Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases L, Spallanzani, IRCCS, Via Portuense 292, 00149, Rome, Italy.
BMC Health Serv Res. 2012 Feb 15;12:38. doi: 10.1186/1472-6963-12-38.
Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy.
We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately.
A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined.
Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.
确定获得研究药物的决定因素对于促进临床研究的公平性和科学性至关重要。我们旨在分析与意大利使用实验性抗逆转录病毒药物相关的因素。
我们研究了意大利抗逆转录病毒治疗初治患者队列（ICoNA）的参与者。所有在 1997 年至 2007 年期间登记后开始接受 cART（≥3 种药物，至少包括两种 NRTI）的 18 岁或以上的患者均纳入本分析。我们进行了随机效应逻辑回归分析，以考虑临床单位内的聚类观察。结局变量是使用实验性抗逆转录病毒药物，定义为在任何治疗开始/改变的情况下，在商业上市之前开始使用的抗逆转录病毒药物。通过临床试验或扩展准入计划（EAP）使用的实验性抗逆转录病毒药物也分别进行了分析。
共分析了 3752 名患者的 9441 个治疗开始/改变的阶段。392 个阶段（360 名患者）涉及实验性抗逆转录病毒药物。多变量分析表明，与整体使用实验性抗逆转录病毒药物相关的因素包括：经验性药物数量（≥8 种药物与“初治”相比：调整后的优势比 [AOR] =3.71）或失败的抗逆转录病毒药物（3-4 种药物和≥5 种药物与 0-2 种药物相比：AOR=1.42 和 2.38）；日历年份（AOR=0.80/年）和治疗改变时的血浆 HIV-RNA 拷贝/ml（≥4 log 与<2 log：AOR=1.55）。患有肝脏合并症的患者（AOR=0.65）和使用 3-4 种药物（与初治相比）（AOR=0.55）接受试验性抗逆转录病毒治疗的概率显著降低，而接受多药治疗的患者（AOR=2.60）的概率增加。通过 EAP 开始实验性抗逆转录病毒治疗的概率随着经验性药物和失败性药物数量的增加而逐渐增加，同时也随着患有肝脏合并症的患者（AOR=1.44；p=0.053）和男同性恋者（与异性恋者相比：AOR=1.67）的增加而增加。与临床单位相关的随机效应的变异性具有统计学意义（p<0.001），但未发现与所检查的临床单位的特定特征有关。
在意大利感染 HIV 的患者中，获得实验性抗逆转录病毒药物的机会似乎主要受到治疗选择枯竭的影响，而不是受社会人口因素的影响。
