FDA Policy On Journal Reprints: Good Or Bad?
20 CommentsBy Ed Silverman // February 16th, 2008 // 9:24 am
On Friday, the agency issued a draft guidance about distribution of journal articles that discuss off-label uses of drugs and devices. In explaining the rationale, Randy Lutter, the FDA’s deputy commish for policy, says “articles that discuss unapproved uses of FDA-approved drugs and devices can contribute to the practice of medicine and may even constitute a medically recognized standard of care. This guidance also safeguards against off-label promotion.”
But is that accurate? The guidance doesn’t say studies of unapproved uses must be from randomized controlled clinical trials. Instead, the proposal says studies should be “adequate and well-controlled clinical investigations that are considered scientifically sound by experts with scientific training.” This opens the door to seeding trials, which encourage off-label usage. Why? These are small trials that lack control groups, which means they’re of limited value. As Merrill Goozner maintains, plenty of second-tier medical journals will line up to publish these.
The FDA also noted the guidance would replace rules that expired in 2006. But as Public Citizen’s Sid Wolfe noted, the regs required companies to submit medical journal articles in advance to the FDA and agree to file within three years a supplemental new drug application for the off-label use it wanted to promote. “These safeguards,” he says, “will no longer be required under today’s proposal.” In other words, there is no incentive for a drugmaker to conduct an appropriate clinical trial to prove its case.
Drug and devicemakers argue the real issue in play is free speech. Consumer advocates and politicians counter that the issue is the appropriate promotion of adquately tested products. But what do you think?
Will the FDA guidance undermine patient safety?
- Yes (73%, 83 Votes)
- No (27%, 31 Votes)
Total Voters: 114
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The Disenchanted Forest
Pharma cries wolf (again)…
You have to feel bad for the poor, oppressed pharmaceutical industry. I mean, even politicians are starting to pick on them (mind you, it’s an election year, the politicians will probably stop) and support consumer advocacy group requests that safegu….
Justice in Michigan
Ed, did you say ….. Friday?
Clearly, this is just the latest in a string of FDA rule-making that is attempting to complete the Bush/WLF et. al. agenda while they still hold power: preemption, shutting down companies’ right (indeed, obligation) to provide appropriate warnings before FDA approval (”Changes Being Effected”), and now legitimating this new level of off-label promotion.
One can only imagine what will happen over the next several Fridays between now and January 08.
In the meantime, can someone clarify the precise policy for off-label under FDAMA? As I recall, there is already opportunity to “make findings known,” although not in a detailing context.
Also, I assume that the proposed rule is also full of immunity provisions related to off-label. Anyone know?
Justice in Michigan
A slip … Of course, I meant January 09. You don’t have to be Freud to understand that one.
When the history of the last eight years of FDA - industry relationship is written, it will be terrific reading. Not that so much will be new, but novel turns on old themes.
Insider
Bad, bad, bad.
Big Pharma have already undermined the journals with their ghostwriters and KOL “shills”.
This is a “last gasp” effort by the Big Pharma moles inside the FDA and Congress lobbyists to feed their master before a change of government.
Doc
Just remember, if pharma cos can disseminate off-label info, it will be done by their sales forces composed primarily by reps that have no science or medical background, but sold lots of cell phones, office equipment, etc. These people will spin off-label info with little knowledge or regard for patient well being, but for their own bigger bonuses.
John
Ed,
Wow! I’m not sure what surprises me more, the individuals who would censor scientific exchange or the folks who believe that Pharma has an appetite for off-label promotion at a time when the FDA is only too happy to slap new black box warnings or demand additional pharmacovigilance studies. If this heightens the ability of a salesperson to discuss the science behind their product we might just move this industry where it needs to go. If reps cannot do that, then they can go back to selling cell phones, office equipment etc. to the same group of professionals who have the most products marketed to them; physicians.
ol cranky
John:
Docs can still obtain reprints and Pharma can still support “independent” research of their products for off-label uses ergo there is no censorship.
Paul
Ahh, this is the kind of stuff that the district attorneys and plaintiff attorneys who are out there chasing potential whistleblowers hate. If one of their fundamental theories based on off-label promotion is undermines, what will they do?
Pharmaceutical Marketing Expert
This is absolutely wonderful. So far drug companies could only hand out studies with off-label info through the medical department. With this proposal the studies could be promoted openly. The only thing needed would be FDA approval for one indication, then any other usese could be claimed in “studies” handed out by drug reps. They might even start hiring more reps again.
sosonj
This proposal would lessen the need for the industry to fund and to conduct proper clinical trials at a time when there is evidence that these trials are sometimes not run and not reviewed by independent researchers. The industry itself should reject this proposed approach because its use will diminish the public’s already shaky trust of big pharma.
Doc
I have managed sales reps for over 10 years, if anyone thinks the average, non-medical trained rep can adequately know what the hell they are talking about, you are dreaming. Get your average sales rep off of their pre-programed sales message and give them an objection or question that addresses wider appropriate therapy in complicated patients with multiple disease states and they are clueless. What they ARE good at is brainstorming with their other non-medical team mates and devising absurd off label spin in order to win the next company sales reward trip. This type of promotion is relentless when backed by big pharma money to “promotional” programs and daily lunches etc. Docs are smart, but they are human beings and can be influenced more than any of them will acknowledge. Opening up off-label rules is a big problem.
Bruce Grant
As used by FDA, “adequate and well-controlled” amounts to a term of art for randomly controlled, double-blind, prospective, clinical trials (RCTs)…and FDA interprets the standards of adequacy and wellness of control pretty strictly, as any marketer who has had a claim turned down because it wasn’t supported by “adequate and well-controlled trials” can testify.
“Seeding trials” would not come into play here, because (a) being initiated by the company and designed to promote the existing indication they are always conducted within labeling; (b) their results are virtually never published; and (c) they are rarely tried these days, since paying doctors an honorarium for being “clinical investigators” in what is essentially a sham trial constitutes a pretty clear violation of the Anti-Kickback Statute.
The big break that industry did get from this Guidance is the lifting of a requirement that they follow up distribution of papers discussion off-label uses with Phase IV trials leading to a Supplemental New Drug Application (SNDA) for the indication — a burden that was probably unworkable to begin with, especially for companies with products in the oncology category, where >80% of usage is off-label.
Paul
Freedom of Speach is still a First Amendment guarantee. Are we undermining doctors’ training, knowledge and ethics by saying they they are too stupid?
someone
Paul,
Publishing and conducting Clinical trials results and scientific/medical information doesn’t fall under the category of “Freedom of Speech”. In fact, I would like to further point out that Freedom of Speech does not tie into anywhere in the business of health care.
As to your question about undermining doctors…. In an article by Trudo Lemmens, LicIur, LLM (Bioethics); Peter A. Singer, MD an earlier study by Avorn was cited in which doctors erroneously thought that their knowledge of two specific drugs was based on scientific knowledge. However, it was shown that their thinking was much more in line with deceptive marketing advertisements….
Why is that? Because Doctors are busy and sometimes (but thankfully not always) they listen to what the rep has to say and they skim these articles for the “highlights”.
In general these guidance rules are fairly good.
Hopefully the savvy patient will know they are being treated off-label and it would be wonderful if the good doctor would provide the patient with access to the study.
At the end of the day the drug has got to stand on it’s own. I think it is particularly great if each and every published paper carried a full disclosure stating that the article was not “ghost written” or “co-authored” by anyone other than the original P.I. It would be really awesome if the approximate dollar amount of the study costs were also listed. I think it is very fair for “consumer” to know what the original investment was…
We need to start working very hard to re establish the trust that has been so seriously eroded.
Guy
Pharmalot,
Your article states: “Instead, the proposal says studies should be ‘adequate and well-controlled clinical investigations that are considered scientifically sound by experts with scientific training.’ This opens the door to seeding trials, which encourage off-label usage. Why? These are small trials that lack control groups…”
There’s a contradiction between the proposal and your interpretation. The proposal says studies should be “well-controlled”. Small trials that lack control groups are not well-controlled.
Ed Silverman
Hi Guy,
I understand your point and someone else also raised this, but it would be helpful if the guidance were specific by saying “randomized controlled clinical trials,” and not leave this open to interpretation or wiggle room. If the final guidance nails this down more specifically, that would be a good thing. And maybe that will happen, given that the 60-day comment period has begun.
Regards
ed
EEJ
Okay, so the rep provides information about a product regarding “unapproved uses”.
Because they are unapproved uses, they aren’t listed on the label of the product (or attached PI), right?
So how does this “safeguard against off-label promotions”?
It sounds to me as if this policy does exactly the opposite.
I think the more doctors that agree to abolish sales representatives from their office, the better! (and this coming from someone whose paycheck depends on big pharma!)
Justice in Michigan
Historical point - I think the language about “adequate and well-controlled studies,” etc. goes back to the Kefauver-Harris amendments passed after thalidomide. It took FDA and industry a while to sort through what that meant, and the emphasis on RCTS in trial requirements came along.
This latest “rule” by FDA seeks to go backward in that respect, using language that sounds reasonable to the uniformed, but is actually fifty years out of date.
Dan
I did not to take time to review all of the above comments, so if I’m duplicating whatever may have been said, my apologies in advance.
Being an experienced pharma rep, I’m well aware that many of not most studies generated by pharma companies are extremenly biased for a variety of reasons, which include financial incentives and statical gymnastics, all with the intent to grow the market share of a particular drug. So, as cynical as it may seem, any off label clinical trial should continued to be questioned for it’s authenticity, for the benefit of the patients ‘Nuff said. And this stance proposed includes even those studies that exist with pharm studies for on label indications as well.
My opinion, it’s a big and serious problem.
Jack2
The guidance specifies that:
A scientific or medical reference publication that is distributed should not be…edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.
To me, that really reduces the number of possible trials, since the manufacturer sponsers most of the publications about their drug.