Common Research Methods -Trials

Controlled Trial 

Definition/How it is conducted: A controlled trial describes research in which there is a comparison of two or more groups, one of them being a control condition, where participants do not receive any intervention, and others being experimental conditions, where participants are receiving some kind of intervention.

Purpose/Benefits: The comparison of the control condition to experimental conditions allows researchers to determine how effective certain treatments are depending on how participants respond.

Example: Examples of controls are: placebo pills, saline injections, positive control groups (meaning those receiving medicine which is already available and which is already benefiting them somewhat), behavioural intervention control groups (for example, those not receiving therapy versus those that are)

Benefits/Limitations: The researchers must ensure that they are using a proper control, to make sure that when they look at differences between the two groups it is because of the treatment and not because of other factors. This is why placebo pills are used, and why the trials are done blind (without the participant knowing if they are receiving the treatment or not) – to ensure that it is the activity of the drug/treatment that is causing a change, and not the expectation of getting any treatment at all that causes a difference in results.

Stages of a Clinical Trial (1-4):

Typically there are four phases of clinical trials, each with a different objective and a different group of people.

Phase 1 Clinical Trial: Safety

Definition/How it is conducted:  This is often the first use of this treatment/drug in humans. It can also be a drug that has been used for a different purpose that is now being used for this particular disease/treatment outcome. 

Purpose/Benefits: Phase 1 typically uses a small sample of participants to look at drug safety, dosage (i.e. to see how much of a drug/intervention you can safely give someone), and side effects. The benefit of a small sample is that it is cost efficient and if there are any adverse effects, they will be confined to a small number of people. 

Example: A clinical trial looking at a treatment for bipolar disorder had 16 healthy participants, and the researchers looked at how quickly the body absorbed and processed the drug. They also noted which participants reported any side effects. 

Benefits/Limitations: This phase is often done with healthy participants, so it is not specifically able to tell if it is helping a certain disease/population of interest. This phase is done with a small sample size, so it is a very early preliminary look at the drug, and results cannot be generalized or substantiated yet.

Phase 3 Clinical Trial: Is this drug better than the current treatment? 

Definition/How it is conducted: This phase focuses on comparing this drug to current treatment methods, and developing a greater understanding of the efficacy and side effects of the drug in an even larger group of participants (usually hundreds to thousands of people). 

Purpose/Benefits: This phase may study different populations, different dosages, and different combinations with other drugs in order to get a clear picture of what will happen when this drug is available to the full population. 

Example: A study looking at a maintenance treatment for opioid use had 287 participants and was done over 6-months to see if there is a statistically significant difference between the placebo group and the treatment group. 
Benefits/Limitations: The limitations of this phase are that there could be some long-term effects that are not captured in this phase.

Phase 2 Clinical Trial: Effectiveness

Definition/How it is conducted:  This phase focuses on how well the intervention can treat the condition in question, as well as continuing to monitor side effects and safety. 

Purpose/Benefits: Phase 2 is used to look at the dose needed to have a therapeutic effect without reaching levels of toxicity. Often in this phase, the new drug/treatment is given to some participants, while others remain on their current treatment or are given a placebo. This is done so the researchers can see a clear comparison between a person who is receiving the treatment and a person who is not. Because treatment has passed through phase 1 prior to starting phase 2, the researchers are now permitted to use a somewhat larger sample size in order to get a better picture of both effectiveness.

Example: A clinical trial with 210 participants compared how the use of a drug, as compared to a placebo, helped to reduce cocaine use.

Benefits/Limitations: This phase is often done with the disease population (for example, if it is a drug to treat cancer, it would be given to individuals with cancer), so side effects must be monitored rigorously.

Phase 4 Clinical Trial: Long-term outcomes and safety

Definition/How it is conducted: Phase 4 is conducted after the drug has been approved to be on the market. 

Purpose/Benefits: Researchers often continue to look at long-term effects as well as side effects and safety. Not all interventions go through a phase 4 clinical trial. 

Example: A study of 54 patients comparing prescription opioid replacement therapies that were already on the market looked at difference between two groups after 6 months of taking the therapies. 

Benefits/Limitations: Though it is essential to look at long-term effects of widely used drugs, once drugs are on the market, a phase 4 trial must make a strong case for why the drug should be pulled from the market/recalled. This can be a long process and some people may already have taken such drugs be



The standard to which comparisons are made in an experiment. The inclusion of a control group allows researchers to make conclusions about whether the treatment in question actually has an effect or not.


A substance that has no pharmacological action that is given in a clinical trial to compare to the active treatment and to control for the effect of the expectation of taking an active drug.

Statistical Significance

This means that the researchers determined that it is unlikely that the difference between the two groups happened purely by chance. Usually there is a standard that the scientific community has agreed on that means that it is unlikely enough to be considered “significant”.

Therapeutic Effect

When a drug or intervention has beneficial effects. Often in clinical trials you want to test how much of a therapeutic effect a drug can have without having toxic effects.

Randomized Control Trials

Randomized Control Trials: Single-Blind

Definition/How it is conducted: Single-blind means that participants are not told if they’ve been assigned to the control condition or experimental condition.

Purpose/Benefits: The benefit of a single-blind study is that, because participants are unaware if they are in the control or experimental condition, any effects of the treatment should be due to the treatment itself. If participants were to know the condition they were assigned to, this may alter participants’ behaviours and responses. 

Example: Researchers are testing the effectiveness of a pain medication. In this example, some participants will receive a placebo and the effects here will be compared against the effects reported by participants who received the real medication. As the research is single-blind, participants will not be told which condition they are in so that the effects are truly a reflection of the presence or absence of the medication, not the participants’ beliefs. 
Benefits/Limitations: Because the participant is unaware of if they received the real treatment or not, we can assume that the measured effect is solely due to the treatment itself, and not some other factor (like a participant’s beliefs or expectancies).

Randomized Control Trials: Double-Blind

Definition/How it is conducted: Double-blind reflects research in which both participants and researchers do not know which condition participants are in.

Purpose/Benefits: As there is a chance that researchers may interact with participants in a different way, or interpret data in a different way if they were to know the condition, double-blind studies prevent this issue.

Example: Researchers are testing the effectiveness of an anti-anxiety pill. In order to assure that the findings are accurate and not misinterpreted by the researchers’ biases, they use a double-blind method. This means that the participants do not know if they are receiving a placebo (in the control condition) or the anti-anxiety pill (in the experimental condition), and also the researchers do not know the condition the participant is assigned to. 
Benefits/Limitations: Because both participants and researchers are unaware of the participants’ condition, double-blind studies increase the chances that a study’s findings are valid and not misrepresented by researchers.


Definition/How it is conducted: A placebo is a substance or treatment given to a participant that should have no effect, but the participant is unaware of this. 

Purpose/Benefits: Placebos are compared to the effectiveness of another substance or treatment that is intended to have an effect on participants. Because the placebo should not affect the participant in any way, this is a good control to compare against.

Example: In order to test the effectiveness of a headache relief medication, researchers give one group of participants a sugar pill (the placebo) and give another group the true headache relief pill. This allows researchers to compare the effect of the headache relief pill to the placebo which should have minimal/no effect.
Benefits/Limitations: The benefit here is that the participants do not know whether they are given the placebo or the active treatment. Because the participants do not know, the measured effects from the placebo or the active treatment mainly come from the real effect (or no effect) associated with the substance they received. However, a key limitation is known as the placebo effect. Occasionally, when participants are given a placebo, they may actually believe that they have been given an active substance and this belief may actually cause changes to the participant. Because of this, those who receive a placebo (the control group) may report minor changes which, though not perfect, gives researchers a somewhat neutral group to compare an active treatment against.

Active Control

Definition/How it is conducted: An active control is a substance or treatment that delivers therapeutic effects to participants, but deemed more “neutral” than the substance or treatment it is being compared to. 

Purpose/Benefits: Active controls are used in cases in which it would be unethical to stop substances or treatments for individuals. They are used as a comparison to other substances or treatments to examine their effectiveness.

Example: Researchers want to test the effectiveness of a new therapy focused on preventing relapse. They need a group to compare these effects against and, because it would be dangerous for individuals to stop their current therapy, they have a control group remain in their standard treatment – the active control.

Benefits/Limitations: By comparing the effects of an active control to another type of treatment, researchers can understand the effectiveness of these newer treatments. However, a key limitation is that participants are affected by the active control, so researchers truly compare another treatment to a condition where there is no effect.


Control Condition

The group of participants against which comparisons are made. The control condition is compared against the experimental condition that receives an active treatment.

Experimental Condition

The group of participants that receive an active substance or treatment. The experimental condition is compared against the control condition who does not receive the treatment or substance of interest.