Crossover designs

Crossover design A clinical trial design in which patients receive, in sequence, the treatment (or the control), and then after a specified time, receive the opposite arm of the trial. This allows patients to serve as their own controls. Randomization should be... 

Randomized Crossover Design Subjects are divided into placebo and active groups. After some time these two groups crossover the initial placebo group now becoming the active group and vice versa. There may be a washout period before the crossover to enable the effect of the placebo and active to wash out. This method requires a smaller number of subjects and is useful in cases for studying rare or more stable illnesses. 

Key - Ineffective, + Effective, CD Crossover design, DB Double blind, GA General anesthesia (postoperative nausea), HG Hyperemesis gravidarum,... 

Subjects are randomised to receive A or P on different occasions in a crossover design. 

Tables 4.3 and 4.4 show examples of parallel and crossover designs, with two alternating...

A preliminary assessment of the effect of food on pharmacokinetics can generally be studied in a single-dose, two-arm, randomised, crossover design. Preliminary information can often be obtained by including a fed occasion in the first, dose-escalating study. This will be insuffi-cent for registration purposes, which require an adequately powered study performed with the final formulation, but the information should be sufficient to indicate whether there is need for restrictions on dosing relative to meals in repeat-dose studies in healthy volunteers and patient clinical trials. 

Crossover designs are susceptible to carry-over effects, that is, the treatment effect from the first period has not worn off at the time of conducting the second period. Tests of analysis can detect carry-over effects, but it is too late then to modify the design. Similarly, period effects may confound the interpretation of cross-over studies, that is, the order in which one treatment occurs in a sequence compared with another influences the response to early treatment. Randomisation usually, but not always, precludes the effect. 

There are two circumstances in which patients act as their own control crossover designs and pre-test, post-test designs. 

Crossover designs The essential feature of a crossover design is that each patient receives at least two of the treatments under consideration. In the simplest two-period two-treatment crossover, with treatments A and B, patients are allocated to one of the treatment sequence AB. As is often the case the most succinct statement of advantages and disadvantages of crossover design is to be found in HiU. 

This latter disadvantage led the crossover design to be described as not the design of choice in clinical trials, where unequivocal evidence of treatment effects is required. Over the last 25 years, many statisticians have been more positive about the place of the crossover design in clinical research. ... 

Of course, the control in a crossover design is not contemporaneous because it occurs within different treatment periods. Nonetheless, such trials are randomised and the effect of differential period effects can be allowed for in the analysis and does not give rise to bias in treatment estimates. 

Food and Drug Administration. A report on the two-period crossover design and its applicability in trials of clinical effectiveness. Minutes of... 

Miller et 1988 n = 12 adolescents S. n = 6 n = 6 Age 10-17 years Treatments in randomized order with 3-week washout period 1. 250-mg elemental Ca as CaCOs (enriched with Ca) Compare CaAbs for CCM versus CaCOa using dual isotope mettiod using a crossover design and measured urinary isotope ratio after 24 h Mean FxAbs SEM results 1. CCM 36.2 2.7% (range 27.3-53.3%) 2. CaC03 26.4 2J2% (range 12.8-39.6%) Ctest for FxAbs difference CCM > CaCOa (p <. 03)... 

Assessed the effect of oligofructose or inulin -h oligofructose vs placebo on Ca Abs in a balanced, randomized, crossover design using dual isotope... 

Assessed benefits due to enhanced Ca absorption resulting from the addition of modest amounts of long-chain inulin enriched widi oligofructose in a balanced randomized crossover design. Ca Abs measured using dual-isotope methodology via the ratio of Ca with Ca (intravenous tracer) as it appeared in urine collected over 48 hr. 

In another study, the difference in fractional absorption between Ca from CCM and CaCOa was tesfed in 12 healthy adolescents (6 males and 6 females) aged 10-17 years using a 2-period crossover design (Miller et al., 1988). The average ( SEM) dietary Ca intake based on a food frequency quesfionnaire was 600.4 65.7 mg/day. The order of Ca supplementation for groups was randomized and for each treatment two tablets were ingested with a standardized breakfast. Each tablet contained... 

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