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1.
Stroke ; 51(8): 2411-2417, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640944

RESUMO

BACKGROUND AND PURPOSE: Patient-centered care prioritizes patient beliefs and values towards wellbeing. We aimed to map functional status (modified Rankin Scale [mRS] scores) and health-related quality of life on the European Quality of Life 5-dimensional questionnaire (EQ-5D) to derive utility-weighted (UW) stroke outcome measures and test their statistical properties and construct validity. METHODS: UW-mRS scores were derived using linear regression, with mRS as a discrete ordinal explanatory response variable in 8 large international acute stroke trials. Linear regression models were used to validate UW-mRS scores by assessing differences in mean UW-mRS scores between the treatment groups of each trial. To explore the variability in EQ-5D between individual mRS categories, we generated receiver operator characteristic curves for EQ-5D to differentiate between sequential mRS categories and misclassification matrix to classify individual patients into a matched mRS category based on the closest UW-mRS value to their observed individual EQ-5D value. RESULTS: Among 22 946 acute stroke patients, derived UW-mRS across mRS scores 0 to 6 were 0.96, 0.83, 0.72, 0.54, 0.22, -0.18, and 0, respectively. Both UW-mRS and ordinal mRS scores captured divergent treatment effects across all 8 acute stroke trials. The sample sizes required to detect the treatment effects using UW-mRS scores as a continuous variable were almost half that required in trials for a binary cut point on the mRS. Area under receiver operator characteristic curves based on EQ-5D utility values varied from 0.66 to 0.81. Misclassification matrix showed moderate agreement between actual and matched mRS scores (kappa, 0.68 [95% CI, 0.67-0.68]). CONCLUSIONS: Medical strategies that target avoiding dependency may provide maximum benefit in terms of poststroke health-related quality of life. Despite variable differences with mRS scores, the UW-mRS provides efficiency gains as a smaller sample size is required to detect a treatment effect in acute stroke trials through use of continuous scores. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096, NCT00716079, NCT01422616, NCT02162017, NCT00120003, NCT02123875. URL: http://ctri.nic.in; Unique identifier: CTRI/2013/04/003557. URL: https://www.isrctn.com; Unique identifier: ISRCTN89712435.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários/normas , Humanos , Modelos Lineares , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Resultado do Tratamento
3.
Anesth Analg ; 130(5): 1133-1146, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32287121

RESUMO

Use of the electronic health record (EHR) has become a routine part of perioperative care in the United States. Secondary use of EHR data includes research, quality, and educational initiatives. Fundamental to secondary use is a framework to ensure fidelity, transparency, and completeness of the source data. In developing this framework, competing priorities must be considered as to which data sources are used and how data are organized and incorporated into a useable format. In assembling perioperative data from diverse institutions across the United States and Europe, the Multicenter Perioperative Outcomes Group (MPOG) has developed methods to support such a framework. This special article outlines how MPOG has approached considerations of data structure, validation, and accessibility to support multicenter integration of perioperative EHRs. In this multicenter practice registry, MPOG has developed processes to extract data from the perioperative EHR; transform data into a standardized format; and validate, deidentify, and transfer data to a secure central Coordinating Center database. Participating institutions may obtain access to this central database, governed by quality and research committees, to inform clinical practice and contribute to the scientific and clinical communities. Through a rigorous and standardized approach to ensure data integrity, MPOG enables data to be usable for quality improvement and advancing scientific knowledge. As of March 2019, our collaboration of 46 hospitals has accrued 10.7 million anesthesia records with associated perioperative EHR data across heterogeneous vendors. Facilitated by MPOG, each site retains access to a local repository containing all site-specific perioperative data, distinct from source EHRs and readily available for local research, quality, and educational initiatives. Through committee approval processes, investigators at participating sites may additionally access multicenter data for similar initiatives. Emerging from this work are 4 considerations that our group has prioritized to improve data quality: (1) data should be available at the local level before Coordinating Center transfer; (2) data should be rigorously validated against standardized metrics before use; (3) data should be curated into computable phenotypes that are easily accessible; and (4) data should be collected for both research and quality improvement purposes because these complementary goals bolster the strength of each endeavor.


Assuntos
Pesquisa Biomédica/normas , Registros Eletrônicos de Saúde/normas , Estudos Multicêntricos como Assunto/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Assistência Perioperatória/normas , Melhoria de Qualidade/normas , Pesquisa Biomédica/tendências , Registros Eletrônicos de Saúde/tendências , Humanos , Avaliação de Resultados em Cuidados de Saúde/tendências , Assistência Perioperatória/tendências , Melhoria de Qualidade/tendências
4.
BMC Endocr Disord ; 20(Suppl 1): 135, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164677

RESUMO

BACKGROUND: Assessment of diet and physical activity and their determinants still remains a demanding task, especially when the objective is to evaluate the efficacy of lifestyle interventions. In the context of the Feel4Diabetes study (a European community based intervention study in families with school aged children and at high risk of developing diabetes), we aimed to develop questionnaires for the assessment of food-frequency and eating behaviors, and physical activity and sedentary behaviors in both parents and school-aged children and a questionnaire for overall family's energy balance-related behaviors. METHODS: Questionnaires were developed to be used in 6 countries under standardized harmonization procedures and included questions regarding not only food intake and physical activity, but also questions of their determinants. A reliability study was conducted in 191 pairs of parents and their children (N = 191). Parents completed the questionnaires on two occasions, within a 1-2 week interval. Reliability was tested by the intra-class correlation coefficients (ICC) of test-retest. RESULTS: Most of the questions in all questionnaires had excellent reliability, assessed as an ICC of > 0.810. Mean ICCs for food-frequency and eating behaviors questionnaires were 0.838 and 0.787, and for physical activity and sedentary behaviors questionnaires were 0.734 and 0.793, in adults and children respectively. Mean ICC for overall family's energy balance-related behaviors and their determinants was 0.659. CONCLUSION: The developed questionnaires showed acceptable reliability and may be valuable tools in the assessment of children's and parents' behaviors related to diet, physical activity, sedentary behavior and overall energy balance in school- and community-based interventions.


Assuntos
Inquéritos sobre Dietas/métodos , Exercício Físico , Comportamentos Relacionados com a Saúde/fisiologia , Inquéritos e Questionários , Adulto , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Inquéritos sobre Dietas/normas , Inquéritos sobre Dietas/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Estilo de Vida , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Psicometria/métodos , Psicometria/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Reprodutibilidade dos Testes , Fatores de Risco , Comportamento Sedentário , Autoavaliação , Inquéritos e Questionários/normas
5.
Neuroimage ; 205: 116210, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31593793

RESUMO

Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. The main objective of this study was to assess the long-term consistency of rsfMRI connectivity maps derived at multiple sites and vendors using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). Nine to 10 min of functional BOLD images were acquired from an adult cognitively healthy volunteer scanned repeatedly at 13 Canadian sites on three scanner makes (General Electric, Philips and Siemens) over the course of 2.5 years. The consistency (spatial Pearson's correlation) of rsfMRI connectivity maps for seven canonical networks ranged from 0.3 to 0.8, with a negligible effect of time, but significant site and vendor effects. We noted systematic differences in data quality (i.e. head motion, number of useable time frames, temporal signal-to-noise ratio) across vendors, which may also confound some of these results, and could not be disentangled in this sample. We also pooled the long-term longitudinal data with a single-site, short-term (1 month) data sample acquired on 26 subjects (10 scans per subject), called HNU1. Using randomly selected pairs of scans from each subject, we quantified the ability of a data-driven unsupervised cluster analysis to match two scans of the same subjects. In this "fingerprinting" experiment, we found that scans from the Canadian subject (Csub) could be matched with high accuracy intra-site (>95% for some networks), but that the accuracy decreased substantially for scans drawn from different sites and vendors, even falling outside of the range of accuracies observed in HNU1. Overall, our results demonstrate good multivariate stability of rsfMRI measures over several years, but substantial impact of scanning site and vendors. How detrimental these effects are will depend on the application, yet our results demonstrate that new methods for harmonizing multisite analysis represent an important area for future work.


Assuntos
Encéfalo/diagnóstico por imagem , Conectoma/normas , Imagem por Ressonância Magnética/normas , Estudos Multicêntricos como Assunto/normas , Adulto , Canadá , Análise por Conglomerados , Conectoma/instrumentação , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/instrumentação , Projetos de Pesquisa
6.
Phys Med Biol ; 64(24): 245013, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31766032

RESUMO

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.


Assuntos
Ensaios Clínicos como Assunto/normas , Estudos Multicêntricos como Assunto/normas , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/normas , Algoritmos , Calibragem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Radioisótopos do Iodo , Imagens de Fantasmas/normas , Impressão Tridimensional , Radiometria/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos
8.
Z Evid Fortbild Qual Gesundhwes ; 146: 15-20, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31473073

RESUMO

BACKGROUND: The bureaucratic and administrative burden for obtaining the obligatory Institutional Review Board (IRB) approval, which confirms the ethical integrity of a scientific project, is high. In order to participate in multicenter studies, most participating centers in Germany require a local second approval. We investigated the variation in the time it took the participating centers of a non-interventional multicenter study to obtain this approval. METHODS: Descriptive investigation of the amount of time it takes to gain an IRB approval for a multicenter observational study on the quality of life of sarcoma patients conducted throughout Germany. Stratified analyses were carried out on the basis of potential predictors of this duration and reasons for requests for revisions by the IRB were identified. RESULTS: 44 applications for ethics approval were submitted to 26 IRBs. To obtain the 25 second approvals took 53.6 days on average (standard deviation 49.8 days, median 34 days). While State Medical Chambers needed an average of 20.3 days for a local second approval, university hospitals needed 72.4 days. 81.3 % of the university IRBs and 33.3% of the IRB of the State Medical Chambers made specific requests. Ten IRBs followed the recommendations of the primary approval without undertaking their own assessment (average 41.3 days), five IRBs examined the application in an abbreviated procedure (51.4 days), and ten examined it thoroughly (67.1 days). CONCLUSION: Submitting ethics approval applications for observational studies in a clinical setting involved considerable effort and long waiting times in 2017 and 2018. Simplified review procedures or a waiver of examination by local IRBs do not necessarily mean shorter processing times. In general, there is a continued need for further progress.


Assuntos
Protocolos Clínicos/normas , Comitês de Ética em Pesquisa , Qualidade de Vida , Ensaios Clínicos como Assunto/normas , Coleta de Dados , Alemanha , Humanos , Estudos Multicêntricos como Assunto/normas
9.
Clin Trials ; 16(5): 512-522, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31331195

RESUMO

BACKGROUND/AIMS: A risk-based approach to clinical research may include a central statistical assessment of data quality. We investigated the operating characteristics of unsupervised statistical monitoring aimed at detecting atypical data in multicenter experiments. The approach is premised on the assumption that, save for random fluctuations and natural variations, data coming from all centers should be comparable and statistically consistent. Unsupervised statistical monitoring consists of performing as many statistical tests as possible on all trial data, in order to detect centers whose data are inconsistent with data from other centers. METHODS: We conducted simulations using data from a large multicenter trial conducted in Japan for patients with advanced gastric cancer. The actual trial data were contaminated in computer simulations for varying percentages of centers, percentages of patients modified within each center and numbers and types of modified variables. The unsupervised statistical monitoring software was run by a blinded team on the contaminated data sets, with the purpose of detecting the centers with contaminated data. The operating characteristics (sensitivity, specificity and Youden's J-index) were calculated for three detection methods: one using the p-values of individual statistical tests after adjustment for multiplicity, one using a summary of all p-values for a given center, called the Data Inconsistency Score, and one using both of these methods. RESULTS: The operating characteristics of the three methods were satisfactory in situations of data contamination likely to occur in practice, specifically when a single or a few centers were contaminated. As expected, the sensitivity increased for increasing proportions of patients and increasing numbers of variables contaminated. The three methods showed a specificity better than 93% in all scenarios of contamination. The method based on the Data Inconsistency Score and individual p-values adjusted for multiplicity generally had slightly higher sensitivity at the expense of a slightly lower specificity. CONCLUSIONS: The use of brute force (a computer-intensive approach that generates large numbers of statistical tests) is an effective way to check data quality in multicenter clinical trials. It can provide a cost-effective complement to other data-management and monitoring techniques.


Assuntos
Ensaios Clínicos Fase III como Assunto/normas , Confiabilidade dos Dados , Estudos Multicêntricos como Assunto/normas , Simulação por Computador , Interpretação Estatística de Dados , Humanos , Controle de Qualidade , Reprodutibilidade dos Testes , Projetos de Pesquisa , Neoplasias Gástricas
10.
Trials ; 20(1): 422, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296253

RESUMO

BACKGROUND: Enrolling participants in clinical trials can be challenging, especially with respect to prophylactic vaccine trials. The vaccination of study personnel in Ebola vaccine trials during the 2014-2016 epidemic played a crucial role in inspiring trust and facilitating volunteer enrollment. We evaluated the ethical and methodological considerations as they applied to an ongoing phase 2 randomized prophylactic Ebola vaccine trial that enrolled healthy volunteers in Guinea, Liberia, Sierra Leone, and Mali in a non-epidemic context. METHODS: On the assumption that the personnel on site involved in executing the protocol, as well as community mobilizers (not involved in the on-site procedures), might also volunteer to enter the trial, we considered both ethical and methodological considerations to set clear rules that can be shared a priori with these persons. We reviewed the scientific and gray literature to identify relevant references and then conducted an analysis of the ethical and methodological considerations. RESULTS: There are currently no regulations preventing a clinical investigator or site staff from participating in a trial. However, the enrollment of personnel raises the risk of undue influence and challenges the basic ethical principle of voluntary participation. The confidentiality of personal medical information, such as HIV test results, may also be difficult to ensure among personnel. There is a risk of disruption of trial operations due to the potential absence of the personnel for their commitment as trial participants, and there is also a potential for introducing differential behavior of on-site staff as they obtain access to accumulating information during the trial (e.g., the incidence of adverse events). Blinding could be jeopardized, given knowledge of product-specific adverse event profiles and the proximity to unblinded site staff. These aspects were considered more relevant for on-site staff than for community mobilizers, who have limited contact with site staff. CONCLUSION: In a non-epidemic context, ethical and methodological considerations limit the collective benefit of enrolling site staff in a vaccine trial. These considerations do not apply to community mobilizers, whose potential enrollment should be considered as long as they meet the inclusion criteria and they are not exposed to any form of coercion.


Assuntos
Ensaios Clínicos Fase II como Assunto/normas , Vacinas contra Ebola/uso terapêutico , Doença pelo Vírus Ebola/prevenção & controle , Estudos Multicêntricos como Assunto/normas , Seleção de Pacientes , Guias de Prática Clínica como Assunto/normas , Pesquisadores/normas , Sujeitos da Pesquisa , África Ocidental , Atitude do Pessoal de Saúde , Ensaios Clínicos Fase II como Assunto/ética , Vacinas contra Ebola/efeitos adversos , Definição da Elegibilidade , Conhecimentos, Atitudes e Prática em Saúde , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Estudos Multicêntricos como Assunto/ética , Seleção de Pacientes/ética , Pesquisadores/ética , Pesquisadores/psicologia , Sujeitos da Pesquisa/psicologia
11.
Neuroimage ; 202: 115967, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31352124

RESUMO

Multi-site studies are becoming important to increase statistical power, enhance generalizability, and to improve the likelihood of pooling relevant subgroups together-activities which are otherwise limited by the availability of subjects or funds at a single site. Even with harmonized imaging sequences, site-dependent variability can mask the advantages of these multi-site studies. The aim of this study was to assess multi-site reproducibility in resting-state functional connectivity "fingerprints", and to improve identifiability of functional connectomes. The individual fingerprinting of functional connectivity profiles is promising due to its potential as a robust neuroimaging biomarker with which to draw single-subject inferences. We evaluated, on two independent multi-site datasets, individual fingerprints in test-retest visit pairs within and across two sites and present a generalized framework based on principal component analysis to improve identifiability. Those principal components that maximized differential identifiability of a training dataset were used as an orthogonal connectivity basis to reconstruct the individual functional connectomes of training and validation sets. The optimally reconstructed functional connectomes showed a substantial improvement in individual fingerprinting of the subjects within and across the two sites and test-retest visit pairs relative to the original data. A notable increase in ICC values for functional edges and resting-state networks were also observed for reconstructed functional connectomes. Improvements in identifiability were not found to be affected by global signal regression. Post-hoc analyses assessed the effect of the number of fMRI volumes on identifiability and showed that multi-site differential identifiability was for all cases maximized after optimal reconstruction. Finally, the generalizability of the optimal set of orthogonal basis of each dataset was evaluated through a leave-one-out procedure. Overall, results demonstrate that the data-driven framework presented in this study systematically improves identifiability in resting-state functional connectomes in multi-site studies.


Assuntos
Encéfalo/diagnóstico por imagem , Conectoma/normas , Imagem por Ressonância Magnética/normas , Estudos Multicêntricos como Assunto/normas , Rede Nervosa/diagnóstico por imagem , Adolescente , Adulto , Encéfalo/fisiologia , Estudos de Coortes , Conectoma/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Estudos Multicêntricos como Assunto/métodos , Rede Nervosa/fisiologia , Adulto Jovem
12.
Trials ; 20(1): 227, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995932

RESUMO

BACKGROUND: Triggered monitoring in clinical trials is a risk-based monitoring approach where triggers (centrally monitored, predefined key risk and performance indicators) drive the extent, timing, and frequency of monitoring visits. The TEMPER study used a prospective, matched-pair design to evaluate the use of a triggered monitoring strategy, comparing findings from triggered monitoring visits with those from matched control sites. To facilitate this study, we developed a bespoke risk-based monitoring system: the TEMPER Management System. METHODS: The TEMPER Management System comprises a web application (the front end), an SQL server database (the back end) to store the data generated for TEMPER, and a reporting function to aid users in study processes such as the selection of triggered sites. Triggers based on current practice were specified for three clinical trials and were implemented in the system. Trigger data were generated in the system using data extracted from the trial databases to inform the selection of triggered sites to visit. Matching of the chosen triggered sites with untriggered control sites was also performed in the system, while data entry screens facilitated the collection and management of the data from findings gathered at monitoring visits. RESULTS: There were 38 triggers specified for the participating trials. Using these, 42 triggered sites were chosen and matched with control sites. Monitoring visits were carried out to all sites, and visit findings were entered into the TEMPER Management System. Finally, data extracted from the system were used for analysis. CONCLUSIONS: The TEMPER Management System made possible the completion of the TEMPER study. It implemented an approach of standardising the automation of current-practice triggers, and the generation of trigger data to inform the selection of triggered sites to visit. It also implemented a matching algorithm informing the selection of matched control sites. We hope that by publishing this paper it encourages other trialists to share their approaches to, and experiences of, triggered monitoring and other risk-based monitoring systems.


Assuntos
Coleta de Dados/normas , Gerenciamento de Dados/normas , Estudos Multicêntricos como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa/normas , Algoritmos , Comitês de Monitoramento de Dados de Ensaios Clínicos/normas , Confiabilidade dos Dados , Humanos , Medição de Risco , Fatores de Risco , Fatores de Tempo
13.
Nurs Res ; 68(3): 227-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31033866

RESUMO

BACKGROUND: Conducting multisite studies has many challenges, including determining the geographic distance between sites, ensuring effective communication, monitoring intervention and data integrity, handling institutional policy variations, seeking institutional review board approval with unique site needs or complex subcontracts, and planning for additional costs. OBJECTIVES: This article discusses common challenges in conducting multisite studies and identifies strategies to overcome these challenges using real-world examples from the literature, the authors' research studies, and their personal experiences. METHODS: A summary of articles on multisite trials conducted within the past 10 years was explored to uncover common challenges in conducting multisite trials. To enrich the context, exemplars from authors' works are included. Based on literature and experience, strategies to combat challenges are summarized. RESULTS: Unique issues related to multisite studies include site selection, use of epicenters/coordinating centers, hiring/managing staff, fidelity monitoring, institutional review board approval, statistical considerations, and approaches to authorship. CONCLUSION: Addressing challenges a priori can improve scientific rigor, reproducibility, and evidence from multisite studies. Given the benefits to scientific rigor, reproducibility, and design, findings from multisite studies are more likely to provide evidence to transform clinical practice and influence policy.


Assuntos
Estudos Multicêntricos como Assunto/normas , Pesquisadores , Sujeitos da Pesquisa , Humanos , Objetivos Organizacionais
14.
J Diabetes Complications ; 33(6): 427-433, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31003926

RESUMO

AIMS: To compare the characteristics and outcomes of people with type 2 diabetes recruited to the LEADER trial to those of participants in the contemporaneous community-based Fremantle Diabetes Study Phase II (FDS2) who fulfilled LEADER entry criteria. METHODS: Baseline characteristics of LEADER and LEADER-eligible FDS2 participants were compared using bivariate methods. Incidence rates of the primary (nonfatal myocardial infarction, nonfatal stroke, cardiovascular disease (CVD) death) and other outcomes in the LEADER placebo group were compared with those in LEADER-eligible FDS2 participants during 3.8 years after entry, the median LEADER follow-up. RESULTS: Of 1551 FDS2 type 2 participants, 323 (20.8%) were LEADER-eligible. Compared with the LEADER sample, they were an average 6 years older, and were less likely to be male, obese and to have prior CVD. There were 3.9 and 2.9 primary outcomes/100 patient-years in LEADER placebo-treated and FDS2 LEADER-eligible patients, respectively. Incidence rates for first myocardial infarction and stroke were 1.9 and 2.1 events/100 patient-years and 1.1 and 1.0 events/100 patient-years, respectively. FDS2 LEADER-eligible patients had a lower CVD death rate of 0.8 versus 1.6/100 patient-years in the LEADER placebo group, but their non-CVD mortality was greater (2.1 versus 1.0/100 patient-years). CONCLUSIONS: These data suggest recruitment bias in type 2 diabetes CVD outcome trials.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Pesquisa Participativa Baseada na Comunidade/normas , Pesquisa Participativa Baseada na Comunidade/estatística & dados numéricos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/mortalidade , Feminino , Humanos , Incidência , Liraglutida/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Mortalidade , Estudos Multicêntricos como Assunto/normas , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento , Austrália Ocidental/epidemiologia
15.
Circ Cardiovasc Qual Outcomes ; 12(3): e004907, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30857413

RESUMO

BACKGROUND: Recent multisite trials reveal striking heterogeneities in results between trial sites. These may be because of population differences indicating different treatment benefits among different types of participants or site anomalies, such as failures to adhere to study protocols that could negatively affect study validity. We sought to determine whether a new data analysis strategy-transportability methods-could suggest site anomalies not readily identified through standard methods. METHODS AND RESULTS: We applied transportability methods to 2 large, multicenter cardiovascular disease treatment trials: the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist; n=3445) comparing spironolactone to placebo for heart failure (for which site anomalies were suspected) and the ACCORD BP trial (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure; n=4733) comparing intensive-to-standard blood pressure treatment (for which site anomalies were not suspected). The transportability methods give expected results by standardizing from one site to another using data on participant covariates. The difference between the expected and observed results was assessed using calibration tests to identify whether treatment-effect differences between sites could be explained by participant population characteristics. Standard regression methods did not detect heterogeneities in TOPCAT between Russia/Georgia study sites suspected of study protocol violations and sites in the Americas ( P=0.12 for difference in primary cardiovascular outcome; P=0.20 for difference in total mortality). The transportability methods, however, detected the difference between Russia/Georgia sites and sites in the Americas ( P<0.001) and found that measured participant characteristics did not explain the between-site discrepancies. The transport methods found no such discrepancies between sites in ACCORD BP, suggesting participant characteristics explained between-site differences. CONCLUSIONS: Transportability methods may be superior to standard approaches for detecting anomalies within multicenter randomized trials and assist data monitoring boards to determine whether important treatment-effect heterogeneities can be attributed to participant differences or potentially to site performance differences requiring further investigation.


Assuntos
Confiabilidade dos Dados , Fidelidade a Diretrizes/normas , Estudos Multicêntricos como Assunto/normas , Guias de Prática Clínica como Assunto/normas , Projetos de Pesquisa/normas , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Interpretação Estatística de Dados , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Resultado do Tratamento
17.
Clin Trials ; 16(3): 290-296, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30866676

RESUMO

BACKGROUND/AIMS: Obtaining ethical approval from multiple institutional review boards is a long-standing challenge to multi-site clinical trials and often leads to significant delays in study activation and enrollment. As of 25 January 2018, the National Institutes of Health began requiring use of a single institutional review board for US multi-site trials. To learn more and further inform the research and regulatory communities around aspects of transitioning to single institutional review board review, this study evaluated the efficiency, resource use, and user perceptions of a nascent institutional review board reliance model (Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance). METHODS: This research was embedded within the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure trial-a multi-site trial of two influenza vaccine formulations. In the first year of the trial, a sample of sites agreed to use the developing Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model and participated in its evaluation. In keeping with a least burdensome approach, short surveys were developed and obtained from each reporting entity (relying sites, non-relying site, lead site, and reviewing institutional review board). Data regarding time to institutional review board approval and site activation, costs, and user perceptions of reliant review were self-reported and collected via the survey form. Quantitative and qualitative analyses were performed, with costs analyzed as actual versus estimated due to the lack of established baseline cost data. RESULTS: A total of 13 sites ceded review and received institutional review board approval. Mean time to approval was substantially faster in sites that ceded review using the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model versus the site that did not cede review (81 vs 121 days). The mean time to approval was also faster than published averages for academic medical centers (81 vs 103 days). Time to first enrollment was faster for ceding sites versus the non-ceding site, and also faster than published averages (126 vs 149 and 169 days, respectively). Costs were higher than estimates for local institutional review board review and approval. Nearly half (47%) the stakeholders reported being very satisfied or satisfied with the reliance experience, although many noted the challenge related to institutional culture change. CONCLUSION: Implementation of a single institutional review board represents a shift in practice and culture for many institutions. Evaluation of the reliance arrangements for this study highlights both the potential of, and challenges for, institutions as they transition to single institutional review board review. Although efficiencies were observed for study start-up, we anticipate a learning curve as institutions and research teams implement necessary process and resource changes to adapt to single institutional review board oversight. Findings may inform research teams but are, however, limited by the relatively small number of sites and lack of a control group.


Assuntos
Pesquisa Biomédica/organização & administração , Ensaios Clínicos como Assunto/organização & administração , Comitês de Ética em Pesquisa/organização & administração , Estudos Multicêntricos como Assunto/normas , National Institutes of Health (U.S.)/organização & administração , Centros Médicos Acadêmicos , Pesquisa Biomédica/normas , Ensaios Clínicos como Assunto/normas , Eficiência Organizacional , Comitês de Ética em Pesquisa/normas , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/economia , National Institutes of Health (U.S.)/normas , Fatores de Tempo , Estados Unidos
18.
Am J Epidemiol ; 188(5): 851-861, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877288

RESUMO

Methodological advancements in epidemiology, biostatistics, and data science have strengthened the research world's ability to use data captured from electronic health records (EHRs) to address pressing medical questions, but gaps remain. We describe methods investments that are needed to curate EHR data toward research quality and to integrate complementary data sources when EHR data alone are insufficient for research goals. We highlight new methods and directions for improving the integrity of medical evidence generated from pragmatic trials, observational studies, and predictive modeling. We also discuss needed methods contributions to further ease data sharing across multisite EHR data networks. Throughout, we identify opportunities for training and for bolstering collaboration among subject matter experts, methodologists, practicing clinicians, and health system leaders to help ensure that methods problems are identified and resulting advances are translated into mainstream research practice more quickly.


Assuntos
Big Data , Bioestatística/métodos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Medicina/estatística & dados numéricos , Saúde Pública , Ensaios Clínicos como Assunto/métodos , Pesquisa Comparativa da Efetividade/métodos , Confidencialidade/normas , Comportamento Cooperativo , Confiabilidade dos Dados , Anonimização de Dados/normas , Métodos Epidemiológicos , Epidemiologia/organização & administração , Humanos , Disseminação de Informação , Relações Interprofissionais , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Estudos Observacionais como Assunto/métodos , Estudos Retrospectivos , Estados Unidos
19.
J Dev Behav Pediatr ; 40(1): 20-31, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30589766

RESUMO

OBJECTIVE: To determine the percentage of children with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and combined ASD + ADHD who had sleep problems documented by developmental-behavioral pediatricians at diagnostic and follow-up visits at 12 US academic medical centers comprising the Developmental-Behavioral Pediatrics Research Network (DBPNet) and to identify the predictors of sleep problem documentation. METHODS: Developmental-behavioral pediatricians completed encounter forms that covered sociodemographic, medical, clinician, and visit factors. There was 1 dependent variable, sleep problem documentation, for which 4 definitions were developed (Model 1 = Sleep Disorder coded; Model 2 = Sleep Disorder or polysomnogram coded; Model 3 = Sleep Disorder, polysomnogram, or sleep medication coded; and Model 4 = Sleep Disorder, polysomnogram, sleep medication, or clonidine coded). RESULTS: Sleep problem documentation was 14.1% for Model 1, 15.2% for Model 2, 17.3% for Model 3, and 19.7% for Model 4. All values were lower (p < 0.001) than the reported prevalence of sleep problems in these conditions. For Model 4, predictors of sleep problem documentation were age group, ethnicity, medical insurance type, and DBPNet site. CONCLUSION: Developmental-behavioral pediatricians in DBPNet under-reported sleep problems in children with ASD and ADHD. Variation among sites was substantial. Care plans for children with ASD and ADHD should specify which treating clinician(s) monitors sleep issues.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Espectro Autista/diagnóstico , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Pediatras/estatística & dados numéricos , Transtornos do Sono-Vigília/diagnóstico , Adulto , Idoso , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/normas , Pediatras/normas , Transtornos do Sono-Vigília/epidemiologia , Estados Unidos/epidemiologia
20.
Cancer ; 124(20): 4064-4071, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30291804

RESUMO

BACKGROUND: Low cancer clinical trial (CCT) enrollment may contribute to survival disparities affecting adolescents and young adults (AYAs) (ages 15-39 years). The objective of this study was to evaluate whether differences in CCT availability related to treatment site could explain the low CCT enrollment. METHODS: This prospective, observational cohort study was conducted at an academic children's hospital and its affiliated but geographically separated adult cancer hospital within a National Cancer Institute-designated Comprehensive Cancer Center. For consecutive, newly diagnosed AYA patients, it was determined whether an appropriate CCT existed nationally, was available at the treatment site, and was used for enrollment. Proportions of AYAs in these categories were compared between sites using the chi-square test. RESULTS: One hundred fifty-two consecutive AYA patients were included from the children's hospital (n = 68; ages 15-20 years) and the adult cancer hospital (n = 84; ages 18-39 years). Although there was no difference in CCT existence for individual AYA patients by site (children's hospital [36 of 68 patients; 52.9%] vs adult cancer hospital [45 of 84 patients; 53.6%]; P = .938), CCT availability was significantly lower at the adult cancer hospital (14 of 84 patients [16.7%] vs 30 of 68 [44.1%] at the children's hospital; P < .001). The proportion of AYAs enrolled was low at both sites (8 of 68 patients [11.8%] vs 6 of 84 patients [7.1%], respectively; P = .327). Fewer existing CCTs were available at the adult cancer hospital (4 of 27 patients [14.8%] vs 8 of 14 patients [57.1%], respectively), and those were directed toward solid tumors and new agents. CONCLUSIONS: Efforts to improve low CCT enrollment among AYAs should be differentiated by treatment site. In the adult setting, these efforts should be aimed at improving CCT availability by overcoming site-level barriers to opening existing CCTs.


Assuntos
Institutos de Câncer/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/terapia , Seleção de Pacientes , Adolescente , Adulto , Fatores Etários , Institutos de Câncer/organização & administração , Ensaios Clínicos como Assunto/organização & administração , Estudos de Coortes , Feminino , Hospitais Pediátricos/organização & administração , Humanos , Masculino , Oncologia/organização & administração , Oncologia/normas , Oncologia/estatística & dados numéricos , Estudos Multicêntricos como Assunto/normas , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Estudos Prospectivos , Transição para Assistência do Adulto/organização & administração , Transição para Assistência do Adulto/normas , Transição para Assistência do Adulto/estatística & dados numéricos , Adulto Jovem
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