Recently, real world studies (RWS) have received increasing attentions. Such studies typically involve patient information, and their results may have potentially significant impact on patient well-being and safety. When reviewing the protocol of real world studies, ethical issues should be carefully considered and assessed. This paper discussed three issues, including the overview of bioethics and its application to classic clinical trials, key features of RWS, and medical ethical considerations on RWS.
Traditional Chinese medicine (TCM) has a long history. In the process of fighting against diseases, TCM has formed a unique theoretical system and the way to think and diagnose. The holistic thinking, and the treatment according to syndrome differentiation are the most prominent characteristics of TCM, which matches with advanced medical concept and direction. The clinical efficacy has always been the basis for the advancement of TCM. However, issues such as the lagging behind of modern research on the evaluation of TCM curative effect, as well as lacking high-quality scientific research evidence, impede the development and promotion of the TCM toward the world. To address the above problems, recent progress in real-word study (RWS) has provided the opportunity for TCM researches, especially for the post-marketing evaluation of Chinese patent medicine (CPM). The formulation of this technical guidance for RWS of CPM is helpful to researchers in carrying out standardized, reasonable and scientific researches, to improve the quality of production and use of real-word evidence, and to promote the advancement of the TCM industry.
Diabetic retinopathy (DR), which is a common complication of diabetic and the main cause of blindness, brings not only a heavy economic burden to society, but also seriously threatens to the patients’ quality of life. Clinical researches on the therapies of DR are active at present, but how to perform a good clinical research with scientific design should be considered with high priority. The randomized controlled trial (RCT) is considered to be the gold standard for evidence-based medicine, but RCT is not always perfect. Limitations still exist in certain circumstance and the conclusions from RCTs also need to be interpreted by an objective point of view before clinical practice. Real world study (RWS) bridges the gap between RCT and clinical practice, in which the data can be easily collected without much cost, and results might be obtained within a short period. However, RWS is also faced with the challenge of not having standardized data and being susceptible to confounding bias. The standardized single disease database for DR and propensity score matching method can provide a wide range of data sources and avoid of bias for RWS in DR.
ObjectivesTo analyze the active areas of real world studies on traditional Chinese medicine in China.MethodsCBM, CNKI, WanFang Data, PubMed and EMbase databases were electronically searched to collect real world studies on traditional Chinese medicine in China from inception to 26th April, 2018. The main research contents (research direction, data sources, and research methods) by Excel were extracted, together with the primary information by BICOMS-2 software and production of the network figures by NetDraw 2.084 software.ResultsEventually, 373 real world studies in traditional Chinese medicine were included, in which the initial one was punished in 2008. The top three ranking of authors involved in real world studies on traditional Chinese were Xie Yanming, Zhuang Yan, Yang Wei, and the top three ranking of institutions were Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences, School of Statistics of Renmin University of China, and the PLA Navy General Hospital. The amount of related studies in Beijing accounted for 74.26%. It was found that the active areas involve real world, hospital information system, real world study, drug combination, and propensity score method. In terms of the main studied contents on the use of traditional Chinese medicine in the real world, in which the top three were Fufang Kushen injection, Dengzhanxixin injection, and Shuxuetong injection. Digestive system disease, nervous system disease and cardiovascular disease received the highest attention rate, specifically stroke, coronary heart disease, virus hepatitis and hypertension. 58.18% studies were retrospective studies, 49.60% of the information were from the hospital information system, and 56.30% studies used data mining to carry out statistical analysis.ConclusionsMost real world studies on traditional Chinese medicine are based on HIS, and use data mining to study Chinese medicine preparations. The research attention on Chinese medicine is higher than that of the method of diagnosis and treatment, similarly the Chinese medicine preparations is higher than traditional Chinese medicine. In future, attention should be paid to traditional Chinese medicine, prescription and traditional methods of diagnosis and treatment, such as moxibustion and scraping.
ObjectiveTo evaluate the efficacy and safety of dupilumab in the treatment of moderate-to-severe asthma. MethodsA retrospective study was conducted among patients with moderate-to-severe asthma who were treated with dupilumab and inhaled corticosteroids (ICS) combined with long acting beta-agonist (LABA) in Department of Respiratory, Beijing Chao-yang Hospital from May, 2021 to April, 2022. Paired t-test or Mann-Whitney U test was applied to compare the Asthma Control Test (ACT) scores, number of acute exacerbations per year, type 2 inflammatory biomarkers, blood total IgE and results of pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1 as percentage of predicted (FEV1%pred), FEV1/FVC, peak expiratory flow (PEF), maximal expiratory flows (MEF) at 75% (MEF75), 50% (MEF50) and 25% (MEF25) of the vital capacity PEF, and maximal mid-expiratory flow (MMEF) or FEF25%-75%, at the end of follow-up with those before treatment. Adverse reactions were recorded during the treatment. ResultsA total of 47 patients with moderate-to-severe asthma were included in the study, among them 17 and 30 received treatment with dupilumab or ICS/LABA. At the time of 12 months after treatment with dupilumab, the patients' ACT score and pulmonary function tests were significantly increased compared with those at the baseline. In contrast, patients' fractional exhaled nitric oxide (FeNO), blood total IgE, blood basophil counts and annual acute exacerbations were significantly decreased in comparison with those at the baseline. The doses of oral corticosteroids added by 7 patients at the baseline was gradually reduced and finally discontinued after treatment of dupilumab. There were 4, 2, 1 and 1 patients developed injection site reaction, pruritus, erythema and fatigue, respectively, which were mild and recovered without treatment. There was no serious adverse reaction observed, and only 1 case developed herpes zoster which was recovered after treatment. ConclusionDupilumab shows marked efficacy in the treatment of moderate-to-severe asthma with favorable safety.
ObjectiveTo analyze the status of real world studies (RWS) through registration information of the Chinese Clinical Trials Registry (ChiCTR). MethodsThe website of ChiCTR was searched with the real world as the search term to collect relevant registered items in the real world from inception to May 4, 2022. Descriptive analysis method was used. ResultsA total of 642 registered items were included. The median sample size was 482 cases. RWS were mainly observational studies, and the number of intervention studies was increasing year by year. There were 267 studies (41.59%) at the stage of post-marketing drugs or phase Ⅳ clinical trials. Most of the main measures were endpoints (56.23%), and the most commonly used was overall survival (15.79%). 62.15% of the registered projects met the minimum requirements for registration. ConclusionThe number of RWS registered by ChiCTR shows an increasing trend. At present, the research purpose of RWSs is unclear, and the completeness of registered studies and the overall content compliance of the studies need to be improved.
Objectives To estimate the elasticity of demand price elasticity and demand income of urban and rural residents’ self-purchase drug use and expenditure, and to analyze the sensitivity of self-purchase drug use and expenditure to the price change of drug purchase, resident income and medical institutions. Methods The data were derived from the fifth health service survey in Heilongjiang province in 2013. The Probit model was used to obtain the partial regression coefficients of the control variables in the regression model, and the demand elasticity of the self-purchase drug use was further measured by the partial regression coefficients, and the demand elasticity of self-purchase expenditure was obtained by the logarithmic regression model. Results A total of 5 289 households (14 431 persons) were included. The demand for self-purchase drug use of Heilongjiang province was 0.374 (P=0.000), the cross-price elasticity of self-purchase drug utilization and service was –0.184 (P=0.000), and the income elasticity was 0.083 (P=0.172). Since the price elasticity of the self-purchase drug expenditure was 0.675 (P=0.000), the income elasticity was 0.144 (P=0.069). Conclusions The use of self-purchased drugs in Heilongjiang province lacks price elasticity and is a necessity. There is a complementary relationship between the use of self-purchase drugs and medical institutions.
ObjectiveTo analyze the neoadjuvant therapy of colorectal cancer in this center in the background of real world data by studying Database from Colorectal Cancer (DACCA) in West China Hospital of Sichuan University.MethodsData was selected from DACCA who was updated on August 15, 2019. After deleting duplicate value, patients whose tumor location and tumor pathologic characteristic showed colon or rectum, as well as adenocarcinoma, mucinous adenocarcinoma, and signet ring cell carcinoma were enrolled.ResultsThere were 2 783, 2 789, 2 790, 2 811, 4 148,3 824, 4 191, 3 676, 4 090, and 499 valid data of T, N, and M stages, clinical stages, tumor site, distance from tumor to anal dentate line, tumor pathologic characteristics, degree of tumor differentiation, neoadjuvant therapy, and compliance, respectively. There were 1 839 lines that " nature of the tumor pathology” was not empty and neoadjuvant scheme for the pure chemotherapy, radiotherapy alone or radiation, and chemotherapy, including 50 lines of signet ring cell carcinoma (2.7%), 299 lines of mucous adenocarcinoma (16.3%), 1 490 lines of adenocarcinoma (81.0%), various kinds of pathology in selection of neoadjuvant therapy difference was statistically significant (χ2=9.138, P=0.041). Except for the data lines with null value in the column of " operation date”, there were 2 234 (82.1%) and 486 (17.9%) effective data lines of " recommended” and " not recommended” for the use of neoadjuvant therapy, respectively. In the years with a large amount of data, among the patients who completed neoadjuvant therapy, the proportion of patients meeting the recommended indications was 27.4%–67.6%, with an average of 47.4%. Patients who did not meet the recommended indications but were recommended (off-label use) accounted for 7.3%–70.0%, with an average of 39.8%. According to regression analysis, the proportion in line with the recommendation (\begin{document}$\hat y $\end{document}=–0.032 5x+66.003 2, P=0.020) varies with the year, and the overall trend shows a gradual decline. The proportion of the use of super indications (\begin{document}$\hat y $\end{document}=–0.054 5x+110.174 6, P=0.002) changed with the year, and the overall trend showed a decline. A total of 1 161 valid data with non-null values of " eoadjuvant therapy regimen” and " recommended or not recommended” showed statistically significant difference in the use rate of neoadjuvant therapy among patients with different recommendation groups (χ2=9.244, P=0.002). " Patient compliance” was shown as " active cooperation” and " passive acceptance”, and " neoadjuvant therapy” was shown as " radiotherapy alone”" chemotherapy alone”, and " chemoradiotherapy” were 470 lines. There was no statistically significant difference in neoadjuvant therapy between patients receiving active and passive treatment (χ2=0.537, P=0.841). The effective data of clinical remission degree meeting the research conditions were 388 lines, including 121 lines of complete response (31.2%), 180 lines of partial response (46.4%), 79 lines of stable disease (20.4%), and 8 lines of progressive disease (2.1%). There was no statistically significant difference in clinical response degree among patients with different neoadjuvant therapy (H=0.435, P=0.783). There were 346 lines with effective data of pathologic tumor regression grade (TRG) meeting the study conditions, including 47 lines with TRG0 (13.6%), 39 lines with TRG1 (11.3%), 180 lines with TRG2 (52.0%), and 80 lines with TRG3 (23.1%). There was no statistical difference in the degree of TRG among patients with different neoadjuvant therapy (H=1.816, P=0.518).ConclusionsThe real world study reflects that in the western regional medical center, the demand for neoadjuvant therapy among the patients with colorectal cancer covered is huge. Although the implementation of neoadjuvant therapy is greatly influenced by the doctor’s recommendation behavior, the selection and recommendation of neoadjuvant therapy according to some specific clinical application guidelines are not fully met. The impact of more behavioral factors requires further in-depth analysis and research.
Objectives To evaluate the clinical outcomes and identify its associated factors in patients with acute coronary syndromes (ACS) in Tianjin city. Methods Data were obtained from Tianjin urban employee basic medical insurance database. Adult patients who were discharged alive after the first ACS-related hospitalization (the index hospitalization) during January, 2012 to December, 2014 and without malignant tumor were included. Clinical outcomes were measured by subsequent major adverse cardiovascular events (MACE) including hospitalization for myocardial infarction (MI) or stroke, all-cause death, or their composite endpoint. Cox model was used to explore the factors associated with MACE. Results 22 041 patients were identified, in which 9.5% experienced MACE during follow-up with a mean number of 1.3 MACEs. 3.1% of patients had MI, 5.7% had stroke and 1.4% had all-cause death. Among patients who experienced MACEs, the average time from index discharge to the 1st MACE was 143.2 days. Patients being older, male or had higher Charlson Comorbidity Index (CCI) were more likely to experience MACE. Patients who had prior stroke and prior all-cause hospitalization were also more likely to experience MACE, whereas patients who had prior angina, prior β-blockers utilization and received percutaneous coronary intervention (PCI) during index event were less likely to experience MACE. Conclusion Stroke is the most common type of MACE among ACS patients in Tianjin, China. Almost half of the 1st MACE occur within the 3 months after ACS. Patients who are older, male, have higher CCI or have prior stroke are at higher risk of MACE.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.