Adisseo France SAS, 03600 Malicorne, France.
Zootests - 5 rue Gabriel Calloet-Kerbrat - 22440 Ploufragan - France.
Poult Sci. 2023 Apr;102(4):102519. doi: 10.1016/j.psj.2023.102519. Epub 2023 Jan 21.
The efficacy of a new molecule is assessed in the pharmaceutical industry through noninferiority tests to establish that it is not unacceptably less efficient than the reference. This method was proposed to compare DL-Methionine (DL-Met) as reference and DL-Hydroxy-Methionine (OH-Met) as alternative, in broiler chickens. The research hypothesized that OH-Met is inferior to DL-Met. Noninferiority margins were determined using 7 datasets comparing broiler growth response between a sulfur amino acid deficient and adequate diet from 0 to 35 d. The datasets were selected from the literature and internal records of the company. The noninferiority margins were then fixed as the largest loss of effect (inferiority) acceptable when OH-Met is compared to DL-Met. Three corn/soybean meal-based experimental treatments were offered to 4,200 chicks (35 replicates of 40 birds). Birds received from 0 to 35 d 1) a negative control diet deficient in Met and Cys; the negative control treatment supplemented on equimolar basis with 2) DL-Met or 3) OH-Met in amounts allowing to reach Aviagen Met+Cys recommendations. The three treatments were adequate in all other nutrients. Growth performance, which was analysed with one-way ANOVA, showed no significant difference between DL-Met and OH-Met. The supplemented treatments improved (P < 0.0001) the performance parameters compared to the negative control. The lower limits of the confidence intervals of the difference between means for the feed intake [-1.34; 1.41], body weight [-57.3; 9.8] and daily growth [-1.64; 0.28], did not exceed the noninferiority margins. This demonstrates that OH-Met was non-inferior to DL-Met.
在制药行业,通过非劣效性试验来评估新分子的疗效,以确定其效率不低于参比药物。这种方法是为了比较 DL-蛋氨酸 (DL-Met) 作为参比药物和 DL-羟蛋氨酸 (OH-Met) 作为替代药物在肉鸡中的效果。研究假设 OH-Met 不如 DL-Met 有效。非劣效性边界是使用 7 个数据集确定的,这些数据集比较了 0 至 35 日龄时含硫氨基酸缺乏和充足饮食对肉鸡生长反应的影响。这些数据集选自文献和公司内部记录。然后,将非劣效性边界固定为当 OH-Met 与 DL-Met 进行比较时可接受的最大效果(劣效性)损失。三种基于玉米/豆粕的实验处理方案提供给 4200 只小鸡(35 个 40 只鸡的重复)。小鸡在 0 至 35 日龄期间接受以下三种处理之一:1)缺乏 Met 和 Cys 的负对照饮食;2)负对照饮食在等摩尔基础上补充 2)DL-Met 或 3)OH-Met,添加量足以达到 Aviagen Met+Cys 的推荐量。所有其他营养素在这三种处理中均充足。采用单因素方差分析对生长性能进行分析,结果表明 DL-Met 和 OH-Met 之间无显著差异。与负对照相比,补充处理显著提高了(P < 0.0001)所有性能参数。平均值之间差异的置信区间下限[-1.34;1.41]、体重[-57.3;9.8]和日增重[-1.64;0.28],均未超过非劣效性边界。这表明 OH-Met 与 DL-Met 等效。