Subscribe to RSS feedPAL & 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Back in February, the FDA published its Draft Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses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Project, National Physicians Alliance, and US PIRG submitted our comments, calling on the FDA not to issue the Draft Guidance as a final Guidance. The FDA’s Draft Guidance would make it much easier for pharmaceutical companies and their salespeople to distribute reprints of medical journal articles discussing off-label uses to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)
April 22nd, 2008 at 9:46 pm
Additional reasons to prevent off-label promotion:
1. Reps typically have no clinical experience or training, so talking off-label could be damaging to patients
2. As reps, off-label would allow them to manipulate qualities about thier promoted meds, which could be equally damaging. This FDA proposal is surreal and absurd.
May 24th, 2008 at 3:04 pm
The FDA and Its Damaging Lack of Citizen Protection
The Food and Drug Administration originated in its primitive form several decades ago to ensure the health and safety of the citizens of the United States. However, their focus seems to have changed the past few decades, as they appear to have formed a pathological alliance with the pharmaceutical industry through the money the industry gives the FDA for various reasons, amounts so large that this money accounts for about half of the FDA’s income, upon information and belief. Results of this relationship, one could posit, have been the progressive and recent approval of unsafe drugs and lack of regulation and monitoring of the pharmaceutical industry that the FDA is obligated to perform, and have failed to do so as much as they should for our benefit, as these unfortunate events have occurred quite often in a progressive matter that is of concern to many.
And the presumed intimacy between these two organizations does in fact seem to continue to worsen, as illustrated with the new proposal by the FDA to allow the pharmaceutical industry’s drug sales reps to discuss their products with prescribers off-label, which means that the FDA may allow and accept the industry possibly creating harm to patients with this proposal due to uncertainty associated with unapproved uses of a drug promoted in this way. Yet the FDA claims that this proposal would enhance the education and knowledge of the prescriber.
A prescriber, upon their own discretion, can in fact prescribe a drug off-label, but historically, however, representatives from the pharmaceutical industry have been prohibited from suggesting this type of activity. In fact, it is a federal offense for such reps to speak off-label about the drugs they promote, and more pharmaceutical companies are being penalized for this behavior in the past in the form of monetary settlements with the Department of Justice. The drug companies that have allowed such criminal offenses, through vicarious liability at times, perhaps, never admit guilt as part of such settlements.
This FDA protocol that is now being considered, called, “Good Reprint Practices”, would require pharmaceutical sales representatives to use what may not truly exist, which is truthful and authentic clinical trials when and if they do speak off-label to prescribers. This in itself lacks etiology for such discussions by drug reps, as many clinical trials may be flawed due to the trials being possibly manipulated by the pharmaceutical companies of the meds involved in such trials, such as by a third party. Additional trial deception involves ghostwriting and invalid authors of such trials, and this is one of many concerns of this FDA protocol. These facts can be validated and have been discovered by others.
Furthermore, this proposal is flawed in that most pharmaceutical reps lack clinical training and the ability for most drug representatives to analyze the unique statistical data regarding this issue accurately is unlikely, for the most part, I surmise. Remember that most drug reps have no medical or clinical training in any objective way, and, in my experience, have no interest is such training. This complicates the idea of this off-label concept due to the ignorance of the reps of the complexities of these once reliable and dependable methods of proof. In addition, the relaxation of previous restrictions regarding off-label promotion could prove to be a catalyst for reps to embellish statements to prescribers for their own benefit in regards to their promoted meds. So, our previous safety association, the FDA, appears to be evolving into our harmful association by suggesting such practices as this with deliberate intent and reckless disregard for public health, so it seems. Yet this situation appears to be of most benefit for drug companies. It’s unbelievable this proposal ever came into existence, with the delusional fallacy that it would be of benefit to patient health, most likely. Furthermore, this may complicate existing patient medication errors, such as in the elderly or dosing for children, complicated by the fact that many are unable to understand label instructions on their med. So there are enough problems with prescribing, and adding this FDA proposal would just make the situation worse. We as citizens are no longer the concern of the FDA, one could conclude.
However, there is freedom of speech. Perhaps another alternative would be to have clinically trained people discuss such issues with prescribers, instead of the drug reps, who, unlike those academically enriched, have the objective of increasing the market share of their promoted meds. Because historically, medications have in fact proven to be beneficial for other disease states other than what a certain med was initially indicated for upon approval. Regardless, awareness needs to happen by the citizens involving tactics that are possibly deceptive such as this and many more activities by the pharmaceutical industry that one could argue are in fact somewhat covert and tacit. As citizens, we have the right to insist of the pharmaceutical company to maintain focus on the interest of others besides themselves. And the health of the public is that interest, and should be demanded by the FDA more than it appears to be presently.
“As far as we can discern, the sole purpose of existence is to kindle a light in the darkness of being.”
—- Carl Jung
Dan Abshear