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1.
Lancet Oncol ; 21(10): e488-e494, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002444

RESUMO

Patient-reported outcome (PRO) measures describe how a patient feels or functions and are increasingly being used in benefit-risk assessments in the development of cancer drugs. However, PRO research objectives are often ill-defined in clinical cancer trials, which can lead to misleading conclusions about patient experiences. The estimand framework is a structured approach to aligning a clinical trial objective with the study design, including endpoints and analysis. The estimand framework uses a multidisciplinary approach and can improve design, analysis, and interpretation of PRO results. On the basis of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use E9(R1) addendum, we provide an overview of the estimand framework intended for a multistakeholder audience. We apply the estimand framework to a hypothetical trial for breast cancer, using physical function to develop specific PRO research objectives. This Policy Review is not an endorsement of a specific study design or outcome; rather, it is meant to show the application of principles of the estimand framework to research study design and add to ongoing discussion. Use of the estimand framework to review medical products and label PROs in oncology can improve communication between stakeholders and ultimately provide a clearer interpretation of patient experience in the development of oncological drugs.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Oncologia/normas , Medidas de Resultados Relatados pelo Paciente , Antineoplásicos/uso terapêutico , Interpretação Estatística de Dados , Desenvolvimento de Medicamentos/legislação & jurisprudência , Desenvolvimento de Medicamentos/normas , Humanos , Comunicação Interdisciplinar , Oncologia/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Projetos de Pesquisa/normas
3.
PLoS One ; 15(9): e0238290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946464

RESUMO

A well-defined protocol for a clinical trial guarantees a successful outcome report. When designing the protocol, most researchers refer to electronic databases and extract protocol elements using a keyword search. However, state-of-the-art database systems only offer text-based searches for user-entered keywords. In this study, we present a database system with a context-dependent and protocol-element-selection function for successfully designing a clinical trial protocol. To do this, we first introduce a database for a protocol retrieval system constructed from individual protocol data extracted from 184,634 clinical trials and 13,210 frame structures of clinical trial protocols. The database contains a variety of semantic information that allows the filtering of protocols during the search operation. Based on the database, we developed a web application called the clinical trial protocol database system (CLIPS; available at https://corus.kaist.edu/clips). This system enables an interactive search by utilizing protocol elements. To enable an interactive search for combinations of protocol elements, CLIPS provides optional next element selection according to the previous element in the form of a connected tree. The validation results show that our method achieves better performance than that of existing databases in predicting phenotypic features.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos como Assunto/normas , Biologia Computacional/métodos , Bases de Dados Factuais , Armazenamento e Recuperação da Informação , Software , Humanos , Interface Usuário-Computador
6.
Ann Epidemiol ; 49: 50-60, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791199

RESUMO

PURPOSE: The U.S. response to the SARS-CoV-2 epidemic has been hampered by early and ongoing delays in testing for infection; without data on where infections were occurring and the magnitude of the epidemic, early public health responses were not data-driven. Understanding the prevalence of SARS-CoV-2 infections and immune response is critical to developing and implementing effective public health responses. Most serological surveys have been limited to localities that opted to conduct them and/or were based on convenience samples. Moreover, results of antibody testing might be subject to high false positive rates in the setting of low prevalence of immune response and imperfect test specificity. METHODS: We will conduct a national serosurvey for SARS-CoV-2 PCR positivity and immune experience. A probability sample of U.S. addresses will be mailed invitations and kits for the self-collection of anterior nares swab and finger prick dried blood spot specimens. Within each sampled household, one adult 18 years or older will be randomly selected and asked to complete a questionnaire and to collect and return biological specimens to a central laboratory. Nasal swab specimens will be tested for SARS-CoV-2 RNA by RNA PCR; dried blood spot specimens will be tested for antibodies to SARS-CoV-2 (i.e., immune experience) by enzyme-linked immunoassays. Positive screening tests for antibodies will be confirmed by a second antibody test with different antigenic basis to improve predictive value of positive (PPV) antibody test results. All persons returning specimens in the baseline phase will be enrolled into a follow-up cohort and mailed additional specimen collection kits 3 months after baseline. A subset of 10% of selected households will be invited to participate in full household testing, with tests offered for all household members aged ≥3 years. The main study outcomes will be period prevalence of infection with SARS-CoV-2 and immune experience, and incidence of SARS-CoV-2 infection and antibody responses. RESULTS: Power calculations indicate that a national sample of 4000 households will facilitate estimation of national SARS-CoV-2 infection and antibody prevalence with acceptably narrow 95% confidence intervals across several possible scenarios of prevalence levels. Oversampling in up to seven populous states will allow for prevalence estimation among subpopulations. Our 2-stage algorithm for antibody testing produces acceptable PPV at prevalence levels ≥1.0%. Including oversamples in states, we expect to receive data from as many as 9156 participants in 7495 U.S. households. CONCLUSIONS: In addition to providing robust estimates of prevalence of SARS-CoV-2 infection and immune experience, we anticipate this study will establish a replicable methodology for home-based SARS-CoV-2 testing surveys, address concerns about selection bias, and improve positive predictive value of serology results. Prevalence estimates of SARS-CoV-2 infection and immune experience produced by this study will greatly improve our understanding of the spectrum of COVID-19 disease, its current penetration in various demographic, geographic, and occupational groups, and inform the range of symptoms associated with infection. These data will inform resource needs for control of the ongoing epidemic and facilitate data-driven decisions for epidemic mitigation strategies.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Coronavirus/genética , Pneumonia Viral/diagnóstico , RNA Viral/isolamento & purificação , Betacoronavirus , Protocolos de Ensaio Clínico como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia
7.
J Card Surg ; 35(10): 2754-2758, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32720394

RESUMO

INTRODUCTION: The impact of sex on the outcomes after coronary artery bypass grafting (CABG) is controversial. The majority of CABG studies are retrospectively collected clinical or registry data, women comprise only a minority, and the reported findings represent the male predominated cohort. This individual patient meta-analysis is aimed at evaluating sex-related differences in outcomes after CABG using high quality data from randomized controlled trials (RCTs). METHODS AND ANALYSIS: A systematic literature search will be performed to identify all CABG RCTs (minimum follow-up: 5 years). Detailed specification for the minimum deidentified patient records' data requirements will be provided to RCT primary contact to request their deidentified data for pooling. The pooled analysis will follow the prospective register of systematic reviews (PROSPERO) and the preferred reporting items for systematic reviews and meta-analyses for individual patient data systematic reviews (PRISMA-IPD) recommendations and will compare sex-related outcomes after CABG. The main hypothesis is that outcomes after CABG are worse in women than in men. We will also test whether treatment effects for off-pump and the use of multiple arterial grafts are present within each sex, and also, whether there are differential treatment effects between sexes. The primary endpoint will be a composite of all-cause mortality, myocardial infarction, stroke, and repeat revascularization at long-term follow up. ETHICS AND DISSEMINATION: Ethics approval and participant consent for the study will be obtained locally by each study team if needed. Data will be disseminated and submitted to peer-reviewed scientific journals and meetings irrespective of study outcome.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Protocolos de Ensaio Clínico como Assunto , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Infarto do Miocárdio , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação , Fatores Sexuais , Acidente Vascular Cerebral , Resultado do Tratamento
8.
BMC Infect Dis ; 20(1): 405, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522244

RESUMO

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.


Assuntos
Antibacterianos/uso terapêutico , Cefixima/uso terapêutico , Sífilis/tratamento farmacológico , Brasil/epidemiologia , Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Penicilina G Benzatina/uso terapêutico , Distribuição Aleatória , Sífilis/microbiologia , Sífilis/prevenção & controle , Resultado do Tratamento , Treponema pallidum/efeitos dos fármacos , Treponema pallidum/isolamento & purificação
9.
Nat Commun ; 11(1): 2685, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483209

RESUMO

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.


Assuntos
Ensaios Clínicos como Assunto/métodos , Filariose Linfática/tratamento farmacológico , Filaricidas/uso terapêutico , Oncocercose/tratamento farmacológico , Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos como Assunto/estatística & dados numéricos , Simulação por Computador , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Humanos , Ivermectina/uso terapêutico , Modelos Biológicos , Oncocercose/parasitologia , Oncocercose/transmissão
10.
J Neurol Sci ; 415: 116935, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32534807

RESUMO

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.


Assuntos
Betacoronavirus/efeitos dos fármacos , Protocolos de Ensaio Clínico como Assunto , Infecções por Coronavirus/tratamento farmacológico , Leucovorina/uso terapêutico , Metotrexato/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Gerenciamento Clínico , Humanos , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Pandemias
12.
Crit Care Resusc ; 22(2): 133-141, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389105

RESUMO

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.


Assuntos
Glicemia/metabolismo , Protocolos de Ensaio Clínico como Assunto , Cuidados Críticos , Diabetes Mellitus Tipo 2/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Austrália , Doença Crônica , Estado Terminal , Diabetes Mellitus Tipo 2/sangue , Humanos , Nova Zelândia
14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(2): 158-162, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32400991

RESUMO

Guidance and reference are provided for protocol designer. The classification of laser medical devices are introduced. The key points such as the selection of control group, evaluation indicators and method, criteria of inclusion and exclusion, and application of blinded, etc. are discussed, and the importance of management of defects in medical device is emphasized.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Equipamentos e Provisões , Lasers , Projetos de Pesquisa
15.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1232-1241, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281330

RESUMO

To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , China , Humanos , Medicina Tradicional Chinesa , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
18.
Cell ; 180(1): 9-14, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31951522

RESUMO

This commentary introduces a new clinical trial construct, the Master Observational Trial (MOT), which hybridizes the power of molecularly based master interventional protocols with the breadth of real-world data. The MOT provides a clinical venue to allow molecular medicine to rapidly advance, answers questions that traditional interventional trials generally do not address, and seamlessly integrates with interventional trials in both diagnostic and therapeutic arenas. The result is a more comprehensive data collection ecosystem in precision medicine.


Assuntos
Estudos Observacionais como Assunto/métodos , Medicina de Precisão/métodos , Projetos de Pesquisa/normas , Big Data , Protocolos de Ensaio Clínico como Assunto , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Estudos Observacionais como Assunto/normas
19.
Am J Bioeth ; 20(1): 31-39, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31896328

RESUMO

Comparative effectiveness studies, referred to here as "usual-care" trials, seek to compare current medical practices for the same medical condition. Such studies are presumed to be safe and involve only minimal risks. However, that presumption may be flawed if the trial design contains "unusual" care, resulting in potential risks to subjects and inaccurately informed consent. Three case studies described here did not rely on clinical evidence to ascertain contemporaneous practice. As a result, the investigators drew inaccurate conclusions, misinformed research participants, and subjects' safety was compromised. Before approving usual-care protocols, IRBs and scientific review committees should evaluate the quality and completeness of information documenting usual-care practices. Guidance from governmental oversight agencies regarding evidence-based documentation of current clinical practice could prevent similar occurrences in future usual-care trials. Accurate information is necessary to ensure that trials comply with government regulations that require minimizing research risks to subjects and accurate informed consent documents.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos como Assunto/ética , Revisão Ética/normas , Projetos de Pesquisa/normas , Erro Experimental/ética , Padrão de Cuidado , Comitês de Ética em Pesquisa , Humanos , Consentimento Livre e Esclarecido , Sujeitos da Pesquisa
20.
Clin Trials ; 17(1): 99-105, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31450958

RESUMO

BACKGROUND: To improve reporting transparency and research integrity, some journals have begun publishing study protocols and statistical analysis plans alongside trial publications. We sought to assess the overall availability and characteristics of protocols and statistical analysis plans of randomized clinical trials published in the top five (by impact factor) general medicine journals. METHODS: All randomized clinical trials published in Annals of Internal Medicine, BMJ, JAMA, Lancet, and NEJM in 2016 were identified. For each randomized clinical trial, we searched for protocols and statistical analysis plans on journal websites (including supplementary material) and in the article, for example, a referenced publication or link to trial or institutional website. Characteristics of randomized clinical trials were extracted from the publication and clinical trial registry. A detailed assessment of protocols and statistical analysis plans was conducted in a 20% random sample of randomized clinical trials. RESULTS: Protocols were available for 299 (82%) trials, ranging from 50% in BMJ to >95% in NEJM and JAMA. Statistical analysis plans were available for 182 (50%) trials and varied from <10% for Annals of Internal Medicine, BMJ, and Lancet to 92% for NEJM. Of the 76 randomized clinical trials in the 20% random sample, 63 (83%) had a protocol but less than half (31; 44%) included an a priori (dated prior to patient enrollment) version of the protocol. Statistical analysis plans were available for 35 (46%) trials, and only 5 (7%) included an a priori version. CONCLUSION: Protocols and statistical analysis plans are publicly available for the majority of trials. However, the a priori versions of these documents are only available for a minority of trials. More attention must be paid to ensuring the public availability of a priori versions.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Publicações Periódicas como Assunto , Editoração , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Transversais , Humanos , Fator de Impacto de Revistas , Modelos Estatísticos , Projetos de Pesquisa
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