A control group refers to a group of clinical trial participants who do not receive the drug or treatment being studied in the trial but instead receive standard of care or a placebo.
The control group plays a fundamental role in clinical trials as they serve as a baseline for determining the effectiveness of the study treatment. A clinical trial can’t be ethically justified unless it can produce scientifically reliable results, which is what a control group helps to do. If participants in an experimental group have a better outcome than those in the control group, than the intervention has been effective.
The World Medical Association (WMA) Declaration of Helsinki says: “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic and therapeutic methods. This does not exclude the use of placebo or no treatment in studies where no proven prophylactic, diagnostic or therapeutic method exists.”
Randomization and Blinding
Randomization and Blinding are two methods that are commonly used to minimize the risk of bias and to ensure that the test treatment and control groups are treated the same throughout the duration of the clinical trial.
Randomization
The participants are randomly divided into two groups (an experimental group and a control group) which ensures that the participant population is similar in both the test and control groups. Randomization is an effective way to collect valuable and accurate data.
Blinding
The method of blinding eliminates bias during a clinical trial. All participants should be treated the same during the trial, except for when receiving the test and control treatment.
The two types of blinding include:
Single-Blind: The participants in the trial aren’t aware of which intervention they are receiving (the experimental treatment or a placebo), but the researchers and medical staff are aware of who’s receiving what treatment.
Double-Blind: The most commonly used during a clinical trial. Both the participants and the researchers don’t know which intervention the participants are receiving.
Types of Control Groups
Control groups are classified depending on the type of treatment used and the method of determining who will be in the group.
Placebo Concurrent Control Group
The Placebo control group is selected using the process of blinding and randomization and are given a ‘dummy treatment’ (a sugar pill that looks like the investigational medication). Placebo control groups show the difference between the treatments and help to prove the efficacy and effectiveness of the investigational medication/treatment. The Placebo control group is amongst the most commonly used in clinical trials and is considered the most thorough test of treatment efficacy for evaluating how effective a medical treatment is.
No Treatment Concurrent Control
Participants are randomly assigned to ‘no treatment’ and ‘treatment’ groups. Both the participants and the trial investigators are aware of which group the participants are assigned to. This control group is only suitable to use when it is impossible to use a double-blind and only when the final results are guaranteed to be objective and not influenced by various factors.
Dose-Response Concurrent Control
A randomized, fixed-dose control group where participants are randomly put into one of several fixed-dose groups. Participants either take a fixed dose or raised to that dose gradually (comparison is made during final dose).
Active (Positive) Concurrent Control
Participants are randomly assigned to test treatment or active control treatment. This control group has two distinct objectives:
- To show efficacy of the investigational treatment by proving that it is as effective as the current, accepted treatment.
- Shows that the investigational treatment is more effective than the active control.
External Control (Including Historical Control)
An externally controlled group which compares a group of participants who take the investigational treatment to participants outside of the study instead of an internal control group. The external control group are either a group of patients who were treated at an earlier time (historical control) or a group who are treated at the same time, but at another trial site. The external groups may be defined (a specific group of participants) or non-defined (a comparator group made up of people with medical knowledge).
Multiple Control Groups
When at least two different control groups are used in a clinical trial (an active control and a placebo). The use of multiple control groups is becoming more common in clinical trials. Several doses of test drug and several doses of an active control, with or without a placebo are used. This control group is useful for actively comparing the potency of two drugs.
Important Factors
- There is no difference between the inclusion/exclusion criteria for the two groups (all variables must be kept as similar as possible).
- Selection of experimental and control groups are random.
- The results of the two groups have to be different enough to prove that the difference hasn’t occurred by chance.
- The investigational treatment is compared with the standard treatment that is already proven to be effective. This determines whether the investigational treatment works better than the one already on the market.
- A randomized controlled trial is a scientific tool for evaluating treatment in groups of research participants with the sole aim of improving medical treatment in the future.