When multiple measures are collected repeatedly over time, redundancy typically exists among responses. The envelope method was recently proposed to reduce the dimension of responses without loss of information in regression with multivariate responses. It can gain substantial efficiency over the standard least squares estimator. In this paper, we generalize the envelope method to mixed effects models for longitudinal data with possibly unbalanced design and time‐varying predictors. We show that our model provides more efficient estimators than the standard estimators in mixed effects models. Improved accuracy and efficiency of the proposed method over the standard mixed effects model estimator are observed in both the simulations and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.
Envelope method was recently proposed as a method to reduce the dimension of responses in multivariate regressions. However, when there exists missing data, the envelope method using the complete case observations may lead to biased and inefficient results. In this paper, we generalize the envelope estimation when the predictors and/or the responses are missing at random. Specifically, we incorporate the envelope structure in the expectation-maximization (EM) algorithm. As the parameters under the envelope method are not pointwise identifiable, the EM algorithm for the envelope method was not straightforward and requires a special decomposition. Our method is guaranteed to be more efficient, or at least as efficient as, the standard EM algorithm. Moreover, our method has the potential to outperform the full data MLE. We give asymptotic properties of our method under both normal and non-normal cases. The efficiency gain over the standard EM is confirmed in simulation studies and in an application to the Chronic Renal Insufficiency Cohort (CRIC) study.
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When the primary outcome is difficult to collect, surrogate endpoint is typically used as a substitute. It is possible that for every individual, treatment has a positive effect on surrogate, and surrogate has a positive effect on primary outcome, but for some individuals, treatment has a negative effect on primary outcome. For example, a treatment may be substantially effective in preventing the stroke for everyone, and lowering the risk of stroke is universally beneficial for a longer survival time, however, the treatment may still causes death for some individuals. We define such paradoxical phenomenon as individual surrogate paradox. The individual surrogate paradox is proposed to capture the treatment effect heterogeneity, which is unable to be described by either the surrogate paradox based on average causal effect (ACE) (Chen et al., 2007) or that based on distributional causal effect (DCE) (Ju and Geng, 2010). We investigate existing surrogate criteria in terms of whether the individual surrogate paradox could manifest. We find that only the strong binary surrogate can avoid such paradox without additional assumptions. Utilizing the sharp bounds, we propose novel criteria to exclude the individual surrogate paradox. Our methods are illustrated in an application to determine the effect of the intensive glycemia on the risk of development or progression of diabetic retinopathy.
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