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2.
JAMA ; 323(2): 123-124, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935012
3.
Nursing ; 50(2): 31-38, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31895198
6.
JAMA ; 323(2): 164-176, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935033

RESUMO

Importance: US law requires testing of new drugs before approval to ensure that they provide a well-defined benefit that is commensurate with their risks. A major challenge for the US Food and Drug Administration (FDA) is to achieve an appropriate balance between rigorous testing and the need for timely approval of drugs that have benefits that outweigh their risks. Objective: To describe the evolution of laws and standards affecting drug testing, the use of new approval programs and standards, expansions of the role and authority of the FDA, and changes in the number of drugs approved from the 1980s to 2018. Evidence: Sources of evidence included principal federal laws and FDA regulations (1962-2018) and FDA databases of approved new drugs (1984-2018), generic drugs (1970-2018), biologics (1984-2018), and vaccines (1998-2018); special development and approval programs (Orphan drug [1984-2018], Fast-Track [1988-2018], Priority Review and its predecessors [1984-2018], Accelerated Approval [1992-2018], and Breakthrough Therapy [2012-2018]); expanded access (2010-2017) and Risk Evaluation and Mitigation Strategies (2008-2018); and user fees paid to the FDA by industry (1993-2018). Findings: From 1983 to 2018, legislation and regulatory initiatives have substantially changed drug approval at the FDA. The mean annual number of new drug approvals, including biologics, was 34 from 1990-1999, 25 from 2000-2009, and 41 from 2010-2018. New biologic product approvals increased from a median of 2.5 from 1990-1999, to 5 from 2000-2013, to 12 from 2014-2018. The median annual number of generic drugs approved was 136 from 1970 to the enactment of the Hatch-Waxman Act in 1984; 284 from 1985 to the enactment of the Generic Drug User Fee Act in 2012; and 588 from 2013-2018. Prescription drug user fee funding expanded from new drugs and biologics in 1992 to generic and biosimilar drugs in 2012. The amount of Prescription Drug User Fee Act fees collected from industry increased from an annual mean of $66 million in 1993-1997 to $820 million in 2013-2017, and in 2018, user fees accounted for approximately 80% of the salaries of review personnel responsible for the approval of new drugs. The proportion of drugs approved with an Orphan Drug Act designation increased from 18% (55/304) in 1984-1995, to 22% (82/379) in 1996-2007, to 41% (154/380) in 2008-2018. Use of Accelerated Approval, Fast-Track, and Priority Review for new drugs has increased over time, with 81% (48/59) of new drugs benefiting from at least 1 such expedited program in 2018. The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017, but total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period. Conclusions and Relevance: Over the last 4 decades, the approval and regulation processes for pharmaceutical agents have evolved and increased in complexity as special programs have been added and as the use of surrogate measures has been encouraged. The FDA funding needed to implement and manage these programs has been addressed by expanding industry-paid user fees. The FDA has increasingly accepted less data and more surrogate measures, and has shortened its review times.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Regulamentação Governamental , Legislação de Medicamentos/tendências , Preparações Farmacêuticas/normas , United States Food and Drug Administration , Aprovação de Drogas/economia , Aprovação de Drogas/estatística & dados numéricos , História do Século XX , Legislação de Medicamentos/história , Estados Unidos
8.
Cancer Treat Rev ; 83: 101944, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830538

RESUMO

The use of adjuvant pertuzumab in HER2-positive early-stage breast cancer has recently been approved by the EMA on the basis of data from the APHINITY trial. Accordingly, we have produced this opinion article with the aim of putting the study data in perspective against other add-on therapeutic strategies, to clarify methodological or statistical doubts about the study, and to define the population of high-risk patients with hormone receptor-negative breast cancer that we agree, in general, should be treated. With this approval, physicians must be well prepared to place the APHINITY study data in context. It is now up to each country to ratify the EMA-approved indications and to agree on reimbursement, and doctors must optimize their use based on knowledge and discussion with patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Aprovação de Drogas , Receptor ErbB-2/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos
9.
Gut ; 69(1): 32-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30979718

RESUMO

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children. METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text. RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text. CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.


Assuntos
Ensaios Clínicos como Assunto/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fatores Etários , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Criança , Ensaios Clínicos como Assunto/normas , Relação Dose-Resposta a Droga , Aprovação de Drogas/métodos , Fármacos Gastrointestinais/administração & dosagem , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Expert Opin Drug Saf ; 19(1): 9-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31868031

RESUMO

Introduction: Reduced drinking has been debated as a treatment goal for heavy drinking alcohol-dependent patients, in whom treatment based on abstinence is not always an option. Nalmefene was the first drug approved by the European Medicines Agency (2013) with the indication of reduced drinking in high drinking risk level alcohol-dependent patients. Six years after its introduction in Europe, data from clinical experience can be compared with those from preclinical studies and pivotal registration studies to evaluate what nalmefene has added to the treatment of AUD.Areas covered: Systematic review of efficacy and safety data of nalmefene use in humans from preclinical, phase III and phase IV studies, including systematic reviews, meta-analyses, cost-effectiveness analyses, and other secondary analyses.Expert opinion: Nalmefene introduces a paradigm change in the treatment of AUD that makes it appealing to patients that are reluctant to embrace abstinence, and facilitate patient-centered care in heavy users. However, information regarding safety data in special populations (e.g., patients with alcohol-related diseases, pregnancy, psychiatric disease), and direct comparisons with other potential drugs for alcohol reduction are further needed. Despite the promising role of nalmefene, there are still some factors that limit its wide prescription further than in specialized settings.


Assuntos
Alcoolismo/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/administração & dosagem , Consumo de Bebidas Alcoólicas/prevenção & controle , Transtornos Relacionados ao Uso de Álcool/tratamento farmacológico , Aprovação de Drogas , Humanos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos
13.
Epidemiol Psychiatr Sci ; 29: e79, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841104

RESUMO

In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it has been used off-label in cases of severe depression. This commentary critically reviewed the evidence on esketamine submitted to the FDA, aiming to draw implications for clinical practice, research and regulatory science.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Depressão/diagnóstico , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Aprovação de Drogas , Medicina Baseada em Evidências , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Estados Unidos , United States Food and Drug Administration
15.
Blood ; 134(16): 1273-1274, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31698435
16.
Drugs Today (Barc) ; 55(10): 605-613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31720558

RESUMO

Plaque psoriasis is the commonest form of psoriasis affecting about 85% of those patients with the condition. Risankizumab was developed as a high-affinity humanized monoclonal antibody specific for the p19 subunit of interleukin-23 (IL-23p19). Clinical trials demonstrated that risankizumab was very effective in patients with moderate to severe plaque psoriasis causing total clearing of the condition as evidenced by Psoriasis Scalp Severity Index (PSSI100) and static Physician's Global Assessment (sPGA) of 0 in more than 50% of patients after 52 weeks of treatment. Risankizumab has been approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy as a dose of 150 mg administered by subcutaneous injection at week 0, week 4 and every 12 weeks thereafter.


Assuntos
Anticorpos Monoclonais/farmacologia , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Psoríase/terapia , Anticorpos Monoclonais Humanizados/farmacologia , Aprovação de Drogas , Humanos , Subunidade p19 da Interleucina-23/imunologia , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
17.
Drugs Today (Barc) ; 55(10): 615-625, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31720559

RESUMO

Sarecycline hydrochloride (Seysara) is a novel, narrow-spectrum tetracycline derivative approved by the U.S. Food and Drug Administration (FDA) in October 2018 for the treatment of inflammatory non-nodular moderate to severe acne vulgaris. It was initially developed by Paratek Pharmaceuticals, Inc. (U.S.) and Allergan plc (U.S.), which later was acquired by Almirall S.A. (Barcelona, Spain). Almirall S.A. obtained U.S. FDA approval of oral sarecycline tablets under the trade name Seysara. Sarecycline exhibits antibacterial activity against important skin/soft tissue pathogens with targeted activity against Cutibacterium acnes--an anaerobic Gram-positive bacterium linked with acne lesions--and also exerts anti-inflammatory effects as do other tetracyclines used in the treatment of acne vulgaris. Interestingly, unlike the broad-spectrum tetracyclines, sarecycline is less potent against aerobic Gram-negative bacilli and anaerobic bacteria associated with endogenous intestinal microbial flora. This provides it with a more specific antibacterial spectra with lower chances of adverse off-target antibacterial effects, thus making it a promising choice of treatment over others in its class. It has also demonstrated low propensity to resistance as compared with other tetracyclines and is also active against tetracycline-resistant Staphylococcus aureus as well as erythromycin- and clindamycin-resistant C. acnes strains. Sarecycline has successfully undergone numerous phase I, phase II and three phase III studies establishing it as a well-tolerated once-daily oral drug available as a tablet for the treatment of patients 9 years of age or above.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Tetraciclinas/uso terapêutico , Aprovação de Drogas , Humanos , Estados Unidos , United States Food and Drug Administration
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