May 2, 2014
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, Maryland 20852
Comments of Members of the Patient, Consumer, and Public Health Coalition
to the U.S. Food and Drug Administration
Revised Draft Guidance For Industry on
“Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices”
Docket No. FDA-2008-D-0053
As members of the Patient, Consumer, and Public Health Coalition, we do not support the Food and Drug Administration revisions to the 2009 guidance on good reprint practices because the revisions will promote off-label use of drugs and devices.
When we originally commented on the 2009 guidance, we stated that it was much too lenient and that it undermined the FDA prohibition on off-label marketing. We noted that the 2009 guidance lowered manufacturers’ incentives to complete clinical trials for new uses for their products.
We also noted that the 1997 Food and Drug Administration Modernization Act (FDAMA) provision that allowed the manufacturers of medical products to distribute medical and scientific information from journal articles about off-label uses of drugs and devices sunset in 2006. If Congress had wanted to continue the practice of using article reprints to inform medical professionals about off-label uses, Congress could have explicitly stated that in the 2007 Food and Drug Administration Amendments Act (FDAAA) or in the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA). Congress did not do so.
All of the short-comings of the 2009 guidance apply to the new guidance, with the substantial added problem that the law no longer allows the use of reprints. We therefore strongly oppose the new guidance, “Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices,” which gives industry a loophole to distribute articles and clinical practice guidelines (CPGs) regarding off-label use of medical products.
In the background section of the revised guidance, the FDA stated that, “While physicians may exercise their professional judgment to make individual patient care decisions, the public health often is not well served when those judgments rest on anecdotal experience or even preliminary scientific study.” The guidance notes that “approval of a drug or medical device for one intended use does not assure its safety and effectiveness for other uses.” This section also notes that under the FD&C Act, an unapproved used of a prescription drug or medical device means that the medical product is considered misbranded. We strongly agree.
However, the FDA sends mixed messages in this guidance. The agency states that it “Recognizes the value to health care professionals of truthful and non-misleading scientific or medical publications on unapproved new uses.” We agree, but as the FDA well knows, articles published in medical journals are often biased because the authors or ghost writers are paid by the company whose product is being studied.
The FDA states that it “continues to recognize that [published] information is in no way a substitute for the FDA premarket review process, which allows FDA to be proactive, rather than reactive, in protecting the public from unsafe or ineffective medical products.” We strongly agree with that statement. Based on their track record, drug makers will use misleading publications to promote off-label use of their products. Major companies such as Pfizer Inc., Johnson & Johnson, Glaxo, Abbott Laboratories, AstraZeneca Pharmaceuticals, and Eli Lilly & Company have been sued or have settled lawsuits for hundreds of millions of dollars for their improper off-label marketing tactics.
We agree with Dr. Catherine DeAngelis, former editor-in-in chief of JAMA, who stated the following about drug makers using reprinted journal articles: “Of course they are doing it promotionally. Why else would they do it?”
Because the overriding purpose for distributing scientific or medical journal, scientific or medical reference texts, or clinical practice guidelines by medical product makers or their representatives is to promote off-label use of the products, not to provide unbiased information, we strongly oppose the FDA’s specific “Recommended Practices” in section III of the draft guidance. This section would provide guidelines for when drug and device makers or their representatives could distribute Scientific or Medical Journal Articles, Scientific or Medical Reference Texts, and Clinical Practice Guidelines to inform medical professionals about off-label uses of drugs and devices. It could be argued that FDA is giving guidance on how to skirt the law against off-label promotion of drugs and devices.
Drugs are often used off-label, with nearly 80 percent of off-label prescriptions lacking “strong scientific evidence,” which means we do not know if their risks outweigh their benefits. In one study, 30 percent of chemotherapy drugs were used off-label. In another study, 83 percent of atypical antipsychotic drugs were used off-label for nursing home residents and the Agency for Healthcare Research and Quality (AHRQ) noted that “Prescribing of the atypicals has expanded beyond the approved indications, but their effectiveness, benefits, and adverse effects in off-label uses are not well understood. ”
The off-label use of medical devices is even more problematic than the off-label use of drugs. As the FDA has used FDASIA to reclassify many high-risk devices, they have frequently used split classifications for devices depending on their intended use, with some uses considered Class II (moderate risk and therefore subject to 510k review) and others considered high-risk, requiring pre-market approval. Device companies have a strong economic incentive to apply for the less expensive 510(k) process and then promote it off-label for high-risk uses. Unlike the off-label uses of drugs, these devices will not have been proven safe for any use in clinical trials. Recent examples of the FDA supporting split classifications include Intra-Aortic Balloon Control Systems, Nonroller-type cardiopulmonary bypass blood pump, external counter-pulsating devices, and a transilluminator device for breast evaluation.
For the above reasons, we strongly oppose the Guidance for Industry, “Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices.” These guidelines are aimed at clarifying guidelines developed before the law regarding distributing scientific and medical publications on unapproved new uses (off-label) of medical products sunset in 2006. It fails to follow the law or to protect patients and the public health. Congress recognized back in1962 with the Kefauver-Harris Amendments that “requiring each new indication and intended use of a product to be approved or cleared by FDA is critical to the protection of the public health.”2 This is as true today as it was 52 years ago, because as the FDA notes, “distribution of scientific and medical publications regarding a medical product is not a substitute for the information contained in FDA-approved product labeling.”2
American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Connecticut Center For Patient Safety
Jacobs Institute of Women’s Health
National Center for Health Research
National Women’s Health Network
Our Bodies Ourselves
Center for Science and Democracy at the Union of Concerned Scientists