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With the promulgation of a series of laws and regulations in our country, the requirement for stand-ardized management of clinical research process are gradually clear, and higher requirements on the following-up review management of ethics committee also are put forward. Through concluding and summarizing 128 noncompli-ance/violation or protocol deviation reports accepted by a hospital in recent two years, this paper analyzed four main problems including that the researchers at management level failed to report or report timely; the researchers reported in irregular filling;the same type of violation/deviation program happened repeatedly and the rectification to the review opinions of ethics committee was ineffective, and also put forward the corresponding suggestions, in order to strengthen and perfect the standard management of noncompliance/violation or protocol deviation report.
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OBJECTIVE:To systematically review the efficacy and safety of different doses of canagliflozin in the treatment of type 2 diabetes,and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from PubMed,Cochrane Library,Clinical Trails.gov,CJFD,Wangfang Database and VIP,randomized controlled trials (RCT) about different doses of canagliflozin in the treatment of type 2 diabetes were collected. Meta-analysis was performed by using Rev Man 5.3 software after data extract and quality evaluation by Cachrane 5.10. RESULTS:Totally 11 RCTs were enrolled,involving 5 399 patients. Results of Meta-analysis showed,canagliflozin 300 mg/d were superior to 100 mg/d in reducing HbA1c[MD=0.14,95%CI(0.09,0.19), P<0.001],FPG[MD=0.40,95%CI(0.20,0.61),P<0.001] and reduction rate of body mass[MD=0.69,95%CI(0.42,0.96),P<0.001],the differences were statistically significant;and there were no significant differences in the incidence of total adverse reac-tions [RR=0.97,95%CI(0.94,1.01),P=0.10],hypoglycemia [RR=1.02,95%CI(0.94,1.10),P=0.67],urinary tract infection[RR=0.96,95%CI (0.78,1.18),P=0.69] in 2 groups;There was significantly different of genital mycotic infection in 2 groups[RR=0.84,95%CI(0.70,1.00),P=0.04]. CONCLUSIONS:Canagliflozin 300 mg/d is better than 100 mg/d in controlling HbA1c,fasting blood glucose and body mass of patients with type 2 diabetes,and the genital mycotic infection should be attentioned.
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ObjectiveTo investigate the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of gemifloxacin tablet in healthy Chinese volunteers and to provide evidences for optimal clinical dosing.MethodsTwenty volunteers were enrolled in the randomized (1∶1) double-blind study,and divided into administration group and control group.Each group received multiple oral doses of 320 mg of gemifloxacin tablet or placebo.The plasma and urine samples for gemifloxacin were analyzed by igh-performance liquid chromatogram(HPLC)-fluorometricmethod. Theminimuminhibition concentrations (MIC)of gemifloxacin against190clinical isolateswere determinedby broth microdilution method.The fAUC0～24 h/MIC and fCmax/MIC,with target value of 25 and 5,were used as the indices to evaluate PK and PD characteristics of gemifloxacin. The cumulative fraction of response (CFR) of gemifloxacin against each bacterium and the probability of target attainment (PTA) under various MIC level were evaluated using Monte Carlo simulation following multiple administration at steady state.ResultsThe Cmax of gemifloxacin after once-daily oral doses for 7 days were (1.55 ±0.32) μg/mL and (1.57±0.31) μg/mL for the first and last dose,while the AUC0～24 h were (7.91±1.52) and (8.91±1.15) h · μg · mL-1,respectively.The accumulation factor was 1.13±0.05.The time-profile of gemifloxacin could be described using two-compartment model and the half-life of distribution and elimination phase were (0.64 ± 0.17) and (7.10 ± 2.10) h,respectively. The cumulative urinary excretion rates within 24 h of gemifloxacin were 34.83 ％ and 38.95 ％ for the first and the last dose,respectively.PD study showed that the MIC90 of gemifloxacin were 0.25 mg/L and 0.125 mg/L against Streptococcus pneumoniae and Moraxelle catarrhalis,respectively,while the MIC90 was 2 mg/L against Hemophilus influenza. However,most of Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) were resistant to gemifloxacin ( MIC90 ＞ 32mg/L).The PTA values of fAUC0～24 h/MIC and fCmax/MIC of gemifloxacin 320 mg daily for 7 days were close to 100％ when MIC was ≤0.06 mg/L.ConclusionsGemifloxacin is rapidly absorbed after oral administration of single doses in healthy Chinese volunteers,and the plasma concentration could reach steady state at the third day,while a minimal accumulation is shown after consecutive 7 days dosing.The PK/PD analysis suggests that the favorable clinical and bacteriological efficacy could be obtained when using thisregimen in treatment of sensitive patients with community-acquired pneumonia and acute exacerbation of chronic obstructive pulmonary disease.
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OBJECTIVE:To develop a HPLC method for the assaying of the principal agent in oxiracetam sodium chloride injection.METHODS:The separation was performed on Intersil CN-3column;the mobile phase was a mixture of acetonitri_ le-water(6∶94)with detection wavelength at214nm,flow rate at0.6ml/min and sample size at5?l under room temperature. RESULTS:The linear correlation of oxiracetam was observed over the concentrations of0.5625to288?g/ml(r=0.9999).The average recovery was99.95%(RSD=1.36%).CONCLUSION:The method is accurate,convenient specific and repro-ducible,and suitable for the determination and quality control of Oxiracetam.
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Based on the collation and analysis of 178 informed consent forms of clinical research projects related to human accepted by the ethical review committee of one hospital in 2007 and 2008,major problems were summarized as follows:the expression was difficult to be understood and was unsuitable for popular apprehension;lack of basic elements or insufficiently informed;inductive or advertising expressions existed,etc.Accordingly,the discussion was made for some recommendations of improvement.