The Pharmaceutical Research and Manufacturers of America contends that FDA has taken a step back in revising its guidance on journal reprints by failing to recognize the benefits of off-label prescribing of approved medicines.

In March, FDA issued a draft guidance revising its 2009 final guidance on good reprint practices for distribution of journal articles on unapproved uses of drugs and devices to health care providers Also see "FDA Reprint Policy Expands To Clinical Practice Guidelines, Medical Reference Texts" - Pink Sheet, 2 March, 2014..

The issue has long been contentious as industry emphasizes the importance of educating physicians about unapproved uses while FDA has set restrictions on what information may be distributed.

The 2009 guidance “unequivocally acknowledged the patient benefits of medically accepted alternative uses of approved medicines,” PhRMA says in its comments on the document. The guidance “further recognized that ‘[t]hese off-label uses or treatment regimens may be important and may even constitute a medically recognized standard of care.’”

By contrast, the revised draft guidance asserts that “while physicians may exercise their professional judgment to make individual patient care decisions, the public health is often not well served when those judgments rest on anecdotal experience or even preliminary scientific study – too often, the promise of safety and effectiveness made by such sources has not been demonstrated when adequate and well-controlled studies are completed.”

The Ovarian Cancer National Alliance also urges FDA to reinsert the language included in its 2009 document. The group says it is concerned that the agency’s revisions will “chill off-label use of drugs and the dissemination of scientific information about non-approved uses.”

PhRMA also recommends that FDA revise the draft guidance so it does not limit scientific communications to “adequate and well-controlled clinical investigations.”

“By imposing the ‘adequate and well-controlled studies’ standard, the draft guidance would effectively prohibit the dissemination of many types of important and useful scientific information, including certain pharmacoeconomic analyses, meta-analyses, subpopulation analyses, and real world evidence and observational studies that describe significant uses, benefits, and risks of medicines that can improve the effectiveness and/or efficiency of patient care,” the association states.

FDA May Face First Amendment Challenge

In an interview, PhRMA VP and Senior Counsel Jeffrey Francer said companies cannot proactively discuss the real world evidence they have about how patients are using medicine, such as for treatment of different tumors, and instead must wait for unsolicited requests from physicians to share it.

“Only physicians who know the right questions to ask will receive this information,” he stated.

Francer said FDA’s position is not tenable in light of the Supreme Court’s 2011 ruling in Sorrell v. IMS Health Inc., which found that a Vermont law prohibiting pharma companies from using information about doctors’ prescribing practices violated the First Amendment.

The court held that the statute disfavored speech that has a particular content and is made by particular speakers, namely pharmaceutical manufacturers Also see "Rx Data Mining Opponents Will Need New Pitch After Supreme Court Strikes Down Vermont Law" - Pink Sheet, 23 June, 2011..

In the case of reprints, Francer said the government is saying only one group cannot provide information that is not from adequate and well-controlled studies.

“I don’t think this discrimination will survive a First Amendment challenge,” Francer said. “It’s probably only a matter of time until the current regime will be challenged.”

FDA seems to agree, and is undertaking a review of its promotional policies ([A#14140423007]).

PhRMA also objects to FDA’s restriction on distribution of reprints in promotional exhibit halls during promotional speakers’ programs. It says that if a scientific or medical journal article or clinical practice guideline is truthful and non-misleading there is no reasoned basis for prohibiting manufacturers from distributing it during one part of a conference and not another.

In addition, PhRMA says there is no reason for FDA to prohibit distribution of reports of healthy volunteer studies published in scientific or medical journals.

What Is A “Trustworthy” Clinical Practice Guideline?

In other comments, LifeCell Corp. objects to the draft guidance’s limitations on the distribution of clinical practice guidelines. FDA recommends that manufacturers only disseminate clinical practice guidelines that are considered “trustworthy” based on the Institute of Medicine’s standards. LifeCell says those criteria are vague and suggests that FDA provide an example of an appropriate clinical practice guideline as an appendix to the guidance.

Further, the company says FDA should remove the requirement that clinical practice guidelines should not be primarily distributed by manufacturers.

The Council of Medical Specialty Societies submitted a one-page comment expressing its support for the revised draft guidance. The group says the document appears to be consistent with its principles for the development of clinical guidelines.

Congress Skeptical Of Draft Guidance

As FDA seems to be steering away from endorsing off-label use, Congress is showing support for it. The House Energy and Commerce Committee recently released a white paper suggesting that drugs could win approval for additional indications based on data obtained from off-label use without having to go through clinical trials ([A#14140502001]).

Meanwhile, several senators are challenging FDA’s practice of issuing draft guidances to convey regulatory policy.

Four Republican members of the Senate Committee on Health, Education, Labor, and Pensions sent a May 6 letter to FDA Commissioner Margaret Hamburg to express “significant concern” about FDA’s use of draft guidances “to make substantive policy changes.”

The signatories, led by Committee Ranking Member Lamar Alexander, R-Tenn., said they are concerned that the agency’s website does not differentiate between draft and final guidances, making it seem they have equal weight and undercutting the purpose of soliciting public comment.

In addition, they said they are concerned that the draft guidances are not being revised, finalized or withdrawn in a timely manner; that stakeholders feel compelled to follow draft guidances as if they were final; and that guidances seemingly do not take into account, or may even conflict with, the scientific community.

With regard to draft guidances being implemented before they are final, the members cite FDA’s draft guidance on abuse-deterrent formulations. They noted that during the committee’s March 13 hearing, Hamburg said the guidance lays out FDA’s current thinking even though it is still in draft form ([A#14140314005]).

In addition, they point to the agency’s draft guidance on cyclosporine emulsion bioequivalence, which was published in June 2013 and criticized by the American Academy of Ophthalmology and American Glaucoma Society.

The committee members asked FDA to provide a list of its Level 1 draft guidances and the timeline for acting on them, the average time FDA has taken to finalized draft guidances in the last year, and how the agency ensures its staff does not follow them in the absence of any other policy or final guidance.

Journal Reprint Guidance: Industry And FDA Still At Odds Over Off-Label Information

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