# Crossover study > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Crossover_study > Markdown URL: https://mediated.wiki/source/Crossover_study.md > Source: https://en.wikipedia.org/wiki/Crossover_study > Source revision: 1345385167 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Research study in medicine}} {{redirect|Crossover experiment|the chemical reaction/mechanism analysis|crossover experiment (chemistry)}} {{more footnotes needed|date=April 2013}} In [medicine](/source/medicine), a '''crossover study''' or '''crossover trial''' is a [longitudinal study](/source/longitudinal_study) in which [subjects](/source/Human_subject_research) receive a sequence of different [treatments](/source/medical_case_management) (or exposures). While crossover studies can be [observational studies](/source/observational_studies), many important crossover studies are [controlled experiment](/source/controlled_experiment)s, which are discussed in this article. Crossover designs are common for experiments in many [scientific discipline](/source/scientific_discipline)s, for example [psychology](/source/Psychology), [pharmaceutical science](/source/pharmaceutical_science), and medicine. [Randomized](/source/Randomization), controlled crossover experiments are especially important in health care. In a randomized [clinical trial](/source/clinical_trial), the subjects are [randomly assigned](/source/Random_assignment) to different arms of the study which receive different treatments. When the trial has a [repeated measures design](/source/repeated_measures_design), the same measures are collected multiple times for each subject. A crossover trial has a repeated measures design in which each [patient](/source/patient) is assigned to a sequence of two or more treatments, of which one may be a [standard treatment](/source/standard_treatment) or a [placebo](/source/placebo). Nearly all crossover are designed to have "balance", whereby all subjects receive the same number of treatments and participate for the same number of periods. In most crossover trials each subject receives all treatments, in a random order. Statisticians suggest that designs should have four periods, which is more efficient than the two-period design, even if the study must be truncated to three periods.Vonesh & Chinchilli (1997)Jones & Kenward (2003) However, the two-period design is often taught in non-statistical textbooks, partly because of its simplicity. ==Analysis== The data is analyzed using the [statistical method](/source/Statistical_inference) that was specified in the [clinical trial protocol](/source/clinical_trial_protocol), which must have been approved by the appropriate [institutional review board](/source/institutional_review_board)s and [regulatory agencies](/source/Regulatory_agency) before the trial can begin. Most clinical trials are analyzed using repeated-measurements ANOVA ([analysis of variance](/source/analysis_of_variance)) or [mixed model](/source/mixed_model)s that include [random effect](/source/random_effect)s. In most longitudinal studies of human subjects, [patients](/source/patients) may withdraw from the trial or become "[lost to follow-up](/source/lost_to_follow-up)". There are statistical methods for dealing with such [missing-data](/source/Missing_data) and "[censoring](/source/Censoring_(statistics))" problems. An important method analyzes the data according to the principle of the [intention to treat](/source/Intention_to_treat_analysis). ==Advantages== A crossover study has two advantages over both a [parallel study](/source/parallel_study) and a non-crossover [longitudinal study](/source/longitudinal_study). First, the influence of [confounding](/source/Confounding_variable) [covariate](/source/covariate)s is reduced because each crossover patient serves as their own [control](/source/Scientific_control).Jones, B., & Kenward, M. G. (2003). Design and analysis of cross-over trials (2nd ed.). Boca Raton, Fla.: Chapman & Hall/CRC. In a randomized non-crossover study it is often the case that different treatment-groups are found to be [unbalanced](/source/Balance_(statistics)) on some covariates. In a controlled, [randomized](/source/randomized) crossover designs, such imbalances are implausible (unless [covariates were to change](/source/Time-varying_covariate) systematically during the study). Second, [optimal](/source/Optimal_design) crossover designs are [statistically efficient](/source/Efficiency_(statistics)), and so require fewer subjects than do non-crossover designs (even other repeated measures designs). Optimal crossover designs are discussed in the graduate textbook by Jones and Kenward and in the review article by Stufken. Crossover designs are discussed along with more general repeated-measurements designs in the graduate textbook by Vonesh and Chinchilli. ==Limitations and disadvantages== These studies are often done to improve the symptoms of patients with [chronic conditions](/source/Chronic_(medicine)). For curative treatments or rapidly changing conditions, cross-over trials may be infeasible or unethical. Crossover studies often have two problems: First is the issue of ["order" effects](/source/Repeated_measures_design), because it is possible that the order in which treatments are administered may affect the outcome. An example might be a drug with many adverse effects given first, making patients taking a second, less harmful medicine, more sensitive to any adverse effect. Second is the issue of "carry-over" between treatments, which [confounds](/source/Confounding) the [estimates](/source/estimates) of the [treatment effects](/source/Effect_size). In practice, "carry-over" effects can be avoided with a sufficiently long "wash-out" period between treatments. However, planning for sufficiently long wash-out periods requires expert knowledge of the [dynamics](/source/Psychodynamics) of the treatment, which is often unknown. == See also == * [Design of experiments](/source/Design_of_experiments) * [Glossary of experimental design](/source/Glossary_of_experimental_design) * [Randomized controlled trial](/source/Randomized_controlled_trial) * [Survival analysis](/source/Survival_analysis) * [N of 1 trial](/source/N_of_1_trial) * [Single-subject design](/source/Single-subject_design) ==Notes== {{Reflist}} == References == * M. Bose and A. Dey (2009). ''Optimal Crossover Designs''. World Scientific. {{ISBN|978-9812818423}} * D. E. Johnson (2010). Crossover experiments. ''WIREs Comp Stat'', 2: 620–625. [http://onlinelibrary.wiley.com/doi/10.1002/wics.109/abstract] * {{cite book | last = Jones | first = Byron |author2=Kenward, Michael G. | title = Design and Analysis of Cross-Over Trials | edition=Third| publisher = London: Chapman and Hall | year = 2014 |isbn=978-0412606403}} * K.-J. Lui, (2016). ''Crossover Designs: Testing, Estimation, and Sample Size''. Wiley. * Najafi Mehdi, (2004). ''Statistical Questions in Evidence Based Medicine''. New York: Oxford University Press. {{ISBN|0-19-262992-1}} * D. Raghavarao and L. Padgett (2014). ''Repeated Measurements and Cross-Over Designs.'' Wiley. {{ISBN|978-1-118-70925-2}} * D. A. Ratkowsky, M. A. Evans, and J. R. Alldredge (1992). ''Cross-Over Experiments: Design, Analysis, and Application.'' Marcel Dekker. {{ISBN|978-0824788926}} * Senn, S. (2002). ''Cross-Over Trials in Clinical Research,'' Second edition. Wiley. {{ISBN|978-0-471-49653-3}} * {{cite book| author=Stufken, J.| chapter=Optimal Crossover Designs |pages=63–90| title=Design and Analysis of Experiments | series=Handbook of Statistics| volume=13|editor1=Ghosh, S. |editor2=Rao, C. R. |editor2-link=Calyampudi Radhakrishna Rao | publisher=North-Holland| year=1996| isbn=978-0-444-82061-7}} * {{cite book | last1 = Vonesh | first1 = Edward F. | last2= Chinchilli |first2= Vernon G. | chapter=Crossover Experiments| pages=111–202|title =Linear and Nonlinear Models for the Analysis of Repeated Measurements | publisher = London: Chapman and Hall | year = 1997 |isbn= 978-0824782481}} {{Experimental design}} {{Statistics|collection|state=collapsed}} Category:Clinical research Category:Clinical trials Category:Design of experiments --- Adapted from the Wikipedia article [Crossover study](https://en.wikipedia.org/wiki/Crossover_study) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Crossover_study?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.