Studies conducted to support registration or approval of veterinary anthelmintics generally follow study design recommendations provided by the VICH (International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products), “Efficacy of Anthelmintics: General Requirements” (VICH GL7). For dose confirmation studies, VICH GL7 provides recommendations for determining that the control animals had an adequate infection “to permit the appropriate standards of efficacy to be met with acceptable statistical and biological certitude/confidence.” In the simulation studies described in this report, we investigated the performance of one method, the statistical criterion given in Section 4.5 of VICH GL7, for evaluating the adequacy of infection in anthelmintic studies, in combination with the conventional criterion of a minimum of six adequately infected animals. We conducted numerical simulations, based on parasite data from previously conducted dose confirmation studies in dogs and cattle, to investigate how the statistical criterion impacts adequacy of infection determinations when used with the conventional criterion at various sample sizes. Simulation studies in common nematode species in both dogs and cattle indicated that under certain circumstances the statistical criterion can guard against overinterpreting the evaluation of adequacy of infection as sample size is increased. However, the statistical criterion may be overly restrictive for samples with adequate infection but containing multiple zero parasite counts and adding it to the conventional criterion does not provide any additional benefit when the sample contains no zero counts. It is important for investigators designing efficacy studies to understand the potential impact this criterion may have when establishing adequacy of infection criteria in study protocols.

为支持兽用驱虫药的注册或批准而进行的研究通常遵循VICH（兽药产品注册的技术要求国际合作）提供的研究设计建议，即“驱虫药的功效：一般要求”（VICH GL7）。对于剂量确认研究，VICH GL7提供了确定对照动物具有足够感染力的建议，“以允许在可接受的统计和生物学确定性/信心下达到适当的功效标准”。在本报告中描述的模拟研究中，我们调查了一种方法的性能，即VICH GL7第4.5节中给出的统计标准，用于评估驱虫药研究中感染的充分性，结合至少六只充分感染动物的常规标准。我们基于先前在狗和牛中进行的剂量确认研究中的寄生虫数据进行了数值模拟，以研究当在不同样本量下与常规标准一起使用时，统计标准如何影响感染确定性。在狗和牛中常见线虫物种的模拟研究表明，在某些情况下，随着样本量的增加，统计标准可以防止过度解释感染的适当性评估。然而，统计标准对于具有足够感染性但包含多个零寄生虫计数的样本可能过于严格，当样本不包含零计数时，将其添加到常规标准中不会提供任何其他好处。对于设计功效研究的研究者来说，重要的是要了解在研究方案中确定感染标准是否适当时该标准可能产生的潜在影响。