. 2009 Aug;34(8):428–440.

Table 1.

Conditions Under Which Information About the Off-Label Uses of Drugs May Be Disseminated

Condition	FDAMA Section 401^†	2009 Guidance^‡
Drug approval	Information must concern a drug or device that has received FDA approval for some use.	Drug-approval status not mentioned.
Commitment to file a supplemental New Drug Application	Manufacturer must have submitted a supplemental New Drug Application for a proposed new use or completed required studies and certified that this application will be submitted within 6 months after initial dissemination (or within 36 months if supporting studies not yet completed); may request exemption from this requirement if studies are prohibitively expensive or unethical.	Not mentioned; companies [are] encouraged to seek approval for new uses of a drug.
Advance provision to the FDA	Manufacturer must submit copy of article and other safety and efficacy information concerning unapproved use 60 days before dissemination.	Not mentioned
Source of underlying clinical data	Information must not be derived from another manufacturer’s clinical research (unless [the] other manufacturer gives permission) and must be from “scientifically sound” clinical investigation.	Information should be based on adequate and well-controlled clinical investigations.
Accuracy	Information must not be false or misleading, must not involve inappropriate conclusions, and must not pose significant risk to public health if relied on. Company may need to include other safety and efficacy information to ensure objectivity and balance.	Information should be truthful and not misleading and should not pose a significant public health risk if relied on.
Provision of countervailing scientific findings	Information must be disseminated along with approved labeling and comprehensive bibliography of publications related to off-label use (including unfavorable studies) and other available information about risks of this use.	Information should be disseminated with approved labeling and comprehensive bibliography of publications related to off-label use, plus representative publications (if any) reaching conclusions regarding this use that are contrary or different.
Required disclosures	Must include prominent disclosure stating that use is not FDA-approved and identifying other products (if any) approved for that use.	Should include prominent disclosure statement regarding unapproved use that identifies study sponsors, discloses relevant financial interests, and mentions any known significant risks not discussed in the publication.
Presentation of journal article	Must provide entire, unabridged article or section of reference publication; no promotional materials may physically accompany it, and company representatives may not verbally promote the new use.	Should provide entire, unabridged article or reference. It should not be marked, highlighted, summarized, or characterized in any way.
Journal requirements	Information must be published in peer-reviewed scientific or medical journal (listed in Index Medicus) and must not have appeared in industry-funded special supplement or publication; unabridged reference texts may also be distributed (including non–peer-reviewed texts if specific unapproved use [is] not highlighted).	Information should be published by an organization with [an] editorial board that involves experts with demonstrated expertise in subject of article and objectively reviews proposed articles, adhering to standard peer-review procedures; organization should adhere to published conflict-of-interest policy; information should not have appeared in an industry-funded special supplement or publication.
Distribution	Distribution must be limited to health care practitioners, pharmacy benefit managers, issuers of health insurance, group health plans, and federal and state agencies (no distribution to consumers).	Information should be provided separately from promotional information; distribution should be limited to health care practitioners and entities such as pharmacy benefit managers, health insurers, and government agencies (no distribution to consumers).
Other avenues of dissemination	Manufacturers may still disseminate information about off-label uses in response to unsolicited requests from health care practitioners.	Manufacturers may still disseminate information about off-label uses in response to unsolicited requests from health care practitioners.

FDA = Food and Drug Administration; FDAMA = FDA Modernization Act.

^†

Data from the FDA and the Code of Federal Regulations.

^‡

Data from the FDA.