Alcabes P, Pezzotti P, Phillips A N, Rezza G, Vlahov D
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Am J Epidemiol. 1997 Oct 1;146(7):543-51. doi: 10.1093/oxfordjournals.aje.a009312.
Because considerable information about progression of human immunodeficiency virus (HIV) infection has been provided by studies of cohorts of individuals with prevalent HIV infection, this study was designed to investigate bias due to onset confounding (differential time-since-infection distributions) and differential length-biased sampling in epidemiologic analyses of data from such cohorts. Subjects were participants in the Italian Seroconverters Study, a seroincident cohort of more than 1,200 adults seen at ambulatory care clinics in Italy, with observed HIV seroconversion in 1980-1988. Acquired immunodeficiency syndrome (AIDS) diagnoses, based on the 1987 Centers for Disease Control case definition, and mortality were ascertained through Italian national registries through 1994. To estimate bias in prevalent cohorts, a series of pseudoseroprevalent (PSP) cohorts were drawn by sampling, from among the total seroincident cohort, prevalent AIDS-free subjects in each calendar year. The relative AIDS risk associated with a given covariate was calculated in each PSP cohort and compared with the relative AIDS risk for that covariate in the seroincident cohort. Relative risks were estimated by both the ratio of AIDS incidence densities and the relative AIDS hazards from proportional hazards regression. Differential length bias was not evident, as assessed in the following way: Among 338 individuals with seroconversion dates in 1983-1986, the relative risk of AIDS for subjects born before 1951 compared with those born more recently was 1.67 (95% confidence interval (CI) 1.30-2.14). Although differential length-biased sampling was expected to bias this relative risk toward 1.0, the observed relative risk for earlier birth ranged from 1.79 to 2.86 in 1987-1992 PSP cohorts. Onset bias was observed: Among 644 subjects with seroconversion in 1980-1988, the AIDS relative risk for 1980-1985 seroconverters compared with 1986-1988 seroconverters was 1.09 (95% CI 0.76-1.55). Onset bias was seen in 1988-1990 PSP cohorts (relative risks for early seroconversion = 1.47, 1.46, and 1.34, respectively); in 1991-1992, relative risks were close to the expected value of 1.09, and CIs on relative risks from all PSP cohorts after 1989 included 1.0. Confounding attributable to differential length-biased sampling in prevalent cohorts does not necessarily bias estimates of the impact of covariates on rate of progression to AIDS. Bias can arise when a covariate suspected of affecting AIDS risk is closely linked to date of acquisition of HIV infection. However, onset bias appears to wane as subjects' dates of infection become more remote.
由于对感染人类免疫缺陷病毒（HIV）个体队列的研究已经提供了关于HIV感染进展的大量信息，本研究旨在调查在对此类队列数据进行流行病学分析时，由发病混杂（感染后时间分布差异）和不同的长度偏倚抽样导致的偏差。研究对象是意大利血清转化者研究的参与者，这是一个在意大利门诊诊所观察到的超过1200名成年人的血清发病队列，在1980 - 1988年期间观察到HIV血清转化。根据1987年疾病控制中心的病例定义确定的获得性免疫缺陷综合征（AIDS）诊断以及死亡率，通过意大利国家登记处确定至1994年。为了估计现患队列中的偏差，通过从整个血清发病队列中抽样，在每个日历年抽取无AIDS的现患受试者，构建了一系列伪血清流行（PSP）队列。在每个PSP队列中计算与给定协变量相关的相对AIDS风险，并与血清发病队列中该协变量的相对AIDS风险进行比较。通过AIDS发病密度比和比例风险回归中的相对AIDS风险来估计相对风险。如下评估，未发现明显的不同长度偏倚：在1983 - 1986年有血清转化日期的338名个体中，1951年以前出生的受试者与近期出生的受试者相比，AIDS的相对风险为1.67（95%置信区间（CI）1.30 - 2.14）。尽管预期不同长度偏倚抽样会使该相对风险偏向1.0，但在1987 - 1992年的PSP队列中，观察到的较早出生者的相对风险范围为1.79至2.86。观察到发病偏差：在1980 - 1988年有血清转化的644名受试者中，1980 - 1985年血清转化者与1986 - 1988年血清转化者相比，AIDS相对风险为1.09（95% CI 0.76 - 1.55）。在1988 - 1990年的PSP队列中可见发病偏差（早期血清转化的相对风险分别为1.47、1.46和1.34）；在1991 - 1992年，相对风险接近预期值1.09，1989年之后所有PSP队列中相对风险的CI包括1.0。现患队列中因不同长度偏倚抽样导致的混杂不一定会使协变量对AIDS进展率影响的估计产生偏差。当怀疑影响AIDS风险的协变量与HIV感染获得日期密切相关时，可能会出现偏差。然而，随着受试者感染日期变得更久远，发病偏差似乎会减弱。
