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3.
Cell Host Microbe ; 27(5): 692-694, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32407706

RESUMO

The viruses causing the SARS outbreak of 2002-2003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes , Ensaios Clínicos como Assunto/normas , Humanos , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/normas
6.
J Dermatolog Treat ; 31(4): 330-332, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32343162

RESUMO

The COVID-19 pandemic has greatly impacted dermatology clinical trial operations due to mandated governmental and institutional shut-downs and newly implemented restrictions. During this unprecedented time, measures should be taken to maintain research conduct compliance while also ensuring the safety of trial staff and participants. Herein, we underscore the challenges facing dermatology trials during the COVID-19 pandemic, and offer strategies to maintain compliant and safe conduct.


Assuntos
Betacoronavirus , Ensaios Clínicos como Assunto , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Dermatopatias , Ensaios Clínicos como Assunto/organização & administração , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Transmissão de Doença Infecciosa do Profissional para o Paciente/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Dermatopatias/terapia
7.
J Infect Dis ; 221(11): 1752-1756, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32232474

RESUMO

Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.


Assuntos
Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Desenvolvimento de Medicamentos/tendências , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/normas , Betacoronavirus/imunologia , Humanos , Licenciamento
11.
Antiviral Res ; 177: 104762, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147496

RESUMO

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.


Assuntos
Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacologia , Antivirais/normas , Betacoronavirus/efeitos dos fármacos , China , Cloroquina/efeitos adversos , Cloroquina/farmacologia , Cloroquina/normas , Ensaios Clínicos como Assunto/normas , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/normas , Hidroxicloroquina/uso terapêutico , Pandemias
12.
Am J Phys Med Rehabil ; 99(3): 191-197, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32079896

RESUMO

OBJECTIVE: We examined and appraised the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement and its extension from the perspective of the reporting of comparison groups (ie, interventions or control conditions against which an experimental intervention is compared) in clinical trials on rehabilitation topics. DESIGN: We downloaded the CONSORT 2010 Statement and all endorsed and unofficial extensions reported on the CONSORT and EQUATOR Web sites. We extracted all statements on the selection, design, delivery, or interpretation of data from comparison groups in clinical trials. We discussed preliminary findings during the Cochrane Rehabilitation Methodology Meeting in Kobe and then further by email before finalizing results. RESULTS: We identified 23 standards reported across the CONSORT 2010 Statement and 10 extensions. Overall, these standards address many, but not all, issues related to reporting of comparison groups in rehabilitation trials. CONCLUSIONS: We recommend that additional standards be created for the selection of types of comparisons, choices around reporting of "usual care," reporting of intended "mechanisms of control," and reporting a rationale for the hypothesized superiority of one intervention over another when superiority trial design are used. Rehabilitation research would benefit from development of a specific checklist and guidelines to help researchers make best use of existing extensions.


Assuntos
Ensaios Clínicos como Assunto/normas , Guias como Assunto , Pesquisa de Reabilitação , Projetos de Pesquisa , Relatório de Pesquisa/normas , Humanos
13.
PLoS One ; 15(2): e0226143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069305

RESUMO

In June 2017, the International Committee of Medical Journal Editors (ICMJE) announced a requirement that authors reporting the results of clinical trials to journals that follow ICMJE recommendations must include an individual participant data (IPD) sharing statement with manuscripts submitted after 01 July 2018. Additionally, all new clinical trials for which enrollment began on or after 01 January 2019 must include a data sharing statement in the trial's publicly posted registration. This study sought to understand whether IPD sharing statements of clinical trials first registered on ClinicalTrials.gov before 01 January 2019 reflected comprehension of the expectations and a willingness to share. To establish baseline characteristics for the prevalence and quality of IPD sharing statements, we examined IPD sharing statements among 2,040 clinical trials first posted on ClinicalTrials.gov between 01 January 2018 and 06 June 2018. Two independent coders further analyzed the quality of the IPD sharing statements of trials whose registration records indicated the intent to share IPD. The vast majority of trials included in this study did not indicate an intent to share IPD (n = 1,928; 94.5%). Among the trials that did commit to sharing IPD (n = 112, 5.5%), significant variability existed in the content and structure of IPD sharing statements. The results of this study suggest that successful compliance with the IPD sharing statement requirements of the ICMJE will require further clarification, enhanced education, and outreach to investigators.


Assuntos
Ensaios Clínicos como Assunto/normas , Políticas Editoriais , Jornalismo Médico/normas , Manuscritos Médicos como Assunto , Escrita Médica/normas , Revelação , Humanos , Disseminação de Informação/métodos
15.
BMJ ; 368: l6802, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964641

RESUMO

OBJECTIVES: To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study). DESIGN: Meta-epidemiological study. DATA SOURCE: Cochrane Database of Systematic Reviews (2013-14). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Meta-analyses with both blinded and non-blinded trials on any topic. REVIEW METHODS: Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding. RESULTS: The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses. CONCLUSION: No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.


Assuntos
Ensaios Clínicos como Assunto , Projetos de Pesquisa Epidemiológica , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/organização & administração , Ensaios Clínicos como Assunto/normas , Humanos , Variações Dependentes do Observador , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Projetos de Pesquisa/normas
17.
PLoS One ; 15(1): e0227975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31968005

RESUMO

OBJECTIVES: Knee joint distraction (KJD) has been evaluated as a joint-preserving treatment to postpone total knee arthroplasty in knee osteoarthritis patients in three clinical trials. Since 2014 the treatment is used in regular care in some hospitals, which might lead to a deviation from the original indication and decreased treatment outcome. In this study, baseline characteristics, complications and clinical benefit are compared between patients treated in regular care and in clinical trials. METHODS: In our hospital, 84 patients were treated in regular care for 6 weeks with KJD. Surgical details, complications, and range of motion were assessed from patient hospital charts. Patient-reported outcome measures were evaluated in regular care before and one year after treatment. Trial patients (n = 62) were treated and followed as described in literature. RESULTS: Patient characteristics were not significantly different between groups, except for distraction duration (regular care 45.3±4.3; clinical trials 48.1±8.1 days; p = 0.019). Pin tract infections were the most occurring complication (70% regular care; 66% clinical trials), but there was no significant difference in treatment complications between groups (p>0.1). The range of motion was recovered within a year after treatment for both groups. WOMAC questionnaires showed statistically and clinically significant improvement for both groups (both p<0.001 and >15 points in all subscales) and no significant differences between groups (all differences p>0.05). After one year, 70% of patients were responders (regular care 61%, trial 75%; p = 0.120). Neither regular care compared to clinical trial, nor any other characteristic could predict clinical response. CONCLUSIONS: KJD as joint-preserving treatment in clinical practice, to postpone arthroplasty for end-stage knee osteoarthritis patient below the age of 65, results in an outcome similar to that thus far demonstrated in clinical trials. Longer follow-up in regular care is needed to test whether also long-term results remain beneficial and comparable to trial data.


Assuntos
Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Osteogênese por Distração/métodos , Osteogênese por Distração/normas , Adulto , Antibacterianos/administração & dosagem , Artroplastia do Joelho , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/fisiopatologia , Cartilagem Articular/cirurgia , Ensaios Clínicos como Assunto/normas , Fixadores Externos , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/normas , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Resultado do Tratamento
18.
Lancet ; 395(10221): 361-369, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958402

RESUMO

BACKGROUND: Failure to report the results of a clinical trial can distort the evidence base for clinical practice, breaches researchers' ethical obligations to participants, and represents an important source of research waste. The Food and Drug Administration Amendments Act (FDAAA) of 2007 now requires sponsors of applicable trials to report their results directly onto ClinicalTrials.gov within 1 year of completion. The first trials covered by the Final Rule of this act became due to report results in January, 2018. In this cohort study, we set out to assess compliance. METHODS: We downloaded data for all registered trials on ClinicalTrials.gov each month from March, 2018, to September, 2019. All cross-sectional analyses in this manuscript were performed on data extracted from ClinicalTrials.gov on Sept 16, 2019; monthly trends analysis used archived data closest to the 15th day of each month from March, 2018, to September, 2019. Our study cohort included all applicable trials due to report results under FDAAA. We excluded all non-applicable trials, those not yet due to report, and those given a certificate allowing for delayed reporting. A trial was considered reported if results had been submitted and were either publicly available, or undergoing quality control review at ClinicalTrials.gov. A trial was considered compliant if these results were submitted within 1 year of the primary completion date, as required by the legislation. We described compliance with the FDAAA 2007 Final Rule, assessed trial characteristics associated with results reporting using logistic regression models, described sponsor-level reporting, examined trends in reporting, and described time-to-report using the Kaplan-Meier method. FINDINGS: 4209 trials were due to report results; 1722 (40·9%; 95% CI 39·4-42·2) did so within the 1-year deadline. 2686 (63·8%; 62·4-65·3) trials had results submitted at any time. Compliance has not improved since July, 2018. Industry sponsors were significantly more likely to be compliant than non-industry, non-US Government sponsors (odds ratio [OR] 3·08 [95% CI 2·52-3·77]), and sponsors running large numbers of trials were significantly more likely to be compliant than smaller sponsors (OR 11·84 [9·36-14·99]). The median delay from primary completion date to submission date was 424 days (95% CI 412-435), 59 days higher than the legal reporting requirement of 1 year. INTERPRETATION: Compliance with the FDAAA 2007 is poor, and not improving. To our knowledge, this is the first study to fully assess compliance with the Final Rule of the FDAAA 2007. Poor compliance is likely to reflect lack of enforcement by regulators. Effective enforcement and action from sponsors is needed; until then, open public audit of compliance for each individual sponsor may help. We will maintain updated compliance data for each individual sponsor and trial at fdaaa.trialstracker.net. FUNDING: Laura and John Arnold Foundation.


Assuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Comportamento Cooperativo , Relatório de Pesquisa/legislação & jurisprudência , Pesquisa Biomédica/legislação & jurisprudência , Ensaios Clínicos como Assunto/normas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estudos de Coortes , Revelação/legislação & jurisprudência , Revelação/normas , Revelação/estatística & dados numéricos , Humanos , Sistema de Registros , Relatório de Pesquisa/normas , Estados Unidos , United States Food and Drug Administration
20.
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
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