Which practice most directly reduces bias by preserving randomization and blinding in a trial?

• A. Increasing sample size
• B. Using historical controls
• C. Using an open-label design
• D. Implementing a double-blind, placebo-controlled design

Answer: (D)

Preserving both randomization and blinding minimizes bias by keeping participants and investigators unaware of who receives the active treatment, while the assignment itself is determined randomly. A double-blind, placebo-controlled design ensures that the random allocation is concealed during enrollment and that neither the participants nor the researchers know which group each person is in. This reduces performance bias (care or behavior that could be influenced by knowledge of treatment) and detection bias (outcome assessment that could be influenced by expectations). The placebo control helps maintain the blind by giving all participants a similar experience, so observed effects are more likely due to the treatment itself rather than expectations or differential care.

Increasing sample size improves precision and power but does not inherently protect randomization or blinding. Using historical controls replaces randomized comparisons with non-random groups and introduces substantial bias. An open-label design reveals the treatment, destroying blinding and increasing bias risk.