• A study design where all patients from a population of interest are initially assigned to one of two groups, one group who gets exposed to the intervention or a second group that does not get exposed to the intervention. 
• After a period of time, an evaluation of the outcome is done and the patients from both groups undergo a period of washout so that the effect from the initial group intervention has been removed. Once this occurs, the subjects will then cross-over into the other group where the process starts over.
  
• This study design provides the advantage of reducing the variability in outcome measures from outside confounders because each patient will serve as his or her own control.

• Reduced influence by confounders since patients serve as their own controls
• Reduced variability in the outcome(s) being measured, thus increasing the precision of estimation
• Smaller sample sizes required
• Having the opportunity to receive both treatments can sometimes be attractive for subjects

• Cannot be done when the subjects can only receive one treatment
• Assumption of no carryover effects (from washout period) is difficult to sometimes accurately test
• May take longer than a randomized clinical trial since patients have to cross over into each arm after an appropriate washout period
• Can be subject to period effects where differences in the effectiveness of an intervention can occur due to the passage of time.  For example:
• Development of tolerance
• Resistance
• Dropouts
• Changes in the disease process being evaluated or treated
  

• Cohort Study
• Case-Control Study
• Randomized Clinical Trial
  

• Noordij M et al. Study designs in clinical research. Nephron Clin Pract 2009;113(3):c218-21.
  
• Tinmouth A et al. Interventional trials: an overview of design alternatives. Transfusion 2007;47:565-67.

Editors:

• Anthony J. Busti, MD, PharmD, FNLA, FAHA
  

Last Reviewed:  July 2015