Comparator (active, placebo, dose-response, no treatment/usual care)

A comparator in clinical trials refers to a treatment, intervention, or condition that is used for comparison against the investigational treatment. This helps to assess the efficacy, safety, and potential benefits or harms of the new intervention. Comparators are essential to determine whether a new treatment is superior, equivalent, or non-inferior to existing therapies.

Types of Comparators:

• Active Comparator: This is a treatment or therapy that is already known to be effective and is used for comparison to the investigational treatment. Active comparators help determine whether the new intervention is better than or at least as effective as an existing, standard treatment.
• Placebo Comparator: A placebo is a substance or treatment that has no therapeutic effect but is used to create a baseline for comparison. It is often used when no standard treatment exists, or when assessing the psychological effects of the treatment itself. Placebo comparators are critical in assessing the true efficacy of the investigational therapy, ensuring the effects are not merely due to patients’ expectations. In phase 3 studies, or any active infection human study, an active and effective comparator is always administered instead of a placebo comparator because the disease is life-threatening, and it is immoral to withhold life-saving therapy.
• Dose-Response Comparator: In this comparison, the effect of different doses of the investigational treatment is assessed. It helps to understand the optimal dose that provides the maximum benefit with minimal adverse effects. This type of comparator is especially relevant when determining the dose range for further clinical trials.
• Standard of Care (SoC) Comparator: This comparator involves comparing the investigational treatment against the SoC. It is used to assess whether the new intervention offers any significant benefit over existing management strategies, particularly in cases where the current treatment is minimal or non-existent.

Each type of comparator has specific uses depending on the clinical question, the phase of the trial, and the available therapies for the condition being treated. Careful selection of comparators is vital for the trial’s design and for obtaining reliable, meaningful results.

Design of clinical trials of antibacterial agents for community-acquired bacterial pneumonia (Clinical Investigations London, 2011)

Usual and unusual care: existing practice control groups in randomized trials of behavioral interventions (Biopsychosocial Science and Medicine, 2011)

Comparator bias: why comparisons must address genuine uncertainties (James Lind Library Bulletin, 2012)

The importance and implications of comparator selection in pharmacoepidemiologic research (Current Epidemiology Reports, 2018)

The selection of comparators for randomized controlled trials of health-related behavioural interventions (Journal of Clinical Epidemiology, 2020)