Hill Andrew, Demasi Ralph
Department of Pharmacology, University of Liverpool, Liverpool, UK.
Antivir Ther. 2005;10(3):367-74.
The three main components of long-term efficacy for a combination of antiretrovirals are: (i) the strength of the antiviral effect, (ii) toxicity profile and (iii) patient acceptability of the regimen. Intent-to-treat (ITT) analysis, where discontinuations and switches are considered failures [ITT, switch equals failure (ITT/S = F)], is a regulatory standard for analysing the efficacy of antiretrovirals. A review of all clinical trials published in FDA product labels was conducted, including all clinical trials of boosted protease inhibitor- or nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy in treatment-naive patients, and all clinical trials of antiretrovirals in treatment-experienced patients. Clinical trials where the results are presented in the standard ITT/S = F method were included. For randomized clinical trials in treatment-naive patients, the majority of treatment discontinuations have been either for toxicity (32%) or patient refusal of treatment (41%), with only 27% of failure endpoints for virological reasons among recent clinical trials in naive patients. Therefore, there is the potential for the results from ITT/S = F analysis to be driven by non-virological endpoints - a new treatment can be classified as 'more efficacious' than control owing to fewer discontinuations due to adverse events or patient preference. In order to understand the intrinsic potency of the antiretroviral regimen under study, ITT analysis needs to be supplemented by standardized as-treated analyses, excluding withdrawals for toxicity or other reasons. To evaluate the efficacy of a treatment strategy or sequential treatment regimens, the 'ITT, switch included' (ITT/SI) method: where changes from the initial randomized treatment are not classified as treatment failure - can be used. However, interpretation of clinical trials using ITT/SI analysis is difficult and depends on the frequency of treatment switching in the different arms of a trial. Conclusions on efficacy from clinical trials can depend on the primary analysis used; most commonly, treatments could be significantly different by ITT/S=F analysis, but then interpreted as equivalent using the ITT/SI or as-treated methods.
（i）抗病毒效果的强度，（ii）毒性特征，以及（iii）治疗方案的患者可接受性。意向性治疗（ITT）分析将停药和换药视为失败[ITT，换药等同于失败（ITT/S = F）]，是分析抗逆转录病毒药物疗效的监管标准。对FDA产品标签中公布的所有临床试验进行了回顾，包括所有以增强型蛋白酶抑制剂或核苷类逆转录酶抑制剂为基础的高效抗逆转录病毒疗法在初治患者中的临床试验，以及抗逆转录病毒药物在经治患者中的所有临床试验。纳入了以标准ITT/S = F方法呈现结果的临床试验。对于初治患者的随机临床试验，大多数治疗中断要么是因为毒性（32%），要么是患者拒绝治疗（41%），在初治患者最近的临床试验中，因病毒学原因导致的失败终点仅占27%。因此，ITT/S = F分析的结果有可能由非病毒学终点驱动——一种新治疗可能因不良事件或患者偏好导致的停药较少而被归类为比对照“更有效”。为了了解所研究的抗逆转录病毒治疗方案的内在效力，ITT分析需要辅以标准化的实际治疗分析，排除因毒性或其他原因导致的停药情况。为了评估一种治疗策略或序贯治疗方案的疗效，可以使用“ITT，包括换药”（ITT/SI）方法：即从初始随机治疗的改变不被归类为治疗失败。然而，使用ITT/SI分析对临床试验进行解读很困难，并且取决于试验不同组中治疗换药的频率。临床试验的疗效结论可能取决于所使用的主要分析方法；最常见的情况是，通过ITT/S = F分析，治疗可能有显著差异，但随后使用ITT/SI或实际治疗方法解释为等效。
