How evidence is graded on this site

Every figure in this section carries the kind of study it came from. The kinds are not interchangeable, and the order below is the order they appear in.

Laboratory (in vitro)

In vitro experiments are performed on cells, tissues or purified molecules outside a living organism. Duval and colleagues describe cell cultures in vitro as frequently used to advance understanding of the mechanisms that underlie cell behavior in vivo, and state that under some circumstances two-dimensional cultures can result in cell bioactivities that deviate appreciably from the in vivo response (Duval et al. 2017, PMID 28615311).

Structural work, such as a cryo-electron microscopy structure of a receptor in complex with a G protein (Zhang et al. 2017, PMID 28538729), is grouped here too, and each structure is shown with the resolution its publication reports.

Preclinical (animal)

Experiments in a living animal. How well animal results carry over to humans has been measured: Olson and colleagues surveyed 150 compounds with 221 human toxicity events identified during clinical development and reported a true positive concordance rate with animal toxicity studies of 71% for rodent and non-rodent species together and 43% for rodents alone (Olson et al. 2000, PMID 11029269). An animal result is recorded as an animal result.

Human phase 1

Under U.S. FDA regulations, phase 1 is the initial introduction of an investigational new drug into humans. Phase 1 studies are typically closely monitored, are designed to determine how the drug is metabolised and acts in humans and the adverse effects associated with increasing amounts, and generally include 20 to 80 subjects. The regulation states that the phases are generally conducted in sequence but may overlap (21 CFR 312.21).

Human phase 2

Phase 2 consists of controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication and to determine the common short-term adverse effects and risks associated with it. They are typically well controlled and closely monitored, and usually involve no more than several hundred subjects (21 CFR 312.21).

Human phase 3

Phase 3 studies are expanded controlled and uncontrolled trials, performed after preliminary evidence suggesting effectiveness has been obtained, and intended to gather the additional information about effectiveness and safety needed to evaluate the overall benefit-risk relationship of the drug. They usually include from several hundred to several thousand subjects (21 CFR 312.21).

Regulatory

Documents issued by a regulator, such as approval records. They are recorded separately from studies, and on the public pages of this library a regulatory statement appears only with the record it is cited to.

Manufacturer disclosure

A press release or investor communication issued by the company that ran a trial, not peer reviewed. It is recorded separately from the peer-reviewed tiers and is not shown on the public pages of this library.

Why results are never combined

No averaged figure, "typical" result, or single headline number appears in this section. Studies differ in population, in what they measured, in when they measured it and in what they compared against. Combining them produces a number that describes no study that was actually run.

Each table here shows one endpoint, at one measurement point, in one population, with every arm the publication reported — including the placebo arm. That is the unit the research was done in, so it is the unit it is shown in.