Pharma Lobbies DC For Off-Label Rights
37 CommentsBy Ed Silverman // April 18th, 2008 // 7:12 am
Drugmakers are descending on Washington to protect their freedom to advertise meds directly to consumers and push for looser government restrictions on off-label promotion, The Wall Street Journal writes.
Ten drugmakers, including Pfizer, Bayer Corp, AstraZeneca and Johnson & Johnson have formed a coalition to push for looser off-label restrictions and will submit their arguments today to the FDA, which has been soliciting comments on its proposed off-label promotion guidelines. They are represented by former FDA Chief Counsel Daniel Troy, who is working with public-relations giant APCO Worldwide. Patient-advocacy organizations such as the National Alliance on Mental Illness and the National Organization for Rare Disorders are also working with the group.
The new coalition supports the ability of drugmakers to disseminate articles from peer-reviewed journals to docs and hospitals to inform them of new conditions for which drugs already on the market could be used, but which the FDA hasn’t formally approved. The FDA’s proposed guidelines prompted Henry Waxman, who chairs the House Oversight and Government Reform committee, to lambast the agency for issuing a guidance he says will allow drugmakers to promote “potentially dangerous uses” of drugs and devices without prior FDA review and approval
Pharma, as you know, is worried about a potential regulatory backlash following the Vioxx and Vytorin scandals. And all three presidential candidates have criticized drugmakers about pricing. Meanwhile, three congressional committees are pursuing various investigations of industry marketing practices. “We have to be concerned that Congress will act too quickly in this atmosphere, without considering the problems they can cause the public by limiting the information flow to consumers,” Bob Hogan, ceo of Cognito Communications, a health-care marketing-strategy firm, tells the paper.
The FDA maintained the rules aren’t being loosened, but clarified. Randy Lutter, the agency’s deputy commissioner for policy, tells the Journal that the guidelines mandate full disclosure of any conflict of interest by journal authors in articles used in off-label promotion.
The push for off-label changes came just as the Journal of the American Medical Association suggested in two reports that Merck played down the potential risk to Alzheimer’s patients of heart attack from Vioxx, and said the drugmaker had ghostwritten many favorable academic articles.
Industry worries about new rules and a chilly climate in Washington were reflected at a conference here Thursday, the Journal writes. More than 60 percent of participants polled during the annual conference sponsored by DTC Perspectives said they think Congress may move to place limits on television advertising by drugmakers, which spend about $5.4 billion annually on TV ads, according to Nielsen Monitor-Plus.
One idea marketers don’t like: A proposal that ads contain a phone number that consumers can call to make complaints to the FDA, which Consumers Union has been pushing.
Pharma is concerned that marketing strategies could be trimmed after the 2008 elections if Democrats strengthen their control in Congress or take the White House. But there are indications that some politicians won’t wait that long. The chairman of the House Committee on Energy and Commerce, Michigan Democrat John Dingell, plans to announce a hearing on direct-to-consumer advertising, to take place in a few weeks. His panel will look at Vioxx, Vytorin and an ad blitz for Pfizer’s Lipitor that used artificial heart inventor and alleged rower Robert Jarvik.
Jack2
Maybe I’m missing something, or maybe it’s changed since 2/15, but the guidance I saw included:
“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.”
Because of that restriction, I don’t see this change having much impact either way.
Dan
Appropriate only if reps are pharmDs or doctors. Absurd in any other situation. How this is allowed is beyond comprehension.
Justice in Michigan
As things now stand, while detailers can’t talk about off-label uses, KOLs can say anything they choose - at meetings, conferences, etc.. Some number of these folks are directly on the take, so I don’t think having a degree of whatever kind is the issue. The issue is the risk/benefit evidence.
As we all know, getting one article in a referreed journal is a far lower hurdle than getting an FDA approved indication. And if the study is important enough, it will not take detailers to get (honest) physicians’ attention.
In any event, the guidelines are already grey enough. Detailers can provide such articles if docs ask about them (which itself can be interpreted liberally). It is really a question of how direct and aggressive a rep is allowed to be when a doc does not raise the question.
So that is the issue: Should reps be able to aggressively _promote_, based on single published studies (again a low bar), indications that the FDA has not yet found scientifically tenable)?
Cocerned
Pharma is regulated. There’s a reason for that! It’s been done so people can’t sell snake oil on the corner anymore to cure what ails you. It’s also so cocaine can’t be sold in a solution a a magic potion. Give us a break! We need more aggressive sales people trying to sell more drug like we need a whole in the head. Big Pharma, accept the regualtions and quit moaning!
Bob Freeman
Given the relative effectiveness of the big PR firms’ and pharma companies’ lobbyists, it is likely that they will get what they want. I would also note that it appears that coporations have been granted certain rights (commercial free speech, for instance) that used to be exclusively individual rights.
I think, still, the simpliest approach is to impose taxes at the States’ level on all promotional activities included, but not limted to, a per capita tax on field-based personnel (sales reps, MSLs, promtional spend (lunches, dinners, CME, gifts to physicians) and to imposing supplemental rebates on drugs that are promoted by DTCA. I would like to see the Federal Medicaid Rebate minimum rebate increased but I think that, too, is unlikely.
A.M. Camus
I don’t think it’s necessarily a surprise that the Washington Lobby is big for anything related to pharma, health care, or insurance. In fact, a recent study found that insurance lobbyists dominate in Washington when compared to other lobbies.
I think the real question is whether or not off-label advertising is tantamount to hard liquor or cigarette sales being pushed on television (which has since been banned). My assertion is that it is; we are, as a nation, addicted to prescription drugs. Others will disagree, but I’ll let the money speak for itself. Just look at what the annual revenue of the top five drug companies is.
Justice in Michigan
Interesting suggestions, Bob. I agree - off-label promotion, even on the level of the Neurontin scam where there was no evidence of safety or efficacy of any kind for some promoted uses - is already reality. There needs to be another way.
As I understand it (could be wrong), Dan Troy did some consulting for Pfizer related to this issue when the civil and criminal fines related to Neurontin promotion were going down. This was shortly before his becoming FDA Chief Counsel.
Justice in Michigan
Monsieur Camus makes an interesting connection. While I think the parallel is a little stretchy, it is also at least “interesting” that Dan Troy’s great victory was his representation of Brown & Williamson successfully when FDA was pushing to regulate tobacco. Pharma and tobacco have worked closely together through groups like the Washington Legal Foundation.
So how is it going with _The Plague_?
Jack2
JIM: As we all know, getting one article in a referreed journal is a far lower hurdle than getting an FDA approved indication. And if the study is important enough, it will not take detailers to get (honest) physicians’ attention.
I don’t think that it’s a trivial hurdle. The drug company can’t have run the study. The drug company can’t even have supported an academic who ran the study. What academic will do a study on a drug for off-label efficacy and not ask the drug company for funding support? Vanishingly few.
I challenge someone to find a study positively supporting the off-label use of ANY BRANDED DRUG, published in the entire year of 2007, peer-reviewed, not financially supported in someway by the sponsoring company.
It’s not that academic researchers can’t run an independent trial for an off-label use. They can. But why would they run it without funding when they can get funding. Wouldn’t you take funding support over no funding support?
I really don’t understand how this change could have much impact either way.
Justice in Michigan
Jack 2 - I think we are understanding things differently. Where does it say the drug company can’t have run or supported the study? In Ed’s post, it says only this:
“The FDA maintained the rules aren’t being loosened, but clarified. Randy Lutter, the agency’s deputy commissioner for policy, tells the Journal that the guidelines mandate full disclosure of any conflict of interest by journal authors in articles used in off-label promotion.”
Disclosure means only that (and, of course, it means potential, not actual, COIs). As far as I know, there is no provision anywhere that the relevant studies cannot be done by company employees and/or others who have a financial relationship with that company. (Peer-review, of course, has nothing to do with sponsorship.)
Do you understand the proposed guidelines differently? Is there a reference for that?
Justice in Michigan
As an example, below are the diclosure and sponsorship guidelines for JAMA, which we would all agree is peer-reviewed. Nothing in them prevents company authorship, sponsorship, and, indeed, study design and execution.
***************************************************
from JAMA guidelines
Conflicts of Interest and Financial Disclosures. A conflict of interest may exist when an author (or the author’s institution or employer) has financial or personal relationships or affiliations that could influence (or bias) the author’s decisions, work, or manuscript. All authors are required to disclose all potential conflicts of interest, including specific financial interests and relationships and affiliations (other than those affiliations listed in the title page of the manuscript) relevant to the subject of their manuscript. Authors should err on the side of full disclosure and should contact the editorial office if they have questions or concerns.
All such disclosures must be listed in the Acknowledgment section at the end of the manuscript. Authors without conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of their manuscript, should include a statement of no such interests in the Acknowledgment section of the manuscript. Failure to include this information in the manuscript may delay evaluation and review of the manuscript.
Authors are expected to provide detailed information about all relevant financial interests and relationships or financial conflicts within the past 5 years and for the foreseeable future (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), particularly those present at the time the research was conducted and through publication, as well as other financial interests (such as patent applications in preparation), that represent potential future financial gain. Although many universities and other institutions have established policies and thresholds for reporting financial interests and other conflicts of interest, JAMA requires complete disclosure of all relevant financial relationships and potential financial conflicts of interest, regardless of amount or value. For example, authors of a manuscript about hypertension should report all financial relationships they have with all manufacturers of products used in the management of hypertension, not only those relationships with companies whose specific products are mentioned in the manuscript. If authors are uncertain about what constitutes a relevant financial interest or relationship, they should contact the editorial office.
For all accepted manuscripts, each author’s disclosures of conflicts of interest and relevant financial interests and affiliations and declarations of no such interests will be published. Decisions about whether such information provided by authors should be published, and thereby disclosed to readers, are usually straightforward. Although editors are willing to discuss disclosure of specific conflicts of interest with authors, JAMA’s policy is one of complete disclosure of all potential conflicts of interest, including specific financial interests and relationships and affiliations (other than those affiliations listed in the title page of the manuscript) relevant to the subject of their manuscript. The policy requesting disclosure of conflicts of interest applies for all manuscript submissions, including letters to the editor and book reviews. If an author’s disclosure of potential conflicts of interest is determined to be inaccurate or incomplete after publication, a correction will be published to rectify the original published disclosure statement.
Authors also are required to report detailed information regarding all financial and material support for the research and work, including but not limited to grant support, funding sources, and provision of equipment and supplies, in the Acknowledgment section of the manuscript.
All authors must also complete and sign a statement on financial disclosures, funding, and support that is part of the Authorship Form.6,7
Funding/Support and Role of Sponsor. All financial and material support for the research and the work should be clearly and completely identified in an Acknowledgment section of the manuscript. The specific role of the funding organization or sponsor in each of the following should be specified: “design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.”6,7
harpy
Ed’s previous post on the guidelines includes this:
“As a result, the law passed in 1997 - which was in place until October 2006 - 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 will no longer be required under today’s proposal.”
In addition, the draft guidance recommends against distribution of special supplements or publications that have been funded by one or more of the manufacturers of the product in the article, and articles that are not supported by credible medical evidence are considered false and misleading and should not be distributed.
From the audio conferences I’e attended, the recommendation is to never let a detailer say anything about off-label uses. The proper way is for an HCP to contact the company and ask - then an MSL or the like can answer specific questions.
Justice in Michigan
Thanks, Harpy. It sounds like the draft guidance - still not law - is recommending against journal supplments and essentially promotional articles. Based on FDA guy Ed quotes, all that is really required is disclosure in whatever context.
Troy & Co. appear to be using the “peer-reviewed journal” rhetoric as a way to suggest a level of objectivity that, as we all know, ain’t necessarily so.
Jack2
I’m interperting it from this statement, JIM:
“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.”
Found here:
http://www.fda.gov/oc/op/goodreprint.html
Justice in Michigan
Thanks, Jack 2. We should look at the whole section which is below. I wouldn’t even call these loopholes. I would call them open tunnels.
First, these are “good reprint practices” - not regulations.
The “good practices” include “full disclosure of any conflict of interest or biases for all authors, contributors, or editors associated with the journal or organization;” Presumably, then, authors who have financial ties with companies are not excluded so long as they dislose those ties.
The bit you cite is ambiguous at best. I doubt very much it would be interpreted to mean a drug or device company could not fund the study as well as design it, and have it authored by people with whom it has financial relationships. “Edited or significantly influenced” is almost surely meant to indicate more “obvious” attempts to manipulate results and their interpretation - which is , to some degree and in many cases, in eye of beholder.
The examples given at the end also suggest what these “good practices” are really about.
But there’s no reason to speculate. Hopefully, there is someone who sees the thread from FDA and knows the answer. Or perhaps Ed, or one of us, could contact FDA and get it.
*******************************************************
When a manufacturer disseminates such medical and scientific information, FDA recommends that the following principles of “Good Reprint Practices” be followed.
A. Types of Reprints/Articles/Reference Publications
A scientific or medical journal article that is distributed should:
be published by an organization that has an editorial board that uses experts who have demonstrated expertise in the subject of the article under review by the organization and who are independent of the organization to review and objectively select, reject, or provide comments about proposed articles, and that has a publicly stated policy, to which the organization adheres, of full disclosure of any conflict of interest or biases for all authors, contributors, or editors associated with the journal or organization;
be peer-reviewed and published in accordance with the peer-review procedures of the organization; and
not be in the form of a special supplement or publication that has been funded in whole or in part by one or more of the manufacturers of the product that is the subject of the article.
A scientific or medical reference publication that is distributed should not be:
primarily distributed by a drug or device manufacturer, but should be generally available in bookstores or other independent distribution channels where medical textbooks are sold;
written, edited, excerpted, or published specifically for, or at the request of, a drug or device manufacturer; or
edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.
The information contained in the above scientific or medical journal article or reference publications should address adequate and well-controlled clinical investigations that are considered scientifically sound by experts with scientific training and experience to evaluate the safety or effectiveness of the drug or device4. The information must not:
be false or misleading, such as a journal article or reference text that is inconsistent with the weight of credible evidence derived from adequate and well-controlled clinical investigations (e.g., where a significant number of other studies contradict the article or reference text’s conclusions), that has been withdrawn by the journal or disclaimed by the author, or that discusses a clinical investigation where FDA has previously informed the company that the clinical investigation is not adequate and well-controlled; or
pose a significant risk to the public health.
The following publications are examples of publications that would not be considered consistent with the Good Reprint Practices outlined in this draft guidance:
letters to the editor;
abstracts of a publication;
reports of Phase 1 trials in healthy subjects; or
reference publications that contain little or no substantive discussion of the relevant investigation or data.
Mark Tosh
I believe there’s a slight ‘clarification’ needed to the way this story was reported this morning in The Wall Street Journal. This reporter was invited to visit the DTC National Conference on Thursday to speak with pharma marketers about DTC advertising and any concerns about possible future restrictions on DTC. (She claimed to be working on a story about DTC marketing and was seeking both sides of the story. In retrospect, it seems she has confused consumer marketing & advertising with off-label promotion to physicians.)
So, in what seems to me like an attempt to add more drama to a mundane news report about pharma filing requested comments to the FDA on off-label guidance, this WSJ reporter took the liberty of using a description that ‘drugmakers are descending on Washington’ — which many marketers were doing to attend the DTC National Conference — and connected that to a completely separate event - the comments made by drug makers on off-label promotion. The result is that her story could lead one to believe that a sizable contingent of the entire pharma marketing community was in Washington to push the off-label issue. In fact, there are two separate events going on here.
I attended the conference — as an editor/employee of DTC Perspectives — and can confirm that off-label marketing was not a topic of this meeting. In my humble view, this is an example of truly shoddy reporting tactics — and is not what one would expect from the WSJ.
Oops, I forgot. There are new owners in charge there now.
Mark Tosh
dtc perspectives
to protect their freedom to advertise meds directly to consumers and push for looser government restrictions on off-label promotion’ was a
Former pharma Marketing Exec
JIM and Jack2 et al,
Good suggestion JIM on contacting the FDA, we need more clarification here. This is potentially quite dangerous, especially when we figure in the preemption issue.
My big concern is what are the requirements for full disclosure with the patients?
This is a bit disconcerting when we have patient advocacy groups being so heavily influenced like this. The thinking that is behind this is that it is the government that is the “bad” cop here and not doing what they need in order to get the drugs to the market quicker. This is the usual story that uninformed patients, who are desperate in many ways get from not only their doctors but from pharma.
The issue that is providing the impetus for this action, the delay in new drug approval, is what really needs to be addressed. Additionally, the public needs to know that there are no delays (in most cases)for drugs that really work. The public has been misinformed on this issue. I can name quite a few that have been fast tracked because they really did work.
My suspicion is that some of this is coming from the Abigail Alliance, which I ave a great deal of empathy for, see website http://www.abigail-alliance.org/
I could be wrong on this.
However, if this turns out to be the case, we would all be much better served if we joined our collective forces on making these drugs available for patients with no other althernative, rather than allow the arbitrary “wholesale” marketing “off-label” use of drugs. I really do believe that it will be abused and really create quite a fiasco.
Can anyone tell me why we would be putting loaded guns in peoples hands? That is what this could very well turn out to be.
I support the fundamental ideas of the Abigail Alliance, but I am not sure this is the right way to go about it. There have been too many problems lately that indicate some Pharma companies cannot manage themselves appropriately.
Do we create a system that would monitor this and if you violate it you are not allow to participate?
Much work is needed.
HorusCat
Appropriate only if reps are pharmDs or doctors. Absurd in any other situation. How this is allowed is beyond comprehension.
Dan, I skipped all the other comments to reply to you. Sitting on my table right now is a copy of a medical school text on clinical neurology. I am reading the whole thing even though my meds only address two disease states, so that I can engage my doctors in intelligent conversation when we do lunch or dinner. For my two disease states, I have read several medical school textbooks. I subscribe to the major journals and attend grand rounds. I think I am perfectly capable of showing a physician a clinical trial that concerns an off-label indication and discussing it with him in an intelligent manner. Or maybe I was imagining things at lunch this week when I told a neurologist about a drug interaction of which he was unaware…
HorusCat
And let’s not forget that “off-label” also encompasses things like dosing changes (hey doc, starting at a lower dose works better than the higher dose recommended in the PI). Pretty stupid that legally I can’t tell my physicians who may be new to my med how experienced physicians are using it ON-LABEL, but dosing differently.
HorusCat
“As things now stand, while detailers can’t talk about off-label uses, KOLs can say anything they choose - at meetings, conferences, etc.. Some number of these folks are directly on the take, so I don’t think having a degree of whatever kind is the issue. The issue is the risk/benefit evidence.”
Justice, this is NOT true and you should know better! If I sponsor a speaker, he can only discuss on-label uses and use FDA-approved data. He may answer an off-label question from a physician after first clearly stating that the question concerns an off-label use, the company does not recommend using the drug in that fashion, and then steering the conversation back on-label.
Let’s get our facts straight, ok?
HorusCat
“think the real question is whether or not off-label advertising is tantamount to hard liquor or cigarette sales eing pushed on television.”
Shall we stop with the BS? There IS no off-label advertising in pharma. None. Handing out a clinical from a peer-reviewed journal is NOT advertising.
Congresscreatures should learn something about what they want to regulate before they try to regulate it. Pursuing indications is very expensive and requires years of trials. Usually, the off-label uses are very closely related to the on-label uses–i.e., using Neurontin for other forms of neuropathy when it was shown to be effective for post-herpetic neuralgia. Or using Lexapro for panic when it has an anxiety indication and all the other SSRIs have the panic indication. Or–as doctors did in their heads–equating the statins as sharing the “class effect” of lowering mortality when only Mevacor and Pravachol had the data.
Doctors are going to use drugs off-label without pharma’s urging or pushing, especially in the CNS area. This is because they are taught pharmacology and physiology and can translate the mechanism of action in one area to a potential benefit in another. Doctors are not imbeciles who can only use medications after a pharma rep has told them how. My doctors continue to surprise me with the creative ways they use my meds.
Justice in Michigan
HC writes, “Let’s get our facts straight, ok?”
HC - Indeed. Facts are the issue. You argue from the perspective of what the manual says, and what, indeed, would be ethical practice. But, in so doing, you effectively deny how easy and often the manual is violated in actuality. And done so with impunity.
Here is a brief bit from Melody Peterson regarding recordings that Parke-Davis made (and distributed) during their consultancy “get-aways” for their physician pals.
“Many of the physicians speaking at these meetings made statements that would have been illegal if they had come from Parke-Davis employees…Doctors, however, could say whatever they pleased. If the FDA questioned the statements, the company could point ouit that the doctor was only stating his personal opinion.” (Daily Meds, 231)
I would like to believe this strategy is a rare one and that the reality is more like the manual you invoke. Based on what I have learned from people in pharma sales who have had the candor to talk about their experiences, I am afraid that “rare” would not be an accurate descriptor.
Can you honestly tell us, from your own experience as a rep, that this does not happen? For the sake of all of us, I appeal to you to deliver the straight facts.
HorusCat
Justice,
Let us leave the Neurontin debacle, since it is the prime cause of much of the regulation we have today.
We recently had a teleconference with a well-known clinician in our geographical area. The objective was to have her do the teleconference live at lunch, then make it available through replay for a couple of weeks. This did not happen. The doctor went off-label in her dosing suggestions, not in indication. The replay was scrapped, and the company sent out letters to all participants emphasizing that her remarks had been off-label. The speaker can no longer be used.
There may indeed be reps out there pushing the envelope for all their worth. But I can tell you more and more of us are refusing to do so, because it is OUR asses on the line. I have had one little all-expense-paid trip to HQ to discuss off-label promotion of a drug, and I am telling you, that will never happen to me again.
We are talking back to the companies, too. We are questioning aggressive quotas that scream for off-label promotion in order to be met.
At the same time, I WOULD like my speakers to be able to address certain kinds of off-label questions, like changes in dosing, and closely related disease states. When I sold Zoloft, for example, if it hadn’t ALREADY been indicated for everything under the sun except toe fungus, I would have wanted to be able to address the group of disorders one might loosely connect under the heading of “anxiety” even without an indication for every one of them.
Justice in Michigan
HC - The question of how much Neurontin was an aberration we can leave as a question.
I appreciate and believe what you write about pushing back “aggressive quotas that scream for off-label promotion.” It’s hard not to imagine that those establishing those quotas aren’t (a) inviting off-label promotion even while (b) showing the film and reading the manual about not doing it. That’s, at least, what I hear from others - a kind of doublespeak that comes from higher up the chain. Sometimes, there’s a wink. At other times, just a bind.
Re: dosing, that’s a fascinating issue rarely addressed here. My impression is that the marketing _trend_ is toward higher dosing, certainly if that’s associated with better LDL numbers, etc.. (We need not retell the Baycol story either.) Otherwise, is it really the case that docs need to learn from reps that smaller doses may be right for different pts? If so, my faith in med. education drops yet another level.
Justice in Michigan
This goes back to earlier colloquy with Jack2. This from a NYT article on the issue appearing tomorrow (Sat):
“The lead author of the JAMA article, Dr. Joseph S. Ross of the Mount Sinai School of Medicine in Manhattan, said this week that his findings helped highlight flaws in the F.D.A. proposal’s reliance on peer-reviewed journals to provide the evidence supporting off-label drug use.
“What does it mean to be peer-reviewed,” Dr. Ross said, “if the company has essentially conceived the article, composed the draft and written the paper?””
Clearly, as Ross understands it, the proposal to allow peer-reviewed articles in off-label promotion does not preclude company sponsorship and authorship.
ol cranky
I know I’m late to the game here but I think it’s important to point out that the FDA’s own Randy Lutter said, in reference to companies providing reprints
In other words, permitting off-label promotion would serve as defacto permission for pharma to create a new standard of care using their products without having to conduct auditable, adequate and well-controlled clinical trials to support the safety or efficacy of this use. Sorry, this is yet another case of the FDA dropping the ball on it’s responsibilities to play cheerleader instead of cop.
horuscat
Since the off-label promotion we’re talking about is distribution of published dlinical trials in peer-reviewed journals, it’s hard to see how this will be pharma “creating” new indications. Pharma usually does trials for RELATED indications; I.e., bipolar depression for a drug that already has a bipolar indication. News flash: docs are already doing that, without evil pharma possessing them like the Exorcist to make them do unspeakable acts.
Justice–what I am saying is the field is fighting back. And it’s not always a case as simple as lowering the dose. Sometimes it’s going faster, or only dosing qhs instead of bid for a few days. Sure, the doc would eventually figure it out–after 5-6 failures. A rep can short-circuit that process.
Justice in Michigan
HC - Glad to hear re: the field. If you haven’t seen it, a post for you over on the aging “F You” thread still hanging on over on the margins.
Re: the guidelines that Jack2 first excerpted and I posted above, they are drafts that the FDA is circulating (hat tip to Gooz News, as Ed would say).
Let’s be specific: the famous JAMA CLASS study publication in which study Pharmacia was seeking FDA approved GI benefit for Celebrex. As published, CLASS appeared to show that. JAMA wrote editorial in praise of cox-2s and Celebrex in particular. And even Bob Temple noted that this probably had an enormous impact on rx’ing Celebrex.
Turns out, of course, it was baloney. CLASS, as it appeared in JAMA, left out the second six months of the data. Once those back in, the GI benefit disappeared.
That is why FDA (which had all the data) did not allow Pharmacia/Pfizer to claim GI benefit for Celebrex. And thus why you won’t find it on the label.
Now let’s say (hypothesis) that Celebrex turns out to have significantly increased CV risks at higher doses. In the new regime as proposed, docs would have been flooded by reps giving them the JAMA editorial and talking up the GI benefit till cows come home. This was, after all, “medical information,” canonized (so it appeared) in JAMA.
So docs would and did start rx’ing Celebrex in much greater numbers. For a benefit that turned out to be bogus. And, in the process, _could_ have ended up killing some number of people because of Pharmacia’s duplicity.
All enshrined in what seems to be the most reliable peer-reviewed journal there is, and even with an editorial.
Bob Temple ended up saying that the “hype” of the article probably “has more impact than our labeling does.”
Undoubtedly, it did.
Is that the future folks want?
Justice in Michigan
Should have included the fact that most of the articles authors were Pharmacia employees and/or consultants.
HorusCat
Justice,
I think the guidelines disallow use of editorials, letters to the editor, etc.?
The question of the quality of the research published in journals is a different one than whether pharma should be allowed to distribute them.
Everyone points out that the authors of the articles have pharma connections. Of course they do!!! Who else is going to fund these studies? Don’t say the government–it is NOT the job of the government to do medical research. It may be appropriate to demand more transparency around the research, but let’s stop with the self-righteous outrage about who writes the articles and does the trials. Of course trials have a commercial purpose; drug companies have an interest in expanding the market for their product. This is a case of different constituencies having interests that merge (scientists are curious, doctors want advances in medicine, patients want better drugs, and drug companies want to make money), while also having some interests that conflict. That is an argument for oversight and regulation–in an environment that is conducive to innovation and risk-taking–not for the sanctimonious outrage expressed by the likes of the Congress creature Waxman.
Justice in Michigan
Whoa! “Congress creature Waxman”?
Anyway, I think you make my point which I first stated above. Getting an article in a referreed journal (like JAMA) is a much lower bar than getting an FDA approved indication. The CLASS example shows that one can get an article in JAMA which is total baloney (or bologna, for the continentals).
You write: “The question of the quality of the research published in journals is a different one than whether pharma should be allowed to distribute them.”
If research published in journals is pretty easy to spin, I think that is absolutely material to whether reps should be allowed to distribute “peer-reviewed” studies related to unapproved uses. So, once again, the distinction you make has logical but not practical relevance.
So the actual question: Should reps be able to hand out potential baloney that appears to support unapproved indications and/or unreal benefits and/or lesser-than-actual risks?
Me and the Wax Creature would vote “No.” Dan Troy and his Ad Company votes “Yes.” I assume that you are with Troy and the Ad Company.
Justice in Michigan
HC - A different question, and one which is genuine and of interest.
I see on another thread that you have a Ph.D. in neuropharmacology (I think I have the field right).
And you are using your training to expand the market for your company (I have no problem with that). But you have also suggested that the sales person and the science person are not always easy to balance. You were once “called on carpet,” you suggest, for pushing sales beyond FDA margins. And you have also, along with others, pushed back from the field against expectations that could tempt at least some to push sales beyond science.
Every field has its high-wire acts so such challenges are not unique or concerning in themselves. But I would be interested in your insights into how you see yourself managing them over the years, as well as other colleagues who you know. What does it take to do it well? What tend to be the reasons when things don’t go so well?
As elsewhere, learning about things I don’t know is, for me, the _best_ thing about Pharmalot.
HorusCat
Justice,
Good questions. Thanks for your interest. We once had a way of recording what went on in our offices, conversations with docs, nurses, etc. I had a product that was not indicated for a certain group of people, but the doctors that served that group of people were in my quota and represented a substantial chunk of it, as a matter of fact. So I, like every other rep, called on those doctors. What I tended to do was the sort of detail companies hate, “Hi, what’s happening? Do you need anything.” But I would record what the doctor said back to me.
At the same time, I and others were whining pretty hard about why those doctors were in our quota. We kept pointing out that it was begging for off-label promotion. Finally, 4 years later, they got taken out. In the meantime, any rep who had recorded notes from conversations with those doctors was interviewed. It was non-adversarial–the company was actually trying to figure out what they had done to encourage off-label promotion. The questions they asked me were about what managers and upper management had told us and had us do. There were no repercussions for the reps involved. I don’t know what happened ultimately, because I left the company, but I was encouraged by that.
As for using my knowledge to expand the market, I don’t know that I do that. I understand how the drugs I sell work and I understand a little about the various parts of the brain, but I’m NOT a doctor. What I can do is engage docs on a scientific level–I think it is more a gestalt they get from me than anything else. My point to Former was that he was being patronizing in suggesting that I have nothing to offer a physician (because they are some sort of deities and I am a peon rep).
You ask very good questions, Justice, and I appreciate your insight. I would say there is a difference between a clinical that addresses an off-label, but related, topic for a drug (i.e., panic for a drug with GAD indication) and a completely off-the-wall off-label indication (bipolar for Neurontin, although I still have a couple of docs who swear by it, go figure.).
Justice in Michigan
Thanks, HC. This is interesting.
So I have to ask a potentially loaded question, but it is again a genuine one. A skeptic reading the account would ask - so why did the company keep sending you to those docs? As you said, they were rx’ing a lot yet the situation was “begging for off-label promotion.”
The skeptic would say - for four years, the company - or field directors - got what they wanted. Then concern about liabiiity set in (was this post-Neurontin?). So they create the scenes of reps coming in to be “sure” that no one was going off label. Creates the appearance of propiety and concern … four years later.
But, as you suggest, it sounds like there may have been splits within the company between different levels of management - or concerns about splits - between groups that were more and less comfortable with tacit or active off-label promoting. Is that any closer to it?
When you say, “record” the conversation, I assume you mean your own notes, not electronic.
Doc
The FDA is insane to loosen off label dissemination (promotion)of information by pharma. The vast majority of sales reps who would deliver this data are not medically trained and biased based on incentive compensation programs - both cash and award trips, annual performance reviews based to a large degree on product sales and forced rankings that can mean loosing your job. Once you open this door, you will reap a whirlwind of baised, unscientific, dollar driven activity by tens of thousands of sales reps with millions of budget dollars to spend. Is that really what the FDA or the public wants? And if you think that doctors can sift through the morass of biased data, think again. They are too busy and concerned with their survival to investigate every detail their reps bring them, besides a large part of the rep job is to develop those strong relationships that DO alter human behavior. Once you are the doctor’s long term trusted ‘friend’, their guard drops - no matter what they think. Marketing departments know that with greater promotional latitude, they don’t need to push off label use, the sales reps will naturally go that direction. It has already happened too many times under current guidance.
HorusCat
Hi Justice,
I hope you find this. I was out-of-pocket for a couple of days: I gave blood and it just wiped me out. I could barely make it through the day for a couple of days. I guess I am getting older–I used to give blood and then go run six miles the same day.
I wish I knew what was going on with the company. I think you are right; there may be a “split” between power groups in the company. I know one thing: the attorneys are clear where they stand! I don’t know: maybe they do a risk-benefit analysis…we stand to earn X dollars, while a penalty would be Y dollars. I am clueless. I just know that I am sticking to the label. That’s my story, and I’m sticking to it. Fortunately, the products I have now don’t lend themselves to off-label use at all. One is a biologic, and you can’t even get it without a confirmed diagnosis for the indicated disease state.
Well, I’m still really tired. I’m going to go take another iron supplement and go to bed. I hate getting old.
Justice in Michigan
Got it. Thanks for word. Hope you feel better soon! (Sounds like they took samples…)