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3.
Lancet Respir Med ; 7(11): 939-940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31645282
4.
J Law Med Ethics ; 47(3): 381-387, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31560631

RESUMO

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

5.
JAMA Netw Open ; 2(7): e197591, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31339546

RESUMO

Importance: The US Food and Drug Administration (FDA) created the exception from informed consent (EFIC) pathway in 1996 to allow some emergency trials to enroll patients without informed consent. To protect individual autonomy and preserve public trust, the FDA requires that EFIC trial investigators consult with community members before a trial may begin. Objectives: To analyze data from surveys conducted as part of community consultation ahead of EFIC trials and assess levels of public approval. Data Sources: All trials granted an EFIC must submit documentation of compliance with EFIC regulations to a publicly available docket at the FDA. Submissions between November 1, 1996, and October 23, 2017, were reviewed. Study Selection: Trials with survey data were included. Data Extraction and Synthesis: Data were extracted between January 2018 and June 2018 and were analyzed between June 2018 and August 2018. The quality and validity of data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A random-effects metaregression was used to assess the association of demographic characteristics with EFIC approval. Main Outcomes and Measures: The primary study outcome was EFIC approval. Results: The FDA docket contained 15 958 pages of material with survey data for 42 448 individuals submitted by 27 trials. Public approval of EFIC varied by question type, with more people willing to approve initiation of EFIC trials in their community (86.5%) than personal enrollment (73.0%), enrollment of a family member (68.6%), or the principle of enrollment without consent (58.4%) (P < .001 for all comparisons). In the United States, African American individuals made up 29.3% of those enrolled in EFIC trials that reported data on race (5064 of 17 302) but only 16.7% of those surveyed as part of community consultation. In the United States and Canada, men made up 42.9% of the surveyed population but 65.6% of those eventually enrolled in EFIC trials (29 961 of 45 694). Groups surveyed with higher proportions of African American and male respondents had lower rates of EFIC approval. Conclusions and Relevance: Public approval of EFIC trials varied by question type and by the respondents' reported race and sex. The demographic characteristics of those surveyed did not match the demographic characteristics of EFIC enrollees. The FDA could strengthen community consultation by standardizing survey instruments and reporting, requiring broader inclusion of African American and male respondents, clarifying the function of surveys in the development and modification of trial protocols, and building more public consensus around the acceptable use of EFIC.

6.
Health Aff (Millwood) ; 37(10): 1605-1614, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30273035

RESUMO

In 1996 the Food and Drug Administration (FDA) created an "exception from informed consent" (EFIC) pathway for trials conducted on people incapacitated by life-threatening conditions with a therapeutic time window too narrow for reliable surrogate consent. The goals were to promote therapeutic innovation and encourage rigorous but ethical experimentation on this vulnerable population. To evaluate outcomes of this pathway, we reviewed the complete FDA docket of EFIC trials from the past two decades, encompassing forty-one trials. Among the 46,964 patients included in this review, ninety-six percent were enrolled without consent, and fewer than 1 percent withdrew before the primary endpoint. Two (8 percent) of the twenty-four superiority trials demonstrated a benefit from the experimental interventions. Many interventions were associated with adverse effects, including increased mortality, neurological deficits, and myocardial infarctions. Nearly one-third of US patients in EFIC trials were African American. While EFIC trials have yielded medical advances, investigators in future trials must pay better attention to managing withdrawals and ensuring fair demographic representation.


Assuntos
Consentimento Livre e Esclarecido , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa/normas , United States Food and Drug Administration , Afro-Americanos/estatística & dados numéricos , Humanos , Projetos de Pesquisa/tendências , Estados Unidos
7.
9.
Stroke ; 48(3): 799-801, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28104835

RESUMO

BACKGROUND AND PURPOSE: Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. METHODS: Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. RESULTS: The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 (P=0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 (P=0.13). CONCLUSIONS: For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined.


Assuntos
Ensaios Clínicos como Assunto , Seleção de Pacientes , Acidente Vascular Cerebral/terapia , Humanos , Sistema de Registros/estatística & dados numéricos , Fatores de Tempo
10.
Neurology ; 86(16): 1543-51, 2016 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-27009262

RESUMO

There is urgent need for clinical trials of novel interventions to reduce the burden of acute ischemic stroke. A key impediment to such trials is slow recruitment. Since obtaining written informed consent in the setting of acute stroke is especially challenging, some experts have endorsed relaxing the requirement for informed consent by permitting verbal consent or waivers to facilitate recruitment. This systematic review of 36 randomized controlled trials of acute interventions for ischemic stroke assesses whether alternatives to written informed consent are associated with increased recruitment rates. After the exclusion of 2 outlier trials that differed from other trials in conduct and interventions studied, no association was observed on univariable analysis (8.9 participants/month in trials requiring written consent vs 6.1 participants/month in trials with alternatives, p = 0.43) or multivariable analysis (when adjusting for the number of centers, number of countries, and exclusions based on modified Rankin Scale scores). Alternatives to written informed consent in acute stroke trials may enable trial designs that would not be feasible otherwise. However, we did not find evidence that, within traditional trial designs, such alternatives are associated with faster recruitment.


Assuntos
Consentimento Livre e Esclarecido , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia
12.
J Neurosurg Spine ; 19(4): 471-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23971762

RESUMO

OBJECT: Myxopapillary ependymomas (MPEs) are rare WHO Grade I tumors found in the conus medullaris, cauda equina, and filum terminale. Treatment generally consists of resection with or without adjuvant radiotherapy. Evidence-based guidelines for surgical management are lacking due to the rarity of this tumor. METHODS: An English-language PubMed search was performed using the key words "myxopapillary" and "ependymoma." Reports describing fewer than 3 patients or those lacking data on the extent of resection or radiotherapy were excluded. A total of 28 articles describing 475 patients met the authors' inclusion criteria. Patients were grouped by extent of resection and whether or not they underwent adjuvant radiotherapy. Differences in recurrence rates were assessed by chi-square test. RESULTS: The overall recurrence rate was 15.5% in patients treated by gross-total resection (GTR) and 32.6% in patients treated by subtotal resection (STR), irrespective of whether they underwent adjuvant therapy (p < 0.001). Regardless of the extent of resection, adjuvant radiotherapy was not associated with a decrease in recurrence rates. The overall recurrence rate was 15.6% in patients who underwent GTR and radiotherapy compared with 15.9% in patients who underwent GTR alone (p = 0.58), and it was 29.3% in patients who underwent STR and radiotherapy compared with 35.1% in those who underwent STR alone (p = 0.53). The difference between recurrence rates for patients who underwent GTR alone versus STR and radiotherapy was statistically significant (p = 0.02). Subgroup analysis demonstrated significantly higher recurrence rates in pediatric patients compared with adults (40.5% vs 23.4%, respectively; p = 0.02). Even in the setting of GTR alone, recurrence rates were higher in pediatric patients (65% vs 7.6%; p < 0.001). CONCLUSIONS: Gross-total resection alone is associated with decreased recurrence rates compared with STR with or without radiotherapy. The authors' results suggest that treatment goals should include attempted GTR whenever possible. The observation that children benefitted from radiation therapy to a greater extent than did adults suggests that biological differences between tumors in these patient populations warrants more rigorous scientific studies.


Assuntos
Ependimoma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Adulto , Fatores Etários , Criança , Terapia Combinada , Ependimoma/patologia , Ependimoma/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Radioterapia Adjuvante , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
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