Objective To evaluate and select essential medicine for diabetes mellitus 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) Six guidelines were included, three of which were evidence-based and published from 2006 to 2011. (2) Five recommended medicines were included according to recommendations and evidence of WHOEML (2011), NEML (2009), CNF (2010) and other guidelines. They were metformin, glibenclamide, glipizide, rosiglitazone and pioglitazone. Domestic evidence of the first three drugs was evaluated. (3) The first three have been marketed with the specifications and dosage forms corresponding to guidelines in China. The FBG cost-effectiveness ratios of metformin with different dosage forms as immediate release compressed tablet, enteric-coated tablet and sustained release capsule were 3.37, 3.76 and 3.50 respectively. 2-hour BG cost-effectiveness ratios of metformin were 3.74, 4.00 and 3.71 respectively. The cost-effectiveness ratio of glibenclamide and glimepiride were 11.23 and 13.81 respectively. Conclusion We offer a recommendation for: (1) Metformin (immediate release tablet/capsule for oral use, 0.25 g), contraindicated in patients with renal insufficiency. (2) Glibenclamide (tablet, 2.5 mg; capsule, 1.75 mg) and glipizide (tablet, 2.5 or 5mg; dispersible tablet, 5 mg), contraindicated in children, women during pregnancy or lactation, patients in the perioperative period of major operation, patients after total pancreatectomy, and patients allergic or adversely reacted to sulfa drug. (3) Evidence-based and standardized primary healthcare guidelines as well as clinical and pharmacoeconomic studies on diabetes mellitus (large-scale, multi-centre, randomized and double-blinded) are needed to produce high-quality local evidence.
ObjectiveTo compare the recommended medicines from malignancy guidelines/consensuses with essential medicines from the 2023 World Health Organization Model List of Essential Medicines (WHO-EML) and the 2018 National Essential Medicine List (NEML) in differences and similarities. MethodsTen guideline databases/association websites including Guidelines International Network, and the American Cancer Society, etc. were systematically searched until July 2023. The latest guidelines/consensuses for ten malignant tumors were screened, including lung cancer, liver cancer, stomach cancer, and other cancers. Recommended medicines were extracted from guidelines/consensuses and compared with WHO and Chinese essential medicines. ResultsA total of 163 guidelines/consensuses were included, extracting 244 recommended medicines, 12 categories, mainly antineoplastic and immunomodulating agents (190 medicines, 10 subcategories). For the 244 recommended medicines, 29.92% (73/244) were included in WHO-EML and 23.36% (57/244) were included in NEML, among which 45 medicines were included both in WHO-EML and NEML, 27 in WHO-EML only, 11 in NEML only, and 161 in neither. ConclusionThe number of recommended medicines in WHO-EML/NEML for ten malignancies is low, and the number in NEML is even much lower than that in WHO-EML. When adjusting medicines for malignant tumors in NEML, reference can be made to specific guidelines/consensuses and WHO-EML to ensure timely inclusion of applicable medicines and strengthen the role of essential medicines in meeting basic medical needs and rational use.
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.
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 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 the treatment of cerebral circulation insufficiency by means of evidence-based approaches based on the burden of disease for township health centers located in the 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 clinical guidelines on transient ischaemic attack/ischaemic stroke were included, all of which were evidence-based clinical guidelines. (2) In total, there were 13 medicines (of five classes) listed in these guidelines. (3) We offer a b recommendation for aspirin as essential medicine for cerebral circulation insufficiency and a weak recommendation for warfarin, clopidogrel, heparin, paracetamol, insulin, normal saline and glucose/dextrose. We made a recommendation against tPA, GPⅡb/Ⅲa and antibiotics according to WHOEML (2011), NEML (2009), CNF (2010), other guidelines and the quantity and quality of evidence. (4) Recommended medicines have been marketed in China and their prices were affordable except Clopidogrel’s. (5) Some results of domestic low-quality studies indicated that recommend medicines were safe and effective, which had significant differences compared to high-quality evidence from foreign studies. Further studies were needed to be confirmed. Conclusion (1) We offer a b recommendation for aspirin and a weak recommendation for warfarin, clopidogrel, heparin, paracetamol, insulin, normal saline and glucose/dextrose. We make a recommendation against tPA, GPⅡb/Ⅲa and antibiotics. (2) There is lack of high-quality evidence from relevant domestic studies, especially on long-term safety and pharmacoeconomic evidence. (3) We propose that more studies should be carried out on the safety, special efficacy and pharmacoeconomic of Chinese medicine, Chinese medicinals and medicine with special efficacy. Besides, we also compare recommended medicine with those of the same class and construct Level 1 to 2 systems of preventing and treating cerebral vascular diseases.
ObjectivesTo systematically review the implementation effects of the full coverage policy for medicines, and to provide evidence for the improvement of National Essential Medicine Policy in China.MethodsWe searched databases including ProQuest, PubMed, CNKI and WanFang Data databases from inception to June 30th 2018 to collect the studies on full coverage policy for medicines. Two reviewers screened literature and extracted related information independently. Then, qualitative analyses were applied to evaluate the impact of the full coverage policy for medicines.ResultsA total of 35 studies on the full coverage policy for medicines were included. Ten studies evaluated the effects of disease control, 12 studies evaluated the impact of the compliance of the patients, 9 studies evaluated the impact on medical expenses and drug costs, 2 studies evaluated the effects of equality, 7 studies evaluated economics, and 11 studies described the improper use and waste of medicines.ConclusionsIn the content of perfecting the selection mechanism and management system, the implementation of the full coverage policy for essential medicines is conducive to promoting equality and accessibility, enhancing drug compliance, improving the diagnosis and treatment of patient diseases ultimately, and making the policy more economical.
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 establish standards, methods and processes for evidence-based evaluation and selection of essential medicine that meet the needs of the 8 pilot township health centers in China. Methods A descriptive analysis was conducted to compare the similarities/differences and the advantages/disadvantages of the standards, methods and processes between the World Health Organization (WHO) essential medicines evaluation and selection, and the GRADE evidence quality and recommend intensity. In combination with the former outcomes of this series of study, the standards, methods and processes of evidence-based evaluation and selection of essential medicines in the domestic pilot township health centers were optimized, restructured and improved. Softwares such as GRADEprofiler were used to assess the quality of evidence. Results a) Localized standards, methods and processes for evidence-based evaluation and selection of essential medicine were established, and the evaluation tool was ascertained; and b) Disease and drug names, guidelines and searching processes for evaluation and selection of essential medicine were developed with standardized, systematic and transparent approaches. Conclusion a) Standards, methods and processes for searching, evaluating and recommending the best evidence are preliminarily established, through comparative analysis on the effectiveness, safety, cost-effectiveness and applicability of the candidate medicines for diagnosing, treating and preventing diseases in township health centers in China; b) Following the principle of “utilizing the best existing evidences and developing the urgently-needed but lacking evidence”, a good exploration was done for the localization, standardization and transparency of the standards, methods and processes of evidence-based evaluation and selection of essential medicine for pilot township health centers.
Objective To evaluate and select essential antihypertensive medicine 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 clinical guidelines on hypertension were included, two of which were evidence-based. (2) Totally there were nine classes and 70 antihypertensive medicines listed in the guidelines. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines, and the quantity and quality of evidence, we offered a b recommendation for nifedipine, verapamil and enalapril and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. We made a recommendation against furosemide and timolol due to the lack of evidence from guidelines. (4) Nine recommended medicines have been marketed with the dosage forms and specifications corresponding to guidelines in China. The prices of metoprolol, amlodipine and enalapril were higher than those of other six (daily cost: metoprolol 3.80 to 7.60 yuan, amlodipine 2.16 to 4.32 yuan, and enalapril 0.86 to 6.88 yuan). As a whole, the prices of recommended antihypertensive medicine were affordable. (5) Results of domestic studies indicated that three bly-recommended medicines (including nifedipine, verapamil and enalapril) were safe, effective, economical and applicable. Conclusion (1) We offer a b recommendation for nifedipine, verapamil and enalapril as antihypertensive medicine and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. (2) There is lack of high-quality evidence from relevant domestic studies, especially on long-term safety and pharmacoeconomic evidence. (3) We propose that more studies should be carried out on the safety, efficacy and pharmacoeconomics of six medicines for which we make a weak recommendation to produce high-quality local evidence.