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1.
Trials ; 21(1): 1028, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353566

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information and inform the development of harm profiles of new treatments. Harms are typically assessed through the collection of adverse events (AEs). Despite AEs being routine outcomes collected in trials, analysis and reporting of AEs in journal articles are continually shown to be suboptimal. One key challenge is the large volume of AEs, which can make evaluation and communication problematic. Prominent practice is to report frequency tables of AEs by arm. Visual displays offer an effective solution to assess and communicate complex information; however, they are rarely used and there is a lack of practical guidance on what and how to visually display complex AE data. METHODS: In this article, we demonstrate the use of two plots identified to be beneficial for wide use in RCTs, since both can display multiple AEs and are suitable to display point estimates for binary, count, or time-to-event AE data: the volcano and dot plots. We compare and contrast the use of data visualisations against traditional frequency table reporting, using published AE information in two placebo-controlled trials, of remdesivir for COVID-19 and GDNF for Parkinson disease. We introduce statistical programmes for implementation in Stata. RESULTS/CASE STUDY: Visualisations of AEs in the COVID-19 trial communicated a risk profile for remdesivir which differed from the main message in the published authors' conclusion. In the Parkinson's disease trial of GDNF, the visualisation provided immediate communication of harm signals, which had otherwise been contained within lengthy descriptive text and tables. Asymmetry in the volcano plot helped flag extreme events that were less obvious from review of the frequency table and dot plot. The dot plot allowed a more comprehensive representation by means of a more detailed summary. CONCLUSIONS: Visualisations can better support investigators to assimilate large volumes of data and enable improved informal between-arm comparisons compared to tables. We endorse increased uptake for use in trial publications. Care in construction of visual displays needs to be taken as there can be potential to overemphasise treatment effects in some circumstances.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Apresentação de Dados , Visualização de Dados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Projetos de Pesquisa/normas , Monofosfato de Adenosina/efeitos adversos , Alanina/efeitos adversos , Antiparkinsonianos/efeitos adversos , Antivirais/efeitos adversos , Gráficos por Computador , Confiabilidade dos Dados , Análise de Dados , Monitoramento de Medicamentos/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Rev Esp Salud Publica ; 942020 Nov 03.
Artigo em Espanhol | MEDLINE | ID: mdl-33140740

RESUMO

OBJECTIVE: The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease. METHODS: This work analyses the evaluation conducted by our Regional Ethics Committees during the initial period of the health emergency (between 13th March and 28th May 2020). RESULTS: 81 research projects were evaluated, 73 of them of regional scope (62 single-centre), 4 national and 4 international. 57 projects obtained a favourable opinion, 4 were withdrawn by the sponsors, 6 did not require ethics approval and 14 did not respond to the clarifications requested up to the date of the study's closure. CONCLUSIONS: The most important research procedures to be analysed in this context are those related to the methodology and informed consent process. It is also essential to address aspects related to the privacy of personal data, and to take into account the workload of the researchers. As an improvement proposal, we think that greater collaboration between the different research teams should be encourage to obtain more robust results.


Assuntos
Infecções por Coronavirus/epidemiologia , Comitês de Ética em Pesquisa , Pneumonia Viral/epidemiologia , Projetos de Pesquisa/normas , Fluxo de Trabalho , Betacoronavirus , Humanos , Consentimento Livre e Esclarecido , Pandemias , Espanha
4.
Respir Med ; 174: 106203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147562

RESUMO

BACKGROUND: Although many patients with coronavirus disease 2019 (Covid-19) require direct admission to the intensive care unit (ICU), some are sent after admission. Clinicians require an understanding of this phenomenon and various risk stratification approaches for recognizing these subjects. METHODS: We examined all Covid-19 patients sent initially to a ward who subsequently required care in the ICU. We examined the timing transfer and attempted to develop a risk score based on baseline variables to predict progressive disease. We evaluated the utility of the CURB-65 score at identifying the need for ICU transfer. RESULTS: The cohort included 245 subjects (mean age 59.0 ± 14.2 years, 61.2% male) and 20% were eventually sent to the ICU. The median time to transfer was 2.5 days. Approximately 1/3rd of patients were not moved until day 4 or later and the main reason for transfer (79.2%) was worsening respiratory failure. A baseline absolute lymphocyte count (ALC) of ≤0.8 103/ml and a serum ferritin ≥1000 ng/ml were independently associated with ICU transfer. Co-morbid illnesses did not correlate with eventual ICU care. Neither a risk score based on a low ALC and/or high ferritin nor the CURB-65 score performed well at predicting need for transfer. CONCLUSION: Covid-19 patients admitted to general wards face a significant risk for deterioration necessitating ICU admission and respiratory failure can occur late in this disease. Neither baseline clinical factors nor the CURB-65 score perform well as screening tests to categorize these subjects as likely to progress to ICU care.


Assuntos
/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Transferência de Pacientes/organização & administração , /genética , /complicações , Comorbidade , Feminino , Ferritinas/sangue , Hospitalização , Humanos , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Pandemias/estatística & dados numéricos , Projetos de Pesquisa/normas , Projetos de Pesquisa/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
7.
Medicine (Baltimore) ; 99(43): e22840, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120812

RESUMO

Up-to-date information on the current progress made in the research and development to control the global COVID-19 pandemic is important. The study aimed to analyze the clinical trial characteristics and vaccine development progress of the new Coronavirus Disease 2019 (COVID-19) registered with the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP).A comprehensive search of COVID-19 clinical trials since the establishment of the ICTRP to June 11, 2020, was conducted to record and analyze relevant characteristics. Chi-Squared test was used to compare the statistical differences between different research types, interventions, and sources.A total of 3282 COVID-19 clinical trials in 17 clinical trial registration centers were registered with the WHO ICTRP. The main research sources for the present study were ClinicalTrials.gov and ChiCTR. There were significant differences in the parameters of study location (P = .000), number of participants (P = .000), study duration (P = .001), research stage (P = .000), randomization procedure (P = .000), and blinding method (P = .000) between the 2 registration sources. There were significant differences in all the parameters between different kinds of intervention methods. Hydroxychloroquine, plasma therapy, and Xiyanping injection were the high-frequency research drugs used. Ten different vaccine studies were registered under phases I-II.Amongst the studies researched, heterogeneity existed for various parameters. Differences in the type of study, interventions, and registration sources of the studies led to significant differences in certain parameters of the COVID-19 clinical trials. The statistics of high-frequency drugs and the progress of vaccine trials may provide an informative reference for the prevention and control of COVID-19.


Assuntos
Betacoronavirus , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Sistema de Registros , Projetos de Pesquisa , Organização Mundial da Saúde , Ensaios Clínicos como Assunto/normas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias , Melhoria de Qualidade , Projetos de Pesquisa/normas , Projetos de Pesquisa/estatística & dados numéricos , Vacinas Virais
13.
PLoS One ; 15(10): e0240159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33079927

RESUMO

Replication is an important tool to promote high quality research and ensure policy makers can rely on studies in making guidelines or funding programs. By ensuring influential studies are replicable we provide assurance that the policies based on these studies are well-founded and the conclusions and recommendations are robust-to different estimation models or different choices. In this paper, we argue that replication is not only useful but necessary to ensure that an author's choice in how to analyse data is not the only factor that determines whether an intervention is effective or not. We also show that while most research is done well and provides robust results, small differences can lead to different interpretations and these differences need to be acknowledged. This special issue highlights 5 such replication studies, which are replications of influential studies on biomedical, social, behavioural and structural interventions for HIV prevention and treatment. We reflect on their findings. Four out of five studies, which conduct push button replication and pure replication, were able to reproduce the results of the original studies with minor differences, mainly due to minor typographical errors or rounding differences. The analysis of the measurement and estimation analyses conducted in these five studies reveals that the original results are not very robust to alternative analytical approaches, especially when these results rely on a small number of observations. In these cases, the original results are weakened. Furthermore, in contrast to the original papers, two of the five included replication studies conducted a theory of change analysis-to explore how or why the interventions work (or do not) not just whether the intervention works or not. These two analyses indicate that the estimated impacts of the interventions are drawn from few mediators. In addition, they demonstrate that, in some cases, a lack of effect may be related to lack of adequate exposure to the intervention rather than inefficacy of the intervention per se. However, overall, the included replication studies show that the results presented in the original papers are trustworthy and robust, especially when based on larger sample sizes. Replication studies can not only verify the results of a study, they can also provide additional insights on the published results, such as how and why an intervention was effective or less effective than expected. They can thus be a tool to inform the research community and/ or policymakers about whether and how interventions could be adopted, which need to be tested further, and which should be discontinued because of their ineffectiveness. Thus, publishing these replication studies in peer-reviewed journals makes the work public and publicized. The work advances knowledge, and publication should be encouraged, as it is for other types of research.


Assuntos
Pesquisa Biomédica/normas , Infecções por HIV/terapia , Projetos de Pesquisa/normas , Fármacos Anti-HIV/uso terapêutico , Terapia Comportamental/métodos , Pesquisa Biomédica/economia , Humanos , Revisão da Pesquisa por Pares , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Apoio à Pesquisa como Assunto/economia , Apoio à Pesquisa como Assunto/normas , Apoio Social
14.
PLoS One ; 15(10): e0228762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33001987

RESUMO

Single-centre studies examining the transgenerational inheritance of pathologies in rodents exposed to pesticides have not always taken important design and analysis issues into account. This paper examines these methodological and statistical issues in detail. Its particular focus is on the estimation of 'litter effects': the tendency for rodents within a litter to be more alike than rodents in different litters. Appropriate statistical models were fitted to published data from a series of widely reported studies carried out at Washington State University. These studies were amalgamated into a single dataset in order to estimate these litter effects and associated treatment effects. Litter effects varied by outcome and were often substantial. Consequently, the effective sample size was often substantially less than the number of observations with implications for the power of the studies. Moreover, the reported precision of the estimates of treatment effects was too low. These problems are exacerbated by unexplained missing data across generations. Researchers in the life sciences could be more cognisant of the guidelines established in medicine for reporting randomised controlled trials, particularly cluster randomised trials. More attention should be paid to the design and analysis of multi-generational rodent studies; their imperfections have important implications for assessments of the evidence relating to the risks of pesticides for public health.


Assuntos
Hereditariedade , Modelos Estatísticos , Projetos de Pesquisa/normas , Roedores , Estruturas Animais/efeitos dos fármacos , Estruturas Animais/patologia , Animais , Humanos , Modelos Animais , Praguicidas/efeitos adversos , Saúde Pública , Tamanho da Amostra , Washington
15.
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
16.
J Gen Intern Med ; 35(11): 3308-3314, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32885373

RESUMO

BACKGROUND: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. OBJECTIVE: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. METHODS: Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach. RESULTS: We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. AUTHORS' CONCLUSION: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.


Assuntos
/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Viés , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos , Projetos de Pesquisa/normas , Resultado do Tratamento
17.
Dev Cogn Neurosci ; 45: 100834, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32906086

RESUMO

The YOUth cohort study aims to be a trailblazer for open science. Being a large-scale, longitudinal cohort following children in their development from gestation until early adulthood, YOUth collects a vast amount of data through a variety of research techniques. Data are collected through multiple platforms, including facilities managed by Utrecht University and the University Medical Center Utrecht. In order to facilitate appropriate use of its data by research organizations and researchers, YOUth aims to produce high-quality, FAIR data while safeguarding the privacy of participants. This requires an extensive data infrastructure, set up by collaborative efforts of researchers, data managers, IT departments, and the Utrecht University Library. In the spirit of open science, YOUth will share its experience and expertise in setting up a high-quality research data infrastructure for sensitive cohort data. This paper describes the technical aspects of our data and data infrastructure, and the steps taken throughout the study to produce and safely store FAIR and high-quality data. Finally, we will reflect on the organizational aspects that are conducive to the success of setting up such an enterprise, and we consider the financial challenges posed by individual studies investing in sustainable science.


Assuntos
Gerenciamento de Dados/métodos , Projetos de Pesquisa/normas , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino
18.
Nat Med ; 26(9): 1364-1374, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908283

RESUMO

The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.


Assuntos
Inteligência Artificial , Revisão da Pesquisa por Pares/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa/normas , Humanos , Relatório de Pesquisa/normas
19.
Nat Med ; 26(9): 1351-1363, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908284

RESUMO

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.


Assuntos
Inteligência Artificial , Ensaios Clínicos como Assunto/métodos , Projetos de Pesquisa/normas , Humanos
20.
J Am Med Inform Assoc ; 27(9): 1476-1487, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32940705

RESUMO

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) outbreak progressed rapidly from a public health (PH) emergency of international concern (World Health Organization [WHO], 30 January 2020) to a pandemic (WHO, 11 March 2020). The declaration of a national emergency in the United States (13 March 2020) necessitated the addition and modification of terminology related to COVID-19 and development of the disease's case definition. During this period, the Centers for Disease Control and Prevention (CDC) and standard development organizations released guidance on data standards for reporting COVID-19 clinical encounters, laboratory results, cause-of-death certifications, and other surveillance processes for COVID-19 PH emergency operations. The CDC COVID-19 Information Management Repository was created to address the need for PH and health-care stakeholders at local and national levels to easily obtain access to comprehensive and up-to-date information management resources. MATERIALS AND METHODS: We introduce the clinical and health-care informatics community to the CDC COVID-19 Information Management Repository: a new, national COVID-19 information management tool. We provide a description of COVID-19 informatics resources, including data requirements for COVID-19 data reporting. RESULTS: We demonstrate the CDC COVID-19 Information Management Repository's categorization and management of critical COVID-19 informatics documentation and standards. We also describe COVID-19 data exchange standards, forms, and specifications. CONCLUSIONS: This information will be valuable to clinical and PH informaticians, epidemiologists, data analysts, standards developers and implementers, and information technology managers involved in the development of COVID-19 situational awareness and response reporting and analytics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Gestão da Informação em Saúde , Pandemias , Pneumonia Viral , Vocabulário Controlado , Centers for Disease Control and Prevention, U.S. , Infecções por Coronavirus/epidemiologia , Assistência à Saúde , Interoperabilidade da Informação em Saúde , Gestão da Informação em Saúde/organização & administração , Gestão da Informação em Saúde/normas , Humanos , Disseminação de Informação , Laboratórios , Pneumonia Viral/epidemiologia , Saúde Pública , Projetos de Pesquisa/normas , Estados Unidos
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