Usage Of Meta-Analysis In Randomized Clinical Trials To Evaluate The Safety

Meta-Analysis was performed in defining the somnolence profile of cetirizine in patients aged6years and older administered a single daily dose of cetirizine10mg compared with Placebo for the relief of seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic urticaria symptoms (CIU) to demonstrate the usage of it for safety data in clinical trial.Firstly, with Cetirizine and Somnolence as keywords, PubMed and PMC, ScienceDirect, Wiley, and Google were retrieved systematically. Secondly, all the retrieved articles were carefully read and screened; the quality was evaluated and useful information was extracted in accordance with the predetermined criteria. Finally, all the data analyses were performed using statistical software SAS9.3. DerSimonian and Laird (D&L) method was used to calculate the combined effect based on fixed effects and random effect model respectively; Q statistic, H statistic and IA2were calculated for heterogeneity analysis and subgroup analysis, subgroup heterogeneity analysis, Galbraith plot, sensitivity analysis and Meta-Regression were also performed to explore the sources of heterogeneity. Totally twelve randomized clinical trials meeting the inclusion criteria for this study were identified. The heterogeneity test based on the twelve clinical trials showed that heterogeneity existed among the trials, corresponding results of subgroup analysis, subgroups heterogeneity test, Galbraith plot, sensitivity analysis and Meta-Regression consistently showed that one-week placebo run-in period is the root cause of heterogeneity. This finding has important guiding significance for the clinical trials design to study the similar drugs in the future. Based on this important discovery, the effect size and conclusion of cetirizine10mg per day compared with placebo in somnolence should be calculated and made for studies with placebo run-in period and those without placebo run-in period, respectively. From subgroup Meta-Analyses for clinical trials without the placebo run-in period, the overall risk difference of cetirizine10mg daily compared with placebo based on the fixed effect model was7.03, with the95%CI (5.01,9.05). The95%CI didn’t include0, indicating that for clinical trials without placebo run-in period, the difference in somnolence rate between cetirizine10mg daily and placebo was statistically significant. The overall risk difference of cetirizine10mg daily compared with placebo based on the fixed effect model was1.09, with the95%CI (-0.16,2.33) for the clinical trials with placebo run-in period. The95%CI included0, indicating that for clinical trials with placebo run-in period, the difference in somnolence rate between cetirizine10mg daily and placebo was not statistically significant. This result will greatly change the opinion of the professionals in medical industry on cetirizine, which is also likely to change doctor’s prescription choice. Overcoming the limitation of the single clinical trial due to sample size, Meta-Analysis applied in the safety data could more appropriately estimate the true difference of Cetirizine10mg daily compared to placebo in somnolence.