The "natural history" of an illness is the course and outcome of that illness in the absence of treatment; and, from this, the title "natural history group" is given to the subjects in a drug trial that receive no treatment of any kind whatsoever and whose illness, as a consequence, is left to run its "natural" course.

First usage

In 1863, Austin Flint (1812–1886) in his report of the first-ever trial that directly compared the efficacy of a placebo treatment with that of an active treatment, spoke of "the natural history of untreated disease".Flint (1863), p.18.

Third arm

The natural history group is often referred to as the "third arm" of a controlled drug trial, from the simple notion that a triad has three arms (or a triskelion has three legs).

The observed outcomes within this group are then compared with the outcomes manifested by a group that has been given the active drug, and with that manifested by a second group who have been given a dummy, placebo drug (thus, the natural history group is the trial's "third arm").

Notes