Reforming clinical research and development in England.
Ontology highlight
ABSTRACT:
SUBMITTER: McNally N
PROVIDER: S-EPMC192853 | biostudies-literature | 2003 Sep
REPOSITORIES: biostudies-literature
Publications
Reforming clinical research and development in England.
McNally Nick N Kerrison Susan S Pollock Allyson M AM
BMJ (Clinical research ed.) 20030901 7414
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Project description: Not available
| S-EPMC1420714 | biostudies-literature
Project description:Under stressful conditions, the heat shock protein 90 (HSP90) molecular chaperone protects cellular proteins (client proteins) from degradation via the ubiquitin-proteasome pathway. HSP90 expression is upregulated in cancers, and this contributes to the malignant phenotype of increased proliferation and decreased apoptosis and maintenance of metastatic potential via conservation of its client proteins, including human epidermal growth factor receptor 2, anaplastic lymphoma kinase, androgen receptor, estrogen receptor, Akt, Raf-1, cell cycle proteins, and B-cell lymphoma 2 among others. Hence, inhibition of HSP90 leads to the simultaneous degradation of its many clients, thereby disrupting multiple oncogenic signaling cascades. This has sparked tremendous interest in the development of HSP90 inhibitors as an innovative anticancer strategy. Based on the wealth of compelling data from preclinical studies, a number of HSP90 inhibitors have entered into clinical testing. However, despite enormous promise and anticancer activity reported to date, none of the HSP90 inhibitors in development has been approved for cancer therapy, and the full potential of this class of agents is yet to be realized. This article provides a review on ganetespib, a small molecule HSP90 inhibitor that is currently under evaluation in a broad range of cancer types in combination with other therapeutic agents with the hope of further enhancing its efficacy and overcoming drug resistance. Based on our current understanding of the complex HSP90 machinery combined with the emerging data from these key clinical trials, ganetespib has the potential to be the first-in-class HSP90 inhibitor to be approved as a new anticancer therapy.
| S-EPMC4521669 | biostudies-literature
Project description:Ramucirumab (IMC-1121B, LY3009806), a fully humanized monoclonal antibody directed against the extracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), is a new therapeutic option that selectively inhibits the human VEGFR-2 with a much greater affinity than its natural ligands. Based on the promising results of both preclinical and early clinical studies, ramucirumab has been tested in different tumor types either alone or in combination with chemotherapy. While it has recently been granted its first US Food and Drug Administration approval for use as a single agent in patients with advanced or metastatic gastric cancer or gastroesophageal junction carcinoma, its role for metastatic breast cancer or advanced non-small-cell lung cancer is still debated. The aims of this review are to recall and discuss the most significant preclinical and clinical studies that led to the development of ramucirumab and to present the results of the randomized clinical trials that have tested its efficacy in different malignancies, including gastric and lung cancer.
| S-EPMC4218907 | biostudies-literature
Project description:IntroductionClinical research participants' perceptions regarding their experiences during research protocols provide outcome-based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants' clinical research experiences. Use of validated surveys measuring patient-centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes.MethodsWe derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion-related validity, and item usefulness. Responses were tested for fit into existing patient-centered dimensions of care and new clinical research dimensions using Cronbach's alpha coefficient.ResultsSurveys were mailed to 18,890 individuals; 4,961 were returned (29%). Survey completion was 89% overall; completion rates exceeded 90% for 88 of 93 evaluable items. Questions fit into three dimensions of patient-centered care and two novel clinical research dimensions (Cronbach's alpha for dimensions: 0.69-0.85).ConclusionsThe validated survey offers a new method for assessing and improving outcomes of clinical research processes.
| S-EPMC3605037 | biostudies-literature
Project description:BackgroundClinical research has frequently not been taught in a practical way, often resulting in a very didactic approach rendering it not very accessible for medical undergraduates. Simulation can provide an immersive, interactive, and reflective experience and may be applied to the clinical research curriculum.MethodsA 7-step model, modified from Kern's six-step approach and Khamis's stepwise model, was used to develop the curriculum. A questionnaire survey on undergraduates' attitude towards, knowledge and practice of clinical research and simulation education was conducted to generate a targeted needs assessment. The simulation framework was integrated into the development of educational strategies. Experts were consulted to assess the curriculum prior to implementation.ResultsTalent construction in China needs an innovative capability-enhanced clinical research curriculum. Sixty-six clinical undergraduates in our school completed the survey. 89.39% (59/66) of them hadn't participated in clinical research, while 93.94% (62/66) would like to conduct clinical trials if possible. 75.76% of respondents didn't have knowledge of or practical abilities in clinical trials. The mean score for practical ability (2.02 ± 0.92) was lower than that of knowledge (2.20 ± 0.93) (P < 0.01). The dimension of case report form got the lowest score among the five dimensions. Participating in clinical research (P = 0.04) and learning for themselves (P < 0.01) by a few students may have increased the total score. The curriculum was designed to simulate the whole process from protocol writing, registration, ethical approval, implementation, and data analysis to reporting based on one case study, and was divided into two parts to simulate different types of research: randomized controlled trials and observational studies. It was conducted in semesters 5 and 7 respectively, both including 16 sessions. After expert consultation, one session having a 29.01% coefficient of variation was adjusted and replaced. The final simulation class design scenario scripts are provided for reference.ConclusionsThe targeted needs assessment exposed medical undergraduates' poor knowledge of and abilities in clinical research. This is the first report of a simulation-based clinical research curriculum developed in China, and adds curriculum development and design details to the limited related published studies.
| S-EPMC9281572 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-08-17 | GSE182195 | GEO
Project description:Developing valid and reliable instruments is crucial but costly and time-consuming in health care research and evaluation. The Food and Drug Administration and the National Institutes of Health have set up guidelines for developing patient-reported outcome instruments. However, the guidelines are not applicable to cases of small sample sizes. Instead of using an exact estimation procedure to examine psychometric properties, our Bayesian Instrument Development (BID) method integrates expert data and participant data into a single seamless analysis. Using a novel set of priors, we use simulated data to compare BID to classical instrument development procedures and test the stability of BID. To display BID to non-statisticians, a graphical user interface based on R and WINBUGS is developed and demonstrated with data on a small sample of heart failure patients. Costs were saved by eliminating the need for unnecessary continuation of data collection for larger samples as required by the classical instrument development approach.
| S-EPMC4034393 | biostudies-literature
Project description:ObjectiveTo create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England.DesignRetrospective cohort study.SettingElectronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England.Participants2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022.Main outcome measuresAge, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 'COVID-19'). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination).ResultsCompared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65-84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score.ConclusionsCPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.
| S-EPMC10806788 | biostudies-literature
Project description:ImportanceTimely identification of patients likely to miss seasonal influenza vaccination (SIV) could help health care practitioners tailor services and gain efficiency.ObjectiveTo develop and validate a predictive model of SIV uptake among at-risk adults.Design, setting, and participantsThis prognostic study constructed a prediction model for vaccine uptake by adults at increased risk of influenza-associated complications. Drawing from the Clinical Practice Research Datalink database's records of primary care data of 324 284 adults routinely collected at general practices across England from January 2011 to December 2016, logistic regression models were trained on data from patients registered from January 2012 to December 2013 and validated with out-of-sample data from patients registered from January 2015 to December 2016. Data were extracted from the database December 2018 and analyzed between September 2019 and December 2019.ExposuresCovariates included sex, age, race/ethnicity, smoking status, socioeconomic status, previous pneumococcal vaccination, prior season SIV uptake, and clinical risk conditions.Main outcomes and measuresThe main outcome was patient-level SIV uptake. Model performance was measured via misclassification rate, Brier score, sensitivity, specificity, and area under the curve.ResultsThe training data sets consisted of 324 284 (aged 18 to 64 years) and 186 426 (aged 65 years or older) patients. The mean (SD) age in the training data among patients aged 18 to 64 years was 45 (13) years; 161 487 (49.8%) were women, and 102 133 (31.5%) were categorized as white. Among patients aged 65 years or older, the mean (SD) age was 77 (8) years; 96 169 (51.6%) were women, and 64 996 (34.9%) were categorized as white. The validation data sets consisted of 35 210 patients aged 18 to 64 years and 25 497 aged 65 years or older. The mean (SD) age in the validation data set among patients aged 18 to 64 years was 42 (14) years; 17 296 (49.1%) were women, and 13 346 (37.9%) were categorized as white. Among patients aged 65 years or older, the mean (SD) age was 73 (8) years; 13 135 (51.5%) were women, and 9641 (37.8) were categorized as white. Among patients aged 18 to 64 years, SIV uptake was 35.9% (95% CI, 35.7%-36.0%) and 32.6% (95% CI, 32.1%-33.1%) for the training and validation data sets, respectively. Among patients aged 65 years or older, SIV uptake was 83.1% (95% CI, 82.9%-83.2%) and 76.1% (95% CI, 75.5%-76.6%) for the training and validation data sets, respectively. Prior season SIV uptake and pneumococcal vaccination status were the best predictors of SIV uptake. Predicted SIV uptake probabilities for patients aged 18 to 64 years were reliable, but biased toward underpredicting, whereas, among patients aged 65 years or older, they were variable and biased toward overpredicting. Briefly, in out-of-sample validation among patients aged 18 to 64 years, misclassification rates were 0.163 to 0.164, Brier scores were 0.124 to 0.125, area under the receiver operating characteristic curve values ranged from 0.876 to 0.877, sensitivity ranged from 0.705 to 0.720, and specificity ranged from 0.896 to 0.902. In patients aged 65 years or older, misclassification rates were 0.120 to 0.125, Brier scores were 0.0953 to 0.0959, area under the receiver operating characteristic curve was 0.877, sensitivity ranged from 0.919 to 0.936, and specificity ranged from 0.680 to 0.753.Conclusions and relevanceThis study suggests that data obtained from primary care records could accurately predict SIV uptake among at-risk adults. Further research is needed to assess the feasibility and efficacy of implementing this model in clinical settings.
| S-EPMC7324952 | biostudies-literature
Project description:Clinical research workforce development efforts have focused on both increasing the size of the workforce of investigators and professionals working in the clinical research enterprise, but also the education and training of those individuals to ensure the quality of study performance to improve the public's health. A major contribution to these efforts has been the establishment of core competencies for clinical research professionals by the Joint Task Force for Clinical Trial Competency. This article reviews the development of the clinical research core competencies, their wide adoption and influence on job descriptions, education, training, and academic accreditation.
| S-EPMC6198073 | biostudies-literature