AIM: To study the validity of the fixed, random, and multivariate meta-analytical models applied in meta-analyses in artificial reproduction technique. METHODS: Based on common characteristics of in vitro fertilizatio...AIM: To study the validity of the fixed, random, and multivariate meta-analytical models applied in meta-analyses in artificial reproduction technique. METHODS: Based on common characteristics of in vitro fertilization(IVF) meta-analyses, we simulated a large number of data to compare results issued from the fixed model(FM) with the random model(RM). For multiple endpoints meta-analysis(MA), we compared the univariate RM with the multivariate model(MM). Finally, we illustrate our findings in re-analyzing a recent MA. RESULTS: In our review, although a homogeneous effect was excluded in 89% of the MAs(11%), FM was utilized in 41 studies(82%). From simulations, a concordance of 59% ± 6% was found between the two tests, with up to 65% of falsely significant results with FM. The Q-test on studies characterized by substantial heterogeneity falsely accepted homogeneity in 46% of studies. Comparing separate univariate RM and MM on multiple endpoints studies, MM reduces the between endpoint discrepancy(BED) of 68%, and increases the power of 57% ± 8%. In the example dealing with the controversial effect of luteneizing hormone supplementation to follicle stimulating hormone during ovarian stimulation in IVF cycles, MM reduced BED by 66%, and consistent effects were found for all the endpoints, irrespective of partial reporting. CONCLUSION: The FM generally may produce falsely significant differences. The RM should always be used. For multiple endpoints, the MM constitutes the best option.展开更多
Racecadotril is an antidiarrhoeal drug with a pure intestinal antisecretory mechanism of action. Aim: To assess racecadotril efficacy, whatever its dose, versus placebo in adult acute diarrhoea. Methods: Individual Pa...Racecadotril is an antidiarrhoeal drug with a pure intestinal antisecretory mechanism of action. Aim: To assess racecadotril efficacy, whatever its dose, versus placebo in adult acute diarrhoea. Methods: Individual Patient Data meta-analysis following multilevel mixed models testing of the significance of the treatment effect adjusted for baseline covariates. Diarrhoea duration was the common main criteria. Results: Four randomized clinical trials (n = 669) were identified with raw data. The clinical global impression evaluated at baseline by the physician was found to be the essential predictor influencing the outcome. As compared to placebo, the 100 mg dose, the minimum effective dose, induced a 80% increase of the recovered patient proportion at anytime (Hazard Ratio = 1.8 [1.3, 2.5], p < 0.001), a 60% increase of the responder proportion i.e. recovery within 3 days (p < 0.001), a 47% reduction of abdominal pain and nausea and an overall 33% decrease of sick days (p < 0.001). In conclusion, as compared to placebo, racecadotril induced several significant effects, such as reducing the diarrhoea duration, the number of stools and associated symptoms, leading to less lost productivity.展开更多
The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of...The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of RC in the symptomatic treatment of acute diarrhoea in adults. Data Sources: A systematic review of MedLine, Cochrane Controlled Trials Register, DARE, and Embase (up to November 2013). Additional studies were identified by contacting clinical experts and the manufacturer. Study Selection and Appraisal: Randomized Controlled Trials performed in adults suffering from acute diarrhoea using RC in one treatment arm. Independent extraction of articles using predefined data fields, and methodological quality measurement assessment. All randomised trials performed in adults suffering from acute diarrhoea with RC as the studied group. Statistics: The main efficacy endpoint was diarrhoea duration defined as time to recovery compared between groups by survival techniques and converted into hazard ratio (HR). We exclusively used a random-effect meta-analytic model. Constipation proportion was the main safety endpoint, evaluated between treatments by the Relative Risks (RR). Results: Twelve randomised trials (2619 patients) met inclusion criteria. Duration of diarrhoea was much shorter in the RC group, the proportion of patients having recovered at any time of the treatment period was 65% higher in the RC group, compared with placebo (HR = 1.65 [1.38-1.97], p < 0.00001, n= 1001). Duration of diarrhoea was similar in the RC and loperamide groups (HR = 1.08 [0.95-1.22], p = 0.24, n = 1618). The proportions of constipated patients were similar in the RC and placebo groups 0.95 [0.24-3.68], p = 0.97), however, about 3 times more constipated patients were found in the loperamide group compared with the RC group (RR = 0.34 [0.22-0.51], p to placebo, RC is characterized by a clinically relevant earlier remission of diarrhoea. When compared to loperamide, diarrhoea duration was similar, however, significantly fewer secondary constipation adverse effects were observed.展开更多
文摘AIM: To study the validity of the fixed, random, and multivariate meta-analytical models applied in meta-analyses in artificial reproduction technique. METHODS: Based on common characteristics of in vitro fertilization(IVF) meta-analyses, we simulated a large number of data to compare results issued from the fixed model(FM) with the random model(RM). For multiple endpoints meta-analysis(MA), we compared the univariate RM with the multivariate model(MM). Finally, we illustrate our findings in re-analyzing a recent MA. RESULTS: In our review, although a homogeneous effect was excluded in 89% of the MAs(11%), FM was utilized in 41 studies(82%). From simulations, a concordance of 59% ± 6% was found between the two tests, with up to 65% of falsely significant results with FM. The Q-test on studies characterized by substantial heterogeneity falsely accepted homogeneity in 46% of studies. Comparing separate univariate RM and MM on multiple endpoints studies, MM reduces the between endpoint discrepancy(BED) of 68%, and increases the power of 57% ± 8%. In the example dealing with the controversial effect of luteneizing hormone supplementation to follicle stimulating hormone during ovarian stimulation in IVF cycles, MM reduced BED by 66%, and consistent effects were found for all the endpoints, irrespective of partial reporting. CONCLUSION: The FM generally may produce falsely significant differences. The RM should always be used. For multiple endpoints, the MM constitutes the best option.
文摘Racecadotril is an antidiarrhoeal drug with a pure intestinal antisecretory mechanism of action. Aim: To assess racecadotril efficacy, whatever its dose, versus placebo in adult acute diarrhoea. Methods: Individual Patient Data meta-analysis following multilevel mixed models testing of the significance of the treatment effect adjusted for baseline covariates. Diarrhoea duration was the common main criteria. Results: Four randomized clinical trials (n = 669) were identified with raw data. The clinical global impression evaluated at baseline by the physician was found to be the essential predictor influencing the outcome. As compared to placebo, the 100 mg dose, the minimum effective dose, induced a 80% increase of the recovered patient proportion at anytime (Hazard Ratio = 1.8 [1.3, 2.5], p < 0.001), a 60% increase of the responder proportion i.e. recovery within 3 days (p < 0.001), a 47% reduction of abdominal pain and nausea and an overall 33% decrease of sick days (p < 0.001). In conclusion, as compared to placebo, racecadotril induced several significant effects, such as reducing the diarrhoea duration, the number of stools and associated symptoms, leading to less lost productivity.
文摘The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of RC in the symptomatic treatment of acute diarrhoea in adults. Data Sources: A systematic review of MedLine, Cochrane Controlled Trials Register, DARE, and Embase (up to November 2013). Additional studies were identified by contacting clinical experts and the manufacturer. Study Selection and Appraisal: Randomized Controlled Trials performed in adults suffering from acute diarrhoea using RC in one treatment arm. Independent extraction of articles using predefined data fields, and methodological quality measurement assessment. All randomised trials performed in adults suffering from acute diarrhoea with RC as the studied group. Statistics: The main efficacy endpoint was diarrhoea duration defined as time to recovery compared between groups by survival techniques and converted into hazard ratio (HR). We exclusively used a random-effect meta-analytic model. Constipation proportion was the main safety endpoint, evaluated between treatments by the Relative Risks (RR). Results: Twelve randomised trials (2619 patients) met inclusion criteria. Duration of diarrhoea was much shorter in the RC group, the proportion of patients having recovered at any time of the treatment period was 65% higher in the RC group, compared with placebo (HR = 1.65 [1.38-1.97], p < 0.00001, n= 1001). Duration of diarrhoea was similar in the RC and loperamide groups (HR = 1.08 [0.95-1.22], p = 0.24, n = 1618). The proportions of constipated patients were similar in the RC and placebo groups 0.95 [0.24-3.68], p = 0.97), however, about 3 times more constipated patients were found in the loperamide group compared with the RC group (RR = 0.34 [0.22-0.51], p to placebo, RC is characterized by a clinically relevant earlier remission of diarrhoea. When compared to loperamide, diarrhoea duration was similar, however, significantly fewer secondary constipation adverse effects were observed.
