Types of trials

Different Types of Trials

Randomized controlled trials (RCTs) can be categorized based on study design, purpose, randomization method, and special design features.

1. Based on Study Design

a. Parallel-Group Randomized Trial

Participants are randomized into two or more groups that receive different interventions.
Example: A trial comparing Drug A vs. placebo, with each participant assigned to only one group.

b. Crossover Randomized Trial

Participants receive multiple interventions in a sequential order, with a washout period in between.
Example: Participants receive Drug A for a period, then switch to Drug B and vice versa.
Useful when within-subject comparisons are needed.

c. Factorial Randomized Trial

Tests multiple interventions simultaneously by randomizing participants into different combinations of treatments.
Example: A 2×2 factorial trial testing Drug A vs. placebo and Exercise vs. No Exercise in four groups.
Efficient for studying interaction effects between interventions.

d. Cluster Randomized Trial

Entire groups (e.g., hospitals, schools, communities) are randomized instead of individuals.
Example: Randomizing clinics to provide standard care vs. an enhanced HIV prevention program.
Useful for population-level interventions.

e. Stepped-Wedge Randomized Trial

All participants eventually receive the intervention, but the rollout is randomized in phases.
Example: A new vaccine program introduced to different regions at different times.
Useful when gradual implementation is required.

2. Based on Purpose

a. Superiority Trial

Tests whether one intervention is better than another (e.g., new drug vs. standard care).

b. Non-Inferiority Trial

Determines whether a new intervention is not worse than an existing treatment by more than a specified margin.

c. Equivalence Trial

Tests whether two treatments produce similar effects within a predefined range.

d. Pragmatic Trial

Evaluates interventions under real-world conditions to assess their effectiveness in routine practice.

e. Explanatory Trial

Conducted in ideal, controlled settings to test an intervention’s biological efficacy.

3. Based on Randomization Method

a. Simple Randomization

Like flipping a coin—each participant has an equal chance of being in any group.

b. Block Randomization

Ensures equal-sized groups by randomizing participants in small blocks (e.g., groups of 4 or 6).

c. Stratified Randomization

Ensures balance within subgroups (e.g., age, sex) before randomization.

d. Adaptive Randomization

Adjusts randomization probabilities as the trial progresses based on accumulating data.

4. Special Designs

a. Platform Trial

A flexible design that allows for multiple interventions to be tested within the same study over time.
Common in COVID-19 and cancer research.

b. Basket Trial

Tests the same treatment in multiple disease types or subgroups.
Example: A targeted cancer therapy tested in different tumor types with the same mutation.

c. Umbrella Trial

Tests multiple treatments in a single disease based on different genetic or molecular characteristics.

Conclusion

The choice of randomized trial depends on study objectives, feasibility, and ethical considerations.

Adapted for educational use. Please cite relevant trial methodology sources when using this material in research or teaching.

Bibliography

Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB. *Fundamentals of Clinical Trials*. 5th ed. Springer; 2015. Chapter on trial designs, including explanatory, pragmatic, crossover, cluster, and equivalence trials.
Piantadosi S. *Clinical Trials: A Methodologic Perspective*. 3rd ed. Wiley; 2017. Provides detailed explanations of trial types including superiority, non-inferiority, and adaptive trials.
Thorpe KE, Zwarenstein M, Oxman AD, et al. A pragmatic–explanatory continuum indicator summary (PRECIS): a tool to help trial designers. CMAJ. 2009;180(10):E47–E57.
Ford I, Norrie J. Pragmatic trials. New England Journal of Medicine. 2016;375(5):454–463. Explains pragmatic vs explanatory trials.
ICH E10. Choice of Control Group and Related Issues in Clinical Trials. International Council for Harmonisation; 2000. Covers controlled trials including placebo, active, and external controls.