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 evaluate and select essential medicine for acute bronchitis 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) Eight guidelines were included (seven foreign guidelines, one domestic guideline; five based on evidence, three based on expert consensus). (2) A result of six RCTs (n=816, low quality) indicated that pentoxyverine had efficiencies of 53% to 82% for cough relief. Among the six RCTs, a result of three RCTs (n=283) indicated that pentoxyverine was slightly less efficient than procaterol (RR=0.86, 95%CI 0.78 to 0.94, P=0.001); a result of two RCTs (n=233) indicated that pentoxyverine was slightly less efficient than Chinese medicinals decoction (RR=0.82, 95%CI 0.74 to 0.91, Plt;0.001). Adverse reaction of pentoxyverine (incidence: 0% to 2.4%) mainly covered nausea, palpitation, etc. Pentoxyverine cost 0.20 yuan (for adult) or 0.08 yuan (for child) daily, which was orally taken and applicable to the target population. (3) A result of six RCTs (n=403, low quality) indicated that the efficiencies of dextromethorphan for cough relief was 47.0% to 95.3%. Among the six RCTs, a result of one RCT (n=283) indicated that dextromethorphan hydrobromide (nasal drop) was more efficient than blank intervention (RR=3.71, 95%CI 1.91 to 7.21); a result of one RCT (n=43) indicated that dextromethorphan (for oral use) was more efficient than placebo (RR=1.74, 95%CI 1.13 to 2.66); a result of one RCT (n=300, moderate quality) indicated that dextromethorphan was more efficient than pentoxyverine (RR=1.16, 95%CI 1.07 to 1.26); a result of one observational study (n=121, low quality) indicated that dextromethorphan given for 5 days had an efficiency of 66.5%. Adverse reaction of dextromethorphan (incidence: 2% to 30%) mainly covered mouth dryness, dizziness, nausea, etc. Conclusion (1) We offer a b recommendation for dextromethorphan used in relieving dry cough due to acute bronchitis. (2) We offer a weak recommendation for pentoxyverine as symptomatic treatment for cough relief. (3) We make a recommendation against antibiotics, β2-agonist bronchodilators and mucolytic agents as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies of acute bronchitis in hopes of producing high-quality local evidence.
ObjectiveTo investigate the type, development time, regional distribution, development methods, structure and contents of therapeutic drug monitoring (TDM) guidelines, so as to provide references for the development of TDM guidelines in China. MethodsGuidelines concerning TDM were electronically retrieved in PubMed, Ovid-EMbase, CNKI, VIP, CBM, WanFang Data, NGC (National Guideline Clearinghouse ), GIN (Guidelines International Network), World Health Organization (WHO) guideline database, official websites of governments and societies associated with TDM from inception to October 2015. Two reviewers independently screened literature, extracted data including basic characteristics, formulation methods and text structure, etc.. Then a descriptive analysis was conducted. ResultsA total of 37 guidelines concerning TDM were included, which involved 4 guidelines for management of TDM, 32 for technical practice and 1 for both of them. The results of analysis showed that: for the integrity of reporting items of guidelines, three (75%) management guidelines ranked grade A, but only 1 (3.13%) technical guidelines ranked grade A. The management specifications of TDM included four aspects as follows: standard terminology, the process specification, quality control and personnel qualification. The recommendations to TDM technology of specific drugs included evidence of TDM, standards and procedures, and personnel qualification. ConclusionThere is a rapid but unbalanced development for abroad TDM guidelines. Most of them are TDM technical guidelines. Evidence-based methods are suggested to be used to develop local TDM guidelines, especially for commonly used medicines and technologies without supporting of existed guidelines.
Objective To evaluate and select essential medicine for acute gastroenteritis 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 were included, two of which were evidence-based. (2) Recommended medicines included eight antidiarrheals (of four classes) and three antemetics. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines and the quantity and quality of evidence, we offered a weak recommendation for ondansetron, metoclopramide, smectite, racecadotril and loperamide applied in the treatment of acute gastroenteritis. We made a recommendation against antibiotics, dexamethasone, kaolin-pectin, activated charcoal, attapulgite and bismuth subsalicylate. (4) Evidence from domestic studies: a result of 14 CCTs (n=1 635, low quality) indicated that in the significant efficiency and total efficiency, smectite (smecta) was superior to routine liquid infusion, norfloxacin, gentamicin or furaxone. Among these 14 CCTs, two CCTs reported smectite (smecta) caused nausea and vomiting (three cases); one CCT reported pain and distention in the abdomen (one case) and general discomfort (one case); and the rest reported no adverse reaction. A result of 10 CCTs (n=1 017, low quality) indicated that for acute diarrhea, racecadotril was superior to routine treatment in the significant efficiency (OR=2.55, 95%CI 1.64 to 3.94, Plt;0.01) and total efficiency (OR=4.32, 95%CI 2.96 to 6.30, Plt;0.01). A result of two CCTs (n=344, low quality) indicated that racecadotril was superior to smectite in the total efficiency in treating acute diarrhea. A result of two CCTs (n=1 056, low quality) indicated that racecadotril was superior to routine treatment in the total efficiency in treating acute adult diarrhea (OR=5.19, 95%CI 3.54 to 7.63, Plt;0.01). A result of two CCTs (n=182, low quality) reported children presented with nausea (two cases). A result of one CCT (n=947, low quality) reported adults presented with constipation (fifteen cases), anorexia (four cases), headache (nine cases) and abdominal pain (one case). Conclusion For acute gastroentitis, we offer a weak recommendation for smectite (powder, for oral use) used in adults (once 3 g, tid., mixed with warm water before intake), child under one year of age (3 g daily, bid.), and child above one year of age (once 3 g, qd. or bid.). Retention enema could be appiled to children with acute gastroenteritis. We also offer a weak recommendation for racecadotril (capsule) used in adults (one capsule, tid., taken continuously less than seven days). Due to the lack of evidence from clinical trials, we make a recommendation against racecadotril applied to women with pregnancy and lactation or children. In order to produce high-quality local evidence, we propose that (1) Further clinical studies should be standardized in diagnosis and criteria. (2) The design and implementation quality of clinical studies should be improved. (3) Original studies on pharmacoeconomic studies and drug applicability are needed.
ObjectivesTo evaluate the characteristics, main contents, key elements and techniques of global drug value assessment tools, especially for those developed for antineoplastic agents, and to provide reference for the establishment of the first value assessment tool for antineoplastic agents in China.MethodsDatabases including MEDLINE, EMbase, CBM, CNKI, VIP, WanFang Data and 19 relevant websites of institutions and societies were searched from inception to October 31st, 2018 to identify all the drug value assessment tools worldwide. Two independent reviewers screened the literatures, extracted the data and cross-checked them according to the inclusion and exclusion criteria. A qualitative analysis was conducted to describe the characteristics of these drug value assessment tools, including the publishing organization, year of publication, country, applicable type of disease and drug category, result display, and etc. Key elements and techniques in terms of evaluation dimensions, sources and levels of evidence, methods and procedures to form the tool were compared.ResultsA total of 12 English drug value assessment tools were included, which were published in 2010 to 2018 exclusively from Europe and North America. The applicable types of diseases and drug categories are not identical. The target users and stakeholders of each tool were slightly different. Evaluation dimensions, sources and levels of evidence, methods and procedures to form the tool were vital issues in value evaluation for drugs.ConclusionsThe structures of existing drug value assessment tools were almost the identical. However, there is no consensus on value definitions, evaluation dimensions, sources of evidence and result display. Methods and procedures to form the tool are not well described. It is urgent to explore and develop a value-oriented, focused and feasible drug assessment tool for antineoplastic agents in order to satisfy the strategic requirements of value-based post-marketing drug reevaluation.
Objective To evaluate and select essential medicine for middle-aged and elderly women with primary osteoporosis 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) 18 guidelines were included, 14 of which were evidence-based or based on expert consensus. Recommended medicines included bisphosphonates, calcitonin, estrogen, parathyroid hormone, selective estrogen receptor modulator, strontium and Chinese patent drug. (2) A result of one quasi-RCT (very low quality) indicated that caltrate D had a better effect on elderly women with primary osteoporosis than calcium gluconate in improving bone mineral density (BMD) (MD=0.04, 95%CI 0.02 to 0.06) and ameliorating bone ache ( RR=2.64, 95%CI 1.40 to 4.96). A few cases treated by caltrate D presented with adverse reaction such as gastrointestinal discomfort, poor appetite, constipation and nausea which disappeared later. Caltrate D (calcium carbonate D3) with good applicability cost 1.00 yuan daily. (3) A result of one RCT (low quality) indicated that alendronate had a better effect than caltrate D in improving L2-L4 BMD (MD=0.06, 95%CI 0.017 to 0.10) and ameliorating bone ache (RR=1.8, 95%CI 1.40 to 2.52). A result of two RCTs (moderate quality) indicated that alendronate plus calcium carbonate plus vitamin D6 had a better effect than calcium carbonate plus vitamin D in improving L2-L4 BMD (MD=0.05, 95%CI 0.02 to 0.08) and reducing blood alkaline phosphatase (MD=–31.9, 95%CI –54.99 to –8.81). There were slight adverse effects mainly including gastrointestinal reaction. Alendronate with fairly poor applicability cost 2.67 yuan daily. (4) A result of one RCT (moderate quality) indicated that after a 3-month treatment, Xian Ling Gu Bao Jiao Nang (name of a Chinese patent drug, abbreviated as XLGB) plus calcium preparation had a better effect than calcium preparation alone (MD=10, 95%CI 0.05 to 0.15). A result of one RCT (moderate quality) indicated that given for 3 to 6 months, XLGB plus calcium preparation was superior to calcium preparation alone in increasing the density of Ward’s triangle and the great femoral trochanter. A result of one RCT (low quality) indicated that XLGB plus calcitriol had a better effect than calcitriol alone in pain relief (RR=1.26, 95%CI 1.04 to 1.52). There were slight adverse effects mainly including reaction in the digestive system, the circulatory system and the skin. XLGB with good applicability cost 4.58 yuan daily. Conclusion We offer a weak recommendation for alendronate applied to middle-aged and elderly women with primary osteoporosis and pain and fracture caused by primary osteoporosis. We also offer a b recommendation for caltrate D and XLGB applied to middle-aged and elderly women with primary osteoporosis and pain and fracture caused by primary osteoporosis. In addition, we propose that the census on elder people with osteoporosis in rural areas should be carried out. More clinical and pharmacoeconomic studies of large-sample, high-quality on alendronate and its calcium preparation for adult osteoporosis are needed in China.
Objective To provide baseline data for further evidence-based evaluation and selection of essential medicine by analyzing the inpatient disease constitution in 8 pilot township health centers located in eastern, central and western China in 2010. Methods The analysis was performed to compare the similarities and differences of both systematic diseases and top 15 single diseases of inpatients in 8 pilot township health centers located in eastern, central and western China in 2010. The Microsoft Excel 2003 and SPSS 13.0 softwares were used for data classification and analysis, and the frequency and composition were used as describing statistical indicators. Results a) The top 5 systematic diseases were respiratory, digestive, circulatory, urinary tract and urogenital systems, as well as the trauma and toxicosis, with accumulative constituent ratio accounting for 71.0%-81.6%; b) The inpatients suffering from top 15 systematic diseases were 10 630, accounting for 61.10%. Each of the respiratory and digestive system contained 6 single diseases including 4 acute and 2 chronic ones, with inpatients accounting for 99.2% and 93.8%, respectively; the circulatory system contained 3 single diseases which were all chronic with inpatient ratio of 84.6%; and c) The chronic diseases were in majority within the top 15 single diseases, which were most commonly seen rather than acute diseases in the pilot township health centers in eastern and central China. The inpatients’ acute diseases were more often seen than chronic diseases in well-off and fundamental township health centers. Conclusion a) The top 5-6 systematic diseases are stable in the pilot township health centers in eastern, central and western China in 2010. The common single inpatient diseases are centralized, which benefits the selection and adjustment of essential medicine for the pilot township health centers in China; b) The capacity building of the western, fundamental and well-off township health centers to diagnose and treat inpatients suffering acute diseases should be promoted; c) The capacity building of the central and general township health centers to diagnose and manage inpatients suffering chronic diseases should be promoted; d) The capacity building of the eastern and well-off township health centers to provide outpatient service should be promoted. The function of the eastern township health centers needs further clarification and improvement; and e) More attention should be paid to diseases prevention, control and treatment for women, children, the elderly and the population with high burden of diseases.
Objective To evaluate and select essential medicine for urolithiasis 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 evidence-based guidelines were included. Based on WHOEML (2011), NEML (2009), CNF (2010) and the quantity and quality of evidence, we made a recommendation for diclofenac sodium, nifedipine, allopurinol and ibuprofen used in symptomatic treatment of urolithiasis. (3) Results of domestic studies (including four RCTs, n=566; two observational studies, n=96) indicated that calculus-removed rates of diclofenac sodium, nifedipine and allopurinol were 91.5%, 86.4%~93.3% and 86.4% respectively with significant differences. Diclofenac sodium daily cost 7.00 to 8.57 yuan, nifedipine 1.48 to 4.44 yuan, and allopurinol 0.24 to 0.82 yuan. Ibuprofen had a total efficiency of 94.5% with a significant difference for alleviating renal colic, which cost 0.11 yuan daily. Four recommended medicines with safety, clinical efficacy, high economical efficiency and applicability had been marketed with specifications and dosage forms corresponding to guidelines in China. Conclusion For urolithiasis: (1) We offer a b recommendation for diclofenac sodium (capsule/tablet, 50 mg×24, or 25 mg×24) which is contradicted in patients with gastrointestinal bleeding and in pregnant women or women with planned pregnancy. (2) We offer a weak recommendation for nifedipine (tablet/capsule, 10 mg×100 or 10 mg×60) which is contraindicated in dialysis-receiving patients with malignant hypertension and should be cautiously used in patients with irreversible renal failure. (3) We offer a weak recommend allopurinol (tablet, 100 mg×100) which is contraindicated in patients with allergic reaction, severe insufficiency of the liver or kidney, or significant lack of blood cells. (4) We offer a b recommendation for ibuprofen (tablet, 20 mg×20) which is contraindicated in patients with allergic reaction to aspirin.
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.
Objective To evaluate and select essential medicine for children with fever and adult gastrointestinal flu caused by common cold 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) 12 guidelines were included, 11 of which were evidence-based or based on expert consensus. We offered a recommendation for medicines used in the treatment including analgesics and antipyretics, decongestants, antihistamines, cough-relieving drug, phlegm-removing drug and drug for gastrointestinal symptoms. (2) A result of four RCTs (very low quality) indicated that in the treatment of children with cold, ibuprofen suspension had an antipyretic effect similar to paracetamol solution (for oral use) with a pooled result of 6-hour efficiency in relieving fever (RR 1.48, 95%CI 0.66 to 3.30, P=0.34). The major adverse effects of ibuprofen suspension included gastrointestinal reaction and profuse sweats (RR=1.23, 95%CI 0.72 to 2.11, P=0.45). With good applicability, ibuprofen suspension (for oral use with no need to be supervised) cost 1.93 yuan daily. (3) A result of three RCTs (low quality) indicated that after given for 30 minutes and one hour, paracetamol solution (suppository) was fairly superior to ibuprofen suspension in lowering the high temperature caused by fever (given for 30 min: MD= –0.16°C, 95%CI –0.21 to –0.11, Plt;0.01; given for one hour: MD= –0.19°C, 95%CI –0.28 to 0.10, Plt;0.01). As to adverse reaction, paracetamol solution (suppository) mainly included anal irritation, skin rashes and profuse sweats, which had a comparative result of incidence with ibuprofen suspension (RR=1.84, 95%CI 0.62 to 5.44, P=0.27). For children with fever, paracetamol solution (suppository) cost 0.90 yuan daily. With good applicability, paracetamol solution (suppository) was administered via the anus. Conclusion (1) We offer a b recommendation for ibuprofen suspension (2 g/100 mL) or acetaminophen (0.1 g/suppository) as symptomatic treatment used in children with fever, pain and discomfort caused by common cold, and for Huo Xiang Zheng Qi Jiao Nang (0.3 g/ capsule) used in adults with gastrointestinal flu. We also offer a weak recommendation for acetylcysteine (injection, 300 mg/mL, 10 mL/ampoule) used in patients with paracetamol poisoning. (2) In order to produce high-quality local evidence, we proposed that large-scale, well-designed, high-quality clinical and pharmacoeconomic studies on ibuprofen suspension and acetaminophen suppository in the treatment of children with fever, pain and discomfort caused by common cold should be further carried out. Besides, we proposed that large-scale, well-designed, high-quality clinical and pharmacoeconomic studies on Chinese patent drugs of Huo Xiang Zheng Qi used in chidren and Huo Xiang Zheng Qi Jiao Nang used in adults should further carried out. Moreover, we suggest that epidemiological investigation as well as clinical and pharmacoeconomic studies of acetylcysteine injection for paracetamol poisoning should be carried out and the instructions of acetylcysteine injection should be added in the guidelines of essential medicine in China. Finally, further studies on evidence of oxymetazoline, dextromethorphan and other Chinese patent drugs with the effect of relieving cough and treating cold should be carried out.