RESUMO
The opioid crisis is a major public health challenge in the United States, killing about 70,000 people in 2020 alone. Long delays and feedbacks between policy actions and their effects on drug-use behavior create dynamic complexity, complicating policy decision-making. In 2017, the National Academies of Sciences, Engineering, and Medicine called for a quantitative systems model to help understand and address this complexity and guide policy decisions. Here, we present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), a dynamic simulation model developed in response to that charge. SOURCE tracks the US population aged ≥12 y through the stages of prescription and illicit opioid (e.g., heroin, illicit fentanyl) misuse and use disorder, addiction treatment, remission, and overdose death. Using data spanning from 1999 to 2020, we highlight how risks of drug use initiation and overdose have evolved in response to essential endogenous feedback mechanisms, including: 1) social influence on drug use initiation and escalation among people who use opioids; 2) risk perception and response based on overdose mortality, influencing potential new initiates; and 3) capacity limits on treatment engagement; as well as other drivers, such as 4) supply-side changes in prescription opioid and heroin availability; and 5) the competing influences of illicit fentanyl and overdose death prevention efforts. Our estimates yield a more nuanced understanding of the historical trajectory of the crisis, providing a basis for projecting future scenarios and informing policy planning.
Assuntos
Overdose de Drogas , Modelos Teóricos , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides , Formulação de Políticas , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Política de Saúde , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Saúde Pública , Risco , Estados Unidos/epidemiologiaRESUMO
The United States FDA has received over 800 botanical investigational new drug applications (IND) and pre-IND meeting requests (PIND) in the years preceding 2018. The current data show that indications for submitted INDs cover nearly every review division of the FDA. Despite increasing global interest in the investigation of botanical mixtures as drug products, only two botanical new drug applications (NDA) have been approved in the U.S.: Veregen in 2006 and Fulyzaq (also known as Mytesi) in 2012. Given botanicals' chemical and biological complexity, efforts in characterizing their pharmacology, demonstrating therapeutic efficacy, and ensuring quality consistency remain scientific and regulatory challenges. The FDA published a revised Botanical Drug Development Guidance for Industry document in December 2016 to address developmental considerations for late-phase trials and to provide recommendations intended to facilitate botanical drug development. Herein, we present an analysis of botanical INDs showing their variety of botanical raw materials (e.g., coming from different geographic regions, single vs multiple herbs), the varied levels of previous human experience, and therapeutic areas, as well as provide an overview of experience and challenges in reviewing botanical drugs.
Assuntos
Aplicação de Novas Drogas em Teste , Proantocianidinas/química , Humanos , Estrutura Molecular , Preparações Farmacêuticas , Estados UnidosAssuntos
Transtornos Relacionados ao Uso de Opioides/terapia , Farmacovigilância , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , United States Food and Drug Administration , Aminas/uso terapêutico , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Uso de Medicamentos/tendências , Gabapentina , Humanos , Loperamida/efeitos adversos , Loperamida/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Padrões de Prática Médica/tendências , Medicamentos sob Prescrição/uso terapêutico , Alcaloides de Triptamina e Secologanina/uso terapêutico , Estados Unidos , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
OBJECTIVE: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. PATIENTS AND METHODS: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. RESULTS: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. CONCLUSIONS: For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing.
Assuntos
Angina Pectoris/tratamento farmacológico , Segurança do Paciente , Placebos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/efeitos adversos , Acetanilidas/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Angina Instável/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Aprovação de Drogas , Inibidores Enzimáticos/uso terapêutico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Prontuários Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Nitratos/uso terapêutico , Variações Dependentes do Observador , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Piperazinas/uso terapêutico , Ranolazina , Medição de Risco/métodos , Fatores de Risco , Falha de TratamentoRESUMO
Significant changes have occurred in the policy landscape surrounding cannabis legalization, production, and use around the globe and across the United States. With widespread availability of novel cannabis and cannabis-based products, there is an urgent need to understand their safety and effectiveness for medical indications. Three primary barriers contribute to the difficulty in initiating research geared toward answering the most pressing public health questions: the US regulatory status of cannabis and cannabinoids, sources for cannabis and cannabinoid study medications, and limited funding and resources to support studies. Despite these hurdles, research is rapidly increasing, and recent changes in the United States have paved the way for exciting new work. Here, challenges and barriers to cannabis and cannabinoid research are described from the perspectives of the National Institute on Drug Abuse, National Institutes of Health; the US Food and Drug Administration; and 2 clinical researchers. Barriers specifically to studying cannabis, cannabinoids, and cancer are emphasized.
Assuntos
Canabinoides , Cannabis , Alucinógenos , Analgésicos , Canabinoides/efeitos adversos , Humanos , Legislação de Medicamentos , Estados Unidos/epidemiologiaRESUMO
Our nation's ongoing prescription opioid abuse crisis, amounting to over 78 billion dollars in health and social costs annually,1 is a critical priority for the US Food and Drug Administration (FDA). As a part of our mission to support the safe and effective use of prescription medicines, the FDA is taking a fresh look at potential scientific and regulatory actions we can take to address this crisis.
Assuntos
Analgésicos Opioides/uso terapêutico , Controle de Medicamentos e Entorpecentes/organização & administração , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico , Medicamentos sob Prescrição/normas , United States Food and Drug Administration/organização & administração , Descoberta de Drogas/organização & administração , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Humanos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/terapia , Manejo da Dor/métodos , Medição de Risco , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normasRESUMO
The FDA's "abstinence" outcome measure for approval of new medications to treat opioid-use disorders has been difficult to achieve; developing and validating alternative meaningful outcomes could facilitate drug development.
Assuntos
Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Aprovação de Drogas/estatística & dados numéricos , Desenvolvimento de Medicamentos/estatística & dados numéricos , Humanos , Estados Unidos , United States Food and Drug AdministrationAssuntos
Analgésicos Opioides/efeitos adversos , Órgãos Governamentais , Pulmão/efeitos dos fármacos , Contramedidas Médicas , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides/complicações , Insuficiência Respiratória/terapia , Comportamento Cooperativo , Humanos , Comunicação Interdisciplinar , Pulmão/fisiopatologia , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Epidemia de Opioides/mortalidade , Transtornos Relacionados ao Uso de Opioides/mortalidade , Prognóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and Drug Administration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and Drug Administration of anticipated shortages. This notification requirement has allowed the Food and Drug Administration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and Drug Administration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and Drug Administration, and communication with all stakeholders is essential.
Assuntos
Soluções para Diálise/provisão & distribuição , Indústria Farmacêutica/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Diálise Peritoneal/métodos , Estoque Estratégico/organização & administração , United States Food and Drug Administration , Comportamento Cooperativo , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Fatores de Tempo , Estados UnidosAssuntos
Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Acessibilidade aos Serviços de Saúde , Manejo da Dor , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Humanos , Estados Unidos , United States Food and Drug AdministrationAssuntos
Analgésicos Opioides , Combinação de Medicamentos , Prescrições de Medicamentos/normas , Hidrocodona , Legislação de Medicamentos , Padrões de Prática Médica/tendências , Medicamentos sob Prescrição , Analgésicos Opioides/uso terapêutico , Humanos , Hidrocodona/uso terapêutico , Modelos Lineares , Padrões de Prática Médica/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Atenção Primária à Saúde/estatística & dados numéricos , Atenção Primária à Saúde/tendências , Estados UnidosRESUMO
The requirement to establish safety of drugs prior to marketing has been in place since 1938 by the US Food, Drug and Cosmetic Act and is by no means a new concept. The efficacy regulations were enacted in 1962 via the Kefauver-Harris Amendment and the drug approval process has evolved thereafter. The assessment of safety and efficacy of drug products is made by pharmaceutical companies during drug development, which then goes through a regulatory review by the US FDA for the determination of market approval or nonapproval. The drug development and regulatory approval processes have endured close ongoing scrutiny by regulatory bodies, the public, US Congress and academic and private organizations and, as a result, have ensured continual refinement. Over the years, evidence has been emerging on varied drug responses in subgroup populations, and the underlying biology associated with age, race and sex as demographic variables have been examined. The resulting growing knowledge of disease burden, treatment response and disparate outcomes has generated opportunities to streamline and improve treatment outcomes in these populations. This article discusses the historical context of women's participation in clinical drug trials submitted to the FDA for regulatory review and approval purposes. The inadvertent consequences of women's exclusion or inadequate representation in past clinical trials and the evidentiary basis for understanding sex differences are also evaluated. Advances in the US regulatory processes to address treatment outcomes that are tied to the topic of this paper, specifically, adverse drug effects in women, are also discussed.
Assuntos
Descoberta de Drogas/legislação & jurisprudência , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Políticas , Caracteres Sexuais , United States Food and Drug Administration/legislação & jurisprudência , Animais , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/métodos , Descoberta de Drogas/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Estados Unidos , United States Food and Drug Administration/tendênciasRESUMO
The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.