Randomized Controlled Trials (RCTs) in Research

Randomized Controlled Trials (RCTs)

• RCTs are the "gold standard" of individual research studies, providing sound evidence about treatment efficacy.
• In RCTs, subjects are randomly allocated to treatment options to ensure unbiased allocation.
• The choice of comparison group affects how we interpret evidence from a trial.
• Comparison of an active agent with an inert substance or placebo is likely to give a more favorable result than comparison with another active agent.
• Comparison with 'usual care' is common when an intervention is a program of care.

Randomization in RCTs

• Randomization ensures that the subjects' characteristics do not affect which treatment they receive.
• Allocation to treatment is unbiased, and differences between groups can be attributed to the treatments alone.
• Randomization makes blindness possible.
• Random allocation is usually done using a computer program based on random numbers.

Blinding in RCTs

• Blinding is when the treatment allocation is concealed from either the subject or assessor or both.
• Blinding is done to avoid conscious or unconscious bias in reported outcomes.
• A trial is double-blind if neither the subject nor the assessor knows which treatment is being given.
• A trial is single-blind if the treatment allocation is concealed from either the subject or the assessor but not both.

Intention to Treat Analysis

• Intention-to-treat (ITT) analysis is the primary analysis of RCTs, where subjects are included in the group to which they were originally allocated.
• ITT analysis provides an unbiased comparison of the treatments.
• If patients change treatment, they should still be analyzed together with patients in their original, randomly allocated group.

Example of RCT

• An RCT evaluated whether introducing allergenic foods to babies at 3 months vs 6 months affects allergy.
• 1303 exclusively breastfed three-month-old infants were randomly assigned to introduce six allergenic foods or to follow the UK recommendation of exclusive breastfeeding to around six months of age.

Limitations of Design

• The choice of control group affects the comparisons between cases and controls.
• Exposure to risk factor data is usually collected retrospectively and may be incomplete, inaccurate, or biased.

Case Control Study

• A case-control study investigates the association between a risk factor and a disease.
• Subjects are selected based on their disease status (cases) and compared to a control group.
• Example: A study investigated the association between genitourinary infections in the month before conception to the end of the first trimester, and gastroschisis.

Cohort Study

• A cohort study is an observational study that aims to investigate causes of disease or factors related to a condition.
• It starts with an unselected group of individuals who are followed up for a set period of time.
• Example: A cohort study examined the relationship between BMI and all-cause mortality in 527,265 U.S. men and women in the National Institutes of Health–AARP cohort.

Difficulties with Cohort Studies

• A large number of subjects is needed to obtain enough individuals who get the disease or condition.
• The length of follow-up may be substantial to get enough diseased individuals.
• There is difficulty in maintaining contact with subjects, particularly if the follow-up is lengthy.
• The resources required may be very high.

Learn about the benefits and methods of Randomized Controlled Trials, the gold standard of individual research studies, and how they provide unbiased evidence about treatment efficacy.