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1.
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
2.
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
3.
Dermatol Surg ; 45(12): 1585-1596, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31569111

RESUMO

BACKGROUND: Many noncollagen dermal fillers (NCDFs) have been approved by the FDA and are currently the second-most performed noninvasive cosmetic procedure. OBJECTIVE: To summarize and compare the clinical trials reviewed by the United States FDA in the approval of NCDFs. METHODS: The FDA Premarket Approval (PMA) site was queried, and the year of approval, indication, design, primary end points, touch-ups, retreatments, and study duration were extracted and tabulated. RESULTS: Twenty-one FDA-approved NCDFs from 2003 to 2018 and 24 Summary of Safety and Effectiveness documents were reviewed. Differences in the trial design and in reporting of data make comparisons difficult. This article provides comparative tables to make interpreting the various trial results more straightforward. LIMITATIONS: Primary efficacy end points and the way that filler volumes were reported varied by company. This article does not focus on secondary end points or safety data. CONCLUSION: A comprehensive and comparative review of clinical trials of NCDFs by the FDA demonstrates that differences in data reporting, especially for touch-ups and retreatments, make filler duration difficult to compare and interpret. Understanding of the trial design will allow the clinician to become more astute and allow for better management of patient expectations in clinical practice.


Assuntos
Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Preenchedores Dérmicos/administração & dosagem , Aprovação de Drogas/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/normas , Preenchedores Dérmicos/normas , Humanos , Projetos de Pesquisa/normas , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normas
4.
BMJ ; 367: l5766, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645328

RESUMO

OBJECTIVE: To determine the extent to which late stage development of new drugs relies on support from public funding. DESIGN: Cohort study. SETTING: All new drugs containing one or more new molecular entities approved by the US Food and Drug Administration (FDA) between January 2008 and December 2017 via the new drug application pathway. MAIN OUTCOME MEASURES: Patents or drug development histories documenting late stage research contributions by a public sector research institution or a spin-off company, as well as each drug's regulatory approval pathway and first-in-class designation. RESULTS: Over the 10 year study period, the FDA approved 248 drugs containing one or more new molecular entities. Of these drugs, 48 (19%) had origins in publicly supported research and development and 14 (6%) originated in companies spun off from a publicly supported research program. Drugs in these groups were more likely to receive expedited FDA approval (68% v 47%, P=0.005) or be designated first in class (45% v 26%, P=0.007), indicating therapeutic importance. CONCLUSIONS: A review of the patents associated with new drugs approved over the past decade indicates that publicly supported research had a major role in the late stage development of at least one in four new drugs, either through direct funding of late stage research or through spin-off companies created from public sector research institutions. These findings could have implications for policy makers in determining fair prices and revenue flows for these products.


Assuntos
Ensaios Clínicos como Assunto/economia , Aprovação de Drogas/economia , Setor Público/economia , Pesquisa Médica Translacional/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estudos de Coortes , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Humanos , Patentes como Assunto/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Pesquisa Médica Translacional/estatística & dados numéricos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/estatística & dados numéricos
5.
Rev. clín. med. fam ; 12(3): 125-131, oct. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-186802

RESUMO

Hasta hace poco los fármacos hipolipemiantes que habían demostrado, de manera consistente y reproducible, capacidad para prevenir la aparición de las enfermedades cardiovasculares, sobre todo de la cardiopatía isquémica, tanto en prevención primaria como secundaria, eran las estatinas. En España, hay comercializadas siete y todas tienen estudios de reducción de eventos clínicos frente a placebo y, en algunos casos de prevención secundaria, de tratamiento intensivo frente al convenciona, menos la pitavastatina que solo cuenta con un estudio que compara dosis altas con dosis bajas de la misma estatina. Tras los fracasos en la prevención cardiovascular del ácido nicotínico, actualmente no comercializado en España, la limitada utilidad de los fibratos y de los ácidos grasos omega 39, solo nos quedan como tratamiento para asociar a las estatinas las resinas de intercambio iónico, habitualmente mal toleradas, y ezetimiba, fármaco que solo tiene estudios de reducción de eventos en asociación con estatinas en pacientes con insuficiencia renal y con síndrome coronario agudo


No disponible


Assuntos
Humanos , Reguladores do Metabolismo de Lipídeos/farmacocinética , Anticolesterolemiantes/farmacocinética , Pró-Proteína Convertases/farmacocinética , Hipercolesterolemia/tratamento farmacológico , Anticorpos Monoclonais/farmacocinética , Doenças Cardiovasculares/prevenção & controle , Ezetimiba/uso terapêutico , Tolerância a Medicamentos , Resultado do Tratamento , Aprovação de Drogas/estatística & dados numéricos
8.
JAMA Netw Open ; 2(5): e193410, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31074812

RESUMO

Importance: The US Food and Drug Administration (FDA) can use postmarketing requirements to mandate pharmaceutical companies to conduct clinical trials after the approval of novel therapeutics. Pharmaceutical companies can also agree to conduct nonmandated clinical trials as postmarketing commitments. However, when therapeutics are approved by the FDA without postmarketing requirements or postmarketing commitments, it is not well known how often pharmaceutical companies voluntarily conduct trials and report results monitoring safety or efficacy after approval. Objective: To characterize postapproval clinical trials sponsored by pharmaceutical companies of therapeutics initially approved by the FDA without clinical postmarketing requirements or commitments. Design, Setting, and Participants: This cross-sectional analysis included postapproval clinical trials conducted with at least 1 site in the United States sponsored by pharmaceutical companies of therapeutics first approved by the FDA from 2009 through 2012. Analyses were conducted June 11, 2018, to November 30, 2018. Main Outcomes and Measures: Postapproval clinical trials registered on ClinicalTrials.gov generating safety or efficacy data, characteristics including whether trials focused on approved or unapproved indications, study design elements, and rates of study completion and results reporting. Results: From 2009 through 2012, the FDA approved 110 novel therapeutics for 120 indications, of which 37 novel therapeutics for 39 indications did not have postmarketing requirements or commitments for new clinical studies at the time of first approval. For 31 therapeutics (83.8%), there were 600 postapproval clinical trials sponsored by pharmaceutical companies. Most trials investigated therapeutics for new indications (363 [60.5%]) or expanded populations of the originally indicated disease (122 [20.3%]). Trials were often small (median [interquartile range] enrollment, 44 [21-131] participants), nonrandomized (359 [59.8%]), unblinded (455 [75.8%]), and lacked comparators (381 [63.5%]). Approximately half of the trials (311 [51.8%]) assessed at least 1 clinical outcome. Of 300 terminated or completed trials, 204 trials (68.0%) had reported results on ClinicalTrials.gov a median (interquartile range) 16 (13-25) months after their primary completion date. For the 96 trials (32.0%) without reported results, a median (interquartile range) 35 (13-62) months had passed since their primary completion date. Conclusions and Relevance: Pharmaceutical companies frequently conducted clinical trials after approval, even when there were no clinical postmarketing requirements or commitments at approval. However, most of these trials evaluated new indications or expanded patient populations rather than monitored approved uses, and nearly half of the trials remained incomplete more than 5 years after original therapeutic approval.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/estatística & dados numéricos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Estudos Transversais , Indústria Farmacêutica/métodos , Humanos , Estados Unidos , United States Food and Drug Administration
9.
Eur J Clin Pharmacol ; 75(9): 1193-1200, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129731

RESUMO

PURPOSE: We aimed to investigate the regulatory approval of drugs for cancers by the US Food and Drug Administration based on the cancer type (major vs. minor), including the use of expedited development programs and duration from Investigational New Drug application (IND) to marketing approval. METHODS: From publicly available records and through a Freedom of Information Act request, we gathered data to evaluate regulatory characteristics and pivotal study design for 115 anticancer drug approvals between 2012 and 2017 and the data were analyzed based on cancer incidence (major vs. minor cancers) and how expedited programs, orphan drug designation, and pivotal study design contribute to expedited approval was studied. RESULTS: Drugs targeting minor cancers more frequently (67%; P = 0.0155) utilized breakthrough therapy designation and/or accelerated approval, both of which significantly contributed to expedited drug approval (median time from IND to approval, 6.4 years; P = 0.0008, 6.2 years; P < 0.0001). Drug approvals for pivotal study design without a comparator arm took significantly less time from IND to approval (median time from IND to approval, 6.2 years; P < 0.0001). CONCLUSIONS: Drugs targeting minor cancers have frequently utilized the expedited development programs; thus, efficiently shortening time to approval. As many of such drugs are approved based on non-comparative pivotal studies, meticulous evaluation and follow-up should be performed for such drugs after their approval.


Assuntos
Antineoplásicos/uso terapêutico , Aprovação de Drogas/estatística & dados numéricos , Neoplasias/tratamento farmacológico , United States Food and Drug Administration/estatística & dados numéricos , Humanos , Incidência , Neoplasias/classificação , Neoplasias/epidemiologia , Produção de Droga sem Interesse Comercial , Projetos de Pesquisa , Estados Unidos
10.
Pediatr Blood Cancer ; 66(8): e27809, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31144772

RESUMO

It is well appreciated that the number of anticancer drugs approved for use in children is a fraction of the number approved for use in cancers that occur in adults. We address this fact by summarizing the relevant U.S. legislation that provides the framework for the evaluation and approval of drugs used to treat children with cancer. In total, the Food and Drug Administration (FDA) has approved 38 new drug applications for pediatric oncology indications, 12 of which were new molecular entities. FDA continues to collaborate with multistakeholders regarding the development of products intended for pediatric cancer and encourages the submission of marketing applications.


Assuntos
Antineoplásicos/uso terapêutico , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Criança , Humanos , Estados Unidos , United States Food and Drug Administration
11.
J Am Acad Dermatol ; 81(3): 867-877, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31103566

RESUMO

The Orphan Drug Act of 1983 (ODA) put in place a set of financial and marketing incentives to stimulate the development of drugs to treat rare diseases, and since its passage, more than 600 orphan drug and biologic products have been brought to market in the United States. Rapid growth in orphan drug approvals in conjunction with high orphan drug prices have triggered concern that drug makers are exploiting certain aspects of the ODA for financial gain and that some pharmaceutical drugs are receiving orphan status where it is not warranted. The landscape of approved therapies for rare skin diseases has not been well described. In this article, we provide a descriptive analysis of the United States Food and Drug Administration-approved orphan drugs for the treatment of rare dermatologic conditions and skin-related cancers since the enactment of the ODA. We discuss policy issues that emerge from the analysis and suggest areas for future research. Next, we elucidate ODA loopholes using dermatologic drugs as examples and propose potential reforms. Finally, we consider future directions for orphan drug development in the field of dermatology.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Aprovação de Drogas/estatística & dados numéricos , Produção de Droga sem Interesse Comercial/estatística & dados numéricos , Doenças Raras/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Aprovação de Drogas/legislação & jurisprudência , Humanos , Motivação , Produção de Droga sem Interesse Comercial/legislação & jurisprudência , Políticas , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
13.
Molecules ; 24(4)2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813407

RESUMO

The Food and Drug Administration approved 59 new drugs (42 New Chemical Entities and 17 Biologics) during 2018. This number breaks the previous record of 53 approved by the same organization in 1996. The 17 new biologics approved in 2018 also represent an important milestone for this kind of drug and they clearly exceed the 12 approved in 2015 and 2017. Herein, the 59 new drugs of the class of 2018 are analyzed from a strictly chemical perspective. The classification has been carried out on the basis of the chemical structure and includes the following: Biologics (antibodies and enzymes); TIDES (peptides and oligonucleotides) and natural products; drug combinations; and small molecules.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Anticorpos/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Indústria Farmacêutica , Humanos , Estrutura Molecular , Preparações Farmacêuticas/química , Estados Unidos , United States Food and Drug Administration
15.
J Manag Care Spec Pharm ; 25(7): 780-792, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30799664

RESUMO

BACKGROUND: Annual spending on retail and nonretail prescription drugs exceeds $450 billion and is projected to outpace growth in all other national health expenditure categories over the next decade. Evergreened reformulations of drugs, defined here as extended-release or other reformulations that came to market more than 2 years after initial approval of the immediate-release product, increase drug spending and delay patient access to extended-release formulations. Reforming drug approval incentives may encourage earlier introduction of extended-release formulations, hastening generic adoption and patient access. OBJECTIVES: To (a) systematically identify evergreened reformulations, defined as reformulations that extend drug exclusivity (i.e., extended-release or other reformulations that came to market more than 2 years after initial approval of the immediate-release product), and (b) estimate the effect on Medicaid spending and the delay in patient access to extended-release formulations. METHODS: Evergreened reformulations were identified using FDA Orange Book drug approval data (1982-2018); these data were used to characterize mean time from initial brand approval to evergreen reformulation approval and subsequent generic approval. Medicaid expenditure data from 2008-2016 were used to estimate increased expenditures from delayed introduction of generic extended-release formulations. Outcome measurements include time from FDA approval of immediate-release brand drug to evergreened reformulation extended-release brand drug approval, annual generic share of immediate-release and extended-release prescriptions in Medicaid, and annual price difference between brand and generic prescriptions in Medicaid. RESULTS: 73 drug active ingredients were subject to evergreened reformulations; these evergreened reformulations increased Medicaid expenditures by $9.35 billion from 2008-2016. Among reformulations that increased expenditures by over $100 million each, the mean time between the initial brand approval and evergreen reformulation approval was 8.1 years (SD = 3.9; median = 8.8; interquartile range [IQR] = 3.7-11.7); across all evergreened reformulations where the initial drug was approved after January 1, 1982, the mean was 7.9 years (SD = 4.3; median = 6.8; IQR = 4.0-11.0). CONCLUSIONS: Evergreened reformulations increase Medicaid drug expenditures and delay patient access to extended-release formulations. Reforming drug approval laws could alter market incentives for evergreened reformulations, decreasing spending and hastening patient access to extended-release products. DISCLOSURES: No outside funding supported this research. The author has no competing interests to disclose.


Assuntos
Medicamentos Genéricos/economia , Acesso aos Serviços de Saúde/economia , Medicaid/economia , Medicamentos sob Prescrição/economia , Aprovação de Drogas/economia , Aprovação de Drogas/estatística & dados numéricos , Custos de Medicamentos/tendências , Gastos em Saúde/estatística & dados numéricos , Gastos em Saúde/tendências , Acesso aos Serviços de Saúde/tendências , Humanos , Medicaid/tendências , Patentes como Assunto , Medicamentos sob Prescrição/administração & dosagem , Fatores de Tempo , Estados Unidos
17.
Int J Pharm ; 563: 273-281, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30664998

RESUMO

Pharmaceutical companies are relying more often on external sources of innovation to boost their discovery research productivity. However, more in-depth knowledge about how external innovation may translate to successful product launches is still required in order to better understand how to best leverage the innovation ecosystem. We analyzed the pre-approval publication histories for FDA-approved new molecular entities (NMEs) and new biologic entities (NBEs) launched by 13 top research pharma companies during the last decade (2006-2016). We found that academic institutions contributed the majority of pre-approval publications and that publication subject matter is closely aligned with the strengths of the respective innovator. We found this to also be true for candidate drugs terminated in Phase 3, but the volume of literature on these molecules is substantially less than for approved drugs. This may suggest that approved drugs are often associated with a more robust dataset provided by a large number of institutes. Collectively, the results of our analysis support the hypothesis that a collaborative research innovation environment spanning across academia, industry and government is highly conducive to successful drug approvals.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Indústria Farmacêutica/estatística & dados numéricos , Parcerias Público-Privadas , Produtos Biológicos , Estados Unidos , United States Food and Drug Administration , Universidades/estatística & dados numéricos
18.
Pharmacol Res ; 139: 166-172, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30408574

RESUMO

The aims of this study were to identify types of deficiencies resulting in delay of approvals for drugs eventually approved by the US FDA and to search for factors associated with higher first-cycle approval rates. Review documents of New Drug Applications approved between 2008 and 2017 were retrieved from the Drugs@FDA database. Basic characteristics of the applications, regulatory actions, and reasons for non-approvals and/or major amendments after first review cycle were investigated. Of 825 applications studied, 446 (54.1%) applications received first-cycle approvals without a review extension resulting from a major amendment. Non-approvals (240, 29.1%) were based primarily on chemistry/manufacturing/controls and safety reasons. A higher first-cycle approval rate was associated with factors related to unmet medical needs or innovative development. The association between higher first-cycle approval rates and innovative drugs or those addressing unmet needs reveals the FDA's commitment in advancing innovation and protecting public health.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Estados Unidos , United States Food and Drug Administration
19.
JAMA Pediatr ; 173(1): 68-74, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452498

RESUMO

Importance: Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies. Objective: To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act. Design and Setting: A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications. Main Outcomes and Measures: Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models. Results: Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information. Conclusions and Relevance: Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.


Assuntos
Pesquisa Biomédica/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Pediatria/legislação & jurisprudência , Vigilância de Produtos Comercializados/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Adolescente , Pesquisa Biomédica/normas , Pesquisa Biomédica/estatística & dados numéricos , Criança , Pré-Escolar , Rotulagem de Medicamentos/estatística & dados numéricos , Seguimentos , Humanos , Lactente , Recém-Nascido , Vigilância de Produtos Comercializados/normas , Modelos de Riscos Proporcionais , Projetos de Pesquisa/legislação & jurisprudência , Projetos de Pesquisa/normas , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration
20.
JAMA Pediatr ; 173(1): 60-67, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452504

RESUMO

Importance: The increasing prevalence of pediatric chronic disease has resulted in increased exposure to long-term drug therapy in children. The duration of recently completed drug trials that support approval for drug therapy in children with chronic diseases has not been systematically evaluated. Such information is a vital first step in forming safety pharmacovigilance strategies for drugs used for long-term therapy in children. Objective: To characterize the duration of clinical trials submitted to the US Food and Drug Administration (FDA) for pediatric drug approvals, with a focus on drugs used for long-term therapy. Design and Setting: A review was performed of all safety and efficacy clinical trials conducted under the Best Pharmaceuticals for Children Act or the Pediatric Research Equity Act and submitted to the FDA from September 1, 2007, to December 31, 2014, to support the approval of drugs frequently used for long-term therapy in children. Statistical analysis was performed from July 1, 2015, to December 31, 2017. Main Outcomes and Measures: Maximum duration of trials submitted to support FDA approval of drugs for children. Results: A total of 306 trials supporting 86 drugs intended for long-term use in children were eligible for the primary analysis. The drugs most commonly evaluated were for treatment of neurologic (25 [29%]), pulmonary (16 [19%]), and anti-infective (14 [16%]) indications. The median maximum trial duration by drug was 44 weeks (minimum, 1.1 week; maximum, 364 weeks). For nearly two-thirds of the drugs (52 [61%]), the maximum trial duration was less than 52 weeks. For 10 of the drugs (12%), the maximum trial duration was 3 years or more. Maximum duration of trials did not vary by therapeutic category, minimum age of enrollment, calendar year, or legislative mandate. Conclusions and Relevance: Pediatric clinical trials designed to sufficiently investigate drug safety and efficacy to support FDA approval are of relatively limited duration. Given the potential long-term exposure of patients to these drugs, the clinical community should consider whether new approaches are needed to better understand the safety associated with long-term use of these drugs.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/estatística & dados numéricos , Pediatria , United States Food and Drug Administration , Criança , Doença Crônica , Esquema de Medicação , Humanos , Farmacovigilância , Fatores de Tempo , Estados Unidos
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