Little has been published in terms of dose‐finding methodology in virology. Aside from a few papers focusing on HIV, the considerable progress in dose‐finding methodology of the last 25 years has focused almost entirely on oncology. While adverse reactions to cytotoxic drugs may be life threatening, for anti‐viral agents we anticipate something different: side effects that provoke the cessation of treatment. This would correspond to treatment failure. On the other hand, success would not be yes/no but would correspond to a range of responses, from small, no more than say 20% reduction in viral load to the complete elimination of the virus. Less than total success matters since this may allow the patient to achieve immune‐mediated clearance. The motivation for this article is an upcoming dose‐finding trial in chronic norovirus infection. We propose a novel methodology whose goal is twofold: first, to identify the dose that provides the most favorable distribution of treatment outcomes, and, second, to do this in a way that maximizes the treatment benefit for the patients included in the study.

中文翻译：

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病毒学的早期剂量寻找试验

关于病毒学的剂量确定方法学，几乎没有发表。除了几篇有关艾滋病毒的论文外，过去25年中剂量寻找方法学的巨大进步几乎全部集中在肿瘤学上。尽管对细胞毒性药物的不良反应可能危及生命，但对于抗病毒药物，我们预计会有所不同：引起停止治疗的副作用。这将对应于治疗失败。另一方面，成功不是“是/否”，而是对应于一系列反应，从微小的病毒负载减少（不超过20％）到完全消除病毒。取得成功的重要性要少于总成功率，因为​​这可能会使患者获得免疫介导的清除率。本文的动机是即将进行的慢性诺如病毒感染剂量寻找试验。