Joint Estimation of Incidence and Diagnostic Error Rates from Irregular Longitudinal Data
针对纵向研究中诊断时间不规则且诊断存在错误的情况，提出联合参数化发病率和错误率的模型，并用EM算法进行最大似然估计，以镰状细胞病患者性成熟诊断数据为例分析。
Abstract Longitudinal studies often involve the repeated diagnosis across time of each patient's status with respect to a progressive categorical process. When the occurrence of a change in status is not readily apparent, two factors can make modeling and assessing the incidence rates of progression difficult. First, because diagnoses may be difficult, they may not be performed with the frequency necessary to pinpoint exact times of incidence. Second, uncertainty in the diagnostic process can obscure identification of the time interval in which incidence occurs. When serial diagnoses are fallible, even small error rates can seriously disrupt interpretation and make using the aforementioned methods difficult or impossible. For example, if false diagnoses (both false positives and negatives) occur independently with probability .05 in a longitudinal study involving four serial diagnoses, 19% of the strings of serial diagnoses would be expected to contain at least one error. If the underlying process is progressive, many of these errors would be noticeable: At face value, some patterns of diagnoses would describe regressions. Errors yielding patterns of diagnoses that are progressive would not be detectable. Simply omitting any subjects with inconsistent patterns from the analysis introduces bias. Another possible approach, using the first reported incidence of progression, also introduces bias (Schlesselman 1977). To analyze clinical data on the diagnosis of sexual maturation among subjects with sickle-cell disease, models are developed for jointly parameterizing incidence and error rates. An EM algorithm is presented that allows tractable maximum likelihood estimation even when the times of diagnoses are irregular and vary among subjects. Likelihood ratio tests are used to assess relationships between categorical covariates and both incidence and error rates. Data from the Cooperative Study of Sickle Cell Disease are analyzed to describe the age distribution for the onset of puberty (according to the Tanner stage index) among homozygous (SS) males. Clear delays in maturation are apparent among SS males. Diagnostic error rates for Tanner staging appear to vary with the subject's age. False-positive diagnoses appear to be more common than false-negative diagnoses.