scholarly journals Methods for meta-analysis of pharmacodynamic dose–response data with application to multi-arm studies of alogliptin

2016 ◽  
Vol 27 (2) ◽  
pp. 564-578 ◽  
Author(s):  
Oliver Langford ◽  
Jeffrey K Aronson ◽  
Gert van Valkenhoef ◽  
Richard J Stevens
Keyword(s):  
Randomized Controlled Trials ◽  
Least Squares ◽  
Dose Response ◽  
Meta Analysis ◽  
Weighted Least Squares ◽  
Controlled Trials ◽  
Response Model ◽  
Response Data ◽  
Randomized Controlled ◽  
The Mean

Standard methods for meta-analysis of dose–response data in epidemiology assume a model with a single scalar parameter, such as log-linear relationships between exposure and outcome; such models are implicitly unbounded. In contrast, in pharmacology, multi-parameter models, such as the widely used Emax model, are used to describe relationships that are bounded above and below. We propose methods for estimating the parameters of a dose–response model by meta-analysis of summary data from the results of randomized controlled trials of a drug, in which each trial uses multiple doses of the drug of interest (possibly including dose 0 or placebo). We assume that, for each randomized arm of each trial, the mean and standard error of a continuous response measure and the corresponding allocated dose are available. We consider weighted least squares fitting of the model to the mean and dose pairs from all arms of all studies, and a two-stage procedure in which scalar inverse-variance meta-analysis is performed at each dose, and the dose–response model is fitted to the results by weighted least squares. We then compare these with two further methods inspired by network meta-analysis that fit the model to the contrasts between doses. We illustrate the methods by estimating the parameters of the Emax model to a collection of multi-arm, multiple-dose, randomized controlled trials of alogliptin, a drug for the management of diabetes mellitus, and further examine the properties of the four methods with sensitivity analyses and a simulation study. We find that all four methods produce broadly comparable point estimates for the parameters of most interest, but a single-stage method based on contrasts between doses produces the most appropriate confidence intervals. Although simpler methods may have pragmatic advantages, such as the use of standard software for scalar meta-analysis, more sophisticated methods are nevertheless preferable for their advantages in estimation.

scholarly journals EXPRESS: The benefit of exercise-based rehabilitation programmes in patients with pulmonary hypertension: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
pp. 204589402110078
Author(s):  
Lu Yan ◽  
Wence Shi ◽  
Zhi-hong Liu ◽  
Qin Luo ◽  
Zhihui Zhao ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pulmonary Hypertension ◽  
Randomized Controlled Trials ◽  
Exercise Capacity ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Mean ◽  
Quality Evidence

Background: Several studies have suggested that exercise capacity and quality of life are reduced in patients with pulmonary hypertension (PH), and exercise-based rehabilitation can improve exercise capacity and quality of life in patients with PH. The aim of this study is to assess the efficacy and safety of exercise-based rehabilitation in patients with PH through a meta-analysis of randomized controlled trials. Methods: We searched PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials up to November 2018. All randomized controlled trials (RCTs) comparing exercise capacity and quality of life between patients undergoing exercise-based rehabilitation and those undergoing non-exercise training were included. Data were extracted separately and independently by two investigators, and discrepancies were arbitrated by the third investigator. We used the random-effects model to analyze the results, the GRADE to assess the risk of bias in the included studies, and I ² statistic to estimate the degree of heterogeneity. Results: Nine RCTs are included, however, only seven RCTs were able to extract data. Including inpatients and outpatients, the total number of participants was 234, most of whom were diagnosed as pulmonary artery hypertension (PAH). The study duration ranged from 3 to15 weeks. The mean six-minute walk distance after exercise training was 51.94 metres higher than control (27.65 to 76.23 metres, n=234, 7 RCTs, low quality evidence), the mean peak oxygen uptake  was 2.96 ml/kg/minute higher (2.49 to 3.43 ml/kg/minute, n=179, 4 RCTs, low-quality evidence) than in the control group . Concluded: Our finding suggest that an exercise-based training program positively influences exercise capacity in patients with PH.

scholarly journals The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 10 (13) ◽  
pp. 2824
Author(s):  
Su-Kiat Chua ◽  
Wei-Ting Lai ◽  
Lung-Ching Chen ◽  
Huei-Fong Hung
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Randomized Controlled Trials ◽  
Diastolic Blood Pressure ◽  
Publication Bias ◽  
Meta Analysis ◽  
Systemic Review ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Mean

Background: The management of hypertension remains suboptimal throughout the world. Methods: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. Results: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = −6.52 mmHg, 95% confidence interval (CI): −8.57 to −4.47; p < 0.001), msDBP (WMD = −3.32 mmHg, 95% CI: −4.57 to −2.07; p < 0.001), maSBP (WMD = −7.08 mmHg, 95% CI: −10.48 to −3.68; p < 0.001), maDBP (WMD = −3.28 mmHg, 95% CI: −4.55 to −2.02, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger’s test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. Conclusion: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.

The effect of zinc supplementation on blood pressure: a systematic review and dose–response meta-analysis of randomized-controlled trials

2020 ◽  
Vol 59 (5) ◽  
pp. 1815-1827 ◽  
Author(s):  
Seyed Mohammad Mousavi ◽  
Manije Darooghegi Mofrad ◽  
Israel Júnior Borges do Nascimento ◽  
Alireza Milajerdi ◽  
Tahereh Mokhtari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Randomized Controlled Trials ◽  
Dose Response ◽  
Zinc Supplementation ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled

scholarly journals Zinc Supplementation and Body Weight: A Systematic Review and Dose–Response Meta-analysis of Randomized Controlled Trials

2019 ◽  
Author(s):  
Shima Abdollahi ◽  
Omid Toupchian ◽  
Ahmad Jayedi ◽  
David Meyre ◽  
Vivian Tam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Weight ◽  
Randomized Controlled Trials ◽  
Dose Response ◽  
Zinc Supplementation ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Anthropometric Measures ◽  
Randomized Controlled

ABSTRACT The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose–response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose–response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I2 = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = −0.55 kg; 95% CI: −1.06, −0.04 kg; P = 0.03; I2 = 31.5%). Dose–response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.

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