Randomized controlled trial

A randomized controlled trial (RCT) is a statistical experiment that aims to assess how well an intervention works or how safe it is. It does this by assigning participants to different groups at random, which helps reduce bias. In a typical setup, at least one group gets the treatment being studied—like a drug, surgery, device, or diet—while other groups receive a different treatment, a placebo, or the usual standard of care.

RCTs are a key tool in modern clinical research and are often seen as a top-tier source of evidence in evidence-based medicine because they can limit selection bias and control for confounding factors. Still, they have been criticized for not always succeeding in reducing bias.

People who join RCTs vary in both known and unknown ways that can affect results, and these differences can't be directly managed. Randomly assigning participants to treatments allows statistical control over these influences. If the trial is well-designed, properly run, and includes enough participants, it can sufficiently control for confounders to provide a useful comparison between treatments.

In clinical research, an RCT usually compares a new treatment to an existing standard of care—called the experimental and control treatments. When no standard treatment exists, a placebo may be used in the control group, and participants are often kept unaware of their assignment (blinding). Ideally, blinding extends to researchers, technicians, data analysts, and evaluators as well. Effective blinding helps isolate the physiological effects of treatments from psychological biases.

Random assignment reduces selection and allocation bias by balancing known and unknown prognostic factors across groups. Blinding reduces other forms of bias from both experimenters and subjects. A well-blinded RCT is considered the gold standard for clinical trials. Such trials are commonly used to test medical treatments and can also provide information on side effects, like drug reactions. They can offer strong evidence that a treatment causes a health effect.

The terms "RCT" and "randomized trial" are sometimes used interchangeably, but "randomized trial" doesn't always imply a control group and can refer to studies comparing multiple treatments without one. Similarly, "RCT" is sometimes expanded as "randomized clinical trial" or "randomized comparative trial," which can cause confusion. Not all randomized trials are controlled trials (some can't be, if controls are impractical or unethical). The term "randomized controlled clinical trial" is common in clinical research, but RCTs are also used in other fields, including many social sciences.

The first known proposal for an RCT came from Jan Baptist van Helmont in his posthumous *Ortus Medicinae* (1648). He suggested testing two fever treatments: one using Galenic methods like bloodletting and purging, and another using his own approach. It's likely he never actually ran the trial, only proposing it.

The first reported clinical trial was conducted by James Lind in 1747 to find a scurvy treatment. Principles for controlled trials were further developed by Irish physician James Henry in 1843. The first blind experiment was done by the French Royal Commission on Animal Magnetism in 1784 to test mesmerism claims. Claude Bernard, in the late 19th century, wrote an early essay advocating that researchers be blinded to the hypothesis being tested—a stark contrast to the Enlightenment view that objective observation required a well-informed scientist. The first study with a blinded researcher was published in 1907 by W. H. R. Rivers and H. N. Webber, investigating caffeine effects.

Randomized experiments first appeared in psychology, introduced by Charles Sanders Peirce and Joseph Jastrow in the 1880s, and in education. The earliest experiments comparing treatment and control groups were published by Robert Woodworth and Edward Thorndike in 1901, and by John E. Coover and Frank Angell in 1907. In the early 20th century, randomized experiments emerged in agriculture thanks to Jerzy Neyman and Ronald A. Fisher, whose research and writings popularized the method.

The first published RCT in medicine was the 1948 paper "Streptomycin treatment of pulmonary tuberculosis," describing a Medical Research Council study. One of its authors, Austin Bradford Hill, is credited with conceiving the modern RCT. Trial design was later influenced by the large-scale ISIS trials on heart attack treatments.