Study DesignGlossary Term
ICH E6(R3) Section 6.4
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.
The double-blind design represents the gold standard for controlled clinical trials, extending concealment of treatment assignments to both participants and the investigators who treat them and assess their outcomes. This comprehensive blinding provides the strongest protection against bias, ensuring that neither participant expectations nor investigator preconceptions can influence behavior, reporting, or assessment. When properly executed, double-blind studies provide the most credible evidence of treatment effects.
Successful double-blinding requires meticulous attention to ensuring that all aspects of the treatment experience are identical across study arms. Investigational products and placebos must be indistinguishable in appearance, packaging, and administration. Procedures must prevent inadvertent unblinding through laboratory values, side effects, or other clues. Interactive response systems can manage randomization and treatment assignment without revealing the blind. Careful planning addresses potential unblinding scenarios and establishes procedures to maintain concealment to the greatest extent possible.
Despite its advantages, double-blinding is not always achievable or appropriate. Treatments with distinctive side effects, different modes of administration, or different dosing schedules may make true double-blinding impossible. In such cases, approaches like the double-dummy technique, in which participants receive both an active and a placebo formulation to maintain blinding, can sometimes preserve concealment. When double-blinding cannot be maintained, trials should employ alternative protections such as blinded outcome assessment, independent adjudication committees, or objective endpoints that are resistant to bias.
Pivotal efficacy trial
"The Phase III registration trial was conducted as a double-blind, placebo-controlled study in which identically appearing capsules were dispensed according to the randomization schedule, with neither participants nor site staff aware of treatment assignments."
Double-dummy design
"Because the investigational drug was administered as a daily tablet while the active comparator required weekly injection, the trial employed a double-dummy design in which all participants received both tablets and injections, with appropriate placebos maintaining the blind."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
The time required for the concentration or amount of a drug in the body to decrease by one-half, reflecting the combined effects of elimination processes.
ICH E6(R3) Section 6.4
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.
The double-blind design represents the gold standard for controlled clinical trials, extending concealment of treatment assignments to both participants and the investigators who treat them and assess their outcomes. This comprehensive blinding provides the strongest protection against bias, ensuring that neither participant expectations nor investigator preconceptions can influence behavior, reporting, or assessment. When properly executed, double-blind studies provide the most credible evidence of treatment effects.
Successful double-blinding requires meticulous attention to ensuring that all aspects of the treatment experience are identical across study arms. Investigational products and placebos must be indistinguishable in appearance, packaging, and administration. Procedures must prevent inadvertent unblinding through laboratory values, side effects, or other clues. Interactive response systems can manage randomization and treatment assignment without revealing the blind. Careful planning addresses potential unblinding scenarios and establishes procedures to maintain concealment to the greatest extent possible.
Despite its advantages, double-blinding is not always achievable or appropriate. Treatments with distinctive side effects, different modes of administration, or different dosing schedules may make true double-blinding impossible. In such cases, approaches like the double-dummy technique, in which participants receive both an active and a placebo formulation to maintain blinding, can sometimes preserve concealment. When double-blinding cannot be maintained, trials should employ alternative protections such as blinded outcome assessment, independent adjudication committees, or objective endpoints that are resistant to bias.
Pivotal efficacy trial
"The Phase III registration trial was conducted as a double-blind, placebo-controlled study in which identically appearing capsules were dispensed according to the randomization schedule, with neither participants nor site staff aware of treatment assignments."
Double-dummy design
"Because the investigational drug was administered as a daily tablet while the active comparator required weekly injection, the trial employed a double-dummy design in which all participants received both tablets and injections, with appropriate placebos maintaining the blind."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
The time required for the concentration or amount of a drug in the body to decrease by one-half, reflecting the combined effects of elimination processes.