Harvard Medical School, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2010 Sep 9;5(9):e12647. doi: 10.1371/journal.pone.0012647.
Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model.
We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS.
The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.
基于模型的分析是在决策分析框架内进行的,它提供了一种系统的方法,可以将疾病的自然史和临床管理策略的有效性信息与人群的人口统计学和流行病学特征结合起来。在针对特定疾病的建模中存在的挑战包括需要识别有影响力的假设,并评估模型的表面有效性和内部一致性。
我们描述了一系列用于适应艾滋病毒疾病计算机模拟模型以适应妇女机构间艾滋病毒研究(WIHS)队列的练习,并评估了我们重新参数化模型以解决与美国艾滋病毒感染妇女相关的政策问题的模型性能使用来自 WIHS 的数据。经验校准目标包括按治疗状况和 CD4 细胞计数分层的 24 个月生存率曲线。未接受治疗的女性中最有影响力的假设包括慢性艾滋病毒相关机会性感染后的死亡率,以及接受治疗的女性中,抗逆转录病毒疗法(HAART)的“临床疗效”以及 HAART 预防 HIV 并发症的能力与病毒学抑制无关。良好拟合的参数集需要降低一线和二线 HAART 的临床疗效,并改善三线和四线方案。使用校准的队列特定模型预测的治疗方案转换率与使用 WIHS 数据独立分析的结果非常接近。
该模型表现出良好的内部一致性和表面有效性,并支持文献中报道的队列异质性。对模型性能的迭代评估可以提供有关不确定假设相对影响的信息,并深入了解队列内和队列之间的异质性。对校准练习的描述可以提高特定疾病模型的透明度。