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      Pharmacovigilance in China: Evolution and future challenges

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          Abstract

          Drug‐related adverse reactions are among the main reasons for harm to patients under care worldwide and even their deaths. The pharmacovigilance system has been proven to be an effective method of avoiding or alleviating such adverse events. In 2019, after two decades of implementation of the drug‐related adverse reaction reporting system, China formally implemented a pharmacovigilance system with the Pharmacovigilance Quality Management Standards and a series of supporting technical documents created to improve the safety of medication given to patients. China's pharmacovigilance system has faced many problems and challenges during its implementation. This spontaneous reporting system is the main source of data for China's medication vigilance activities, but it has not provided sufficiently powerful evidence for regulatory decision‐making. In conformity with the health‐centred drug regulatory concept, the Chinese government has accelerated the speed of examination and approval of urgently needed clinical drugs and orphan drugs along with the requirement to improve the safety supervision of these drugs after their listing. China's marketing authorization holders (MAHs) must strengthen their pharmacovigilance capabilities as the primary responsible departments for drug safety. Chinese medical schools generally lack professional courses on pharmacovigilance. The regulatory authorities have recognized such problems and have made efforts to improve the professional capacity of pharmacovigilance personnel and to strengthen cooperation with stakeholders through the implementation of an action plan of medication surveillance and the establishment of a patient‐based adverse events reporting system and active surveillance systems, which will help China bridge the gap to bring its pharmacovigilance practice up to standards.

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          Under-reporting of adverse drug reactions : a systematic review.

          The purpose of this review was to estimate the extent of under-reporting of adverse drug reactions (ADRs) to spontaneous reporting systems and to investigate whether there are differences between different types of ADRs. A systematic literature search was carried out to identify studies providing a numerical estimate of under-reporting. Studies were included regardless of the methodology used or the setting, e.g. hospital versus general practice. Estimates of under-reporting were either extracted directly from the published study or calculated from the study data. These were expressed as the percentage of ADRs detected from intensive data collection that were not reported to the relevant local, regional or national spontaneous reporting systems. The median under-reporting rate was calculated across all studies and within subcategories of studies using different methods or settings. In total, 37 studies using a wide variety of surveillance methods were identified from 12 countries. These generated 43 numerical estimates of under-reporting. The median under-reporting rate across the 37 studies was 94% (interquartile range 82-98%). There was no significant difference in the median under-reporting rates calculated for general practice and hospital-based studies. Five of the ten general practice studies provided evidence of a higher median under-reporting rate for all ADRs compared with more serious or severe ADRs (95% and 80%, respectively). In comparison, for five of the eight hospital-based studies the median under-reporting rate for more serious or severe ADRs remained high (95%). The median under-reporting rate was lower for 19 studies investigating specific serious/severe ADR-drug combinations but was still high at 85%. This systematic review provides evidence of significant and widespread under-reporting of ADRs to spontaneous reporting systems including serious or severe ADRs. Further work is required to assess the impact of under-reporting on public health decisions and the effects of initiatives to improve reporting such as internet reporting, pharmacist/nurse reporting and direct patient reporting as well as improved education and training of healthcare professionals.
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            Traditional Chinese medicine for COVID-19 treatment

            1 Summary The current 2019-nCoV outbreak is moving rapidly [1], the cumulative number of confirmed cases in mainland China has reached 80151, with 47,204 (58.89 %) cured cases and 2943 (3.67 %) deaths as of 2-Mar-2020, and no specific drug has been discovered for Coronavirus Disease 2019 (COVID-19). However, a number of clinical practice results showed that traditional Chinese medicine (TCM) plays significant role in the treatment of COVID-19, bringing new hope for the prevention and control of COVID-19. TCM has a long history and played an indispensable role in the prevention and treatment of several epidemic diseases. During the SARS epidemic in 2003, the intervention of TCM has also achieved remarkable therapeutic effect. During the treatment period of COVID-19, more than 3100 medical staff of TCM were dispatched to Hubei province, and TCM scheme was included in the guideline on diagnosis and treatment of COVID-19 [2], and TCM experts fully participate in the whole rescue process. The decoction, Chinese patent medicine, acupuncture and other characteristic therapy of TCM was comprehensively employed, mainly treated based on syndrome differentiation. Specific TCM wards were set up, and established the designated hospital, moreover, TCM team participates in treatment collectively. Currently, the total number of confirmed cases treated by TCM has reached 60,107 [3]. In 102 cases of mild symptoms treated with TCM, the clinical symptom disappearance time was shortened by 2 days, the recovery time of body temperature was shortened by 1.7 days, the average length of stay in hospital was shortened by 2.2 days, the improvement rate of CT image was increased by 22 %, the clinical cure rate was increased by 33 %, 27.4 % reduction in the rate of common to severe cases and 70 % increase in lymphocyte.3 In addition, in the treatment of severe patients with TCM, the average length of stay in hospital and the time of nucleic acid turning negative has been shortened by more than 2 days. From current treatment results, TCM based on an over-all symptoms of 2019-nCoV pneumonia patients, has suggested to prescribe prescription that are likely to be effective, such as qingfei paidu decoction (QPD), gancaoganjiang decoction, sheganmahuang decoction, qingfei touxie fuzheng recipe, etc. QPD which consisted of Ephedrae Herba, Glycyrrhizae Radix et Rhizoma Praeprata cum Melle, Armeniacae Semen Amarum, Gypsum Fibrosum, Cinnamomi Ramulus, Alismatis Rhizoma, Polyporus, Atractylodis Macrocephalae Rhizoma, Poria, Bupleuri Radix, Scutellariae Radix, Pinelliae Rhizoma Praepratum cum Zingibere et Alumine, Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Farfarae Flos, Belamcandae Rhizoma, Asari Radix et Rhizoma, Dioscoreae Rhizoma, Aurantii Fructus Immaturus, Citri Reticulatae Pericarpium, and Pogostemonis Herba, has been promoted as a general prescription in the diagnosis and treatment plan of COVID-19 in China [2]. Among the 701 confirmed cases treated by QPD, 130 cases were cured and discharged, clinical symptoms of 51 cases disappeared, 268 cases of symptoms improved, and 212 cases of stable symptoms without aggravation [3]. The effective cure rate of QPD against COVID-19 is over 90 %. According to the theory of TCM, the target organ location of COVID-19 is the lung, and the etiology attribute is “damp and toxin plague”. The network pharmacology analysis showed that QPD has an overall regulatory effect via multi-component and multi-target. The primary site of pharmacological action is the lung, as 16 herbs to lung meridian, which indicated that the decoction is mainly specific for lung diseases. In addition, it can play the role of dehumidification through the rise and fall of the spleen and stomach, and exhibited the protection for heart, kidney and other organs. Among the potential targets screen, most of them co-expressed with ACE-2, the receptor of COVID-19, indicating the potential improvement of COVID-19. It can inhibit the replication of COVID-19 by acting on multiple ribosomal proteins. COVID-19 can lead to strong immune response and inflammatory storm [4]. Functional enrichment analysis showed that QPD could inhibit and alleviate excessive immune response and eliminate inflammation by regulating immune related pathway and cytokine action related pathway [5]. Furthermore, through the prediction of molecular docking, it was found that patchouli alcohol, ergosterol and shionone in the formula had better anti−COVID-19 effect, which provided new molecule structures for new drug development [6]. Here, we take one highly suspected COVID-19 patient treated with TCM as a case example to show its effectiveness [7]. The male patient was on a business trip in Wuhan for several days before the onset of the disease. During the admission period, fever and cough were repeated, and respiratory rales of both lungs were not obvious. Western medicine was used firstly, including orally take oseltamivir phosphate capsule, intravenous infusion of ganciclovir, aerosol inhalation of recombinant human interferon a1b, etc. Although the nucleic acid test was negative, the results of chest CT showed that the fusion of two lung ground glass shadows was enlarged and the density was increased, which was more advanced than that of admission (Fig. 1 a-1c). As the serious illness, combined with the patient's performance of damp-heat syndrome, and the heat is more serious than damp, QPD was added for treatment. On the night of administration, the body temperature dropped to 36.2 ℃, and then tended to be normal. After 6 days of treatment, chest CT was better than before, tracheobronchial shadow was normal, and inflammation was obviously absorbed (Fig. 1d). The patient had no fever or asthenia, coughing occasionally, and the rales of two lungs were weaker than before. After discharge, continue to take 7 doses of the prescription, occasionally cough, no special discomfort was found. The clinical symptoms and imaging examination of the patients improved significantly after the treatment, reflecting the advantages of TCM. Fig. 1 Comparison of chest CT results of patients. (a), chest CT on January 24; (b), chest CT on January 28; (c), chest CT on January 30; (d), chest CT on February 4. Fig. 1 TCM has own characteristics such as holistic concept, balance of Yin and Yang, syndrome differentiation and treatment, strengthening the body resistance to eliminate pathogenic factors. TCM has thousands of years of experience in regulating the body and enhancing the resistance to epidemic diseases, with unique insights and prevention and control experience. For mild and common patients, the early intervention of TCM can effectively prevent the disease from transforming into severe and critical disease. In the severe cases, TCM has won time for rescuing them by improving symptoms (http://www.scio.gov.cn/xwfbh/xwbfbh/wqfbh/42311/42560/index.htm). Treatment practice of COVID-19 showed that early intervention of TCM is important way to improve cure rate, shorten the course of disease, delay disease progression and reduce mortality rate. Furthermore, the reason why TCM works is not only to inhibit the virus, but might block the infection, regulate the immune response, cut off the inflammatory storm, and promote the repair of the body. Moreover, the prevention and control measures of COVID-19 fully reflect the ideology of “preventive treatment of disease”. Apart from the epidemic diseases recorded in the Han Dynasty should be isolated, the preventive measures of TCM also include psychology, sports, diet, medication, etc. In the next prevention and control work of COVID-19, it should give full play to the advantages of TCM in syndrome differentiation and the whole therapeutic effect, reduce the complications as well as death rate. Besides, the scientific research should also be carried out on the TCM with definite curative effective of COVID-19, to comprehensively evaluating its action mechanism and in-depth understanding COVID-19. Declaration of Competing Interest There are no conflicts to declare.
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              Under-Reporting of Adverse Drug Reactions

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                Author and article information

                Contributors
                jinanshb@126.com
                sunfeng@bjmu.edu.cn
                pharmacy302xxh@126.com
                Journal
                Br J Clin Pharmacol
                Br J Clin Pharmacol
                10.1111/(ISSN)1365-2125
                BCP
                British Journal of Clinical Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                0306-5251
                1365-2125
                16 March 2022
                February 2023
                16 March 2022
                : 89
                : 2 , Themed Issue: Global Pharmacovigilance ( doiID: 10.1111/bcp.v89.2 )
                : 510-522
                Affiliations
                [ 1 ] National Center for ADR Monitoring Beijing China
                [ 2 ] NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance Beijing China
                [ 3 ] Center for Drug Evaluation, NMPA Beijing China
                [ 4 ] Department of Epidemiology and Biostatistics, School of Public Health Peking University Beijing China
                [ 5 ] Center for Evaluation, Jiangsu Medical Products Administration Nanjing Jiangsu China
                [ 6 ] Gansu Center for Drug and Medical Devices Adverse Reaction Monitoring Lanzhou Gansu China
                [ 7 ] Lingyun Zhou, Sanofi (China) Investment Co., Ltd, Shanghai Branch Shanghai China
                [ 8 ] China Military Institute of Chinese Medicine Fifth Medical Center of Chinese PLA General Hospital Beijing China
                Author notes
                [*] [* ] Correspondence

                Haibo Song, National Center for ADR Monitoring, China, No. 128, Jianguo Road, Chaoyang District, Beijing, 100022, P.R. China.

                Email: jinanshb@ 123456126.com

                Feng Sun, Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, P.R. China.

                Email: sunfeng@ 123456bjmu.edu.cn

                Xiaohe Xiao, China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, P.R. China.

                Email: pharmacy302xxh@ 123456126.com

                Author information
                https://orcid.org/0000-0003-4334-6805
                Article
                BCP15277
                10.1111/bcp.15277
                10078654
                35165914
                cf816b9d-0a55-4b4d-9b96-cfd5b962ea41
                © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 15 January 2022
                : 14 October 2021
                : 02 February 2022
                Page count
                Figures: 2, Tables: 2, Pages: 13, Words: 9566
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 72074011
                Funded by: The second batch of Key Projects of Scientific Act for Drug Regulation of China
                Award ID: [2021]37‐10
                Categories
                Invited Review
                Global Pharmacovigilance–Invited Review
                Custom metadata
                2.0
                February 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:06.04.2023

                Pharmacology & Pharmaceutical medicine
                china,current situation,perspective,pharmacovigilance
                Pharmacology & Pharmaceutical medicine
                china, current situation, perspective, pharmacovigilance

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