Successful blinding is not trivial. In a placebo-controlled trial, a placebo must be created to look, smell, and taste just like the intervention. For example a concern for a trial evaluating the effects of minocycline on cognitive function may be that minocycline can cause a change in skin pigmentation, thus unblinding the intervention. Blinding can be challenging or impractical in many trials. For example surgical trials often cannot be double-blind for ethical reasons. The effects of the intervention may also be a threat to the blind. For example, an injection site reaction of swelling or itching may indicate an active intervention rather than a sham injection. Researchers could then consider using a sham injection that induces a similar reaction