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Purpose: Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off‐label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma. Methods: In this serial cross‐sectional study, we identified quarterly cohorts of children (0–18 years) with moderate‐to‐severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time‐series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6–11‐year‐old children compared with 12–18‐year‐olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6–11‐year‐old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6–11‐year‐old children. Results: We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6–11‐year‐old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27–89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21–94, p = 0.003) compared with 12–18‐year‐old children. Conclusions: The use of omalizumab among asthmatic children aged 6–11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Usually, the administration of drugs by feeding tube in dysphagic patients involves handling of marketing licenses outside their term, due to the lack of suitable formulations. This circumstance has put health professionals in the dilemma of choosing the formulation whose manipulation possibly does not alter the effectiveness of the drug. In this regard, a practical guide providing indications on the prescription, handling, and administration of drugs through enteral feeding tube could be of paramount utility. For this purpose, we have considered the 1047 solid oral pharmaceutical forms included in the formulary of San Paolo Hospital (Savona, Italy). From our analysis, it emerges that 95% of medicinal products are worryingly used off-label and 40% have to be managed by the hospital pharmacists without having suitable indications by either the manufacturers or by literature studies. To fill this gap, we have compiled a detailed table containing missing indications derived from pharmacist expertise and evidence-based practices, with the aim that the sharing of our procedures will contribute to make uniform pharmacological therapies from one hospital to another. This study will allow doctors to have easy access to information on drugs that can be prescribed and nurses to become familiar only with the pharmaceutical forms that can be administered. [ABSTRACT FROM AUTHOR]

Lin Liu, Hong-Yu Yang, Yan Lou, Jing Miao, Xiao-Yang Lu, Qing-Wei Zhao, Rong-Rong Wang, Sai-Ping Jiang,* Xing-Guo Zhang* Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Background and purpose: Off-label prescriptions for critically ill patients pose several ethical and legal dilemmas for intensive care unit (ICU) clinicians. Yet, few data are available on the prevalence of this practice in critical care environment in China. This nationwide survey was performed to evaluate the conditions of off-label prescriptions in ICU within China.Methods: The survey was performed at the scene of the national ICU conferences in 2016. ICU clinicians attending the congress from 23 provinces across the country were invited. The features of the clinician’s off-label prescription practice were investigated and analyzed.Results: A total of 1,318 ICU clinicians completed the anonymous questionnaire. Of these, 76.2% prescribed off-label in clinical practice. A significant difference (p

Objective: To examine psychotropic medication prescription practices in federal Canadian penitentiaries.Method: 468 files were drawn from a purposive sample of thirteen Canadian federal institutions representing the five regions, different security levels, and male and female designated facilities. Information on the names of all psychotropic medications prescribed, indications for use, dosage, frequency, and route of administration was retrieved. Designation of approved or off-label use of medications was determined by consulting: (1) the Health Canada (2016) Drug Product Database, (2) the Canadian Compendium of Pharmaceuticals and Specialties 2016, and (3) the American Hospital Formulary Service Drug Information 2016. Prescription rates were examined by gender, Indigenous ancestry, drug class, institutional infractions, and current offence.Results: 36.2% of prescriptions for psychotropic medication were coded as 'off-label'. Anxiolytic/hypnotics drugs were the psychotropic drugs most commonly used for off-label purposes. There were no differences in the prevalence of approved versus off-label prescriptions based on Indigenous ancestry or gender, and no pattern of elevated off-label prescription practices for offenders involved in institutional misconducts or those sentenced for the most serious crimes.Conclusions: The rates of prescribing 'off-label' psychotropic medication are not elevated relative to other correctional settings or to rates cited in Canadian surveys conducted in the community. [ABSTRACT FROM AUTHOR]

Résumé La prise en charge médicamenteuse des adolescents est un sujet d’actualité délicat en psychiatrie. Le Centre de crise pour adolescents (CCA) de notre établissement permet l’accueil et la prise en charge adaptée de ces jeunes patients en « crise » psychique. La récurrence des prescriptions de psychotropes hors AMM a motivé la réalisation par la pharmacie, en lien avec le psychiatre responsable du service, d’un état des lieux sur les pratiques de l’unité, avec pour objectifs l’évaluation de ces prescriptions et la réflexion sur des moyens de documentation et sécurisation du hors AMM. Le contenu de 832 ordonnances prescrites sur une année (2011) est recueilli rétrospectivement dans un fichier Excel ® , complété avec les données issues du dossier patient informatisé. Ainsi, 32 psychotropes (DCI) de différentes classes ont été prescrits aux 129 patients, âgés de 11 à 18 ans, hospitalisés dans le service. Le taux de prescriptions hors AMM est de 38 %, si l’on considère uniquement l’âge des patients et de 56,4 % si l’on y ajoute un non-respect de l’AMM vis-à-vis de l’indication. Ce travail confirme la problématique de la prescription médicamenteuse dans cette population, en lien avec le manque de données françaises concernant l’utilisation des psychotropes chez l’adolescent. Il a également permis la mise en place d’actions pour optimiser les conditions de prise en charge des adolescents dans l’unité : documents d’aide à la prescription, rappel de la nécessité de documenter le hors AMM et de l’importance du suivi biologique et clinique, en lien avec la ville, pour les psychotropes. The medical care of adolescents is a delicate current topic in psychiatry. The Crisis center for adolescents (CCA) of our establishment allows the reception and the adapted medical care of these young patients in a state of psychic “crisis”. The recurrence of off-label prescriptions of psychotropic medications justified the realization by the pharmacy team, in collaboration with the psychiatrist responsible for the service, of an investigation of the service practices, in order to evaluate these prescriptions and reflect on the means of documentation and securisation of off-label prescriptions. The contents of 832 prescriptions made in 2011 were collected retrospectively in an Excel ® file, and were supplemented with the data resulting from the computerized patient file. Thus, 32 psychotropic drugs of various classes were prescribed to the 129 patients, aged from 11 to 18, who were hospitalized in the service. The rate of off-label prescriptions is of 38%, if we only consider the age of the patients, and of 56.4% if we add to it a non-observance of respect to the indication. This work confirms the problem of medical prescriptions in this population, due to the lack of French data concerning the use of psychotropics in the adolescents. It also allowed the setting up of actions to optimize the conditions of the medical care of adolescents in the unit: documents of assistance for the medical prescription, recall of the need to document off-label prescriptions and of the importance of biological and clinical follow-ups, in collaboration with the city, for psychotropic drugs. [ABSTRACT FROM AUTHOR]

Résumé En instituant les recommandations temporaires d’utilisation (RTU), la « loi Bertrand » du 29 décembre 2011 a eu pour objectif d’encadrer les prescriptions de médicaments en dehors des conditions prévues par leurs autorisations de mise sur le marché (AMM). L’introduction en droit français d’un système organisant la prescription et la prise en charge de médicaments en dehors de leur AMM constitue une innovation ne comportant actuellement aucun équivalent dans l’Union européenne. Initialement, la mise en place des RTU visait à sécuriser les prescriptions hors AMM dans un objectif de santé publique et à inciter les laboratoires pharmaceutiques à déposer une extension d’AMM pour leurs médicaments. Cependant, la nécessité de déroger à l’AMM pour des considérations d’ordre économique est également apparue. Alors qu’aujourd’hui seules trois RTU ont été octroyées, des interrogations juridiques et techniques subsistent sur les dernières évolutions apportées à ce dispositif par la loi de financement rectificative de la sécurité sociale du 8 août 2014. À l’origine, les dérogations étaient limitées aux situations thérapeutiques pour lesquelles il n’existait pas d’alternative médicamenteuse appropriée disposant d’une AMM ou d’une autorisation temporaire d’utilisation (ATU). Désormais, les prescriptions de médicaments hors AMM sont autorisées, sous réserve qu’il n’existe pas de spécialité de même principe actif, de même dosage et de même forme pharmaceutique disposant d’une AMM ou d’une ATU dans l’indication ou les conditions d’utilisation considérées. Ces évolutions illustrent la difficulté des pouvoirs publics à concilier besoins de santé publique, risques sanitaires et considérations économiques dans le domaine du médicament. Since 2012, France has implemented a new framework for regulating off-label drug use. The law number 2011–2012, December 29, 2011 aimed to control off-label drug use for safety purposes and introduced into the French law a quite unique regulatory process called the “Temporary Recommendations for Use” (RTUs). This process temporarily authorizes drugs that are prescribed outside their marketing authorization and ensures the reimbursement for the drug for the designated indication. It also aims to encourage pharmaceutical firms to submit application dossiers for an extension of their marketing authorizations. RTUs, which are approved by a national expert committee, were originally limited to the therapeutic situations for which there was no appropriate authorized alternative drug. However, the need to bypass the marketing authorization appeared for economic concerns. Whereas today only three RTU are granted, legal and technical issues remain about the latest changes made to this process. Off-label prescriptions are now permitted, provided that there is no medicine of the same active ingredient, the same dosage and the same pharmaceutical form with a marketing authorization or a temporary authorization for use (ATU) in the indication covered by the RTU. These developments illustrate the difficulty of public policies to balance public health needs, safety and economic goals. [ABSTRACT FROM AUTHOR]

Context: ADHD is the most common mental disorder in school-aged children. In France, methylphenidate is the only drug authorized for ADHD. Here, we describe the pattern of ADHD diagnosis and methylphenidate prescription to children and adolescents from 2010 to 2019., Methods: We conducted a retrospective cohort study of all beneficiaries of the French general health insurance scheme (87% of the population, 58 million people). We extracted information for all children and adolescents aged 0-17 years who received: (1) A diagnosis of ADHD (34,153 patients). (2) At least one methylphenidate prescription (144,509 patients). We analyzed the clinical, demographic, institutional, and social parameters associated with ADHD diagnosis and methylphenidate consumption in France., Results: The ADHD diagnosis among children and adolescents increased by 96% between 2010 and 2019. ADHD diagnosis affects more boys than girls. About 50.6% of children hospitalized with a diagnosis of ADHD in 2017 also had another psychiatric diagnosis. The rate of children hospitalized with an ADHD diagnosis and treated with MPH varied between 56.4 and 60.1%. The median duration of MPH treatment for a 6-year-old ADHD child initiated in 2011 is 7.1 years. In 2018, 62% of ADHD children were receiving at least one psychotropic medication. Between 2010 and 2019, methylphenidate prescription increased by +56% for incidence and +116% for prevalence. The prevalence of methylphenidate prescription reached between 0.61 and 0.75% in 2019. Boys are predominantly medicated. The median duration of treatment among 6-year-olds in 2011 was 5.5 years. The youngest children received the longest treatment duration. Diagnoses associated with methylphenidate prescription did not always correspond to the marketing authorization. Among children receiving the first prescription of methylphenidate, 22.8% also received one or more other psychotropic drugs during the same year. A quarter of initiations and half of renewals were made outside governmental recommendations. Educational and psychotherapeutic follow-up decreased from 4.1% in 2010 to 0.8% in 2019. French children and adolescents, who were the youngest in their class were more likely to be diagnosed (55%) and prescribed methylphenidate (54%). Children from disadvantaged families had an increased risk of ADHD diagnosis (41.4% in 2019) and methylphenidate medication (25.7% in 2019)., Competing Interests: SP declares that his research is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. SP le CIRNEF and the université de Rouen Normandie are responsible for this research. BT as founder and CEO of Median Conseil, has worked with several clients tied to the healthcare or nutrition domains, namely: Grunenthal, Lundbeck, Octapharma, Kiowa, Baxter, Physidia, Nestlé, Alexion, Amgen, Ipsen, Mallinkrodt, Merck, Pharma Mar, Takeda, Thea, 3M, Urgo. None of the studies conducted for these clients dealt with child psychiatry or psychotropic medications. BT and Median Conseil were responsible for processing the data for this research., (Copyright © 2022 Ponnou and Thomé.)

In this case study from litigation, we show how ghostwriting of clinical trial results can contribute to the manipulation of data to favor the study medication. Study 329 for paroxetine pediatric use was negative for efficacy and positive for harm. Yet the ghostwritten publication from this study concluded that paroxetine provided evidence of efficacy and safety and continues to be influential. Despite the role of named authors in revisions of the manuscript, the sponsor company remained in control of the message. [ABSTRACT FROM AUTHOR]

Abstract: The data guiding the dosing, efficacy and safety of medicines for children have lagged substantially as compared to the information available for adults. As a consequence, pediatricians faced with the prospect of confining their practice to medicines with adequate information have frequently resorted to prescribing medicines for unapproved uses (different dose, frequency, age group, route, indication or formulation). Although a long time in coming, the past decade, have witnessed a new era in drug development for children — an era that is still in its infancy, but which is currently showing signs of maturation. This review will give some of the history and current progress in pharmacological research and pediatric drug development. [Copyright &y& Elsevier]

Introduction: Psoriasis affects 0.5% of children in Europe, with moderate to severe clinical forms in 15-35% of cases warranting the use of systemic treatments. Few treatments are licensed for childhood psoriasis. In this study, we analyzed the frequency of such prescriptions., Materials and Methods: Our study was based on 3 retrospective cohort trials conducted in France between 2012 and 2018: χ-Psocar (313 children with psoriasis seen in hospitals), PsoLib (207 children seen in a private practice), and BiPe (134 children on biotherapies). Our evaluation was centered on off-label use. To avoid duplicates between cohorts, analysis focused on each cohort independently., Results: In the χ-Psocar study, in 34.8% of cases, use of at least one off-label treatment, mainly topical vitamin D (36.0%), and systemic treatments (methotrexate and cyclosporine) was noted, on account of either the clinical type of psoriasis (13.7%) or patient age (24.6%). In the PsoLib study, in 41.5% of cases, at least one off-label treatment was noted, mainly combined calcipotriol-betamethasone (24.2%), ciclopirox shampoo (7.2%) and systemic treatments (n=20). The main reason was patient age (41.5%). In the BiPe study, in 97.0% of cases, at least one off-label treatment was noted. These prescriptions mainly concerned a combination of calcipotriol-betamethasone (68.7%) and tacrolimus (11.2%) along with systemic treatment comprising methotrexate, cyclosporin, methoxsalen or apremilast (n=125), but also biotherapies (n=85). The biotherapies were used off-label since at that time they had not yet been granted marketing authorisation., Discussion: This study focused on 3 cohorts of children with psoriasis seen either in private practice or in a hospital setting, and it involved all types of treatment. Off-label prescriptions ranged from one-third to almost 100% of the children, depending on the individual cohorts. The prescribed drugs were topical treatments, conventional systemic drugs and biotherapies. Off-label prescription is not strictly prohibited in France provided it is within a well-defined regulatory framework. Where there is a rich bibliography, confident recommendations may be made. Unfortunately, in childhood psoriasis, the literature and recommendations are very limited, leaving prescribers with considerable individual responsibilities. Review of the license concerning children with psoriasis, a push to conduct therapeutic studies and the drafting of recommendations all appear necessary., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To analyze the prevalence of use of off-label and unlicensed drugs in a pediatric intensive care unit of a University Hospital., Method: An observational, descriptive, prospective six week pilot study in a Pediatric Intensive Care Unit. Hospitalized patients aged between 0 and 18 years were included. Each prescribed drug was evaluated taking into account indication and condition of use, according to the information available on the Summary of Product Characteristics established by the European Medicines Agency. A sequential algorithm was defined allowing drug classification in unlicensed, off-label or approved., Results: Forty-two patients were included. A total of 696 prescriptions, involving 102 different drugs, were analyzed. All patients had at least one off-label prescription, and a median of 8.9 off-label prescriptions was obtained. Of the total prescriptions, 8.6% were unlicensed and 53.9% corresponded to off-label use. The main reason for off-label use was by indication, followed by age and dose. A lineal tendency between off-label drug use and patient age was observed, where off-label use increased as patient age decreased. The drugs most commonly used off-label were: atropine, etomidate, dipyrone and ranitidine, and unlicensed drugs: spironolactone, sildenafil, acetazolamide and hydrochlorothiazide., Conclusion: Pediatric Intensive Care Units are characterized by a high ratio of off-label and unlicensed prescriptions. The scarce number of studies performed in this specific and complex sub-population added inconveniency to the current lack of data on safety and efficacy for drugs in paediatrics. Performing studies with these characteristics allows us to document practice on paediatric drug utilisation are required., (Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)