The term originated in the seminal work of determining the causality of smoking-related disease (The Surgeon General's Advisory Committee on Smoking and Health [1964]).
Other important criteria in evaluations of disease and adverse event causality include consistency, strength of association, specificity and a meaningful temporal relationship.
"[1]The preliminary research leading up to a randomized clinical trial (RCT) of a drug or biologic has been termed "plausibility building".
This involves the gathering and analysis of biochemical, tissue or animal data which are eventually found to point to a mechanism of action or to demonstrate the desired biological effect.
Since large, definitive RCTs are extremely expensive and labor-intensive, only sufficiently promising therapies are thought to merit the attention and effort of final confirmation (or refutation) in them.