What is a Randomized Control Trial (RCT)?

A randomized control trial (RCT) is a type of study design that involves randomly assigning participants to either an experimental group or a control group to measure the effectiveness of an intervention or treatment.

Randomized Controlled Trials (RCTs) are considered the “gold standard” in medical and health research due to their rigorous design.

Control Group

A control group consists of participants who do not receive any treatment or intervention but a placebo or reference treatment. The control participants serve as a comparison group.

The control group is matched as closely as possible to the experimental group, including age, gender, social class, ethnicity, etc.

Because the participants are randomly assigned, the characteristics between the two groups should be balanced, enabling researchers to attribute any differences in outcome to the study intervention.

Since researchers can be confident that any differences between the control and treatment groups are due solely to the effects of the treatments, scientists view RCTs as the gold standard for clinical trials.

Random Allocation

Random allocation and random assignment are terms used interchangeably in the context of a randomized controlled trial (RCT).

Both refer to assigning participants to different groups in a study (such as a treatment group or a control group) in a way that is completely determined by chance.

The process of random assignment controls for confounding variables, ensuring differences between groups are due to chance alone.

Without randomization, researchers might consciously or subconsciously assign patients to a particular group for various reasons.

Several methods can be used for randomization in a Randomized Control Trial (RCT). Here are a few examples:

1. Simple Randomization: This is the simplest method, like flipping a coin. Each participant has an equal chance of being assigned to any group. This can be achieved using random number tables, computerized random number generators, or drawing lots or envelopes.
2. Block Randomization: In this method, participants are randomized within blocks, ensuring that each block has an equal number of participants in each group. This helps to balance the number of participants in each group at any given time during the study.
3. Stratified Randomization: This method is used when researchers want to ensure that certain subgroups of participants are equally represented in each group. Participants are divided into strata, or subgroups, based on characteristics like age or disease severity, and then randomized within these strata.
4. Cluster Randomization: In this method, groups of participants (like families or entire communities), rather than individuals, are randomized.
5. Adaptive Randomization: In this method, the probability of being assigned to each group changes based on the participants already assigned to each group. For example, if more participants have been assigned to the control group, new participants will have a higher probability of being assigned to the experimental group.

Computer software can generate random numbers or sequences that can be used to assign participants to groups in a simple randomization process.

For more complex methods like block, stratified, or adaptive randomization, computer algorithms can be used to consider the additional parameters and ensure that participants are assigned to groups appropriately.

Using a computerized system can also help to maintain the integrity of the randomization process by preventing researchers from knowing in advance which group a participant will be assigned to (a principle known as allocation concealment). This can help to prevent selection bias and ensure the validity of the study results.

Blinding (Masking)

Binding, or masking, refers to withholding information regarding the group assignments (who is in the treatment group and who is in the control group) from the participants, the researchers, or both during the study.

A blinded study prevents the participants from knowing about their treatment to avoid bias in the research. Any information that can influence the subjects is withheld until the completion of the research.

Blinding can be imposed on any participant in an experiment, including researchers, data collectors, evaluators, technicians, and data analysts.

Good blinding can eliminate experimental biases arising from the subjects’ expectations, observer bias, confirmation bias, researcher bias, observer’s effect on the participants, and other biases that may occur in a research test.

In a double-blind study, neither the participants nor the researchers know who is receiving the drug or the placebo. When a participant is enrolled, they are randomly assigned to one of the two groups. The medication they receive looks identical whether it’s the drug or the placebo.

Figure 1 . Evidence-based medicine pyramid. The levels of evidence are appropriately represented by a pyramid as each level, from bottom to top, reflects the quality of research designs (increasing) and quantity (decreasing) of each study design in the body of published literature. For example, randomized control trials are higher quality and more labor intensive to conduct, so there is a lower quantity published.

Advantages

Prevents bias

In randomized control trials, participants must be randomly assigned to either the intervention group or the control group, such that each individual has an equal chance of being placed in either group.

This is meant to prevent selection bias and allocation bias and achieve control over any confounding variables to provide an accurate comparison of the treatment being studied.

Because the distribution of characteristics of patients that could influence the outcome is randomly assigned between groups, any differences in outcome can be explained only by the treatment.

High statistical power

Because the participants are randomized and the characteristics between the two groups are balanced, researchers can assume that if there are significant differences in the primary outcome between the two groups, the differences are likely to be due to the intervention.

This warrants researchers to be confident that randomized control trials will have high statistical power compared to other types of study designs.

Blinding

Since the focus of conducting a randomized control trial is eliminating bias, blinded RCTs can help minimize any unconscious information bias.

In a blinded RCT, the participants do not know which group they are assigned to or which intervention is received. This blinding procedure should also apply to researchers, health care professionals, assessors, and investigators when possible.

“Single-blind” refers to an RCT where participants do not know the details of the treatment, but the researchers do.

“Double-blind” refers to an RCT where both participants and data collectors are masked of the assigned treatment.

Limitations

Costly and Timely

Some interventions require years or even decades to evaluate, rendering them expensive and time-consuming.

It might take an extended period of time before researchers can identify a drug’s effects or discover significant results.

Requires large sample size

There must be enough participants in each group of a randomized control trial so researchers can detect any true differences or effects in outcomes between the groups.

Researchers cannot detect clinically important results if the sample size is too small.

Change in population over time

Because randomized control trials are longitudinal in nature, it is almost inevitable that some participants will not complete the study, whether due to death, migration, non-compliance, or loss of interest in the study.

This tendency is known as selective attrition and can threaten the statistical power of an experiment.

Ethics

Randomized control trials are not always practical or ethical, and such limitations can prevent researchers from conducting their studies.

For example, a treatment could be too invasive, or administering a placebo instead of an actual drug during a trial for treating a serious illness could deny a participant’s normal course of treatment. Without ethical approval, a randomized control trial cannot proceed.

Fictitious Example

An example of an RCT would be a clinical trial comparing a drug’s effect or a new treatment on a select population.

The researchers would randomly assign participants to either the experimental group or the control group and compare the differences in outcomes between those who receive the drug or treatment and those who do not.

Real-life Examples

• Preventing illicit drug use in adolescents: Long-term follow-up data from a randomized control trial of a school population (Botvin et al., 2000).
• A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure (Demetroulis et al., 2001).
• A randomized control trial to evaluate a paging system for people with traumatic brain injury (Wilson et al., 2009).
• Prehabilitation versus Rehabilitation: A Randomized Control Trial in Patients Undergoing Colorectal Resection for Cancer (Gillis et al., 2014).
• A Randomized Control Trial of Right-Heart Catheterization in Critically Ill Patients (Guyatt, 1991).
• Preventing illicit drug use in adolescents: Long-term follow-up data from a randomized control trial of a school population (Botvin et al., 2000).
• Berry, R. B., Kryger, M. H., & Massie, C. A. (2011). A novel nasal excitatory positive airway pressure
  (EPAP) device for the treatment of obstructive sleep apnea: A randomized controlled trial. Sleep, 34,
  479–485.
• Gloy, V. L., Briel, M., Bhatt, D. L., Kashyap, S. R., Schauer, P. R., Mingrone, G., . . . Nordmann, A. J. (2013,
  October 22). Bariatric surgery versus non-surgical treatment for obesity: A systematic review and
  meta-analysis of randomized controlled trials. BMJ, 347.
• Streeton, C., & Whelan, G. (2001). Naltrexone, a relapse prevention maintenance treatment of alcohol
  dependence: A meta-analysis of randomized controlled trials. Alcohol and Alcoholism, 36 (6), 544–552.

References

Akobeng, A.K., Understanding randomized controlled trials. Archives of Disease in Childhood, 2005; 90: 840-844.

Bell, C. C., Gibbons, R., & McKay, M. M. (2008). Building protective factors to offset sexually risky behaviors among black youths: a randomized control trial. Journal of the National Medical Association, 100 (8), 936-944.

Bhide, A., Shah, P. S., & Acharya, G. (2018). A simplified guide to randomized controlled trials. Acta obstetricia et gynecologica Scandinavica, 97 (4), 380-387.

Botvin, G. J., Griffin, K. W., Diaz, T., Scheier, L. M., Williams, C., & Epstein, J. A. (2000). Preventing illicit drug use in adolescents: Long-term follow-up data from a randomized control trial of a school population. Addictive Behaviors, 25 (5), 769-774.

Demetroulis, C., Saridogan, E., Kunde, D., & Naftalin, A. A. (2001). A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Human Reproduction, 16 (2), 365-369.

Gillis, C., Li, C., Lee, L., Awasthi, R., Augustin, B., Gamsa, A., … & Carli, F. (2014). Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer. Anesthesiology, 121 (5), 937-947.

Globas, C., Becker, C., Cerny, J., Lam, J. M., Lindemann, U., Forrester, L. W., … & Luft, A. R. (2012). Chronic stroke survivors benefit from high-intensity aerobic treadmill exercise: a randomized control trial.
Neurorehabilitation and Neural Repair, 26
(1), 85-95.

Guyatt, G. (1991). A randomized control trial of right-heart catheterization in critically ill patients. Journal of Intensive Care Medicine, 6 (2), 91-95.

MediLexicon International. (n.d.). Randomized controlled trials: Overview, benefits, and limitations. Medical News Today. Retrieved from https://www.medicalnewstoday.com/articles/280574#what-is-a-randomized-controlled-trial

Wilson, B. A., Emslie, H., Quirk, K., Evans, J., & Watson, P. (2005). A randomized control trial to evaluate a paging system for people with traumatic brain injury. Brain Injury, 19 (11), 891-894.