ObjectiveComparing the worldwide Essential Medicines Lists for Children (EMLcs) and National Essential Medicine List (NEML) of China (2012 edition), to provide evidence for establishing EMLc of China. MethodWe searched the official websites of WHO and Ministry of Health of some countries to identify published EMLcs. We compared the situation of updating, the number and classification of medicines, and the dosage forms between these EMLcs and NEML of China (2012). ResultBy August 2013, the WHO, India and South Africa had established EMLc. The number of medicines of NEML of China (2012) ranked first in the four lists. The WHO, India and China classified the medicines by pharmacologic action, while South Africa classified it by anatomical therapeutic chemical (ATC) classification. Except the WHO, India, South Africa and China did not have specific medicines for neonatal care or medicines for diseases of joints. The main administration routes in these four lists were oral administration, injection, and topical application. There were medicine restrictions in EMLcs of WHO and India, while no medicine restrictions in lists of South Africa and China. ConclusionMedicines listed in NEML of China (2012) do not match children's disease burden of China. The applicable dosage forms for children are few and the medicine restrictions are absent for the list. So this list is not suitable for Children.
Objective To evaluate and select essential medicine for herniated lumbar disc based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Six clinical guidelines on herniated lumbar disc were included, five of which were evidence-based. (2) In total, there were 35 medicines (of four classes) listed in the guidelines. (3) We offer a b recommendation for paracetamol and ibuprofen as essential medicine and a weak recommendation for aspirin, indometacin and diazepam according to WHOEML (2011), NEML (2009), CNF (2010), clinical guidelines and the quantity and quality of evidence. (4) Five recommended medicines have been marketed in China with the dosage forms and specifications corresponding to guidelines and their prices were affordable (0.31 to 3.38 yuan daily). (5) Results of domestic low-quality studies indicated that ibuprofen and aspirin were effective with efficiencies of 63% to 84.5%; however, both of which were less effective than other trial medicines (efficiencies: 88.60% to 95.2%). We didn’t find any efficacy or pharmacoeconomic evidence of other medicines in Chinese literature databases. Conclusion (1) Pharmacotherapy should focus on symptomatic treatment of herniated lumbar disc. (2) We offer a b recommendation for paracetamol and ibuprofen used in the treatment of herniated lumbar disc and a weak recommendation for aspirin, indometacin and diazepam. (3) There is lack of evidence and high-quality guidelines on pharmacotherapy of lumbar intervertebral disc in China, especially pharmacoeconomic evidence. (4) We propose that guidelines should be established in basis of evidence so as to effectively direct clinical treatment. The effect of medicine in clinical practice should be based on current evidence from inside and outside China.
Objectives We conducted a literature review of 33 kinds of Traditional Chinese medicine injections (CMIs) on the national essential medicine list (2004 edition) of China in ADR articles to retrieve basic ADR information and research trends related to CMIs and to provide evidence for the research and development as well as the rational use of CMIs, particularly pharmacovigilance and risk management of CMIs. Methods We electronically searched Chinese Biomedical Literature Database (CBM, Jan. 1978-April 2009), the China National Knowledge Infrastructure Database (CNKI, Jan. 1979-April 2009), Chinese Science and Technology Periodical Database (VIP, Jan. 1989-April 2009) and the Traditional Chinese Medicine Database (Jan. 1984 April 2009). We also retrieved the websites of Ministry of Health and State Food and Drug Administration, to collect data about CMIs ADRs reports and regulations from “Newsletter of Adverse Drug Reactions” (Issue 1 to 22). Then we descriptively analyzed all the results on the year published, periodicals and types of study design of included ADR literatures, the major CMIs as well as the regulations about their ADRs. Results (1) There were 5 405 citations found in total and 2160 were removed because of duplication. After screening the title, abstract and full text of the selected papers, 1 010 studies finally met the eligible criteria. (2) The total and cumulative amount of research articles published about CMIs ADRs significantly increases over time. (3) The included 1,010 articles were scattered among 297 periodicals. A total of 55 journals on pharmaceutical medicine, containing 399 articles, accounted for 39.50% of total; 64 journals on traditional Chinese medicine and pharmaceutical medicine, containing only 197 articles, amounted for 19.50% of total. Only 22 periodicals were included on the core journals of the Beijing University List (2008 edition) (8.94% of the total journals in the list), which published 129 articles (12.77% of the total articles published). (4) We categorized the articles included into eight categories based on their content and study methodology. There were: 348 case reports and 254 case series which accounted for 34.46% and 25.15% of the total articles, 119 overviews (11.78%), 116 randomized controlled trials (11.49%), 78 cross-sectional studies (7.72%), 61 ADR literature analyses (6.04%), and 28 non-randomized controlled clinical studies (2.77%). (5) In the three of top ten journals, "Adverse Drug Reactions Journal", "China Medical Herald", and "Chinese Pharmaceuticals" published literature accounted for 5.84%, 3.76% and 2.67% of the total respectively. (6) The reports of ADRs to Shuanghuanglian, Qingkailing and Yuxingcao injections were the most in all reports for CMIs (All the three injections had more than 200 articles, accounting for 41.95% of the total). The Ministry of Health and the State Food and Drug Administration took measures to supervise them. (7) The four kinds of CMIs (Shuanghuanglian, Ciwujia, Yuxingcao, and Yinzhihuang injections) among the top 5 reported ADR literatures were removed from the market or were suspended for sale. The varieties and numbers of reports for CMIs ADRs have relationship with the supervision to them. Conclusions (1) Articles published on CMIs ADRs increased year by year, but overall the research is of low quality and is scattered in a large number of sources. (2) It is very urgent to create a clear standard to grade ADRs of CMIs for the risk management. (3) It is necessary to enforce safety re-evaluation work for CMIs and to promote the clinical rational use.
Objective To evaluate and select essential medicine for chronic obstructive pulmonary diseases (COPD) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Nine guidelines were included (eight foreign guidelines, one domestic guideline; seven based on evidence, two based on expert consensus). (2) A result of one domestic RCT (n=72, high quality) indicated that tiotropium could significantly improve pulmonary function of severe COPD patient complicated with respiratory failure and increase their quality of life (SGRQ score: MD=–10.8%, 95%CI –12.2% to –9.4%). A result of one RCT (n=156, moderate quality) with 3-month follow-up indicated that tiotropium could significantly improve the proportion of measured value to expected value of FEV1 in patients with mild and moderate COPD in stationary phase (MD=10.3%, 95%CI 8.1% to 12.5%). A result of two RCTs (n=160, low quality) indicated that compound ipratropium bromide had efficiencies of 84.2% to 87.5% for moderate and severe COPD. A result of one RCT (n=60, moderate quality) indicated that salmeterol/fluticasone (inhalation) was superior to placebo for improving mild and moderate COPD in stationary phase. A result of one RCT (n=725, moderate quality) indicated that tiotropium combined with salmeterol/fluticasone for COPD in stationary phase was superior to tiotropium alone. A result of one RCT (n=110, low quality) indicated that nebulized budesonide inhalation had an efficiency of 86.8% for acute exacerbation of COPD (AECOPD) and an incidence of 7.9% as to adverse reaction that mainly included laryngo-pharyngeal irritation. (3) Imipenem, meropenem, cefoperazone/ sulbactam and ceftazidime were effective for COPD with low drug resistance rates in treating COPD caused by non-ICU pathogens (less than 8%). Conclusion (1) We offer a b recommendation for tiotropium, ipratropium, salbutamol, formoterol, salmeterol and theophylline used in the treatment of COPD in stationary and exacerbation phases, a b recommendation for streptococcus pneumoniae and influenza vaccines in preventing the deterioration of COPD, a b recommendation for inhaled corticosteroids (ICS) used in the treatment of COPD in stationary phase and a b recommendation for corticosteroids (for oral use) for AECOPD. (2) We offer a b recommendation for cefoperazone/sulbactam, imipenem and meropenem used in the treatment of moderate and severe AECOPD. (3) We offer a weak recommendation for ceftazidime, ciprofloxacin, lavofloxacin, moxifloxacin, amoxicillin amp; clavulanate potassium, amoxicillin, azithromycin, clarithromycin and doxycycline as first-line and second-line antibiotics for mild and moderate AECOPD, and a weak recommendation for compound sulfamethoxazole, cefatriaxone, cefotaxime and cefuroxime used in the treatment of severe and extremely severe COPD, mucolytic agents used in the treatment of stable COPD with difficult expectoration. (4) We make a recommendation against antibiotics, expectorants and corticosteroids (for oral use) as routine use in stationary phase of COPD.
Objective To evaluate and select essential medicine for acute and chronic gastritis using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines for acute gastritis and seven guidelines for chronic gastritis were included. The recommended included omeprazole, ranitidine and domperidone. (2) A result of three CCTs (n=315, low quality) indicated that omeprazole was superior to famotidine and ranitidine in alleviating symptoms of chronic gastritis such as pain or discomfort in the upper abdomen, regurgitation, a burning sensation in the heart, distention and fullness in the upper abdomen (71.2% vs. 47.3%, 94.4% vs. 84.3%, Plt;0.05). A result of one RCT (n=100, low quality) and two CCTs (n=213, low quality) indicated that in HP eradication rates, omeprazole triple therapy and the control intervention had no significant difference (OR=1.09, 95%CI 0.44 to 2.70, Pgt;0.05). A result of one RCT (n=100, low quality) indicated that omeprazole caused no adverse reaction. A result of five CCTs (n=528, low quality) indicated that adverse reaction of omeprazole included poor appetite (two cases), nausea and vomiting (four cases), headache or vertigo (one case) and increased transaminase (one case). Omeprazole cost eight yuan (tablet) or four yuan (capsule) daily. (3) HP eradication rates of ranitidine bismuth citrate was higher than the control group (OR=2.05, 95%CI 1.29 to 3.25, P=0.002). A result of 15 RCTs (n=3 638, high quality) indicated adverse reaction of ranitidine bismuth citrate mainly included symptoms in the digestive system. A result of one RCT (n=100, low quality) indicated ranitidine bismuth citrate and omeprazole triple therapy had no significant difference (Pgt;0.05) and ranitidine bismuth citrate caused no adverse reaction. Ranitidine cost 0.36 yuan (tablet), 0.40 yuan (capsule) or 2.7 to 5.4 yuan (injection) daily. (4) A result of two CCTs (n=133, low quality) indicated that compared with the control intervention, domperidone was more efficient without adverse reaction in improving indigestion, promoting gastric emptying effect, and alleviating pain and distention in the upper abdomen, belching and regurgitation. Domperidone cost 1 to 1.3 yuan daily. (5) All kinds of recommended medicines are listed and legalized in China Pharmacopoeia (2010) and CNF (2010). (6) In clinical setting, above-recommended medicines should be applied strictly according to the CNF (2010) and the National Clinical Prescription Guidelines for Essential Medicine. Conclusion For acute and chronic gastritis, indigestion and HP eradication: (1) We offer a b recommendation for omeprazole (immediate release tablet/capsule for oral use, 10 mg/tablet) which should be cautiously used in children, elderly people, and women during pregnancy or lactation. (2) We offer a b recommendation for ranitidine (immediate release tablet/capsule for oral use, 150 mg/tablet) which should be cautiously used in patients with severe insufficiency in the liver or kidney, women in the pregnancy or lactation, and children under eight years of age.
Objective To evaluate and select essential medicine for acute exacerbation of chronic bronchitis (AECB) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines were included (four foreign guidelines, one domestic guideline; three based on evidence, two based on expert consensus). (2) Medicines recommended at least twice by the National Essential Medicine List (NEML, 2009 version) and Chinese National Formulary (CNF) contained: ipratropium bromide (four times), amoxicillin amp; clavulanate potassium (three times), and corticosteroid (three times), cefuroxime (twice), ciprofloxacin (twice), levofloxacin (twice), salbutamol (twice) and dextromethorphan (twice). (3) As for domestic study evidence, a result of one RCT indicated that amoxicillin amp; clavulanate potassium had efficiencies of 92.3% to 94.7% (n=77, low quality). A result of three RCTs (n=275, low quality) indicated that cefuroxime had efficiencies of 67.6% to 90% and an incidence of 5% as to adverse reaction that mainly included skin rashes, diarrhea, etc. A result of two RCTs (n=120, low quality) indicated that ciprofloxacin had efficiencies of 78.3% to 86.6%, bacterial clearance rates of 72.7% to 86.5% and the incidences of 8.7% to 16.2% as to adverse reaction that mainly included gastrointestinal reaction, skin rashes, etc. A result of seven RCTs (n=523, low quality) indicated that levofloxacin had efficiencies of 72.5% to 94.5%, bacterial clearance rates of 82.1% to 95.8% and the incidences of 5% to 7.5% as to adverse reaction. A result of two RCTs (n=239, low quality) indicated that salbutamol had efficiencies of 85.4% to 96.7%. A result of one RCT (n=95, low quality) indicated that ipratropium bromide had efficiencies of 98%. A result of five RCTs (n=466, low quality) indicated that the combined use of budesonide and bronchodilators had efficiencies of 93.4% to 97.8%. Conclusion (1) We offer a b recommendation for cefuroxime, amoxicillin amp; clavulanate potassium, ciprofloxacin and levofloxacin used in the treatment of AECB. (2) We offer a b recommendation for glucocorticoid (budesonide, aerosol) and anticholinergic bronchodilator (ipratropium bromide) and a weak recommendation for short-acting β2-agonist bronchodilator (salbutamol) and antitussive agent (dextromethorphan) for alleviating symptoms due to AECB. (3) We make a recommendation against mucolytic agents and theophylline as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies on AECB and outcome indicator should be improved in order to produce high-quality local evidence.
Objective To evaluate and select essential medicine for the treatment of coronary heart disease by means of evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) 11 clinical guidelines on coronary heart disease were included, three of which are evidence-based guidelines. (2) Totally, those guidelines contained 61 medicines (of 13 classes). (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines and the quantity and quality of evidence, we made a b recommendation for nitroglycerin, isosorbide dinitrate, metoprolol, nifedipine, verapamil, enalapril and aspirin as essential medicine for coronary heart disease. We made a weak recommendation for amlodipine, clopidogrel, heparin, propranolol, simvastatin and streptokinase. (4) 13 recommended medicines have been marketed in China and their prices were affordable. (5) Results of domestic low-quality studies indicated that nitroglycerin, isosorbide dinitrate, metoprolol, aspirin and heparin were effective for coronary heart disease. We didn’t find systematic reviews or pharmacoeconomic studies on the recommended medicines in Chinese literature databases. Conclusion For coronary heart disease: (1) We offer a b recommendation for nitroglycerin, isosorbide dinitrate, metoprolol, nifedipine, verapamil, enalapril and aspirin and a weak recommendation for propranolol, amlodipine, clopidogrel, heparin, simvastatin and streptokinase. (2) There is lack of high-quality evidence from relevant domestic studies, especially on pharmacoeconomic evaluation. (3) We propose that more studies should be carried out on clinical guideline of coronary heart disease and pharmacoeconomic comparison should be also made between recommended medicine and medicine of the same class.
Objective To compare the newest essential medicine lists (EMLs) of China and the World Health Organization (WHO) in 2009, so as to provide the evidence for the selection, adjustment and implementation of the newest national EML of China. Methods Differences in the procedures of selection, implementation and the categories as well as the number of medicines in 2009 EMLs of the WHO and China were compared by descriptive analysis. Result Principles and procedures of selecting and updating EML of China were based on those of the WHO EML. However, the transparency of procedures, methods of selection, and evidence of efficacy, safety, cost-effectiveness and suitability were not enough. Essential medicines of the WHO were categorized by the Anatomical-Therapeutic-Chemical (ATC) classification system, while those of China were classified by clinical pharmacology. Twenty-one identical categories of the first class were found in the two lists. There were 8 and 3 unique categories in the WHO EML and China EML, respectively. A total of 358 and 255 medicines (including medicines in its explanation) were included in the EMLs of the WHO and China, respectively, with 133 identical medicines as well as 206 and 108 unique medicines. There were 51 antiinfective medicines in China EML, accounting for half of the WHO EML. Forty medicines were the same in both lists, and 11 and 60 anti-infective medicines were unique in EMLs of China and the WHO, except for 40 identical medicines. Among them, 22 and 31 antibacterials were included in the lists of the WHO and China with 17 identical medicines. Antifungal, antituberculosis and antiviral medicines in China EML were fewer than those in the WHO EML. The numbers of the identical medicines acting on the respiratory, digestive, and nervous systems and hormones in the both lists were 1, 7, 9, and 17, respectively, while the unique ones in China EML were 6, 12, 7, and 14, respectively. However, most of them were selected without adequate evidence in efficacy and safety. The medicines acting on cardiovascular system were 19 and 29 in both lists with 14 identical medicines. Some antihypertensive and antiarrhythmic medicines were included in China EML with similar mechanism, whereas some of them were excluded by the EML. Conclusion The total numbers of both EMLs are close to each other with half of the identical medicines. The selection of China EML mostly meets the needs of disease burden in China. However, the transparency of selection and evidence are not enough. We suggest that health authorities should cooperate with other stakeholders to promote the transparency of selection, to enhance the capacity of producing high-quality evidence, to develop related technical documents and guidelines, and to disseminate and monitor the implementation of EML.
Objective To evaluate and select essential medicine for abortion using evidence-based approaches based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Four guidelines on medicine for abortion were included, two of which are based on evidence. (2) Included guidelines referred to eight essential medicines used in drug abortion and four antibiotics used after abortion surgery. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guideline and the quantity and quality of evidence, we offered a b recommendation for misoprostol, mifepristone, oxytocin except prostaglandins used in abortion. (4) Published literature on oxytocin, misoprostol and mifepristone were found. Oxytocin with the dosage form and specification corresponding to guidelines has been marketed in China. Oxytocin (in vial, 10 U∶1 mL) cost 1.5 yuan/injection. Mifepristone (tablet, 25 mg×1) cost 13.0 to 27.5 yuan/tablet. Misoprostol (0.2 mg×3) cost 2.8 to 3.7 yuan/ tablet. (5) Results of domestic studies indicated that mifepristone combined with misoprostol and oxytocin was safe, efficient, convenient and applicable to the treatment of abortion. Conclusion For abortion: (1) We make a recommendation for mifepristone plus misoprostol. Mifepristone (25 to 50 mg/tablet) is orally taken twice a day, continually for 2 to 3 days, the total dose of 150 mg for three days. Misoprostol (0.2 mg/ tablet) 0.6 mg is orally given on an empty stomach within 36 to 48 hours after the intake of mifepristone. (2) Oxytocin (5 to 10 U in vial) injected after delivering the placenta can reduce the volume and time of vaginal bleeding. In future, clinical study should be standardized in order to improve design and implementation quality.
Objective To evaluate and select essential medicine for acute cholecystitis using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Three guidelines were included (two foreign guidelines, one domestic guideline; two based on evidence, one based on expert consensus). (2) Results of two RCTs (n=200, low quality) and two CCTs (n=230, low quality) indicated efficiencies of ampicillin/sulbactam, piperacillin/tazobactam, ciprofloxacin combined with metronidazole, and ceftazidime combined with metronidazole were 92.5%, 92.6%, 92.5% and 91.3%. A result of three RCTs (n=661, low quality) indicated that lavofloxacin had efficiencies of 82.2% to 95.8% which were 84.4% to 94.7% when combined with metronidazole. A result of three RCTs (n=553, low quality) indicated that for acute cholecystitis, ceftriaxone had an efficiency of 90.0%, cefuroxime 73.7% and cefoperazone/sulbactam 95.6% (Efficiency: ceftriaxone 93.3%, cefuroxime 82.5% and cefoperazone/sulbactam 92.3%, when combined with metronidazole). A result of one RCT (n=72, low quality) indicated that cephazoline had an efficiency of 70.9% with bacteria resistance rates of 70% for G+ and 87% for G. Conclusion (1) We offer a b recommendation for piperacillin/tazobactam and cefoperazone/sulbactam used in the treatment of acute cholecystitis (mild, moderate and severe). We offer a b recommendation for meropenem, imipenem/cilastatin and metronidazole as alternatives for severe acute cholecystitis. (2) We offer a weak recommendation for ceftazidime and cefepime used in the treatment of severe acute cholecystitis and a weak recommendation for cefotiam, ampicillin/sulbactam and cefuroxime used in the treatment of acute cholecystitis (mild and moderate). We offer a weak recommendation for lavofloxacin and ciprofloxacin used in the treatment of acute cholecystitis (mild and severe) and a weak recommendation for ceftriaxone used in the treatment of acute cholecystitis (mild, moderate and severe). (3) We make a recommendation against cephazoline as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies of acute cholecystitis and outcome indicator should be improved in order to produce high-quality local evidence.