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3.
Clin Pharmacol Ther ; 107(4): 886-902, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31863452

RESUMO

Clinical translation of drug-drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and link them to clinical consequences. Consequently, we developed information retrieval (IR) models to retrieve DDI and drug-gene interaction (DGI) evidence from 25 million PubMed abstracts and distinguish DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for US Food and Drug Administration (FDA) approved and withdrawn drugs. Additionally, information extraction models were developed to extract DDI-pairs and DGI-pairs from the IR-retrieved abstracts. An overlapping analysis identified 986 unique DDI-pairs between all 3 types of evidence. Another 2,157 and 13,012 DDI-pairs and 3,173 DGI-pairs were identified from known clinical PK/PD DDI, clinical PD DDI, and DGI evidence, respectively. By integrating DDI and DGI evidence, we discovered 119 and 18 new pharmacogenetic hypotheses associated with CYP3A and CYP2D6, respectively. Some of these DGI evidence can also aid us in understanding DDI mechanisms.


Assuntos
Mineração de Dados/métodos , Interações Medicamentosas/fisiologia , Descoberta do Conhecimento/métodos , Farmacogenética/métodos , Pesquisa Médica Translacional/métodos , United States Food and Drug Administration , Mineração de Dados/tendências , Humanos , Farmacogenética/tendências , Pesquisa Médica Translacional/tendências , Estados Unidos , United States Food and Drug Administration/tendências
5.
Nat Rev Endocrinol ; 15(6): 366-374, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842650

RESUMO

Five years ago, an ambitious collaboration, the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA; henceforth CLARITY), was launched by three US agencies. The goal was to provide a definitive evaluation of bisphenol A (BPA) and explain disparities between traditional regulatory studies and findings from independent investigators. BPA or vehicle-treated rats from an FDA facility were used in a guideline study and animals and/or tissues were provided to academic researchers for analysis. An interim summary released in February 2018 by the FDA concluded that currently authorized uses of BPA continue to be safe. We disagree. In this Perspectives, we summarize the goals, design and problems of CLARITY. We conclude that, despite its flaws, CLARITY provides important insight and, taken together, the data provide compelling evidence that low-dose BPA exposure induces marked adverse effects. Indeed, the greatest number of effects were observed at doses 20,000 times lower than the current 'safe' dose of BPA for humans.


Assuntos
Disruptores Endócrinos/toxicidade , Testes de Toxicidade/métodos , United States Food and Drug Administration/legislação & jurisprudência , Animais , Compostos Benzidrílicos/toxicidade , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Humanos , Fenóis/toxicidade , Testes de Toxicidade/tendências , Estados Unidos , United States Food and Drug Administration/tendências
7.
Reg Anesth Pain Med ; 44(1): 100-106, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640660

RESUMO

BACKGROUND AND OBJECTIVES: Dorsal root ganglion stimulation is an emerging therapy in the treatment of chronic pain. Compared with traditional spinal cord stimulation, it allows a discretely targeted stimulation profile and may act via differing mechanisms of action. Despite these advantages, little is known about the complications associated with this new modality. METHODS: We queried the MAUDE (Manufacturer and User Facility Device Experience) database for all entries named 'Dorsal root ganglion stimulator for pain relief' reported between May 1, 2016 and December 31, 2017. We verified these data through the Office of the Freedom of Information Act at the US Food and Drug Administration. We then eliminated duplicate entries and categorized each complication based on the event description. A secondary analysis was performed to characterize the serious adverse events and the severity of new neurologic symptoms and infections. RESULTS: We identified 979 unique episodes following our process of deduplication. Almost half (47%) of entries were categorized as device-related complications, a quarter (28%) as procedural complications, with the remainder as patient complaints (12%), serious adverse events (2.4%), and 'other' complications (4.6%). The majority of complications were managed surgically with revision (n = 488; 49.8%) rather than explant (n = 161; 16.4%) events, respectively. CONCLUSIONS: The 'Dorsal root ganglion stimulator for pain relief' device has been publicized as a breakthrough in neuromodulation technologies. As with any new technology, we must proceed with caution and re-evaluate effectiveness as information becomes available. The MAUDE database has provided safety data unique for this device that will aid in informed consent and further refinement of this innovative therapy.


Assuntos
Bases de Dados Factuais , Gânglios Espinais , Manejo da Dor/métodos , Estimulação da Medula Espinal/métodos , United States Food and Drug Administration , Bases de Dados Factuais/tendências , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/etiologia , Gânglios Espinais/fisiologia , Humanos , Dor/diagnóstico , Dor/etiologia , Manejo da Dor/efeitos adversos , Estudos Retrospectivos , Estimulação da Medula Espinal/efeitos adversos , Estados Unidos/epidemiologia , United States Food and Drug Administration/tendências
9.
Nicotine Tob Res ; 21(7): 991-995, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29401309

RESUMO

The Food and Drug Administration has announced the potential for mandated lowering of nicotine levels in combustible cigarettes. The World Health Organization has recommended a lowering of cigarette filler nicotine levels to below 0.4 mg/g. To devise appropriate nicotine control strategies, regulators must consider technical feasibility, timelines for compliance, and potential impediments to implementation. Outlined here is previously unsummarized information on genetic approaches that might be used to reduce nicotine levels in cured tobacco leaves. For the benefit of regulators, altered alkaloid or toxicant profiles that might result by implementation of some of these methodologies are discussed. Also mentioned are potential licensing or regulatory impediments to use of some of the technologies per se. Implications: An understanding of technical feasibility of plant-based nicotine reduction technologies, along with the potential for corresponding alterations in alkaloid or toxicant profiles, is needed by regulators to develop effective nicotine control strategies with minimal impediments or undesirable consequences.


Assuntos
Alcaloides/efeitos adversos , Nicotina/efeitos adversos , Produtos do Tabaco/efeitos adversos , United States Food and Drug Administration , Organização Mundial da Saúde , Alcaloides/genética , Engenharia Genética/métodos , Engenharia Genética/tendências , Humanos , Nicotina/genética , Estados Unidos , United States Food and Drug Administration/tendências
11.
Nicotine Tob Res ; 21(7): 979-984, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30165494

RESUMO

INTRODUCTION: Research on electronic cigarette (e-cigarette) warnings has primarily focused on addiction warnings, such as the one soon to be required by the Food and Drug Administration (FDA) in the United States. However, reduced-risk warnings, similar to the warnings recently proposed for smokeless tobacco products, remain a future possibility for e-cigarettes. Thus, this brief report compares e-cigarette health risk perceptions based on reduced-risk warnings and the FDA addiction risk warning, and considers whether these warnings differ in believability, ease of comprehension, and perceptions about the clarity of risk communication. METHODS: A quota sample of 672 smokers, e-cigarette users, dual users, and nonusers participated in this between-subjects experiment. Study participants were randomly assigned to one of three warning conditions, including the FDA-mandated addiction warning and two reduced-risk warnings. After exposure to the warning statement, participants responded to measures of health risk perceptions, believability, ease of comprehension, and perception about the clarity of risk communication. RESULTS: Results reveal that the addiction warning is perceived as more believable, easier to comprehend, and more clearly communicating the health risks of e-cigarettes use compared with the reduced-risk warnings. In addition, overall health risk perceptions and addiction risk perceptions based on the addiction warning are greater than health risk perceptions based on the reduced-risk warnings. In contrast, specific disease-related risk perceptions such as cancer, heart disease, lung disease, and harm to an unborn baby are greater for the reduced-risk warnings. CONCLUSIONS: This study provides a comparison of the forthcoming FDA-mandated e-cigarette addiction warning and reduced-risk warnings that have begun to be considered in the literature on a number of critical outcomes. IMPLICATIONS: This research provides a greater understanding of how variations of e-cigarette warnings, including addiction and reduced-risk warnings, are perceived by smokers, e-cigarette users, dual users, and nonusers. Specifically, findings show that overall health risk perceptions and addiction risk perceptions based on the addiction warning are greater than risk perceptions based on the reduced-risk warnings. In contrast, specific disease-related risk perceptions, such as cancer and heart disease, are greater for the reduced-risk warnings.


Assuntos
Comportamento Aditivo/psicologia , Sistemas Eletrônicos de Liberação de Nicotina , Rotulagem de Produtos/tendências , Comportamento de Redução do Risco , Fumantes/psicologia , United States Food and Drug Administration/tendências , Adulto , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/prevenção & controle , Feminino , Humanos , Masculino , Rotulagem de Produtos/métodos , Tabaco sem Fumaça , Estados Unidos/epidemiologia
12.
Clin Pharmacol Ther ; 105(1): 92-100, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415479

RESUMO

In 2010, Congress created an abbreviated application pathway for biosimilars, versions of approved biologics made by different manufacturers. However, as of November 1, 2018, the US Food and Drug Administration (FDA) had approved only 13 biosimilars under this pathway, of which just 6 were available for patients to use. We review the history of US regulation of biologics and identify manufacturing, regulatory, and marketing issues that have limited biosimilar market entry and uptake, concluding with recommendations for reform.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Aprovação de Drogas/métodos , Indústria Farmacêutica/métodos , United States Food and Drug Administration , Medicamentos Biossimilares/química , Indústria Farmacêutica/tendências , Humanos , Medicamentos sob Prescrição/química , Medicamentos sob Prescrição/uso terapêutico , Estados Unidos , United States Food and Drug Administration/tendências
13.
15.
Drug Saf ; 41(12): 1397-1410, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30167992

RESUMO

INTRODUCTION: Adverse drug reactions (ADRs) are associated with significant health-related and financial burden, and multiple sources are currently utilized to actively discover them. Social media has been proposed as a potential resource for monitoring ADRs, but drug-specific analytical studies comparing social media with other sources are scarce. OBJECTIVES: Our objective was to develop methods to compare ADRs mentioned in social media with those in traditional sources: the US FDA Adverse Event Reporting System (FAERS), drug information databases (DIDs), and systematic reviews. METHODS: A total of 10,188 tweets mentioning adalimumab collected between June 2014 and August 2016 were included. ADRs in the corpus were extracted semi-automatically and manually mapped to standardized concepts in the Unified Medical Language System. ADRs were grouped into 16 biologic categories for comparisons. Frequencies, relative frequencies, disproportionality analyses, and rank ordering were used as metrics. RESULTS: There was moderate agreement between ADRs in social media and traditional sources. "Local and injection site reactions" was the top ADR in Twitter, DIDs, and systematic reviews by frequency, ranked frequency, and index ranking. The next highest ADR in Twitter-fatigue-ranked fifth and seventh in FAERS and DIDs. CONCLUSION: Social media posts often express mild and symptomatic ADRs, but rates are measured differently in scientific sources. ADRs in FAERS are reported as absolute numbers, in DIDs as percentages, and in systematic reviews as percentages, risk ratios, or other metrics, which makes comparisons challenging; however, overlap is substantial. Social media analysis facilitates open-ended investigation of patient perspectives and may reveal concepts (e.g. anxiety) not available in traditional sources.


Assuntos
Adalimumab/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Bases de Dados de Produtos Farmacêuticos/normas , Estudo de Prova de Conceito , Mídias Sociais/normas , United States Food and Drug Administration/normas , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Anti-Inflamatórios/efeitos adversos , Bases de Dados de Produtos Farmacêuticos/tendências , Humanos , Mídias Sociais/tendências , Revisões Sistemáticas como Assunto , Estados Unidos/epidemiologia , United States Food and Drug Administration/tendências
16.
Curr Opin Crit Care ; 24(5): 379-384, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30156568

RESUMO

PURPOSE OF REVIEW: Regulatory guidance for design, conduct and analysis of studies of nosocomial pneumonia, including ventilator-associated pneumonia, has undergone substantial evolution over the past three decades. This review summarizes this evolutionary process and the current status of guidance. RECENT FINDINGS: The US Food and Drug Administration and the European Medicines Agency have taken different approaches to defining endpoints for studies of nosocomial pneumonia, especially with regard to the primary endpoint. Both agencies accept a noninferiority design. Independent efforts to develop new endpoints and bridge existing discordances have been fruitful. SUMMARY: Transatlantic differences in the approach to study of nosocomial pneumonia complicate study design and analysis, but they will hopefully be resolved in future iterations of regulatory agency guidance.


Assuntos
Pneumonia Associada a Assistência à Saúde , United States Food and Drug Administration/estatística & dados numéricos , Análise de Variância , Europa (Continente) , Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto , Estados Unidos , United States Food and Drug Administration/tendências
17.
PLoS Negl Trop Dis ; 12(8): e0006695, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30092022

RESUMO

Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Descoberta de Drogas/legislação & jurisprudência , Descoberta de Drogas/tendências , Indústria Farmacêutica/tendências , Medicina Tropical , United States Food and Drug Administration/legislação & jurisprudência , Humanos , Estados Unidos , United States Food and Drug Administration/tendências
18.
Nicotine Tob Res ; 20(8): 940-948, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986104

RESUMO

Introduction: In 2011 the US Food and Drug Administration launched the Population Assessment of Tobacco and Health (PATH) Study to gather information for regulatory activities authorized by the Family Smoking Prevention and Tobacco Control Act (TCA). Methods: Data were drawn from the first wave of the PATH survey, involving interviews of 32 320 civilian and non-institutionalized adults. In addition to conventional classifications for current, former and never smoking and e-cigarette use, we used PATH questions to classify former and current triers of these products. Descriptive statistics were used to describe the prevalence, patterns of, and reasons for e-cigarette use, and the perceptions of nicotine and e-cigarettes among user groups, according to smoking status. Results: The prevalence of current smoking was 18%; an additional 3.1% of participants were current triers. The prevalence of current e-cigarette use was 2.4% (1.0% every day, 1.4% some days), with another 3.2% as current triers. The majority of nonsmokers who were current e-cigarette users were already current (56%) or former (34%) cigarette triers. Reasons for e-cigarette use were similar across subgroups, but patterns of use were different. Majorities of participants believed that nicotine is the main substance driving tobacco use, that nicotine causes most cancers, and that e-cigarettes were less harmful than cigarettes. Conclusions: E-cigarettes were used primarily by current smokers and recent former smokers. The main reasons for use center around perceptions that e-cigarettes are less harmful than cigarettes to users and others. Implications: This study reports detailed information about the prevalence, patterns of, and reasons for e-cigarette use in the first (baseline) wave of the PATH Study in 2014. In addition to conventional categories for current, former and never smoking and e-cigarette use, the PATH questionnaire facilitated classification of new usage groups consisting of current and former triers of these products, which may impact prevalence estimates.


Assuntos
Inquéritos Epidemiológicos/tendências , Vigilância da População , Vaping/epidemiologia , Vaping/tendências , Adulto , Fumar Cigarros/epidemiologia , Fumar Cigarros/terapia , Fumar Cigarros/tendências , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Vigilância da População/métodos , Prevalência , Prevenção do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar/tendências , Estados Unidos/epidemiologia , United States Food and Drug Administration/tendências , Vaping/terapia , Adulto Jovem
19.
J Am Assoc Nurse Pract ; 30(6): 312-319, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29878963

RESUMO

BACKGROUND AND PURPOSE: In 2013, the Advisory Committee of the Food and Drug Administration determined hydrocodone combination medications (HCMs) needed tighter regulation due to high abuse potential; they recommended upscheduling HCMs from Schedule III to II. The purpose of this study was to examine the effect of upscheduling of HCMs on pain management practices of advanced practiced registered nurses (APRNs) in Oklahoma. METHODS: In this qualitative study, 25 participants described their primary care experiences after the upscheduling. A thematic analysis was used to understand the effects on APRN pain management practices. CONCLUSIONS: The upscheduling of HCMs has greatly affected the pain management practices of APRNs in a state where Schedule II narcotic prescribing is forbidden. Findings will assist APRNs with improving patient access to care, implementing practice regulations, and exploring options for alternative pain therapies in primary care. IMPLICATIONS FOR PRACTICE: Upscheduling of HCMs has had a severe impact on APRNs, affecting their prescribing practices and leading to increased referrals. They noted limited treatment options, increased health care costs, and decreased access to care. The APRNs understand the problem of prescription opioid abuse, diversion, and misuse. A consensus model could standardize the regulatory process for APRNs, increase interstate mobility for practice, and increase access to APRN care nationwide.


Assuntos
Hidrocodona/classificação , Profissionais de Enfermagem/psicologia , Manejo da Dor/tendências , Padrões de Prática Médica/normas , Prática Avançada de Enfermagem/métodos , Analgésicos Opioides/classificação , Analgésicos Opioides/uso terapêutico , Humanos , Hidrocodona/uso terapêutico , Entrevistas como Assunto/métodos , Profissionais de Enfermagem/legislação & jurisprudência , Profissionais de Enfermagem/normas , Manejo da Dor/métodos , Padrões de Prática Médica/tendências , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Substâncias/enfermagem , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Estados Unidos , United States Food and Drug Administration/organização & administração , United States Food and Drug Administration/tendências
20.
Prev Med ; 113: 153-155, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29866276

RESUMO

In July 2017, the Food and Drug Administration (FDA) announced that it wants to reduce the nicotine in cigarettes to make them less addictive. Also, it is delaying for several years a key regulation affecting cigars and e-cigarettes, including flavored vaping products that tend to appeal to younger consumers. Specifically, it postponed the requirement that such products be approved by the agency. Both actions are part of a comprehensive plan to eventually wean smokers off conventional cigarettes and steer them toward less harmful alternative forms of nicotine. With its new approach to the fight against smoking, the FDA has unquestionably made great strides toward more effectively addressing the prevalence of related deaths and diseases in the U.S. However, much important work must be undertaken before this ultimate goal can be accomplished. For instance, further research into long-term effects of e-cigarettes must be conducted before these products can truly be seen as safer alternatives to combustible cigarettes. Additionally, public education is necessary to inform smokers about the range of tobacco products available and the actual harms associated with their use. Finally, the agency might have to work alongside the powerful tobacco industry to minimize potential legal challenges and to convince businesses that a shift to low-nicotine products and e-cigarettes is best for their future success and for the health of the American citizenry.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Redução do Dano , Produtos do Tabaco/legislação & jurisprudência , United States Food and Drug Administration/legislação & jurisprudência , Comportamento Aditivo , Humanos , Nicotina/análise , Saúde Pública , Prevenção do Hábito de Fumar , Dispositivos para o Abandono do Uso de Tabaco , Estados Unidos , United States Food and Drug Administration/tendências
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