentially screened titles, abstracts, and full texts, with independent validation. Data regarding general information and study methods including statistical analysis were extracted. Study quality was assessed using Newcastle-Ottawa Scale (NOS). Investigated drugs were ranked and compared with data on the prevalence of pediatric drug use. Three thousand nine hundred twenty-six abstracts were screened for eligibility and inclusion, and 164 articles were included in the review. Most studies were from North America (46.7%). Only 78 studies (47.6%) reported the design: 90.8% were cohort studies. Neonates were least frequently investigated. The drugs that were most often studied included systemic antibacterials (11.4%), psycholeptics (7.9%), and antiepileptics (7.6%). Adjustment for confounding was made using propensity scores in 8.5% of the studies. Studies that did not report the design were of lower quality. Many effectiveness studies were done on antineoplastic agents, which are not frequently used and few studies on analgesics and drugs for obstructive airway diseases which are frequently prescribed. There is ample opportunity to improve comparative effectiveness research for drugs used in pediatrics. Routinely prescribed drugs were seldom investigated. Modern methods for confounding adjustment, such as propensity scores, were rarely used.