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1.
Cancer Treat Rev ; 94: 102167, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33652263

RESUMO

BACKGROUND: The Fragility Indexquantifies the reliability of positive trials by estimating the number of events, which would change statistically significant results to non-significant results. METHODS: We identified randomized trials supporting drug approvals by the US FDA between 2009 and 2019 in lung, breast, prostate, and colon cancers and in melanoma. We reconstructed survival tablesand calculated the number of events, which would result in a non-significant result for the primary endpoint. The FI was then compared to the number of patients in each trial who withdrew consent or were lost to follow-up. Regression analyses were used to explore associations between RCT characteristics and FI and trials in which FI was lower or equal to number of participants who withdrew consent or were lost to follow-up. RESULTS: Among 81 RCTs, the median FI was 28. The median number of patients who withdrew consent or were lost to follow up was 27. FI was equal or lower than the number of patients who withdrew consent or were lost to follow-up in 47 trials (58%). There was a modest increase in FI over time (p = 0.02). Trials with overall survival as the primary endpoint (p = 0.006) and those in the palliative setting (p < 0.001) had lower FI. There was no association with trial sample size or duration of follow-up. FINDINGS: Statistical significance of RCTs in common solid tumours can be reversed often with a small number of additional events. Post-approval RCTs or real-world data analyses should be performed to ensure results of registration trials are robust.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Antineoplásicos/normas , Ensaios Clínicos Fase II como Assunto/normas , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/normas , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Intervalo Livre de Doença , Aprovação de Drogas/métodos , Aprovação de Drogas/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Reprodutibilidade dos Testes
5.
Ther Innov Regul Sci ; 55(3): 553-557, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33367967

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-19; HCoV-19; COVID-19) has affected all daily activities. Has it also affected the number of United States (FDA) drug approvals over time? The short answer from empirical time series forecasting is not yet. Care should be taken as the crisis continues through maintaining the scientific, economic, political, and social supportive structures to sustain momentum. This conclusion is based on analyzing the results of (non-overlapping) forecasting routines (viz., complex exponential smoothing, auto-regressive fractionally integrated moving average, extreme learning machine, and multi-layer perceptron) performed on longitudinal (1939-present) FDA (CDER) drug approvals taking into regard pre- and extant-COVID-19 eras. This is an initial study and there are caveats with the approach, and as such, all data and programs are provided to support replication of the results and furthering of the investigation.


Assuntos
COVID-19 , Aprovação de Drogas/estatística & dados numéricos , United States Food and Drug Administration/estatística & dados numéricos , Previsões , Humanos , Estados Unidos
6.
BMJ ; 371: m3434, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028575

RESUMO

OBJECTIVE: To characterize the therapeutic value of new drugs approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) and the association between these ratings and regulatory approval through expedited programs. DESIGN: Retrospective cohort study. SETTING: New drugs approved by the FDA and EMA between 2007 and 2017, with follow-up through 1 April 2020. DATA SOURCES: Therapeutic value was measured using ratings of new drugs by five independent organizations (Prescrire and health authorities of Canada, France, Germany, and Italy). MAIN OUTCOME MEASURES: Proportion of new drugs rated as having high therapeutic value; association between high therapeutic value rating and expedited status. RESULTS: From 2007 through 2017, the FDA and EMA approved 320 and 268 new drugs, respectively, of which 181 (57%) and 39 (15%) qualified for least one expedited program. Among 267 new drugs with a therapeutic value rating, 84 (31%) were rated as having high therapeutic value by at least one organization. Compared with non-expedited drugs, a greater proportion of expedited drugs were rated as having high therapeutic value among both FDA approvals (45% (69/153) v 13% (15/114); P<0.001) and EMA approvals (67% (18/27) v 27% (65/240); P<0.001). The sensitivity and specificity of expedited program for a drug being independently rated as having high therapeutic value were 82% (95% confidence interval 72% to 90%) and 54% (47% to 62%), respectively, for the FDA, compared with 25.3% (16.4% to 36.0%) and 90.2% (85.0% to 94.1%) for the EMA. CONCLUSIONS: Less than a third of new drugs approved by the FDA and EMA over the past decade were rated as having high therapeutic value by at least one of five independent organizations. Although expedited drugs were more likely than non-expedited drugs to be highly rated, most expedited drugs approved by the FDA but not the EMA were rated as having low therapeutic value.


Assuntos
Aprovação de Drogas , Avaliação de Medicamentos , Serviços de Informação sobre Medicamentos , Disseminação de Informação , Vigilância de Produtos Comercializados , Aprovação de Drogas/métodos , Aprovação de Drogas/estatística & dados numéricos , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Serviços de Informação sobre Medicamentos/organização & administração , Serviços de Informação sobre Medicamentos/normas , Serviços de Informação sobre Medicamentos/estatística & dados numéricos , Europa (Continente) , Humanos , Vigilância de Produtos Comercializados/métodos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Desenvolvimento de Programas , Melhoria de Qualidade , Estudos Retrospectivos , Estados Unidos
9.
JAMA Netw Open ; 3(4): e203284, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315070

RESUMO

Importance: Since the introduction of the Fast Track designation in 1988, the number of special regulatory programs available for the approval of new drugs and biologics by the US Food and Drug Administration (FDA) has increased, offering the agency flexibility with respect to evidentiary requirements. Objective: To characterize pivotal efficacy trials supporting the approval of new drugs and biologics during the past 3 decades. Design, Setting, and Participants: This cross-sectional study included 273 new drugs and biologics approved by the FDA for 339 indications from 1995 to 1997, from 2005 to 2007, and from 2015 to 2017. Main Outcomes and Measures: Therapeutics were classified by product type and therapeutic area as well as orphan designation and use of special regulatory programs, such as Priority Review and Accelerated Approval. Pivotal trials were characterized by use of randomization, blinding, types of comparators, primary end points, number of treated patients, and trial duration, both individually and aggregated by each indication approval. Results: A total of 273 new drugs and biologics were approved by the FDA in these 3 periods (107 [39.2%] in 1995-1997; 57 [20.9%] in 2005-2007; and 109 [39.9%] in 2015-2017), representing 339 indications (157 [46.3%], 64 [18.9%], and 118 [34.8%], respectively). The proportion of therapeutic approvals using at least 1 special regulatory program increased (37 [34.6%] in 1995-1997; 33 [57.9%] in 2005-2007; and 70 [64.2%] in 2015-2017), as did indication approvals receiving an orphan designation (20 [12.7%] in 1995-1997; 17 [26.6%] in 2005-2007, and 45 [38.1%] in 2015-2017). The most common therapeutic areas differed over time (infectious disease, 53 [33.8%] in 1995-1997 vs cancer, 32 [27.1%] in 2015-2017). When considering the aggregate pivotal trials supporting each indication approval, the proportion of indications supported by at least 2 pivotal trials decreased (80.6% [95% CI, 72.6%-87.2%] in 1995-1997; 60.3% [95% CI, 47.2%-72.4%] in 2005-2007; and 52.8% [95% CI, 42.9%-62.6%] in 2015-2017; P < .001). The proportion of indications supported by only single-group pivotal trials increased (4.0% [95% CI, 1.3%-9.2%] in 1995-1997; 12.7% [95% CI, 5.6%-23.5%] in 2005-2007; and 17.0% [95% CI, 10.4%-25.5%] in 2015-2017; P = .001), whereas the proportion supported by at least 1 pivotal trial of 6 months' duration increased (25.8% [95% CI, 18.4%-34.4%] in 1995-1997; 34.9% [95% CI, 23.3%-48.0%] in 2005-2007; and 46.2% [95% CI, 36.5%-56.2%] in 2015-2017; P = .001). Conclusions and Relevance: In this study, more recent FDA approvals of new drugs and biologics were based on fewer pivotal trials, which, when aggregated by indication, had less rigorous designs but longer trial durations, suggesting an ongoing need for continued evaluation of therapeutic safety and efficacy after approval.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/estatística & dados numéricos , Preparações Farmacêuticas , Produtos Biológicos , Estudos Transversais , Humanos , Estados Unidos , United States Food and Drug Administration
12.
Gac. sanit. (Barc., Ed. impr.) ; 34(2): 133-140, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-196049

RESUMO

OBJECTIVE: To compare the use of health technology assessment (HTA) as a tool to support pricing and reimbursement (P&R) of new medicines in Spain with England, Sweden, France and Germany. METHOD: For each country, the literature is used to identify the purpose and timing of the P&R decision, the HTA and decision-making procedures used to generate evidence, and the criteria used to make decisions. RESULTS: Results are presented as a summary of the HTA landscape for P&R of new medicines in each country.comparisons are made between Spain and other countries regarding the procedure and implementation of HTA. CONCLUSIONS: Based on these assessments, we made recommendations for how HTA might develop in Spain with the aim of improving governance and efficiency. Spain has made considerable progress in recent years, but still falls short of international standards in terms of independence of the HTA agencies and decision-making committees from political influence and industrial policy, the setting of prices of medicines in relation to health gain, improve the transparency of the process and results of the evaluation, and promote the participation of stakeholders. In common with other countries, Spain needs to clarify the role of cost-effectiveness criteria. Further progress needs to be made to coordinate effort across the various agencies, strengthen technical staff, and ensure equitable access to medicines between regions


OBJETIVO: Comparar el uso de la evaluación de tecnologías sanitarias (ETS) como instrumento para apoyar la fijación de precios y el reembolso de nuevos medicamentos en España con otros países europeos como Inglaterra, Suecia, Francia y Alemania. MÉTODO: Se realiza una revisión de la literatura para identificar, en cada país, el objetivo y la cronología de la decisión, los procedimientos para realizar la ETS y los criterios para tomar decisiones. RESULTADOS: Se presenta una descripción narrativa de la situación en cada país y una comparación entre España y otros países sobre los procedimientos y la implementación de ETS. CONCLUSIONES: Basándose en estas evaluaciones, se propone una serie de recomendaciones para mejorar el proceso. España ha avanzado significativamente en ETS en los últimos años, pero aún falta garantizar la independencia de las agencias de ETS, eliminar la influencia de la política económica e industrial de los comités de decisiones sanitarias, fijar precios basados en el valor terapéutico, mejorar la transparencia del proceso y de los resultados de las evaluaciones, y por último, aumentar la participación de los grupos de interés. Al igual que en otros países de su entorno, España tiene que clarificar el papel de la evaluación económica como criterio de decisión. Hace falta una mejor coordinación entre las diversas agencias que participan en ETS en España, fomentar el personal técnico y monitorizar la equidad de acceso a nuevos medicamentos entre las comunidades autónomas


Assuntos
Humanos , Aprovação de Drogas/estatística & dados numéricos , Medicamentos de Referência , Preço de Medicamento , Acesso a Medicamentos Essenciais e Tecnologias em Saúde , Espanha , Europa (Continente) , Avaliação da Tecnologia Biomédica/tendências
13.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127360

RESUMO

BACKGROUND: Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan indications. METHODS: We classified the 402 orphan indications the US Food and Drug Administration approved between 2010 and 2018 as "pediatric" if they were approved for children only or targeted pediatric diseases. We determined the number of unique diseases targeted by pediatric orphan indications and calculated the proportion that were for (1) novel drugs, (2) non-novel drugs approved to treat ≥1 common disease, and (3) non-novel drugs approved only to treat rare diseases. Among pediatric orphan indications eligible for US Food and Drug Administration breakthrough designation (granted to drugs potentially representing major therapeutic advances), we calculated the proportion receiving this designation. RESULTS: Of the 402 orphan indications, 136 (33.8%) were pediatric. These 136 indications targeted 87 unique diseases; 21 diseases were targeted by ≥1 indication. Of the 136 pediatric orphan indications, 60 (44.1%) were for novel drugs, 45 (33.1%) were for non-novel drugs approved to treat ≥1 common disease, and 31 (22.8%) were for non-novel drugs approved only to treat rare diseases. Among 97 indications eligible for breakthrough designation, 20 (20.6%) received this designation. CONCLUSIONS: Recent orphan drug development has increased the availability of treatments for pediatric rare diseases. Most pediatric orphan indications expanded use of existing drugs, and many targeted the same disease. Some indications may represent breakthroughs, but substantial unmet need for treatments remains for most pediatric rare diseases.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Produção de Droga sem Interesse Comercial/estatística & dados numéricos , Doenças Raras/tratamento farmacológico , Criança , Rotulagem de Medicamentos/estatística & dados numéricos , Humanos , Produção de Droga sem Interesse Comercial/classificação , Estados Unidos
14.
Am J Public Health ; 110(5): 731-733, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32191523

RESUMO

Objectives. To determine the effect of new therapies and trends toward reduced mortality rates of melanoma.Methods. We reviewed melanoma incidence and mortality among Whites (the group most affected by melanoma) in 9 US Surveillance, Epidemiology, and End Results registry areas that recorded data between 1986 and 2016.Results. From 1986 to 2013, overall mortality rates increased by 7.5%. Beginning in 2011, the US Food and Drug Administration approved 10 new treatments for metastatic melanoma. From 2013 to 2016, overall mortality decreased by 17.9% (annual percent change [APC] = -6.2%; 95% confidence interval [CI] = -8.7%, -3.7%) with sharp declines among men aged 50 years or older (APC = -8.3%; 95% CI = -12.2%, -4.1%) starting in 2014. This recent, multiyear decline is the largest and most sustained improvement in melanoma mortality ever observed and is unprecedented in cancer medicine.Conclusions. The introduction of new therapies for metastatic melanoma was associated with a significant reduction in population-level mortality. Future research should focus on developing even more effective treatments, identifying biomarkers to select patients most likely to benefit, and renewing emphasis on public health approaches to reduce the number of patients with advanced disease.


Assuntos
Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Fatores Etários , Idoso , Aprovação de Drogas/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Programa de SEER , Fatores Sexuais , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , United States Food and Drug Administration
15.
Molecules ; 25(3)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050446

RESUMO

During 2019, the US Food and Drug Administration (FDA) approved 48 new drugs (38 New Chemical Entities and 10 Biologics). Although this figure is slightly lower than that registered in 2018 (59 divided between 42 New Chemical Entities and 17 Biologics), a year that broke a record with respect to new drugs approved by this agency, it builds on the trend initiated in 2017, when 46 drugs were approved. Of note, three antibody drug conjugates, three peptides, and two oligonucleotides were approved in 2019. This report analyzes the 48 new drugs of the class of 2019 from a strictly chemical perspective. The classification, which was carried out on the basis of chemical structure, includes the following: Biologics (antibody drug conjugates, antibodies, and proteins); TIDES (peptide and oligonucleotides); drug combinations; natural products; and small molecules.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Descoberta de Drogas/estatística & dados numéricos , Indústria Farmacêutica/tendências , United States Food and Drug Administration/estatística & dados numéricos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Aprovação de Drogas/história , Aprovação de Drogas/legislação & jurisprudência , Combinação de Medicamentos , Descoberta de Drogas/história , Indústria Farmacêutica/história , Drogas em Investigação/química , Drogas em Investigação/uso terapêutico , História do Século XXI , Humanos , Imunoconjugados/química , Imunoconjugados/uso terapêutico , Estrutura Molecular , Oligonucleotídeos/química , Oligonucleotídeos/uso terapêutico , Peptídeos/química , Peptídeos/uso terapêutico , Relação Estrutura-Atividade , Estados Unidos , United States Food and Drug Administration/história , United States Food and Drug Administration/legislação & jurisprudência
16.
Clin Ther ; 42(2): 305-320.e0, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32008723

RESUMO

PURPOSE: The present study aimed to examine the differences between enrolled subject populations and use of combination therapies as defined by the pivotal clinical trial protocols and the approved indications of anticancer drugs as determined by 3 major regulatory agencies. METHODS: Thirty-eight approvals were collected that received market authorization from the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) between January 2010 and September 2018 for initial approval of an anticancer drug or for an expanded therapeutic indication for a previously approved anticancer drug, based on the same pivotal clinical trial(s). The subject eligibility criteria of the pivotal clinical trials and the approved indications as established by these agencies were compared, and the differences were categorized according to patient biomarkers status, prior treatment status, and the use of combination therapies. FINDINGS: In 20 (53%) approvals, there was a discrepancy between biomarker status of enrolled subjects in the pivotal trial and the therapeutic indication. In 7 of these cases, the biomarkers were used to diagnose the target cancer or to stratify the study subjects in the pivotal trial. In 9 cases, the biomarker discrepancies were related to minor histologic subtypes of the target cancer. Regarding prior treatment status, the FDA and the EMA generally approved indications for the same treatment line as the pivotal trials, whereas the PMDA did not restrict approval to untreated patients when the pivotal trial included only treatment-naive subjects. In 14 approvals, the FDA and the EMA designated the same co-administered drugs as part of the approved indications in line with the pivotal trials. However, the PMDA did not specify the co-administered drugs in 2 approvals and did not require combination therapy in 1 case. IMPLICATIONS: In principle, the approved therapeutic indications should be determined by the characteristics of the pivotal trial subjects and combination therapies. The use of biomarkers can be essential for identifying those patients who are most likely to benefit from a drug. Unfortunately, biomarker-defined subgroups are often insufficient in size to allow meaningful interpretation of results. Consequently, regulatory agencies may deviate from one another and from the pivotal trial protocol when interpreting study results and attempting to define the optimal treatment population. The PMDA-approved indications deviated more liberally from the pivotal trial protocols regarding specification of prior treatment status and the use of co-administered drugs.


Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Aprovação de Drogas/organização & administração , Europa (Continente) , Governo Federal , Órgãos Governamentais/estatística & dados numéricos , Humanos , Japão , Pesquisa Qualitativa , Estados Unidos
17.
Med Care ; 58(3): 194-198, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32106163

RESUMO

INTRODUCTION: New drug products are tested for safety and efficacy in clinical trials before being approved for use in medical practice. Clinical trial data are often misreported or underreported to ClinicalTrials.gov and in the medical literature. There is limited research on clinical trial characteristics for Food and Drug Administration (FDA) approved drugs, particularly examining differences in characteristics across different approval pathways or therapeutic indications. METHODS: Data from the Aggregate Analysis of ClinicalTrials.gov (AACT) were used to compare the characteristics of completed clinical trials for drugs approved by the FDA in 2015 and 2016 across different approval pathways (expedited vs. nonexpedited) and therapeutic indications (oncology vs. nononcology). RESULTS: There were 59 novel therapeutic drugs approved by the FDA in 2015 and 2016. A search of the AACT database yielded 955 studies that were associated with these 59 drugs. Median Phase 2 trial enrollment was smaller for drugs granted expedited approval compared with drugs without expedited approval (60 vs. 94; P=0.0079) and for oncology drugs compared with nononcology drugs (53 vs. 92; P<0.001). In general, trials across all phases were less likely to be blinded for drugs that received expedited approval compared with drugs without expedited approval and for oncology drugs compared with nononcology drugs. CONCLUSIONS: The characteristics of clinical trials differ across different approval pathways and therapeutic indications. More research is needed to determine whether the information from clinical trials of approved drugs is sufficient to adequately inform the public regarding their potential benefits and harms.


Assuntos
Ensaios Clínicos como Assunto , Bases de Dados Factuais , Aprovação de Drogas/estatística & dados numéricos , Oncologia/estatística & dados numéricos , United States Food and Drug Administration/estatística & dados numéricos , Estudos Transversais , Gerenciamento de Dados , Humanos , Oncologia/tendências , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration/normas
18.
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
19.
Cancer ; 126(6): 1315-1321, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31794076

RESUMO

BACKGROUND: Fusions are increasingly pursued as oncology therapeutic targets. The current study evaluated differences in outcomes for fusion versus nonfusion targets. METHODS: Outcomes were compared for patients with fusions versus those with other alterations for US Food and Drug Administration-approved single agents (from package inserts) and for patients treated at the University of California at San Diego. RESULTS: A total of 28 drugs approved by the US Food and Drug Administration (6189 patients) were included in the analysis. The median response rate was 68% versus 50% for fusions versus nonfusion matches (odds ratio [OR], 1.67; P < .0001); solid tumor therapies had an OR of 2.07 (P < .0001) and hematologic therapies had an OR of 3.35 (P < .0001) for fusion versus nonfusion targets. The University of California at San Diego analysis included 79 patients in whom fusions were treated of the 2455 patients screened. Patients matched to fusions were found to have a longer median progression-free survival (PFS) (11.6 months; 95% CI, 4.0-35.4 months) compared with those unmatched to fusions (4.9 months; 95% CI, 3.5-8.8 months) (P = .034). Patients with fusions matched to other alterations present in the tumor had a median PFS that was indistinguishable from that of those patients with fusions who were treated with unmatched therapy (4.0 months vs 5.0 months; P = .75). CONCLUSIONS: Significantly higher response rates and a longer PFS were observed when targeting fusions compared with nonfusions. The observations reported in the current study suggest that fusions are important targets and that additional studies are needed to confirm that optimized therapy may require targeting fusions, even in the presence of other alterations.


Assuntos
Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Intervalo Livre de Progressão , California , Aprovação de Drogas/estatística & dados numéricos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Humanos , Estimativa de Kaplan-Meier , Razão de Chances , Resultado do Tratamento , Estados Unidos
20.
Eur J Ophthalmol ; 30(2): 321-349, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30832499

RESUMO

OBJECTIVES: Regulatory approval of new medicines requires a thorough assessment of the potential clinical benefits and risks. Study end-points are expected to demonstrate a clinically relevant treatment effect that will translate into direct patient benefits. This study sought to review the ophthalmic medicines with European Union-wide approval granted via the Centralised Procedure and characterise the key efficacy end-points underpinning the demonstration of clinical benefit. METHODS: This study was a retrospective review of published data pertaining to the European regulatory authorisation of centrally approved ophthalmic products between 1999 and 2017, inclusive. All sources and data consulted are in the public domain. European Public Assessment Reports published by the European Medicines Agency were consulted for data concerning the pivotal clinical efficacy studies supporting the applications. Data analyses were descriptive. RESULTS: The European Medicines Agency have authorised 30 products via the Centralised Procedure between 1999 and 2017. For these products, a total of 24 additional approvals for line extensions or additional therapeutic indications were granted. Four products have been approved for orphan indications, including one approval 'under exceptional circumstances' and one 'Conditional Marketing Authorisation'. Approvals for products in retina (36%) and glaucoma (28%) indications together accounted for the majority of authorisations, with trial end-points predominantly based on visual acuity and intraocular pressure parameters, respectively. Products were also approved for indications in ocular surface disease, inflammation, optic neuropathy and surgical adjuncts, with a range of functional and anatomical end-points. CONCLUSION: Approvals for ophthalmic medicines have been granted for a range of clinical indications, representing a considerable portion of available major therapeutics for practitioners. Benefit-risk assessments rely on clinical trial data demonstrating a clearly relevant patient benefit.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , União Europeia , Humanos , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
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