Linear models are some of the most straightforward and commonly used modelling approaches. Consider modelling approximately monotonic response data arising from a time-related process. If one has knowledge as to when the process began or ended, then one may be able to leverage additional assumed data to reduce prediction error. This assumed data, referred to as the "anchor," is treated as an additional data-point generated at either the beginning or end of the process. The response value of the anchor is equal to an intelligently selected value of the response (such as the upper bound, lower bound, or 99th percentile of the response, as appropriate). The anchor reduces the variance of prediction at the cost of a possible increase in prediction bias, resulting in a potentially reduced overall mean-square prediction error. This can be extremely effective when few individual data-points are available, allowing one to make linear predictions using as little as a single observed data-point. We develop the mathematics showing the conditions under which an anchor can improve predictions, and also demonstrate using this approach to reduce prediction error when modelling the disease progression of patients with amyotrophic lateral sclerosis.

The estimation of carry-over effects is a difficult problem in the design and analysis of clinical trials of treatment sequences including cross-over trials. Except for simple designs, carry-over effects are usually unidentifiable and therefore nonestimable. Solutions such as imposing parameter constraints are often unjustified and produce differing carry-over estimates depending on the constraint imposed. Generalized inverses or treatment-balancing often allow estimating main treatment effects, but the problem of estimating the carry-over contribution of a treatment sequence remains open in these approaches. Moreover, washout periods are not always feasible or ethical. A common feature of designs with unidentifiable parameters is that they do not have design matrices of full rank. Thus, we propose approaches to the construction of design matrices of full rank, without imposing artificial constraints on the carry-over effects. Our approaches are applicable within the framework of generalized linear mixed-effects models. We present a new model for the design and analysis of clinical trials of treatment sequences, called Antichronic System, and introduce some special sequences called Skip Sequences. We show that carry-over effects are identifiable only if appropriate Skip Sequences are used in the design and/or data analysis of the clinical trial. We explain how Skip Sequences can be implemented in practice, and present a method of computing the appropriate Skip Sequences. We show applications to the design of a cross-over study with 3 treatments and 3 periods, and to the data analysis of the STAR*D study of sequences of treatments for depression.