Efficient crossover designs in the presence of interactions between direct and carry-over treatment effects

Crossover designs, or repeated measurements designs, are used for experiments in which t treatments are applied to each of n experimental units successively over p time periods. Such experiments are widely used in areas such as clinical trials, experimental psychology and agricultural field trials. In addition to the direct effect on the response of the treatment in the period of application, there is also the possible presence of a residual, or carry-over, effect of a treatment from one or more previous periods. We use a model in which the residual effect from a treatment depends upon the treatment applied in the succeeding period; that is, a model which includes interactions between the treatment direct and residual effects. We assume that residual effects do not persist further than one succeeding period.A particular class of strongly balanced repeated measurements designs with n=t² units and which are uniform on the periods is examined. A lower bound for the A-efficiency of the designs for estimating the direct effects is derived and it is shown that such designs are highly efficient for any number of periods p=2,…,2t.     

A Class of Experimental Designs Balanced for First Residuals

In this paper a new class of designs involving sequences of treatments balanced for first residual effects has been introduced. These designs require only t experimental units for 2t periods, t being the number of treatments to be tested. A unified method of constructing these designs for all values of t (≥2) along with an appropriate method of analysis is presented. Besides, their efficiency relative to some well known designs is investigated.     

A nonparametric procedure for the analysis of balanced crossover designs

The authors propose nonparametric tests for the hypothesis of no direct treatment effects, as well as for the hypothesis of no carryover effects, for balanced crossover designs in which the number of treatments equals the number of periods p, where p ≥ 3. They suppose that the design consists of n replications of balanced crossover designs, each formed by m Latin squares of order p. Their tests are permutation tests which are based on the n vectors of least squares estimators of the parameters of interest obtained from the n replications of the experiment. They obtain both the exact and limiting distribution of the test statistics, and they show that the tests have, asymptotically, the same power as the F‐ratio test.     

NESTING OPTIMAL MAIN EFFECTS PLANS AND OPTIMAL FOLDOVER DESIGNS

ABSTRACT

Optimal main effects plans (MEPs) and optimal foldover designs can often be performed as a series of nested optimal designs. Then, if the experiment cannot be completed due to time or budget constraints, the fraction already performed may still be an optimal design. We show that the optimal MEP for 4t factors in 4t + 4 points does not contain the optimal MEP for 4t factors in 4t + 2 points nested within it. In general, the optimal MEP for 4t factors in 4t + 4 points does not contain the optimal MEPs for 4t factors in 4t + 1, 4t + 2, or 4t + 3 points and the optimal MEP for 4t + 1 factors in 4t + 4 points does not contain the optimal MEPs for 4t + 1 factors in 4t + 2 or 4t + 3 points. We also show that the runs in an orthogonal design for 4t factors in 4t + 4 points, and the optimal foldover designs obtained by folding, should be performed in a certain sequence in order to avoid the possibility of a singular X'X matrix.     

Extension and necessity of Cheng and Wu conditions

Repeated Measurement Designs, with two treatments, n (experimental) units and p periods are examined. The model examined is with uncorrelated observations following a continuous distribution with constant variance and the parameters of interest are (i) the difference of direct effects and (ii) the difference of residual effects. In this paper (a) the difference of Universal optimality and Φ-optimality is clarified and (b) the sufficient conditions of Cheng and Wu (1980) are extended to include the case n=2 mod 4, p even, (c) also it is shown that these conditions are also necessary for Φ-optimality for estimating direct as well as residual effects, and (d) a method is proposed to construct Φ-optimal designs and examples are given when n even and p=3, n=0 mod 4 and p=4, n=2 mod 4 and p=4. In the last case the estimated parameters in the optimal design are correlated.     

Tables of Cyclic Incomplete Block Designs: r=k

Initial blocks and efficiencies are given for cyclic incomplete block designs in the range t= 10(1)60 and r=k= 3(1)10. The designs have been selected by search procedures using optimality criteria which maximize the efficiency factor.     

Minimal circular strongly balanced repeated measurements designs in periods of three different sizes

Repeated measurements designs (RMD) are widely used in medicine, pharmacology, animal sciences, and psychology. If there is a restriction on the total number of treatments, some experimental units can receive on the total length of time while some experimental units can remain in the trial, then RMD in periods of unequal sizes should be used. In this article, some infinite series are developed to generate the minimal circular strongly balanced RMD in periods of three different sizes p₁, p₂, and p₃, where 2 ≤ p₃ < p₂ ≤ 10.     

Construction of circular partially balanced-Repeated measurement designs using cyclic shifts

Repeated measurement designs are widely used in medicine, pharmacology, animal sciences and psychology. These designs balance out the residual effects. The situations where balanced repeated measurements designs require a large number of the subjects, partially-balanced repeated measurements designs should be used. In this paper some infinite series are developed which provide circular partially-balanced repeated measurement designs for p (periods) even. Catalogues of circular partially-balanced repeated measurement designs are also presented for v (treatments) ≤ 100 with p = 5, 7 & 9.     

Reverse Foldovers for Blocked 2 m−k Fractional Factorial Designs

Two-level regular fractional factorial designs are often used in industry as screening designs to help identify early on in an experimental process those experimental or system variables which have significant effects on the process being studied. When the experimental material to be used in the experiment is heterogenous or the experiment must be performed over several well-defined time periods, blocking is often used as a means to improve experimental efficiency by removing the possible effects of heterogenous experimental material or possible time period effects. In a recent article, Li and Jacroux (2007 Li , F. , Jacroux , M. (2007). Optimal foldover plans for blocked 2 ^m?k fractional factorial designs. J. Statsist. Plann. Infer 137:2434–2452. [Google Scholar]) suggested a strategy for constructing optimal follow-up designs for blocked fractional factorial designs using the well-known foldover technique in conjunction with several optimality criteria. In this article, we consider the reverse foldover problem for blocked fractional factorial designs. In particular, given a 2^(m+p)?(p+k) blocked fractional factorial design D, we derive simple sufficient conditions which can be used to determine if there exists a 2^{(m+p?1)?(p?1+k+1)} initial fractional factorial design d which yields D as a foldover combined design as well how to generate all such d. Such information is useful in developing an overall experimental strategy in situations where an experimenter wants an overall blocked fractional factorial design with “desirable” properties but also wants the option of analyzing the observed data at the halfway mark to determine if the significant experimental variables are obvious (and the experiment can be terminated) or if a different path of experimentation should be taken from that initially planned.     

On the E-optimality of complete block designs under a mixed interference model

In experiments in which the response to a treatment can be affected by other treatments, the interference model with neighbor effects is usually used. It is known that circular neighbor balanced designs (CNBDs) are universally optimal under such a model if the neighbor effects are fixed (Druilhet, 1999) or random (4 and 7). However, such designs cannot exist for every combination of design parameters. In the class of block designs with the same number of treatments as experimental units per block, a CNBD cannot exist if the number of blocks, b  , is equal to p(t−1)±1$p(t-1)\pm 1$, where p is a positive integer and t is the number of treatments. Filipiak et al. (2008) gave the structure of the left-neighboring matrix of E-optimal complete block designs with p  =1 under the model with fixed neighbor effects. The purpose of this paper is to generalize E-optimality results for designs with p∈N$p\in \mathbb{N}$ assuming random neighbor effects.     

Optimal two treatment repeated measurement designs for three periods

Repeated Measurement Designs, with two treatments, n (experimental) units and p periods are examined, the two treatments are denoted A and B. The model with independent observations within and between treatment sequences is used. Optimal designs are derived for: (i) the difference of direct treatment effects and the difference of residual effects, (ii) the difference of direct treatment effects, and (iii) the difference of residual effects. We prove that for three periods when n is odd the optimal design in the three cases (i), (ii), and (iii) is determined by taking the sequences BAA and ABB in numbers differing by one. If n is even, the optimal design in cases (i), (ii), and (iii) is again the same, by taking the sequences ABB and BAA in equal numbers. In case (i), for n even or odd, in the optimal design there is no correlation between the two estimated parameters. For n even, case (i) was solved by Cheng and Wu in 1980. The above imply that with two treatments in practice are preferable to use three periods instead of two.     

Some new construction of circular weakly balanced repeated measurements designs in periods of two different sizes

Abstract

Balanced repeated measurements designs (RMDs) balance out the residual effects. Williams Latin square designs work as minimal combinatorial balanced as well as variance balanced for RMDs for p (period sizes) = v (number of treatments). If minimal balanced RMDs cannot be constructed for the situations where p must be less than v then weakly balanced RMDs should be preferred. In this article, some generators are developed to generate circular weakly balanced RMDs in periods of two different sizes. To obtain the proposed designs, some construction procedures are also described for some of the cases where we could not develop generators.     

ON TRANSITION PROBABILITIES OF SKIP-FREE MARKOV CHAINS

Consider an ergodic Markov chain X(t) in continuous time with an infinitesimal matrix Q = (q_ij) defined on a finite state space {0, 1,…, N}. In this note, we prove that if X(t) is skip-free positive (negative, respectively), i.e., q_ij, = 0 for j > i+ 1 (i > j+ 1), then the transition probability p_ij(t) = Pr[X(t)=j | X(0) =i] can be represented as a linear combination of p_0N(t) (p^(m)_(N0)(t)), 0 ≤ m ≤N, where f^(m)(t) denotes the mth derivative of a function f(t) with f⁽⁰⁾(t) =f(t). If X(t) is a birth-death process, then p_ij(t) is represented as a linear combination of p_0N^(m)(t), 0 ≤m≤N - |i-j|.     

A-Optimal and MV-Optimal Incomplete Block Designs for Comparing Successive Treatments

Consider an incomplete block experiment in which observations are taken from t treatments using an incomplete block design with b blocks of size k < t. Suppose the interest is in estimating the differences of effects of successive treatments. This may occur, for example, if the treatments are different dosages or concentrations of a compound. This article presents A-optimal and MV-optimal incomplete block designs for estimating the the differences of successive treatment effects. Tables of optimal designs are given for k < t ≤ 5 with b ≤ 40.     

Circular balanced repeated measurement designs in periods of three different sizes

Abstract

Repeated measurement designs are widely used in medicine, pharmacology, animal sciences and psychology. If there is a restriction on the total number of treatments, some experimental units can receive on the total length of time while some experimental units can remain in the trial, then repeated measurements designs with unequal period sizes should be used. In this article, some infinite series are developed to generate the minimal balanced repeated measurement designs in periods of three different sizes p₁, p₂ and p₃, where 2?≤?p₃?<?p₂ ≤ 10 and p₂?<?p₁.     

Equi-information robust designs: Which designs are possible?

The effects of missing observations in a designed experiment are reviewed. Conditions are determined for a design to retain equal information, i.e. the same generalized variance of unknown parameters, when either any single or any pair of observations is lost. Some examples of designs with this property are given. Although there are many designs which retain equal information for the loss of exactly t observations, where t = 1,2,3,…, it is shown that it is not possible to obtain any design which retains equal information when any one and any two and also any three observations are missing.     

Optimal Designs for Approximating a Stochastic Process with Respect to a Minimax Criterion

We study the problem of approximating a stochastic process Y = {Y(t: t ∈ T} with known and continuous covariance function R on the basis of finitely many observations Y(t ₁,), …, Y(t _n ). Dependent on the knowledge about the mean function, we use different approximations ? and measure their performance by the corresponding maximum mean squared error sub _t∈T E(Y(t) ? ?(t))². For a compact T ? ? ^p we prove sufficient conditions for the existence of optimal designs. For the class of covariance functions on T ² = [0, 1]² which satisfy generalized Sacks/Ylvisaker regularity conditions of order zero or are of product type, we construct sequences of designs for which the proposed approximations perform asymptotically optimal.     

Attainability of the Upper Bounds for the Mean Past Lifetime of Parallel System Components

Among reliability systems, one of the basic systems is a parallel system. In this article, we consider a parallel system consisting of n identical components with independent lifetimes having a common distribution function F. Under the condition that the system has failed by time t, with t being 100pth percentile of F(t = F ^?1(p), 0 < p < 1), we characterize the probability distributions based on the mean past lifetime of the components of the system. These distributions are described in the form of a specific shape on the left of t and arbitrary continuous function on the right tail.     

Two-Level Designs in Blocks of Size Two in Which All Main Effects and Two-Factor Interactions Are Estimable

There are many problems in the real world for which it is necessary to perform two points in one block. In this situation, information about certain treatments may be indistinguishable from, or confounded with, blocks. If the experimenter wants to estimate all main effects and two-factor interactions in which two points are in one block, then how to perform the blocking schemes is an important topic to study. In this article, we combine several 2 ^k?p fractions from same or different family to obtain better combined designs requiring fewer runs than those appearing in the literature.     

Hypercubic designs and applications

In this paper we develop relatively easy methods for constructing hypercubic designs from symmetrical factorial experiments for t=v ^m treatments with v=2, 3. The proposed methods are easy to use and are flexible in terms of choice of possible block sizes.