Off-label uses are generally recognized as medically accepted indications if they are supported in either 1) one or more authoritative compendia, and none list it as not indicated, unsupported, not recommended, or equivalent terms; or 2) in peer-reviewed medical literature. Reliable evidence must demonstrate that the proposed off-label use to treat the specified medical condition is safe and effective, and that the beneficial effects of the treatment outweigh its risks.
Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications in which original manuscripts are published only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication. In order for a use to be supported by clinical research, it must have been studied in at least two clinical trials conducted at different centers, and the results must have been published in national or international peer-reviewed journals with an editorial committee composed of physicians. Peer-reviewed medical literature does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).
According to the National Cancer Institute, clinical trials are usually conducted in a series of steps called phases. These are outlined as follows: