Persistent efficacy: importance and impact of trial design.

The persistent efficacy of some anthelmintics brings advantages in nematode control in domestic animals. However, scientific assessment of persistent efficacy is relatively new, and a feature of published data has been variability in the reported endpoint for this activity. Trial design and method of calculating efficacy have a large bearing on the results obtained. Three types of studies used to evaluate the persistent efficacy of anthelmintics are briefly discussed and compared. In the first type of study, animals are treated followed by a single infection at 7, 14 or more days after treatment. The reduction in worm counts compared to an untreated control group gives a good indication of the persistent efficacy of the product at each time point. One control group can be used for several time points. In the second type of study, the animals are treated and then infected daily from day 1 until 7 days, 14 days or longer after treatment. The animals are slaughtered approximately 3 weeks after the last infection. This approach may better mimic a natural infection but the results obtained are an average reduction over the whole infection period. At the end of the evaluated period, the actual protection may be considerably lower than the average. From this test, it is difficult to define when the protection decreases or disappears. In this test, a control group is required for each period. In the third type of study, a modification of the second, the animals are treated and infected as before but animals are slaughtered soon (2-5 days) after the last infection. Based on the reduction of, for example, the different Ostertagia stages a more specific determination of the persistent efficacy 0-3 days (L3), 3-7 (EL4), 7-14 (LL4 + EL5) and more than 14 days (LL5 + adults) before slaughter can be obtained. Only two groups of animals are required to cover a 3 week period and the average efficacies can be reduced to about one week.