Due to the competition of new drug research and clinical requirement, speeding up drug development and marketing requires faster and more flexible clinical trial design that meets the ethical requirements. Different adaptive designs have emerged in clinical trials of different stages and purposes, for trial efficiency improvement. Adaptive design is more widely used in the field of oncology. Compared with traditional design, adaptive design is more complicated and requires higher level of methodology from researchers. Therefore, implementing adaptive design requires careful consideration and adequate preparation. This paper aims to summarize the design of adaptive methods used in different trial stages so as to provide reference for clinical research designers and implementers.
Randomized controlled trial has been the "gold standard" for clinical trials, in which randomization serves as a fundamental principle of clinical trials and plays an important role in balancing covariates. The allocation probability in traditional design is fixed, while that in adaptive randomization can alter during the experiment according to the specified plan to achieve the purposes of balancing the sample size, maximizing the benefit of patient, or balancing covariates etc. In this study, the adaptive randomization methods applied in clinical trials are discussed to explore their advantages and disadvantages for providing reference for the randomization of clinical trials.
ObjectiveTo investigate factors influencing the results of bronchodilator reversibility tests (BDT) in mild to moderate asthma, and to develop a model predicting the result of BDT in this population. Methods A cross-sectional study was designed to recruit patients with forced expiratory volume in the first second (FEV1) ≥ 70% predicted from the Australasian Severe Asthma Network during 2014 to 2021, whose asthma diagnosis was confirmed by a positive bronchial challenge test. Structural questionnaires, BDT, fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood sampling were conducted. Patients were further divided into positive group and negative group according to their BDT result. Then the comparative analysis between two groups, correlation analysis, and multivariate logistical regression were performed. Logistic models for predicting BDT result were developed using variables screened through LASSO regression. Results A total of 334 patients were included. Compared with the BDT negative group (n=240), the BDT positive group (n=94) was found to have worse airway obstruction in lung function, asthma control and quality of life, higher eosinophil counts in both peripheral blood and induced sputum, and higher FeNO. According to the multivariate regression, the positive BDT results significantly correlated with Asthma Control Questionnaire score, Asthma Questionnaire of Life Quality score, FEV1%pred, MMEF%pred, FEV1/FVC, blood and sputum eosinophil counts and FeNO. A total of 326 patients were included in the training set, and FEV1%pred, MMEF%pred, FEV1/FVC, smoking pack years, blood and sputum eosinophil counts and FeNO were then screened out by LASSO regression as stable predictors. The areas under the receiver operating characteristic curve of the 3 prediction models (P<0.001) constructed using the variables above ranged from 0.810 to 0.834. Internal validation was performed, and both the discrimination (0.810, 0.834 and 0.812, respectively) and the calibration (0.135, 0.133 and 0.192, respectively) of the models were acceptable. Conclusion The BDT results of patients with mild to moderate asthma were associated with asthma control, lung function, systemic or airway eosinophilia and FeNO, and models including lung function, eosinophils, and FeNO, etc. could predict the BDT results well.
Systematic reviews can provide important evidence support for clinical practice and health decision-making. In this process, literature screening and data extraction are extensively time-consuming procedures. Natural language processing (NLP), as one of the research directions of computer science and artificial intelligence, can accelerate the process of literature screening and data extraction in systematic reviews. This paper introduced the requirements of systematic reviews for rapid literature screening and data extraction, the development of NLP and types of machine learning; and systematically collated the NLP tools for the title and abstract screening, full-text screening and data extraction in systematic reviews; and discussed the problems in the application of NLP tools in the field of systematic reviews and proposed a prospect for its future development.
ObjectiveTo explore whether education and management of medical care integration can improve asthma control. MethodsA prospective, 12-month, cohort study was undertaken in a real-world setting based on Australasian severe asthma network (ASAN). A total of 516 patients with stable asthma were consecutively recruited, who received education and management of medical care integration, and step-wise anti-asthma regimens determined by physicians’ standard practice. Furthermore, inhaled corticosteroid (ICS) adherence, lung function, asthma symptom control and exacerbation were assessed at 1, 3, 6, and 12 months. ResultsAt the end of 12 months, ICS adherence (47.7% vs. 81.5%, P<0.05), lung function, and asthma symptoms were assessed by asthma control text (ACT) [20 (16, 23) vs. 23 (21, 24), P<0.05], which were significantly improved in comparison to the status at baseline, and 86.0% of patients achieved total/well-controlled level of asthma. The exacerbation (14.2% vs. 36.2%, P<0.01) and hospitalizations (8.5% vs. 15.3%, P<0.01) because of asthma for the following year significantly decreased compared with those in the past year. The multivariate regression analysis indicated that poor ICS adherence (RR=1.52, 95%CI 1.02 to 2.25, P=0.039), depression symptoms (RR=1.19, 95%CI 1.05 to 1.34, P=0.007), and exacerbation during the past year (RR=2.81, 95%CI 1.49 to 5.27, P=0.001) were associated with an increased risk of future exacerbation. ConclusionIn a real-world setting, most of asthmatics achieve total/well-controlled asthma by education and management of medical care integration including shared decision-making between physicians and patients and step-wise anti-asthma regimens. ICS adherence and depression symptoms independently predict asthma exacerbations, and strengthening education and management of medical care integration, esp. psychological nursing, would improve asthma control levels.
ObjectivesTo develop a tool to assess the credibility of cohort studies regarding anticoagulants treatment for patients with atrial fibrillation.MethodsMEDLINE, EMbase and CBM databases were retrieved for eligible studies on the methodological quality and credibility of the cohort study. The retrieval period was from inception to December 19th, 2017, and the languages were limited to Chinese and English. Based on the search results, the items on the methodology quality of the research or the credibility of the results were collected. Through brainstorming of the core group, the collected items were expanded and sorted out to a preliminary scale. Furthermore, we conducted 4 rounds of internal expert seminars to discuss and evaluate the preliminary scale content and discuss the scale framework. Finally, we organized domestic authoritative experts to conduct 4 external evaluations on the scale and formed the final scale.ResultsA total of 7 734 literatures were obtained from primary search, in which 17 of which were included. Fifty-five tools with 780 items for the quality assessment of observational studies were collected from the included studies. After removing duplicated keywords with similar meanings, we obtained the " keyword pool” with 46 keywords, which were preliminarily formed 46 items. After discussion of the core group, which aimed to supplement the potential items, eliminate the items irrelevant to methodology, and integrate the items with partial overlapping meanings, a preliminary scale of 43 items was formed. According to the four rounds of internal expert consultative meetings, these items were integrated to form a preliminary scale of 40 items. After further evaluation by four rounds of external expert consultative meetings, a consensus was reached and a scale of 21 items from seven domains (i.e., definition of question, measurement, follow-up, confounder, missing data, statistical analysis, and results assessment) was finally formed.ConclusionsThis study developed an assessment tool for the credibility of the results from the cohort studies regarding anticoagulants treatment in patients with atrial fibrillation, which has practical clinical value. Clinicians can refer to the results of credibility assessment by using this tool to better assist clinical decision-making in clinical practice. In addition, in the preparation of relevant guidelines, this tool can be used to assess the credibility of results from cohort studies.
The development of evidence-based clinical practice guidelines is a sophisticated and systematic process, often requiring multidisciplinary efforts. The traditional approach to developing and updating clinical practice guidelines is usually time-consuming. These limitations obstacle the effective use of guideline recommendations and efficient transformation of most recent research evidence into practice. The MAGIC system is a novel method system for rapid creation and dissemination of high-quality clinical recommendations, including rapid creation of trustworthy recommendations, thus ensuring the scientific and efficient production of clinical practice guidelines; facilitating rapid dissemination and dynamic updating of clinical practice guidelines through recommendation release system (i.e., MAGICapp); and helping promote the production of relevant high-quality original research evidence by identifying the insufficiency of evidence in the process of creation of guideline recommendations. Ultimately, a complete closed-loop digital and trustworthy evidence ecosystem is developed. In order to further promote the effective transformation of research evidence into guideline recommendations, MAGIC China Center was established. We anticipate that the Center will assist the further development and effective use of clinical practice guideline in China.
ObjectiveTo construct the comprehensive evaluation indicator system of Chinese patent medicines for ischemic stroke, to determine the weight of indicators, and to provide references for the comprehensive evaluation of the efficacy, safety, and economy of Chinese patent medicines.MethodsTwo rounds of expert consultation by Delphi method were applied to establish the comprehensive evaluation indicator system of Chinese patent medicines for ischemic stroke, and the weight of each indicator was determined by the analytic hierarchy process method.ResultsQuestionnaire recovery rates of 2 rounds were 92.59% and 96.00%, the expert authority coefficient was greater than 0.7, and the coordination coefficients of experts in the total index were 0.224 and 0.370 (P<0.001). A three-level comprehensive evaluation indicator system for Chinese patent medicines for ischemic stroke was established and the three first-level indicators included efficacy, safety, and economy. And there were 15 second-level indicators, and 33 third-level indicators. Through the analytic hierarchy process method, the weights of each first-level indicator were 0.626 4, 0.301 2, and 0.072 4, respectively.ConclusionThe comprehensive evaluation indicator system contains efficacy, safety and economy, and provides a basis for a comprehensive evaluation of Chinese patent medicines for ischemic stroke. The indicator system is of great significance for the design of outcomes for clinical trials of ischemic stroke, the conduction of systematic reviews, and the development of clinical practice guidelines for ischemic stroke patients when selecting study outcomes.