ABSTRACT In Statistics, the experiments are often used to try to identify the procedures that have significant impact on the input and output levels which factors should be manipulated to achieve the desired results. Design and analysis of experiments have been widely developed since the first works of Fisher, on the 20’s of the 20th century. Crossover Designs have been growing up fast and play arelevant role in areas such as Medicine, Pharmaceutical Sciences and Bio-Sciences in general. In our work we will present a historical review on Crossover Designs as well challenges on this issue for future research. DESCRIPTION as some new
Carla Noronha1, Teresa Oliveira.1,2
UAb – Universidade Aberta, Portugal, email@example.com CEAUL – Center of Statistics and Applications,firstname.lastname@example.org
Review and Challenges
BRIEF HISTORY Initially, crossover designs have wide application in agriculture century. XIX. According to Jones and Kenward (2003) early studies have occurred in 1853 due to a controversy that has arisen between Sir John Bennett Lawes, a British scientist and farmer Baron Justus von Liebig in Giessen, German chemist, researcher in thefield of Agricultural and Biological Chemistry , about the nutrition of plants (1840). Lawes, associated with Gilbert, English chemist, who was known to have spent almost his entire career trying to develop chemical methods that improve agriculture, a partnership that would last decades, argued that the plants needed the existing calcium in the bones of a more soluble for better nutrition.Eventually carry out a series of experiments at Rothamsted Experimental Station, the first season of experience existing farm, located in Hertfordshire, England, that these experiments consisted of animal bones dissolved in sulfuric acid for subsequent distribution to the crops. The patent was registered by Gilbert in 1842, under the name "super phosphate". TESTS These are some of the tests used in aCrossover Design Study: Paralel Crossover trial clinical trial Aprox. Normal Data Non Normal Data ADVANTAGES performance comparison between treatments envolving reps decrease in the size of the sample cost reduction increase in the power of precision removing the variability of the subject T-test 2 samples Wilcoxon or Mann Whitney crossover T-test pairs Wilcoxon
In a crossover trial subjects arerandomly allocated to study arms where each arm consists of a sequence of two or more treatments given consecutively. The simplest model is the AB/BA study. Subjects allocated to the AB study arm receive treatment A first, followed by treatment B, and vice versa in the BA arm. Crossover trials allow the response of a subject to treatment A to be contrasted with the same subject's response totreatment B. Removing patient variation in this way makes crossover trials potentially more efficient than similar sized, parallel group trials in which each subject is exposed to only one treatment. In theory treatment effects can be estimated with greater precision given the same number of subjects. Crossover trials are generally restricted to the study of short term outcomes in chronic diseases orprocesses because the disease or process needs to persist long enough for the investigator to expose the subject to each of the experimental treatments and measure the response. Also the treatment must be one that does not permanently alter the disease or process under study. The principal drawback of the crossover trial is that the effects of one treatment may “carry over” and alter the response tosubsequent treatments. The usual approach to preventing this is to introduce a washout (no treatment) period between consecutive treatments which is long enough to allow the effects of a treatment to wear off. A variation is to restrict outcome measurement to the latter part of each treatment period. Investigators then need to understand the likely duration of action of a given treatment and...
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