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BACKGROUND: The National Institutes of Health has advocated for improved minority participation in clinical research, including clinical trials and observational epidemiologic studies since 1993. An understanding of Mexican Americans (MAs) participation in clinical research is important for tailoring recruitment strategies and enrollment techniques for MAs. However, contemporary data on MA participation in observational clinical stroke studies are rare. We examined differences between Mexican Americans (MAs) and non-Hispanic whites (NHWs) participation in a population-based stroke study. METHODS: We included 3,594 first ever stroke patients (57.7% MAs, 48.7% women, median [IQR] age 68 [58-79]) from the Brain Attack Surveillance in Corpus Christi Project, 2009-2020 in Texas, USA, who were approached and invited to participate in a structured baseline interview. We defined participation as completing a baseline interview by patient or proxy. We used log-binomial models adjusting for prespecified potential confounders to estimate prevalence ratios (PR) of participation comparing MAs with NHWs. We tested interactions of ethnicity with age or sex to examine potential effect modification in the ethnic differences in participation. We also included an interaction between year and ethnicity to examine ethnic-specific temporal trends in participation. RESULTS: Baseline participation was 77.0% in MAs and 64.2% in NHWs (Prevalence Ratio [PR] 1.20; 95% CI, 1.14-1.25). The ethnic difference remained after multivariable adjustment (1.17; 1.12-1.23), with no evidence of significant effect modification by age or sex (Pinteraction by age = 0.68, Pinteraction by sex = 0.83). Participation increased over time for both ethnic groups (Ptrend < 0.0001), but the differences in participation between MAs and NHWs remained significantly different throughout the 11-year time period. CONCLUSION: MAs were persistently more likely to participate in a population-based stroke study in a predominantly MA community despite limited outreach efforts towards MAs during study enrollment. This finding holds hope for future research studies to be inclusive of the MA population.
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Estudios Clínicos como Asunto , Americanos Mexicanos , Accidente Cerebrovascular , Blanco , Anciano , Femenino , Humanos , Masculino , Etnicidad , Americanos Mexicanos/estadística & datos numéricos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etnología , Texas/epidemiología , Blanco/estadística & datos numéricos , Población Blanca , Estudios Clínicos como Asunto/estadística & datos numéricos , Selección de Paciente , Persona de Mediana Edad , Participación del Paciente/estadística & datos numéricosRESUMEN
Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences influence the frequency and severity of pharmacological side effects. A large number of clinical trials to develop new therapeutic approaches and vaccines for COVID-19 are ongoing. We investigated the inclusion of sex and/or gender in COVID-19 studies on ClinicalTrials.gov, collecting data for the period January 1, 2020 to January 26, 2021. Here, we show that of the 4,420 registered SARS-CoV-2/COVID-19 studies, 935 (21.2%) address sex/gender solely in the context of recruitment, 237 (5.4%) plan sex-matched or representative samples or emphasized sex/gender reporting, and only 178 (4%) explicitly report a plan to include sex/gender as an analytical variable. Just eight (17.8%) of the 45 COVID-19 related clinical trials published in scientific journals until December 15, 2020 report sex-disaggregated results or subgroup analyses.
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COVID-19/terapia , Estudios Clínicos como Asunto/estadística & datos numéricos , COVID-19/epidemiología , Femenino , Humanos , Masculino , Selección de Paciente , SARS-CoV-2 , Factores SexualesRESUMEN
Importance: After US Food and Drug Administration (FDA) approval of a new drug, sponsors can submit additional clinical data to obtain supplemental approval for use for new indications. Objective: To characterize pivotal trials supporting recent supplemental new indication approvals of drugs and biologics by the FDA and to compare them with pivotal trials that supported these therapeutics' original indication approvals. Design, Setting, and Participants: This is a cross-sectional study characterizing pivotal trials supporting supplemental indication approvals by the FDA between 2017 and 2019 and pivotal trials that supported these therapeutics' original indication approvals. Data analysis was performed from August to October 2020. Main Outcomes and Measures: Number and design of pivotal trials supporting both supplemental and original indication approvals. Results: From 2017 to 2019, the FDA approved 146 supplemental indications for 107 therapeutics on the basis of 181 pivotal efficacy trials. The median (interquartile range) number of trials per supplemental indication was 1 (1-1). Most trials used either placebo (77 trials [42.5%; 95% CI, 35.6%-49.8%]) or active comparators (65 trials [35.9%; 95% CI, 29.3%-43.1%]), and most of these multigroup trials were randomized (141 trials [99.3%; 95% CI, 96.0%-100.0%]) and double-blinded (106 trials [74.5%; 95% CI, 66.6%-81.0%]); 80 trials (44.2%; 95 CI, 37.2%-51.5%) used clinical outcomes as the primary efficacy end point. There was no difference between oncology therapies and those approved for other therapeutic areas to have supplemental indication approvals be based on at least 2 pivotal trials (11.5% vs 20.6%; difference, 9.1%; 95% CI, 2.9%-21.0%; P = .10). Similarly, there was no difference in use of randomization (98.3% vs 100.0%; difference, 1.7%; 95% CI, 1.6%-5.0%; P = .43) among multigroup trials, although these trials were less likely to be double-blinded (50.8% vs 92.3%; difference, 41.5%; 95% CI, 27.4%-55.5%; P < .001); overall, these trials were less likely to use either placebo or active comparators (64.9% vs 86.7%; difference, 21.8% 95% CI, 9.8%-33.9%; P < .001) or to use clinical outcomes as their primary efficacy end point (27.5% vs 61.1%; difference, 33.6%; 95% CI, 14.1%-40.9%; P < .001) and were longer (median [interquartile range], 17 [6-48] weeks vs 95 [39-146] weeks). Original approvals were more likely than supplemental indication approvals to be based on at least 2 pivotal trials (44.0% [95% CI, 33.7%-42.6%] vs 15.8% [95% CI, 10.7%-22.5%]; difference, 28.2%; 95% CI, 17.6%-39.6%; P < .001) and less likely to be supported by at least 1 trial of 12 months' duration (27.6% [95% CI, 17.9%-35.0%] vs 54.8% [95% CI, 46.7%-62.6%]; difference, 27.2%; 95% CI, 14.5%-37.8%; P < .001). Pivotal trial designs were otherwise not significantly different. Conclusions and Relevance: These findings suggest that the number and design of the pivotal trials supporting supplemental indication approvals by the FDA varied across therapeutic areas, with the strength of evidence for cancer indications weaker than that for other indications. There was little difference in the design characteristics of the pivotal trials supporting supplemental indication and original approvals.
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Productos Biológicos/normas , Estudios Clínicos como Asunto/normas , Aprobación de Drogas/métodos , Reposicionamiento de Medicamentos/normas , Medicamentos bajo Prescripción/normas , Proyectos de Investigación/normas , United States Food and Drug Administration/normas , Estudios Clínicos como Asunto/estadística & datos numéricos , Estudios Transversales , Humanos , Proyectos de Investigación/estadística & datos numéricos , Estados Unidos , United States Food and Drug Administration/estadística & datos numéricosAsunto(s)
Estudios Clínicos como Asunto/estadística & datos numéricos , Análisis de Datos , Medición de Resultados Informados por el Paciente , Interpretación Estadística de Datos , Humanos , Funciones de Verosimilitud , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Calidad de Vida , Análisis de Regresión , Sesgo de Selección , Programas InformáticosRESUMEN
OBJECTIVES: International regulations require Investigator's Brochures (IBs) to compile all available evidence that inform the risk-benefit assessment for the newly planned clinical trial. This study examined the adherence of IBs to the basic principles of evidence synthesis when compiling prior clinical studies. STUDY DESIGN AND SETTING: For 97 IBs for phase I/II trials reviewed at one German research ethics committee we assessed the reporting on search, appraisal, and synthesis procedures for prior clinical studies. For a random subsample of 30 IBs, we evaluated the quality of reporting of the compiled 247 prior clinical studies. RESULTS: Only 2% of all 97 IBs reported a comprehensive search strategy, provided a critical appraisal of the compiled prior clinical studies or presented respective study results in a structured manner. For the 247 prior clinical studies compiled in 30 IBs, the information required to appraise their risk of bias (eg, sample size calculation or baseline characteristics) was rarely reported. CONCLUSION: When compiling all available evidence supporting the rationale for the proposed clinical study IBs do not acknowledge the broadly established principles for reviewing and reporting evidence. This may impact negatively on the trustworthiness and efficiency of risk-benefit assessment.
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Investigación Biomédica/ética , Investigación Biomédica/normas , Estudios Clínicos como Asunto/ética , Estudios Clínicos como Asunto/normas , Exactitud de los Datos , Folletos , Informe de Investigación , Investigación Biomédica/estadística & datos numéricos , Estudios Clínicos como Asunto/estadística & datos numéricos , Estudios Transversales , Alemania , Guías como Asunto , Humanos , Proyectos de Investigación/estadística & datos numéricosAsunto(s)
Betacoronavirus , Estudios Clínicos como Asunto/estadística & datos numéricos , Infecciones por Coronavirus/terapia , Salud Global/estadística & datos numéricos , Neumonía Viral/terapia , Sistema de Registros/estadística & datos numéricos , Comités Consultivos , COVID-19 , Infecciones por Coronavirus/epidemiología , Francia/epidemiología , Humanos , Estudios Observacionales como Asunto/estadística & datos numéricos , Pandemias , Neumonía Viral/epidemiología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Medición de Riesgo , SARS-CoV-2 , Experimentación Humana Terapéutica/éticaRESUMEN
BACKGROUND: Research requires high-quality ethical and governance scrutiny and approval. However, when research is conducted across different countries, this can cause challenges due to the differing ethico-legal framework requirements of ethical boards. There is no specific guidance for research which does not involve non-medicinal products. AIM: To describe and address differences in ethical and research governance procedures applied by research ethics committees for non-pharmaceutical palliative care studies including adult participants in collaborative European studies. DESIGN: An online survey analysed using descriptive statistics. SETTING/PARTICIPANTS: Eighteen principal investigators in 11 countries conducting one of three European-funded studies. RESULTS: There was variation in practice including whether ethical approval was required. The time to gain full approvals differed with the United Kingdom having governance procedures that took the longest time. Written consent was not required in all countries nor were data safety monitoring committees for trials. There were additional differences in relation to other data management issues. CONCLUSION: Researchers need to take the differences in research approval procedures into account when planning studies. Future research is needed to establish European-wide recommendations for policy and practice that dovetail ethical procedures and enhance transnational research collaborations.
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Estudios Clínicos como Asunto , Comités de Ética en Investigación , Cuidados Paliativos , Estudios Clínicos como Asunto/estadística & datos numéricos , Comités de Ética en Investigación/estadística & datos numéricos , Europa (Continente) , Humanos , Cuidados Paliativos/ética , Cuidados Paliativos/estadística & datos numéricos , Calidad de Vida , Factores de Tiempo , Reino UnidoRESUMEN
OBJECTIVE: This metaresearch of the clinicaltrials.gov database aims to evaluate how clinical research on palliative care is conducted within the setting of advanced cancer. METHODS: Clinicaltrials.gov was searched to identify registered studies recruiting patients with cancer, and investigating issues relevant to palliative care. The European Organisation for Research and Treatment of Cancer QLQ-C15-PAL (Quality of Life in palliative cancer care patients) questionnaire was taken into account to define the research domains of interest. Studies investigating cancer-directed therapy, management of cancer treatment-related adverse events and diagnostic tests were excluded. Publication status was crosschecked using PubMed. RESULTS: Of 3950 identified studies, 514 were included. The most frequent reason for exclusion was cancer-directed therapy (2491). In 2007-2012, 161 studies were registered versus 245 in 2013-2018. Included studies were interventional (84%) or observational (16%). Most studies were monocentric (60%), sponsored by academia (79%), and conducted in North America (57%) or Europe (25%). Seventy-nine per cent of studies evaluated a heterogeneous population (>1 tumour type). Interventional studies most frequently investigated systemic drugs (34%), behavioural interventions (29%) and procedures for pain (24%). Pain, quality of life and physical function were the most frequently studied research domains (188, 95 and 52 studies, respectively). The most applied primary outcome measures were efficacy/symptom control (61%), quality of life (14%) and feasibility (12%). Only 16% of the closed studies had published results in PubMed. CONCLUSIONS: Our study describes the heterogeneous landscape of studies conducted to address the issues of patients with advanced cancer in palliative care. Albeit the observed increase in the number of studies over the last decade, the generalisation of the results brought by the existing trials is limited due to methodological issues and lack of reporting. A greater effort is needed to improve clinical research that supports evidence-based palliative cancer care.
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Estudios Clínicos como Asunto/estadística & datos numéricos , Enfermería de Cuidados Paliativos al Final de la Vida , Neoplasias/terapia , Cuidados Paliativos , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.
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Antiinflamatorios , Antineoplásicos , Ácido Elágico/farmacología , Granada (Fruta)/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Células Cultivadas , Estudios Clínicos como Asunto/métodos , Estudios Clínicos como Asunto/estadística & datos numéricos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/estadística & datos numéricos , Ácido Elágico/aislamiento & purificación , Ácido Elágico/uso terapéutico , Frutas/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
BACKGROUND: From 2013 the World Medical Association's Declaration of Helsinki explicitly requires pre-registration of a study involving human subjects. The registration gives a chance for improvement of design and avoidance of bias. OBJECTIVE: The aim of this article was to describe process of bearing decision to create regional registry of clinical studies for Balkan countries. METHODS: After finding relevant studies about research registries and designing the concept and structure of future regional registry an article was published in IJBH journal. The article was than used as basis for discussion at 2020 meeting of Academy of Medical Sciences of Bosnia and Herzegovina (AMSBH), and final decision was made by the Academy to create the research registry. RESULTS: Regional registry of clinical studies will be under the auspices of AMSBH and web-based, with the option of online registration of new studies. The data required to be entered in the moment of registration relate to key elements of research plan: topic, variables, sample, type of the study and the study population. After applying for registration of a clinical study, the authors will soon receive the review made by the AMSBH expert committee. The application could be accepted, rejected or returned for major or minor revision. After an application is accepted, it will be deposited in the searchable database and given the registration number. CONCLUSION: The AMSBH's decision to create the regional registry of clinical studies will satisfy needs of researchers from Balkan countries in the first place, who share cultural and lingual similarities. It will also help with increasing standards of clinical research in the region.
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Investigación Biomédica/estadística & datos numéricos , Investigación Biomédica/normas , Estudios Clínicos como Asunto/estadística & datos numéricos , Estudios Clínicos como Asunto/normas , Guías como Asunto , Sistema de Registros/estadística & datos numéricos , Sistema de Registros/normas , Bosnia y Herzegovina , HumanosRESUMEN
In long-term clinical studies, recurrent event data are sometimes collected and used to contrast the efficacies of two different treatments. The event reoccurrence rates can be compared using the popular negative binomial model, which incorporates information related to patient heterogeneity into a data analysis. For treatment allocation, a balanced approach in which equal sample sizes are obtained for both treatments is predominately adopted. However, if one treatment is superior, then it may be desirable to allocate fewer subjects to the less-effective treatment. To accommodate this objective, a sequential response-adaptive treatment allocation procedure is derived based on the doubly adaptive biased coin design. Our proposed treatment allocation schemes have been shown to be capable of reducing the number of subjects receiving the inferior treatment while simultaneously retaining a test power level that is comparable to that of a balanced design. The redesign of a clinical study illustrates the advantages of using our procedure.
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Ensayos Clínicos Adaptativos como Asunto/estadística & datos numéricos , Biometría/métodos , Estudios Clínicos como Asunto/estadística & datos numéricos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/terapia , Distribución Binomial , Simulación por Computador , Interpretación Estadística de Datos , Humanos , Modelos Estadísticos , Distribución de Poisson , Tamaño de la Muestra , Factores de Tiempo , Resultado del TratamientoRESUMEN
Ordinal responses are common in clinical studies. Although the proportional odds model is a popular option for analyzing ordered-categorical data, it cannot control the type I error rate when the proportional odds assumption fails to hold. The latent Weibull model was recently shown to be a superior candidate for modeling ordinal data, with remarkably better performance than the latent normal model when the data are highly skewed. In clinical trials with ordinal responses, a balanced design is common, with equal sample allocation for each treatment. However, a more ethical approach is to adopt a response-adaptive allocation scheme in which more patients receive the better treatment. In this paper, we propose the use of the doubly adaptive biased coin design to generate treatment allocations that benefit the trial participants. The proposed treatment allocation scheme not only allows more patients to receive the better treatment, it also maintains compatible test power for the comparison of treatment efficiencies. A clinical example is used to illustrate the proposed procedure.
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Sesgo , Protocolos Clínicos , Estudios Clínicos como Asunto/estadística & datos numéricos , Modelos Estadísticos , Humanos , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Testing anti-cancer agents with multiple disease subtypes is challenging and it becomes more complicated when the subgroups have different types of endpoints (such as binary endpoints of tumor response and progression-free survival endpoints). When this occurs, one common approach in oncology is to conduct a series of small screening trials in specific patient subgroups, and these trials are typically run in parallel, independent of each other. However, this approach does not consider the possibility that some of the patient subpopulations respond similarly to therapy. In this article, we developed a simple approach to jointly model subgroups with mixed-type endpoints, which allows borrowing strength across subgroups for efficient estimation of treatment effects.
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Estudios Clínicos como Asunto/estadística & datos numéricos , Determinación de Punto Final , Oncología Médica , Antineoplásicos/uso terapéutico , Glioma/tratamiento farmacológico , Humanos , Modelos Estadísticos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous infusion who achieved the target pharmacokinetic/pharmacodynamic (PK/PD) index, which was defined as free concentrations four times more than the minimum inhibitory concentration (CMI) for 100% of the dosing interval (100% fT≥ 4 x MIC). METHOD: Preliminary data from a larger prospective clinical study analysing the PK/PD behaviour of ß-lactams antibiotics continuous infusion (CI) in critical patients. The study was conducted in the intensive care units of a tertiary university hospital for adults (June 2015-May 2017). Inclusion criteria: normal renal function (glomerular renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and treatment with standard dose ß-lactams CI. Concentrations at steady state (Css) conditions were determined using UHPLC-MS/MS. We selected the highest susceptible MIC for all likely organisms according to European Commitee on Antimicrobial Susceptibility Testing's (i.e. piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for Pseudomonas aeruginosa; meropenem: 2 mg/L for any microorganism). In addition, a subanalysis of patients was conducted using actual MIC values. RESULTS: 61 patients were enrolled (25 to meropenem and 36 to piperacillin/tazobactam). Average age was 59 (15) years and median GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the PK/PD target, without differences between both microorganisms. For piperacillin/tazobactam, 61% and 11% of patients reached the target, with enterobacteriaceae and Pseudomonas as suspected microorganisms, respectively. The pathogen was isolated in 35 (57%) patients: 94% reached the target PK/PD, without differences between both antibiotic therapies. CONCLUSIONS: Standard doses of meropenem CI are sufficient to achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections with high MICs (Pseudomonas aeruginosa or enterobacteriaceae). However, higher doses of piperacillin/tazobactam could be considered to achieve this goal. In patients with isolated microorganisms, a standard dose of both antibiotic therapies would be sufficient to achieve the target. Therapeutic drug monitoring is highly recommended for therapeutic optimization.
Objetivo: Determinar el porcentaje de pacientes, a los que se les administró dosis estándar de piperacilina/tazobactam o meropenem en perfusión continua, que alcanzaban el índice farmacocinético/farmacodinámico diana definido como el 100% del intervalo de administración en que las concentraciones de antibiótico libre fueron cuatro veces iguales o superiores a la concentración mínima inhibitoria (100% fT ≥ 4 x CMI).Método: Datos preliminares obtenidos de un estudio clínico prospectivo que analiza el comportamiento farmacocinético/farmacodinámico de los antibióticos betalactámicos administrados en perfusión continua en pacientes críticos. Se realizó en unidades de cuidados intensivos de un hospital universitario de tercer nivel, desde junio de 2015 a mayo de 2017. Criterios de inclusión: adultos con función renal correcta (filtrado glomerular según la fórmula CKD-EPI ≥ 60 ml/min/1,73 m2) y tratados con dosis estándar de antibióticos betalactámicos en perfusión continua. Las concentraciones en estado de equilibrio estacionario fueron determinadas mediante cromatografía líquida acoplada a espectrometría de masas (UHPLC- MS/MS). Se utilizaron valores de concentración mínima inhibitoria teóricos para microorganismos más resistentes (piperacilina/ tazobactam: 16 mg/l para Pseudomonas aeruginosa y 8 mg/l para Enterobacteriaceae; meropenem: 2 mg/l, independientemente del microorganismo). Además, se realizó un subanálisis de los pacientes con aislamiento microbiológico (concentraciones mínimas inhibitorias reales).Resultados: Se incluyeron 61 pacientes (25 meropenem y 36 piperacilina/ tazobactam). Edad media 59 años (15), mediana de filtrado glomerular 95 ml/min/1,73 m2 (83-115). Mediana de concentraciones en estado de equilibrio estacionario libre: 16 mg/l (11- 29) meropenem y 40 mg/l (21-51) piperacilina. El 88% de los pacientes tratados con meropenem alcanzaron el objetivo farmacocinético/farmacodinámico, sin diferencias entre Enterobacteriaceae y Pseudomonas. En el caso de piperacilina/tazobactam, el 61% y el 11% de los pacientes alcanzaron la diana, considerando Enterobacteriaceae y Pseudomonas como microorganismo sospechoso. Un total de 35 (57%) pacientes presentaron aislamiento microbiológico. El 94% de ellos alcanzaron la diana, sin diferencias entre los dos antibióticos.Conclusiones: Ante la sospecha de infecciones por microorganismos con concentraciones mínimas inhibitorias elevadas (Pseudomonas aeruginosa o enterobacterias), se observa que dosis convencionales de meropenem en perfusión continua son suficientes para lograr la diana 100% fT≥ 4 x MIC. Sin embargo, se requerirían dosis superiores de piperacilina/tazobactam. En casos de aislamiento microbiológico, dosis estándar de ambos antibióticos fueron suficientes para lograr la diana. La monitorización farmacocinética es altamente recomendable para la optimización terapéutica.
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Antibacterianos/administración & dosificación , Enfermedad Crítica/terapia , Meropenem/administración & dosificación , Combinación Piperacilina y Tazobactam/administración & dosificación , Adulto , Anciano , Antibacterianos/sangre , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Estudios Clínicos como Asunto/estadística & datos numéricos , Infección Hospitalaria/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Femenino , Hospitales Universitarios , Humanos , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Masculino , Meropenem/sangre , Meropenem/farmacocinética , Meropenem/uso terapéutico , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Combinación Piperacilina y Tazobactam/sangre , Combinación Piperacilina y Tazobactam/farmacocinética , Combinación Piperacilina y Tazobactam/uso terapéutico , Estudios Prospectivos , Infecciones por Pseudomonas/tratamiento farmacológico , Centros de Atención TerciariaRESUMEN
Importance: Analyses of female representation in clinical studies have been limited in scope and scale. Objective: To perform a large-scale analysis of global enrollment sex bias in clinical studies. Design, Setting, and Participants: In this cross-sectional study, clinical studies from published articles from PubMed from 1966 to 2018 and records from Aggregate Analysis of ClinicalTrials.gov from 1999 to 2018 were identified. Global disease prevalence was determined for male and female patients in 11 disease categories from the Global Burden of Disease database: cardiovascular, diabetes, digestive, hepatitis (types A, B, C, and E), HIV/AIDS, kidney (chronic), mental, musculoskeletal, neoplasms, neurological, and respiratory (chronic). Machine reading algorithms were developed that extracted sex data from tables in articles and records on December 31, 2018, at an artificial intelligence research institute. Male and female participants in 43â¯135 articles (792â¯004â¯915 participants) and 13â¯165 records (12â¯977â¯103 participants) were included. Main Outcomes and Measures: Sex bias was defined as the difference between the fraction of female participants in study participants minus prevalence fraction of female participants for each disease category. A total of 1000 bootstrap estimates of sex bias were computed by resampling individual studies with replacement. Sex bias was reported as mean and 95% bootstrap confidence intervals from articles and records in each disease category over time (before or during 1993 to 2018), with studies or participants as the measurement unit. Results: There were 792â¯004â¯915 participants, including 390â¯470â¯834 female participants (49%), in articles and 12â¯977â¯103 participants, including 6â¯351â¯619 female participants (49%), in records. With studies as measurement unit, substantial female underrepresentation (sex bias ≤ -0.05) was observed in 7 of 11 disease categories, especially HIV/AIDS (mean for articles, -0.17 [95% CI, -0.18 to -0.16]), chronic kidney diseases (mean, -0.17 [95% CI, -0.17 to -0.16]), and cardiovascular diseases (mean, -0.14 [95% CI, -0.14 to -0.13]). Sex bias in articles for all categories combined was unchanged over time with studies as measurement unit (range, -0.15 [95% CI, -0.16 to -0.13] to -0.10 [95% CI, -0.14 to -0.06]), but improved from before or during 1993 (mean, -0.11 [95% CI, -0.16 to -0.05]) to 2014 to 2018 (mean, -0.05 [95% CI, -0.09 to -0.02]) with participants as the measurement unit. Larger study size was associated with greater female representation. Conclusions and Relevance: Automated extraction of the number of participants in clinical reports provides an effective alternative to manual analysis of demographic bias. Despite legal and policy initiatives to increase female representation, sex bias against female participants in clinical studies persists. Studies with more participants have greater female representation. Differences between sex bias estimates with studies vs participants as measurement unit, and between articles vs records, suggest that sex bias with both measures and data sources should be reported.
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Reglas de Decisión Clínica , Estudios Clínicos como Asunto , Almacenamiento y Recuperación de la Información/métodos , Selección de Paciente , PubMed/estadística & datos numéricos , Sexismo , Adulto , Estudios Clínicos como Asunto/normas , Estudios Clínicos como Asunto/estadística & datos numéricos , Estudios Transversales , Precisión de la Medición Dimensional , Procesamiento Automatizado de Datos , Femenino , Humanos , Masculino , Sexismo/prevención & control , Sexismo/estadística & datos numéricosRESUMEN
PURPOSE: The aim of this study was to investigate the potential added value of combining propensity score (PS) methods with multivariable linear regression (MLR) in estimating the average treatment effect on the treated (ATT) in nonrandomized studies with health-related quality of life (HRQoL) outcomes. METHODS: We first used simulations to compare the performances of different PS-based methods, either alone or in combination with further MLR adjustment, in estimating ATT. PS methods were, respectively, optimal pair (OPM) and full (OFM) PS matching, subclassification on the PS (SBC), and the inverse probability of treatment weighting (IPTW). We simulated several scenarios, according to different sample sizes, proportions of treated vs untreated subjects, and types of HRQoL outcomes. We also applied the same methods to a real clinical data set. RESULTS: OPM and IPTW provided the closest Type I error to the nominal threshold α = 0.05 across all scenarios. Overall, both methods showed also lower variability in estimates than SBC and OFM. SBC performed worst, generally providing the highest levels of bias. Further MLR adjustment lessened bias for all methods, however providing higher Type I error for SBC and OFM. In the real case, all methods provided similar ATT estimates except for one outcome. CONCLUSIONS: Our findings suggest that for sample sizes up to n = 200, OPM and IPTW are to be preferred to OFM and SBC in estimating ATT on HRQoL outcomes. Specifically, OPM performed best in sample sizes of n ≥ 80, IPTW for smaller sample sizes. Additional MLR adjustment can further improve ATT estimates.
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Estudios Clínicos como Asunto/métodos , Estudios Clínicos como Asunto/estadística & datos numéricos , Modelos Estadísticos , Puntaje de Propensión , Calidad de Vida , Resultado del Tratamiento , Sesgo , Simulación por Computador , Humanos , Modelos Lineales , Método de Montecarlo , Tamaño de la MuestraRESUMEN
Over one billion of the world's population are smokers, with increasing tobacco use in low- and middle-income countries. However, information about the methodology of studies on tobacco control is limited. We conducted a literature search to examine and evaluate the methodological designs of published tobacco research in Sub-Saharan Africa (SSA) over the past 50 years. The first phase was completed in 2015 using PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials. An additional search was completed in February 2017 using PubMed. Only tobacco/smoking research in SSA countries with human subjects and published in English was selected. Out of 1796 articles, 447 met the inclusion criteria and were from 26 countries, 11 of which had one study each. Over half of the publications were from South Africa and Nigeria. The earliest publication was in 1968 and the highest number of publications was in 2014 (n = 46). The majority of publications used quantitative methods (91.28%) and were cross-sectional (80.98%). The commonest data collection methods were self-administered questionnaires (38.53%), interviews (32.57%), and observation (20.41%). Around half of the studies were among adults and in urban settings. We conclud that SSA remains a "research desert" and needs more investment in tobacco control research and training.
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Estudios Clínicos como Asunto/métodos , Proyectos de Investigación/estadística & datos numéricos , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , África del Sur del Sahara , Estudios Clínicos como Asunto/estadística & datos numéricos , HumanosRESUMEN
Background: Functional Neurology (FN), mainly practiced by chiropractors, proposes to have an effect or a benefit on varied clinical cases, from debilitating diseases to performance enhancement in asymptomatic people. Objectives and design: A critical review of publications captured in and from the journal Functional Neurology, Rehabilitation, and Ergonomics (FNRE) was performed in order to investigate whether there is evidence on clinical effects or benefits of FN. This review had five research objectives, three relating to the type of literature available through this journal, and two in relation to design and methodological aspects of the included studies. Method: All issues of the FNRE journal were searched (October 2017), including a handsearch of their lists of other relevant publications. In order to find evidence in relation to the effect or benefit of FN, the search was restricted to prospective clinical research studies with a control group, claiming or appearing to deal with the topic. The review was undertaken by two independent reviewers using two checklists, one relating to study description, and one on quality. Results were reported narratively. Results: Nine articles were found. The FNRE journal contained 168 authored texts, of which 36 were research studies (21%). Four of these were clinical research studies on FN effect or benefit (2%). Another five were obtained through the handsearch. The included studies were conducted on adults or children, symptomatic or not, and investigated various interventions consisting of single or multiple stimuli, of varied nature, all primarily said to be provided to stimulate brain areas. Conditions included attention deficit disorders, attention deficit and hyperactivity disorders, autism-spectrum disorders, cortical visual impairment, traumatic brain injury, and migraine. Balance and the "blind spot" were investigated in healthy subjects. Major design and methodological issues were identified and discussed for all the nine studies; only four were considered as (potentially) appropriate for further scrutiny. However, these were of low methodological quality and, therefore, no robust evidence could be found in relation to the effect or benefit of the tested FN interventions. Conclusions: This journal contains no acceptable evidence on the effect or benefit of FN in relation to various conditions and purported indications for intervention.
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Quiropráctica/métodos , Estudios Clínicos como Asunto/normas , Neurología/métodos , Proyectos de Investigación/normas , Estudios Clínicos como Asunto/estadística & datos numéricos , Humanos , Estudios ProspectivosRESUMEN
Thorough knowledge of the structure of analyzed data allows to form detailed scientific hypotheses and research questions. The structure of data can be revealed with methods for exploratory data analysis. Due to multitude of available methods, selecting those which will work together well and facilitate data interpretation is not an easy task. In this work we present a well fitted set of tools for a complete exploratory analysis of a clinical dataset and perform a case study analysis on a set of 515 patients. The proposed procedure comprises several steps: 1) robust data normalization, 2) outlier detection with Mahalanobis (MD) and robust Mahalanobis distances (rMD), 3) hierarchical clustering with Ward's algorithm, 4) Principal Component Analysis with biplot vectors. The analyzed set comprised elderly patients that participated in the PolSenior project. Each patient was characterized by over 40 biochemical and socio-geographical attributes. Introductory analysis showed that the case-study dataset comprises two clusters separated along the axis of sex hormone attributes. Further analysis was carried out separately for male and female patients. The most optimal partitioning in the male set resulted in five subgroups. Two of them were related to diseased patients: 1) diabetes and 2) hypogonadism patients. Analysis of the female set suggested that it was more homogeneous than the male dataset. No evidence of pathological patient subgroups was found. In the study we showed that outlier detection with MD and rMD allows not only to identify outliers, but can also assess the heterogeneity of a dataset. The case study proved that our procedure is well suited for identification and visualization of biologically meaningful patient subgroups.