PAL & Others to FDA: Don’t Loosen Off-Label Rules
We write frequently on this blog about “off label” marketing — that’s the practice of prescription drug & medical device companies illegally promoting their products for uses or conditions that are not approved by the FDA. Here’s the “elevator” version of what off-label marketing is and why it’s illegal:
Before any prescription drug can be sold in the U.S., the Food and Drug Administration must find that the drug is “safe and effective” for the conditions that the company wants to sell it for and at the dosages that it seeks to sell. However, once it’s on the market, a doctor can prescribe it for any condition or purpose or type of patient, regardless of whether the FDA approved it for that or not.
In some specialties (particularly oncology), off-label is very common and is the so-called “standard of care.” Important new uses for drugs have at times been found through off-label prescribing. Since many drugs are not tested on children as part of FDA approval, much (possibly most?) pediatric prescribing is off-label.
So off-label prescribing is perfectly legal (as long as it doesn’t go so far afield that it constitutes malpractice) and is not regulated by the FDA. However, off-label marketing is very much illegal – it’s considered “misbranding” under section 502(a) of the Food Drug and Cosmetics Act (FDCA). In other words, a drug company cannot promote a drug for off-label purposes — because the off-label use has not been shown to be safe and effective, is an end-run around the FDA’s approval process, and eliminates the drug company’s incentive to submit an application to have the off-label use approved.
Back in February, the FDA published its Draft Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices and requested public comment on its proposed rules.
Today, we at Prescription Access Litigation, along with our colleagues at The Prescription Project, National Physicians Alliance, and US PIRG submitted our comments, calling on the FDA not to issue the Draft Guidance as a final Guidance. The FDA’s Draft Guidance would make it much easier for pharmaceutical companies and their salespeople to distribute reprints of medical journal articles discussing off-label uses to physicians.
It is ironic that the FDA is working to make it easier for drug companies to market drugs for off-label purposes when there have been so many revelations and allegations of egregious illegal off-label marketing in the past few years, including off-label marketing of Pfizer’s Neurontin (which resulted in a $430 Million settlement with the U.S. Attorney and state Attorneys General), and of Eli Lilly’s Zyprexa.
Among the reasons we cite for why the FDA’s draft guidance is a bad idea:
“Distribution of single studies by pharmaceutical representatives is not an effective way to facilitate evidence based decision making and thus does not prioritize patient safety or public health. Specifically:
- Early evidence is often contradicted.
- Single trials can be misleading and may not adequately assess drug effectiveness or safety.
- Statistically, any individual study has a good chance of coming to the wrong conclusion.
- Trials stopped early for benefit are found to be less striking on further review.
The Draft Guidance would allow drug companies to distribute journal articles from any peer-reviewed medical journal. However, as we point out in our comments:
“The FDA drug approval process requires review of all data regarding a drug, both published and unpublished. In contrast, the editorial review processes employed by peer reviewed journals do not. Journal review processes vary widely and publication in a peer reviewed journal is not in and of itself a guarantee of quality.
- FDA approval requires access to full data.
- Journal reviewers only have access to what has previously been published.
- Published studies may lack appropriate controls, design or statistical analysis.
- Industry has the potential to fund and publish individual studies with substantial bias.
- Industry-funded trials and reviews are more likely than independent evaluations to be favorable toward the sponsor’s drug.
- Publication bias means negative studies are less likely to be known by reviewers.
- Industry, motivated to sell more product, could selectively choose to distribute studies that show its products in a favorable light.
- Industry has frequently been shown to play an invisible role in funding and even “ghost writing” published studies that are published under the names of academic physicians.
- FDA lacks resources to review all distributed studies and ensure they meet a high standard.
To see our comments in their entirety, go here.
To see the other comments that have been submitted and the full text of the draft guidance, go here.
The New England Journal of Medicine ran a terrific “Sounding Board” piece just last week on this topic by Drs. Jerry Avorn & Aaron Kesselheim of Brigham & Women’s Hospital: Pharmaceutical Promotion to Physicians and First Amendment Rights (subscription required)