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I wonder please if cross over trials are only applicable to drug treatments ? or maybe also to vaccines ? I can't imagine they are appropriate for surgical interventions or for devices, laser or radiotheray interventions ?? many thanks for views

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Crossover trials are used most often for drug treatments but the design can be suitable for the study of other interventions that do not permanently alter the disease or process under study.

In a 2009 publication about 519 randomized trials published in December 2000, Mills et al. identified 127 that were crossover trials. They reported that:

"In total, 30/127 (24%) trials measured drug pharmacokinetics, 36/127 (28%) were non-drug interventions while almost half, 61/127 (48%) were studies of drug efficacy."

Mills EJ, Chan AW, Wu P, Vail A, Guyatt GH, Altman DG. Design, analysis, and presentation of crossover trials. Trials. 2009;10:27. Published 2009 Apr 30. doi:10.1186/1745-6215-10-27 https://pubmed.ncbi.nlm.nih.gov/19405975/

A published systematic assessment of the topic areas for more recent crossover trials could not be identified.

PERMANENT ALTERATION OF THE DISEASE OR PROCESS

The crossover trial is not suitable for the study of a treatment that permanently alters the disease or process under study.

See Sibbald B, Roberts C. Understanding controlled trials. Crossover trials. BMJ. 1998;316(7146):1719. doi:10.1136/bmj.316.7146.1719 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113275/

“…..the treatment must be one that does not permanently alter the disease or process under study.”

Thus, crossover trials would not be suitable for the study of surgical procedures, other procedures (like laser and radiotherapy) that alter body organs or structures, or interventions that involve the permanent implantation of a device.

But there are procedures whose effect is not permanent. One example of such a procedure is acupuncture. Crossover trials can be suitable in the study of acupuncture and this design has been used to evaluate acupuncture. Here is a published example.

https://pmlegacy.ncbi.nlm.nih.gov/pubmed/28060186

There are devices whose effect is not permanent. Examples are blood pressure monitoring devices.

VACCINES

Crossover trials have been used to study vaccines. Published examples are:

Kotloff KL, Wasserman SS, O'Donnell S. Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial. Infect Immun. 1992;60:4430-2. PubMed PMID: 1398956; PubMed Central PMCID: PMC257485.

Bryan JP, Henry CH, Hoffman AG. Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. Vaccine. 2000;19:743-50. PubMed PMID: 11115695.

Nicholson KG, Nguyen-Van-Tam JS. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Lancet. 1998 Jan;351(9099):326-31. PubMed PMID: 9652613.

GENERAL USES OF CROSSOVER DESIGNS

Experts advise that:

“Crossover trials are generally restricted to the study of short term outcomes in chronic diseases or processes 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.”

See Sibbald B, Roberts C. Understanding controlled trials. Crossover trials. BMJ. 1998;316(7146):1719. doi:10.1136/bmj.316.7146.1719 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113275/

NUTRITION

Crossover trials to study nutrition are common. Some recent (Fall 2020) published examples are:

Cros J, Bidlingmeyer L, Rosset R, et al. Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women. Nutr Diabetes. 2020;10:1. doi: 10.1038/s41387-019-0104-y. PubMed PMID:32066654; PubMed Central PMCID: PMC7026094.

Koutsos A, Riccadonna S, Ulaszewska MM, et al. Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: a randomized, controlled, crossover trial. Am J Clin Nutr. 2020;111:307-318. doi: 10.1093/ajcn/nqz282. PubMed PMID: 31840162; PubMed Central PMCID: PMC6997084.

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