Questions often arise as to whether the "off-label” use of marketed drugs, biologics and medical devices constitutes research which requires IRB approval.
Physicians may sometimes use legally available drugs, biologics or devices for other than their FDA-approved indications when they determine that such "off-label" use is in the best interests of the patient. "Off-label" use should be consistent with good medical practice and the best interests of the patients and should be the based on firm scientific rationale and sound medical evidence. Physicians should be well informed about the product and maintain records of the product's use and effects.
It is sometimes difficult to determine whether "off-label" use of drugs, biologics or devices is for therapeutic or research purposes or both because there is often little evidence of the safety and efficacy of the drugs, biologics or medical devices for the proposed use. The key to determining whether the "off-label" use is therapeutic or research is the physician's intent. If the intent is investigational (i.e. the seeking of generalizable knowledge of the drug, biologic or device's safety or efficacy or if the "off-label" use is intended to prove or disprove a hypothesis or to answer a question, then the use should be considered research requiring the submission of an IND (Investigational New Drug Application) or IDE (Investigational Device Exemption) from the FDA (unless the FDA specifies in writing that an IND or IDE is not required) and IRB approval for the study [c.f. 21 CFR 312.3(b)].
Submission of an IND or IDE and IRB review/approval are not required when the 'off-label' use of a marketed drug, biologic or device is not intended for research but rather is intended only for the practice of medicine or when all of the following six conditions for the "off-label" use are met [21 CFR 312.2(b)(1)]:
1) It is not intended to be reported to the FDA in support of a new indication for use or to support any other significant change in the labeling for the drug
2) It is not intended to support a significant change in the advertising for the product
3) It does not involve a route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product
4) It is conducted in compliance with the requirements for IRB review and informed consent [21 CFR parts 56 and 50, respectively]
5) It is conducted in compliance with the requirements concerning the promotion and sale of drugs [21 CFR 312.7]
6) It does not intend to invoke 21 CFR 50.24 which is the regulation on waiving informed consent requirements for emergency research [NOTE – Regulations on the permissible, one-time emergency use of a test article with notification to the IRB within 5 days are 21 CFR 56.102(d) and 21 CFR 56.104(c)]