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Background: The existing data on enrollment trends of historically underserved racial and ethnic children in clinical trials are limited. Objective: We sought to evaluate documentation and representation of race and ethnicity in pediatric asthma clinical trials in the United States. Methods: This is a cross-sectional study of United States-based interventional trials studying pediatric asthma that were completed between 2008 and 2022 and registered on ClinicalTrials.gov. Enrollment disparities were assessed by using the measure enrollment prevalence difference (EPD) (defined as the median difference between the proportion of participants enrolled and asthma prevalence in the US population by race and ethnicity). Results: Of the 67 trials reviewed, 53 (79.2%) and 36 (53.7%) reported on race and ethnicity at ClinicalTrials.gov, respectively. Most participants were White (39.1%), Black (37.1%), or non-Hispanic (66.1%). Black, Hispanic, multiracial, and White children were enrolled in the expected proportions based on their contribution to asthma burden. However, American Indian or Alaska Native (AI/AN) (EPD = -1 [95% CI = -1 to -1]) and Asian children (EPD = -3 [95% CI = -3 to -3]) were underrepresented relative to disease burden in these respective groups. Fewer Black children were enrolled in drug or device trials (ß = -0.80 [95% CI = -1.60 to -0.01]) than in other trials. Fewer Hispanic children were enrolled in early-phase than late-phase trials (ß = -2.42 [95% CI = -3.66 to -1.19]). Conclusions: Enrollment in pediatric asthma trials conducted in the United States was commensurate with the demographics of children affected by asthma for most racial and ethnic groups, but American Indian or Alaska Native and Asian children were underrepresented. Concerted efforts are needed to promote inclusion of these underserved groups in future trials.
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Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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When the primary endpoints in randomized clinical trials require long term follow-up or are costly to measure, it is often desirable to assess treatment effects on surrogate instead of clinical endpoints. Prior to adopting a surrogate endpoint for such purposes, the extent of its surrogacy on the primary endpoint must be assessed. There is a rich statistical literature on assessing surrogacy in the overall population, much of which is based on quantifying the proportion of treatment effect on the primary endpoint that is explained by the treatment effect on the surrogate endpoint. However, the surrogacy of an endpoint may vary across different patient subgroups according to baseline demographic characteristics, and limited methods are currently available to assess overall surrogacy in the presence of potential surrogacy heterogeneity. In this paper, we propose methods that incorporate covariates for baseline information, such as age, to improve overall surrogacy assessment. We use flexible semi-non-parametric modeling strategies to adjust for covariate effects and derive a robust estimate for the proportion of treatment effect of the covariate-adjusted surrogate endpoint. Simulation results suggest that the adjusted surrogate endpoint has greater proportion of treatment effect compared to the unadjusted surrogate endpoint. We apply the proposed method to data from a clinical trial of infliximab and assess the adequacy of the surrogate endpoint in the presence of age heterogeneity.
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Biomarcadores , Infliximab , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Infliximab/uso terapêutico , Determinação de Ponto Final/estatística & dados numéricos , Resultado do Tratamento , Estatísticas não Paramétricas , Simulação por ComputadorRESUMO
Importance: Concerns over the mental health of young people have been increasing over the past decade, especially with the rise in mental health burden seen during the COVID-19 pandemic. Examining trends in mental health-related outpatient visits provides critical information to elucidate contributing factors, identify vulnerable populations, and inform strategies to address the mental health crisis. Objective: To examine characteristics and trends in mental health-related outpatient visits and psychotropic medication use among US adolescents and young adults. Design, Setting, and Participants: A retrospective cross-sectional analysis of nationally representative data from the National Ambulatory Medical Care Survey, an annual probability sample survey, was conducted from January 2006 to December 2019. Participants included adolescents (age 12-17 years) and young adults (age 18-24 years) with office-based outpatient visits in the US. Data were analyzed from March 1, 2023, to September 15, 2023. Main Outcomes and Measures: Mental health-related outpatient visits were identified based on established sets of diagnostic codes for psychiatric disorders. Temporal trends in the annual proportion of mental health-related outpatient visits were assessed, including visits associated with use of psychotropic medications. Analyses were stratified by age and sex. Results: From 2006 to 2019, there were an estimated 1.1 billion outpatient visits by adolescents and young adults, of which 145.0 million (13.1%) were associated with a mental health condition (mean [SD] age, 18.4 [3.5] years; 74.0 million females [51.0%]). Mental health-related diagnoses were more prevalent among visits by male (16.8%) compared with female (10.9%) patients (P < .001). This difference was most pronounced among young adults, with 20.1% of visits associated with a psychiatric diagnosis among males vs 10.1% among females (P < .001). The proportion of mental health-related visits nearly doubled, from 8.9% in 2006 to 16.9% in 2019 (P < .001). Among all outpatient visits, 17.2% were associated with the prescription of at least 1 psychotropic medication, with significant increases from 12.8% to 22.4% by 2019 (P < .001). Conclusions and Relevance: In this cross-sectional study, there were substantial increases in mental health-related outpatient visits and use of psychotropic medications, with greater overall burden among male patients. These findings provide a baseline for understanding post-pandemic shifts and suggest that current treatment and prevention strategies will need to address preexisting psychiatric needs in addition to the effects of the COVID-19 pandemic.
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COVID-19 , Saúde Mental , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Criança , Adulto , Estudos Transversais , Pacientes Ambulatoriais , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologiaRESUMO
The utilization of the human immune system as a therapeutic modality has materialized in the form of novel biologics known as immune effector cells (IECs). However, currently approved IECs rely on autologous cells for manufacturing that are funneled through costly centralized supply chains leading to long wait times and potentially increased mortality. Alternative models for manufacturing at or near the point-of-care in a distributed and local approach are being proposed to overcome such a bottleneck. Cell processing facilities for minimally manipulated products, as well as academic good manufacturing practice facilities, are being considered for such manufacturing tasks. However, the infrastructure and the practices of these facilities remains unstudied. Here, we surveyed the cell processing facilities accredited by the Foundation for Accreditation of Cellular Therapy (FACT) in the United States to better understand their preparedness for local manufacturing of IECs. A structured survey consisting of 40 items was distributed to the directors of 157 facilities. The survey evaluated 6 domains, including facility characteristics, quality practices, personnel, use of automation, experience with IECs, and the perception of the point-of-care model. Thirty-eight facilities completed the survey (24.2%). Most facilities were involved in handling IEC products (35/38, 92.1%), and the majority had infrastructure to support basic operations and quality control such as viability (36/36, 100%), identity (33/36, 91.7%), and sterility (33/36, 91.7%). The quality practices varied among the facilities depending on the types of products processed. A slight majority implemented automation in their workflows (22/38, 57.9%). Facilities expressed a general interest in adopting point-of-care models (23/38, 61%), with financial and human resources identified as the most significant constraints. In conclusion, FACT-accredited cell processing facilities may provide the infrastructure required for local manufacturing. However, there is a need for standardization and minimum quality requirements to effectively implement such models.
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Acreditação , Humanos , Inquéritos e Questionários , Estados Unidos , Terapia Baseada em Transplante de Células e Tecidos/normasRESUMO
Searching for trials is a key task in systematic reviews and a focus of automation. Previous approaches required knowing examples of relevant trials in advance, and most methods are focused on published trial articles. To complement existing tools, we compared methods for finding relevant trial registrations given a International Prospective Register of Systematic Reviews (PROSPERO) entry and where no relevant trials have been screened for inclusion in advance. We compared SciBERT-based (extension of Bidirectional Encoder Representations from Transformers) PICO extraction, MetaMap, and term-based representations using an imperfect dataset mined from 3632 PROSPERO entries connected to a subset of 65,662 trial registrations and 65,834 trial articles known to be included in systematic reviews. Performance was measured by the median rank and recall by rank of trials that were eventually included in the published systematic reviews. When ranking trial registrations relative to PROSPERO entries, 296 trial registrations needed to be screened to identify half of the relevant trials, and the best performing approach used a basic term-based representation. When ranking trial articles relative to PROSPERO entries, 162 trial articles needed to be screened to identify half of the relevant trials, and the best-performing approach used a term-based representation. The results show that MetaMap and term-based representations outperformed approaches that included PICO extraction for this use case. The results suggest that when starting with a PROSPERO entry and where no trials have been screened for inclusion, automated methods can reduce workload, but additional processes are still needed to efficiently identify trial registrations or trial articles that meet the inclusion criteria of a systematic review.
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Ensaios Clínicos como Assunto , Aprendizado de Máquina , Revisões Sistemáticas como Assunto , Automação , PublicaçõesRESUMO
This cross-sectional study uses information gathered from ClinicalTrials.gov to assess the inclusion of children in COVID-19 interventional trials conducted in the US.
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COVID-19 , Ensaios Clínicos como Assunto , Seleção de Pacientes , Criança , HumanosRESUMO
This cohort study examines the frequency of postdischarge follow-up visits among US emergency department encounters for bronchiolitis and assesses whether follow-up was associated with decreased hospital reutilization or increased treatment with nonrecommended medications.
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Bronquiolite , Serviços Médicos de Emergência , Humanos , Seguimentos , Pacientes Ambulatoriais , Serviço Hospitalar de Emergência , Bronquiolite/epidemiologia , Bronquiolite/terapiaRESUMO
Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES -1.18 years [95% CI -2.05, -0.32]), had fewer respiratory symptoms (RD -0.15 [95% CI -0.33, -0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD -0.35 [95% CI -0.64, -0.07]), lower lymphocyte count (ES -0.16 × 109/uL [95% CI -0.30, -0.01]), lower C-reactive protein (ES -28.5 mg/L [95% CI -46.3, -10.7]), and lower troponin (ES -0.14 ng/mL [95% CI -0.26, -0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES -1.6 years [95% CI -2.5, -0.8]), had less frequent SIRS (RD -0.18 [95% CI -0.30, -0.05]), lower lymphocyte count (ES -0.39 × 109/uL [95% CI -0.52, -0.25]), lower troponin (ES -0.16 ng/mL [95% CI -0.30, -0.01]) and less frequently received anticoagulation therapy (RD -0.19 [95% CI -0.37, -0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (-1.3 days [95% CI -2.3, -0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.
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BACKGROUND: Exploratory pediatric cannabis poisonings are increasing. The aim of this study is to provide a national assessment of the frequency and trends of diagnostic testing and procedures in the evaluation of pediatric exploratory cannabis poisonings. METHODS: This is a retrospective cross-sectional study of the Pediatric Health Information Systems database involving all cases of cannabis poisoning for children age 0-10 years between 1/2016 and 12/2021. Cannabis poisoning trends were assessed using a negative binomial regression model. A new variable named "ancillary testing" was created to isolate testing that would not confirm the diagnosis of cannabis poisoning or be used to exclude co-ingestion of acetaminophen or aspirin. Ancillary testing was assessed with regression analyses, with ancillary testing as the outcomes and year as the predictor, to assess trends over time. RESULTS: A total of 2001 cannabis exposures among 1999 children were included. Cannabis exposures per 100,000 ED visits increased 68.7% (95% CI, 50.3, 89.3) annually. There was a median of 4 (IQR 2.0, 6.0) diagnostic tests performed per encounter. 64.5% of encounters received blood tests, 28.8% received a CT scan, and 2.4% received a lumbar puncture. Compared to White individuals, Black individuals were more likely to receive ancillary testing (OR 1.52 [95% CI, 1.23, 1.89]). Compared to those 2-6 years, those <2 years were more likely to receive ancillary testing (OR 1.55 [95% CI, 1.19, 2.02). We found no significant annual change in the odds of receiving ancillary testing (OR 1.04 [95% CI, 0.97, 1.12]). CONCLUSIONS: We found no change in the proportion of encounters associated with ancillary testing, despite increases in exploratory cannabis poisonings over the study period. Given the increasing rate of pediatric cannabis poisonings, emergency providers should consider this diagnosis early in the evaluation of a pediatric patient with acute change in mental status. While earlier use of urine drug screening may reduce ancillary testing and invasive procedures, even a positive urine drug screen does not rule out alternative pathologies and should not replace a thoughtful evaluation.
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Importance: Enrolling racially and ethnically diverse pediatric research participants is critical to ensuring equitable access to health advances and generalizability of research findings. Objectives: To examine the reporting of race and ethnicity for National Institutes of Health (NIH)-funded pediatric clinical trials and to assess the representation of pediatric participants from different racial and ethnic groups compared with distributions in the US population. Design, Setting, and Participants: This cross-sectional study included NIH-funded pediatric (ages 0-17 years) trials with grant funding completed between January 1, 2017, and December 31, 2019, and trial results reported as of June 30, 2022. Exposures: National Institutes of Health policies and guidance statements on the reporting of race and ethnicity of participants in NIH-funded clinical trials. Main Outcomes and Measures: The main outcome was reporting of participant race and ethnicity for NIH-funded pediatric clinical trials in publications and ClinicalTrials.gov. Results: There were 363 NIH-funded pediatric trials included in the analysis. Reporting of race and ethnicity data was similar in publications and ClinicalTrials.gov, with 90.3% (167 of 185) of publications and 93.9% (77 of 82) of ClinicalTrial.gov reports providing data on race and/or ethnicity. Among the 160 publications reporting race, there were 43 different race classifications, with only 3 publications (1.9%) using the NIH-required categories. By contrast, in ClinicalTrials.gov, 61 reports (79.2%) provided participant race and ethnicity using the NIH-specified categories (P < .001). There was racially and ethnically diverse enrollment of pediatric participants, with overrepresentation of racial and ethnic minority groups compared with the US population. Conclusions and Relevance: This cross-sectional study of NIH-funded pediatric clinical trials found high rates of reporting of participant race and ethnicity, with diverse representation of trial participants. These findings suggest that the NIH is meeting its directive of ensuring diverse participant enrollment in the research it supports.
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Etnicidade , Grupos Minoritários , Estados Unidos , Humanos , Criança , Estudos Transversais , Minorias Étnicas e Raciais , National Institutes of Health (U.S.)RESUMO
Importance: The US Food and Drug Administration (FDA) is building a national postmarketing surveillance system for medical devices, moving to a "total product life cycle" approach whereby more limited premarketing data are balanced with postmarketing surveillance to capture rare adverse events and long-term safety issues. Objective: To assess the methodological requirements and feasibility of postmarketing device surveillance using endovascular aneurysm repair devices (EVARs), which have been the subject of safety concerns, using clinical data from a large health care system. Design, Setting, and Participants: This retrospective cohort study included patients with electronic health record (EHR) data in the Veterans Affairs Corporate Data Warehouse. Exposure: Implantation of an AFX Endovascular AAA System (AFX) device (any of 3 iterations) or a non-AFX comparator EVAR device from January 1, 2011, to December 21, 2021. Main Outcomes and Measures: The primary outcomes were rates of type III endoleaks and all-cause mortality; and rates of these outcomes associated with AFX devices compared with non-AFX devices, assessed using Cox proportional hazards regression models and doubly robust causal modeling. Information on type III endoleaks was available only as free-text mentions in clinical notes, while all-cause mortality data could be extracted using structured data. Device-specific information required by the FDA is ascertained using unique device identifiers (UDIs), which include factors such as model numbers, catalog numbers, and manufacturer-specific product codes. The availability of UDIs in EHRs was assessed. Results: In total, 13â¯941 patients (mean [SD] age, 71.8 [7.4] years) received 1 of the devices of interest (AFX with Strata [AFX-S]: 718 patients [5.2%]; AFX with Duraply [AFX-D]: 404 patients [2.9%]; or AFX2: 682 patients [4.9%]), and 12 137 (87.1%) received non-AFX devices. The UDIs were not recorded in the EHR for any patient with an AFX device, and partial UDIs were available for 19 patients (0.1%) with a non-AFX device. This necessitated the development of advanced natural language processing tools to define the cohort of patients for analysis. The study identified a significantly higher risk of type III endoleaks at 5 years among patients receiving any of the AFX device iterations, including the most recent version, AFX2 (11.6%; 95% CI, 8.1%-15.1%) compared with that among patients with non-AFX devices (5.7%; 95% CI, 2.2%-9.2%; absolute risk difference, 5.9%; 95% CI, 2.3%-9.4%). However, there was no significantly higher all-cause mortality for any of the AFX device iterations, including for AFX2 (19.0%; 95% CI, 16.0%-22.0%) compared with non-AFX devices (18.0%; 95% CI, 15.0%-21.0%; absolute risk difference, 1.0%; 95% CI, -2.1% to 4.1%). Conclusions and Relevance: The findings of this cohort study suggest that clinical data can be used for the postmarketing device surveillance required by the FDA. The study also highlights ongoing challenges to performing larger-scale surveillance, including lack of consistent use of UDIs and insufficient relevant structured data to efficiently capture certain outcomes of interest.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Idoso , Prótese Vascular , Endoleak/etiologia , Correção Endovascular de Aneurisma , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentaçãoRESUMO
OBJECTIVES: The development of medical devices for children faces unique challenges that have contributed to a paucity of devices specifically designed and tested for children. Increased knowledge on research activities for pediatric devices can guide optimal study design and ensure timely dissemination of clinical findings. METHODS: We performed a cross-sectional analysis of interventional studies registered on ClinicalTrials.gov, initiated January 1, 2017, through December 12, 2022, evaluating a Food and Drug Administration-regulated class II or III device, and enrolling any pediatric patients (aged ≤17 years). Data were extracted from ClinicalTrials.gov on study characteristics and from Devices@FDA on device features. For completed studies, we determined whether results were reported in a peer-reviewed publication as of December 27, 2022. RESULTS: Among 482 studies, 406 (84.2%) examined a class II device and 76 (15.8%) a class III device. The most common device types were diabetes-related devices (N = 57, 11.8%) and monitors and measurement devices (N = 39, 8.1%). Most studies were single-center (N = 326, 67.6%), used a nonrandomized (N = 255, 52.9%), open label (N = 350, 72.6%) design, and were funded by academic institutions (N = 278, 57.7%) or industry (N = 142, 29.5%). A total of 291 (60.4%) studies included a primary outcome of only efficacy without safety endpoints. Among completed studies, more than half (N = 64, 51.6%) enrolled <50 participants and 71.0% (N = 88) <100. After median follow-up of 3.0 years, results were available in publications for 27 (21.8%) completed studies. CONCLUSIONS: Our findings serve to inform programs and initiatives seeking to increase pediatric-specific device development. In addition to considerations on ensuring rigorous trial design, greater focus is needed on timely dissemination of results generated in pediatric device studies.
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Projetos de Pesquisa , Criança , Humanos , Estudos Transversais , Estados Unidos , United States Food and Drug Administration , AdolescenteRESUMO
This cross-sectional study assesses declared data sharing in publications for a recent set of pediatric clinical trials funded by the US National Institutes of Health (NIH).
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Disseminação de Informação , National Institutes of Health (U.S.) , Estados Unidos , Humanos , CriançaAssuntos
Legislação de Medicamentos , Neoplasias , Criança , Humanos , Estados Unidos , União Europeia , Neoplasias/terapiaRESUMO
BACKGROUND: Many new molecular entities enter clinical development to evaluate potential therapeutic benefits for oncology patients. We characterized adult and pediatric development of the set of new molecular entities that started clinical testing in 2010-2015 worldwide. METHODS: We extracted data from AdisInsight, an extensive database of global pharmaceutical development, and the FDA.gov website. We followed the cohort of new molecular entities initiating first-in-human phase I clinical trials in 2010-2015 to the end of 2020. For each new molecular entity, we determined whether it was granted US Food and Drug Administration (FDA) approval, studied in a trial open to pediatric enrollment, or stalled during development. We characterized the cumulative incidence of these endpoints using statistical methods for censored data. RESULTS: The 572 new molecular entities starting first-in-human studies in 2010-2015 were studied in 6142 trials by the end of 2020. Most new molecular entities were small molecules (n = 316, 55.2%), antibodies (n = 148, 25.9%), or antibody-drug conjugates (n = 44, 7.7%). After a mean follow-up of 8.0 years, 173 new molecular entities did not advance beyond first-in-human trials, and 39 were approved by the FDA. New molecular entities had a 10.4% estimated probability (95% confidence interval = 6.6% to 14.1%) of being approved by the FDA within 10 years of first-in-human trials. After a median of 4.6 years since start of first-in-human trials, 67 (11.7%) new molecular entities were tested in trials open to pediatric patients, and 5 (0.9%) were approved for pediatric indications. CONCLUSIONS: More efficient clinical development strategies are needed to evaluate new cancer therapies, especially for children, and incorporate approaches to ensure knowledge gain from investigational products that stall in development.
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Neoplasias , Estados Unidos , Humanos , Adulto , Criança , Neoplasias/tratamento farmacológico , Oncologia , Aprovação de Drogas , Desenvolvimento de Medicamentos , United States Food and Drug AdministrationRESUMO
This Viewpoint reviews activities to increase pediatric medical device development, assesses ongoing challenges, and recommends strategies to strengthen pediatric programs.
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Equipamentos Médicos Duráveis , Criança , HumanosRESUMO
INTRODUCTION: Prescription drug monitoring programs are state-run databases designed to support safe prescribing of controlled substances and reduce prescription drug misuse. We analyzed healthcare claims data to determine the association between prescription drug monitoring programs with mandated provider review and adolescent and young adult benzodiazepine prescription dispensing and overdose. METHODS: We performed a state-level retrospective cohort study to evaluate the association between implementation of prescription drug monitoring programs with mandated provider review and benzodiazepine prescription dispensing and benzodiazepine-related overdoses among adolescents (13-18 years) and young adults (19-25 years) between 1 January 2008 and 31 December 2019. Data were obtained from a United States commercial health insurance company. RESULTS: There were 74,539 (1.8%) adolescents and 246,760 (4.0%) young adults with at least one benzodiazepine prescription dispensed. Benzodiazepine overdoses occurred among 1,569 (0.04%) and 3,202 (0.05%) adolescents and young adults, respectively. Implementation of a prescription drug monitoring program with mandated provider review was associated with a 6.8% (95% CI, 1.6-11.8) yearly reduction in benzodiazepine prescription dispensing among adolescents and a 12.5% (95% CI, 9.3-15.5) yearly reduction among young adults. There was no decrease in benzodiazepine overdoses in either age group (-15.4% [95% CI, -21.5 to 3.0] and -8.0% [95% CI, -18.0 to 3.2] yearly change in adolescents and young adults, respectively). DISCUSSION: Consistent with prior work, our study did not find an association between prescription drug monitoring program implementation and reduction in benzodiazepine-related overdoses among adolescents and young adults. However, the substantial reduction in benzodiazepine prescription dispensing is encouraging. CONCLUSION: Prescription drug monitoring programs were associated with decreases in benzodiazepine prescription dispensing, but not benzodiazepine-related overdoses in this cohort of adolescents and young adults. These findings serve to inform development of further policies to address rising rates of benzodiazepine misuse and overdose in this patient population.
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Overdose de Drogas , Programas de Monitoramento de Prescrição de Medicamentos , Humanos , Adolescente , Adulto Jovem , Estados Unidos , Estudos Retrospectivos , Benzodiazepinas , Analgésicos Opioides/uso terapêutico , Overdose de Drogas/epidemiologia , Prescrições de MedicamentosRESUMO
This study examines practices related to trial registration and results submission in ClinicalTrials.gov and publication of pediatric clinical trials funded by the National Institutes of Health.
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Ensaios Clínicos como Assunto , Disseminação de Informação , National Institutes of Health (U.S.) , Criança , Humanos , National Institutes of Health (U.S.)/economia , Sistema de Registros , Estados Unidos , Ensaios Clínicos como Assunto/economiaRESUMO
STUDY OBJECTIVE: Prescription opioid use is associated with substance-related adverse outcomes among adolescents and young adults through a pathway of prescribing, diversion and misuse, and addiction and overdose. Assessing the effect of current prescription drug monitoring programs (PDMPs) on opioid prescribing and overdoses will further inform strategies to reduce opioid-related harms. METHODS: We performed interrupted time series analyses to measure the association between state-level implementation of PDMPs with annual opioid prescribing and opioid-related overdoses in adolescents (13 to 18 years) and young adults (19 to 25 years) between 2008 and 2019. We focused on PDMPs that included mandatory reviews by providers. Data were obtained from a commercial insurance company. RESULTS: Among 9,344,504 adolescents and young adults, 1,405,382 (15.0%) had a dispensed opioid prescription, and 6,262 (0.1%) received treatment for an opioid-related overdose. Mandated PDMP review was associated with a 4.2% (95% CI, 1.9% to 6.4%) reduction in annual opioid dispensations among adolescents and a 7.8% (95% CI, 4.7% to 10.9%) annual reduction among young adults. For opioid-related overdoses, mandated PDMP review was associated with a 16.1% (95% CI, 3.8 to 26.7) and 15.9% (95% CI, 7.6 to 23.4) reduction in annual opioid overdoses for adolescents and young adults, respectively. CONCLUSION: PDMPs were associated with sustained reductions in opioid prescribing and overdoses in adolescents and young adults. Although these findings support the value of mandated PDMPs as part of ongoing strategies to reduce opioid overdoses, further studies with prospective study designs are needed to characterize the effect of these programs fully.