In selecting a control group, which statement best describes acceptable comparisons?

• A. Controls may be placebo, no treatment, an active comparator, or a different dose of the experimental drug.
• B. Controls must always be placebo only.
• C. Controls must be treated as historical controls.
• D. Controls must be no treatment only.

Answer: (A)

In a trial, the control group should provide a meaningful baseline to determine whether the experimental treatment has added benefit or risk. That means the comparison can be a placebo, a no-treatment condition, an active comparator (standard therapy), or a different dose of the experimental drug to explore dose-response. Each option serves a purpose: placebo or no treatment helps show the drug’s effect beyond natural disease progression; an active comparator assesses relative efficacy against established therapy; a different dose helps find the optimal amount and safety profile. Historical controls are not acceptable for most prospective trials due to bias from non-concurrent data. Limiting controls to only no treatment or placebo ignores scenarios where standard care or dose-ranging is necessary.