RESUMO
Investment, collaboration, and coordination have been key.
Assuntos
Pesquisa Biomédica , COVID-19 , Humanos , Pesquisa Biomédica/economia , Pesquisa Biomédica/tendências , COVID-19/prevenção & controle , COVID-19/terapia , National Institutes of Health (U.S.) , Investimentos em Saúde , Cooperação Internacional , Vacinas contra COVID-19 , Ensaios Clínicos como AssuntoRESUMO
This Viewpoint discusses the benefits of streamlined point-of-care trial designs in clinical research, using lessons learned from the UK RECOVERY study of dexamethasone dosing for patients with COVID-19 and hypoxia.
Assuntos
Ensaios Clínicos como Assunto , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Reino Unido , Projetos de PesquisaRESUMO
As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti-SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti-SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.
Assuntos
Anticorpos Monoclonais/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , SARS-CoV-2/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , COVID-19/imunologia , Humanos , Imunização Passiva/efeitos adversos , National Institutes of Health (U.S.) , Estados Unidos , United States Food and Drug Administration , Soroterapia para COVID-19Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Etnicidade/classificação , Preparações Farmacêuticas , Grupos Raciais/classificação , Produtos Biológicos/uso terapêutico , Tratamento Farmacológico , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Grupos Raciais/estatística & dados numéricos , Estados Unidos/etnologia , United States Food and Drug AdministrationAssuntos
Política Nutricional , Sódio na Dieta , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Política Nutricional/legislação & jurisprudência , Sódio na Dieta/administração & dosagem , Sódio na Dieta/normas , Estados Unidos , Adulto JovemRESUMO
A 2001 U.S. Government Accountability Office (GAO) report indicated 8 of 10 drugs withdrawn from the U.S. market between 1997 and 2000 posed greater risk to women than men. We examined drugs withdrawn from the market for safety-related reasons from January 1, 2001, to January 1, 2018. To be included, drugs must be listed as discontinued on Drugs@FDA and either listed in the Federal Register or cited in literature as being withdrawn for safety-related reasons. Biologics, over-the-counter products, and medical devices were excluded. During the 17-year time span, 19 drugs were withdrawn from the market for safety-related reasons, fewer drugs per year compared to the 3-year period examined in the GAO report. Food and Drug Administration (FDA) has not recommended the market removal of any drug approved since 2005 due to the time from the start of the Q wave to the end of the T wave (QT) interval prolongation resulting in torsades de pointes (TdP) or other abnormal heart rhythms. Furthermore, no drugs approved after the implementation of FDA's 2009 guidance on drug-induced liver injury (DILI) have been withdrawn because of hepatoxicity. All, but one of the drugs discontinued from the market for safety-related reasons during the period examined were approved between 1957 and 2002. TdP and DILI are two relevant examples of drug-induced adverse events posing greater risk to women than men. FDA has made measurable progress incorporating consideration of sex and gender differences into drug trial development and FDA review of these data, supporting inclusion of women in clinical trials, providing a comprehensive drug safety review, and advancing postmarket surveillance and risk assessment, thus strengthening FDA's ability to protect public health.
Assuntos
Preparações Farmacêuticas , Feminino , Humanos , Masculino , Medicamentos sem Prescrição , Responsabilidade Social , Estados Unidos , United States Food and Drug AdministrationRESUMO
Recruiting and retaining diverse populations in clinical research is critically important. Over the years, we have seen improvements in the representation of women in clinical trials submitted in FDA marketing applications, and we are encouraged by the potential for new strategies to further their representation.
Assuntos
Marketing , Feminino , HumanosRESUMO
In response to a rapid increase in drug development activity during the past two decades, the Food and Drug Administration's Center for Drug Evaluation and Research launched a multi-year effort in 2017 to modernize the program by which new drug products are regulated, known as the New Drugs Regulatory Program. Following a detailed analysis of FDA activities in new drug development, premarket review, and postmarket monitoring, the Office of New Drugs was restructured to therapeutically align its clinical offices and to add new cross-functional offices for regulatory support. An interdisciplinary review process for new drug and biologics applications was rolled out to reduce redundancy and produce review documents that effectively communicate the scientific basis for the regulatory decision. The investigational new drug (IND) review process was also streamlined. During the next 2 years, the modernization initiative will seek to attract and retain new scientific and regulatory staff, improve postmarket safety monitoring, increase efficiency of drug review via technology-enabled workflows, and standardize the capture and use of scientific data to inform future regulatory decisions. The modernization effort will position the New Drugs Regulatory Program to continually improve and adapt to innovations in science, technology, and drug development.
Assuntos
Produtos Biológicos , Preparações Farmacêuticas , Avaliação de Medicamentos , Drogas em Investigação , Humanos , Estados Unidos , United States Food and Drug AdministrationAssuntos
Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/tratamento farmacológico , Aprovação de Drogas , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticoagulantes/uso terapêutico , Antivirais/efeitos adversos , Biomarcadores , COVID-19 , Vacinas contra COVID-19 , Participação da Comunidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Avaliação de Medicamentos , Indústria Farmacêutica , Humanos , Imunomodulação , Cooperação Internacional , Pandemias/prevenção & controle , Plasma , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration , Carga Viral/efeitos dos fármacos , Vacinas Virais , Tratamento Farmacológico da COVID-19Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Pesquisa Biomédica/normas , COVID-19 , Aprovação de Drogas , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/uso terapêutico , Parcerias Público-Privadas , SARS-CoV-2 , Estados Unidos , United States Department of Defense , United States Dept. of Health and Human Services , United States Food and Drug AdministrationRESUMO
This work summarizes the benefit and risk of the results of clinical trials submitted to the US Food and Drug Administration of therapies for the treatment of non-small cell lung cancer (NSCLC) using number needed to benefit (NNB) and number needed to harm (NNH) metrics. NNB and NNH metrics have been reported as potentially being more patient centric and more intuitive to medical practitioners than more common metrics, such as the hazard ratio, and valuable to medical practitioners in complementing other metrics, such as the median time to event. This approach involved the characterization of efficacy and safety results in terms of NNB and NNH of 30 clinical trials in advanced NSCLC supporting US Food and Drug Administration approval decisions from 2003 to 2017. We assessed trends of NNB over time of treatment (eg, for programmed death 1 inhibitors) and variation of NNB across subpopulations (eg, characterized by epidermal growth factor receptor mutation, programmed death ligand 1 expression, Eastern Cooperative Oncology Group performance status, age, and extent of disease progression). Furthermore, the evolution of NNB of treatments for advanced NSCLC was charted from 2003 to 2017. Across subpopulations, NNB, on average, was 4 patients for approved targeted therapies in molecularly enriched populations, 11 patients for approved therapies in nonmolecularly enriched populations, and 23 patients for withdrawn or unapproved therapies. Furthermore, the NNB analysis showed variation for attributes of epidermal growth factor receptor mutations, level of programmed death 1 expression, Eastern Cooperative Oncology Group performance status, etc. When considering the best-case subpopulations and available drugs, the NNB frontier reduced from an estimated value of 7.7 in 2003 to an estimated value of 2.5 in 2017 at the estimated median overall survival-equal to 6 months-of an untreated patient.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Assistência Centrada no PacienteRESUMO
Importance: Health care practitioners and patients must have information to support their confidence in the quality of prescription pharmaceuticals. Objective: To determine whether there were clear and substantive differences in major quality attributes between difficult-to-make solid oral dosage form pharmaceutical products marketed in the US. Design, Setting, and Participants: This quality improvement study analyzed US Food and Drug Administration-collected samples of 252 drug products marketed in the US and manufactured in the US, Canada, Europe, India, and the rest of Asia. These drug products were immediate-release solid oral dosage forms considered difficult to make on the basis of product quality history. This sampling included 35 innovator and 217 generic drug samples manufactured by 46 different firms containing 17 different active ingredients. Statistical analysis was performed from February to November 2019. Main Outcomes and Measures: All products were tested within their shelf life on the basis of the legally recognized tests of the US Pharmacopeia for the major quality attributes of dosage unit uniformity and dissolution. These tests measure dosage consistency and drug release, respectively. The consistency of either attribute was used to calculate a process performance index to describe the variability in manufacturing. Results: All 252 drug product samples met the US market standards for dosage unit uniformity and dissolution, although the process performance index (Ppk) for dissolution fell below the level of 4-sigma capability (ie, <1 error per 1600) for 11 different manufacturers and for generics in 4 of 5 regions, including the US. As part of a retrospective analysis, manufacturers performing above the median Ppk for either dissolution or dosage unit uniformity submitted fewer product quality defect reports (mean field alert reports of 0.22 and 0.63, respectively) than those falling at or below the median Ppk for these attributes (mean field alert reports of 2.1 and 1.7, respectively). Conclusions and Relevance: All samples met the US market standards for dosage unit uniformity and dissolution, indicating acceptability for use by patients regardless of manufacturer or region. To our knowledge, this is the largest sampling study of pharmaceutical manufacturers for the US market and these data provide objective insight into the quality of prescription drugs with high manufacturing risks.
Assuntos
Preparações Farmacêuticas/análise , Preparações Farmacêuticas/normas , Cápsulas/análise , Cápsulas/normas , Medicamentos Genéricos/análise , Medicamentos Genéricos/normas , Controle de Qualidade , Melhoria de Qualidade , Comprimidos/análise , Comprimidos/normas , Estados UnidosRESUMO
BACKGROUND: The opioid crisis highlights the need to increase access to naloxone, possibly through regulatory approval for over-the-counter sales. To address industry-perceived barriers to such access, the Food and Drug Administration (FDA) developed a model drug facts label for such sales to assess whether consumers understood the key statements for safe and effective use. METHODS: In this label-comprehension study, we conducted individual structured interviews with 710 adults and adolescents, including 430 adults who use opioids and their family and friends. Eight primary end points were developed to assess user comprehension of each of the key steps in the label. Each of these end points included a prespecified target threshold ranging from 80 to 90% that was evaluated through a comparison of the lower boundary of the 95% exact confidence interval. RESULTS: The results for performance on six primary end points met or exceeded thresholds, including the steps "Check for a suspected overdose" (threshold, 85%; point estimate [PE], 95.8%; 95% confidence interval [CI], 94.0 to 97.1) and "Give the first dose" (threshold, 85%; PE, 98.2%; 95% CI, 96.9 to 99.0). The lower boundaries for four other primary end points ranged from 88.8 to 94.0%. One exception was comprehension of "Call 911 immediately," but this instruction closely approximated the target of 90% (PE, 90.3%; 95% CI, 87.9 to 92.4). Another exception was comprehension of the composite step of "Check, give, and call 911 immediately" (threshold, 85%; PE, 81.1%; 95% CI, 78.0 to 83.9). CONCLUSIONS: Consumers met thresholds for sufficient understanding of six of eight components of the instructions in the drug facts label for naloxone use and came close on two others. Overall, the FDA found that the model label was adequate for use in the development of a naloxone product intended for over-the-counter sales.
Assuntos
Analgésicos Opioides/intoxicação , Compreensão , Rotulagem de Medicamentos , Overdose de Drogas/tratamento farmacológico , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Adolescente , Adulto , Rotulagem de Medicamentos/legislação & jurisprudência , Overdose de Drogas/terapia , Regulamentação Governamental , Humanos , Entrevistas como Assunto , Estados Unidos , United States Food and Drug AdministrationRESUMO
Drug regulators such as the US Food and Drug Administration (FDA) make decisions about drug approvals based on benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision making about new drugs to treat renal cell carcinoma (RCC). Fifteen FDA decisions on RCC drugs based on clinical trials whose results were published from 2005 to 2018 were identified and analyzed. The benefits and risks of the new drug in each clinical trial were quantified relative to comparators (typically the control arm of the same clinical trial) to estimate whether the benefit-risk was positive or negative. A sensitivity analysis was demonstrated using pazopanib to explore the magnitude of uncertainty. FDA approval decision outcomes for the clinical trials assessed were consistent and logical using this benefit-risk framework.