Friday, August 31, 2007
A View from the Trenches: Delaware
"Although the spin that one hears from the pharmaceutical industry and some physician organizations is that these practices [giving lavish gifts to docs] have been clamped down upon; the author knows for a fact that this is not true. I have seen many instances of physicians and even mid-level providers making their patients wait in their exam rooms [while] they were in their offices or even in the hallways negotiating additional funding for a weekend at a regional or local hotel or resort, not just for themselves, but for their children as well. I have seen doctors set themselves up with things such as free tee times, free dinners at expensive eateries, airline flights, mixers, or arrangements to be a 'speaker' or 'consultant' even though they seemed to lack even the most basic knowledge of recent studies concerning the specific topic..."
Dr. Campo concludes, "We are physicians, not prostitutes. It is time that at least some of us act more like the former."
Campo D. Big Pharma. Del Med J 79: 243-45, June 2007.
Physicians' Denial of Side Effects: Brainwashed by Whom?
Golomb et al. went after samples of the population known to have suffered side effects from statin drugs. Of those they surveyed who had widely-reported statin side effects such as muscle aches, 87 percent talked with their physicians about their symptoms, in virtually all cases with the patient and not the physician initiating the discussion. Only 39 percent then reported that the physician had endorsed the possibility that the symptoms might be caused by the statin. Nearly a third of the physicians dismissed the possibility, and 29 percent were noncommittal.
Why should physicians be so ready to deny that these symptoms were medication-caused side effects? Let me note first that in my own practice as a family physician, I was usually slow to diagnose this side effect syndrome. The reason is that a patient may be on statins for months or years before the symptoms appear. It is then hard to think of an association between the drug and the problem. But to my credit, if the patient actually reminded me that these symptoms might be statin-related, I would hope I would then have said, "oh, yeah" and at least been open-minded. (Let's face it, no one is taking a statin to be cured of a deadly disease he has right this minute. Mostly we are aiming for long term prevention. What's the harm of stopping the statin for a few weeks to see if the symptoms go away or not?)
So the first reason that strikes me, to be in this state of denial, is the physician's ego. When the patient says that the statin we prescribed might be causing a side effect, it might sound to us like, "You did this to me." This could lead to a wrong-headed and ultimately inexcusable, but emotionally understandable defensive denial.
Another possibility also looms. If the vast majority of physicians get most of their drug information from industry sources; and if (as is reviewed in HOOKED) most industry sources, especially drug reps, say less about side effects than any other bit of information about the drugs--then the physician's reflex denial that the drug could be causing side effects might be one more example of pharmaceutical marketing-induced brainwashing.
Golomb BA, McGraw JJ, Evans MA, Dimsdale JE. Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance. Drug Safety 30:669-675, 2007.
Ganguli I. Is your doctor in denial? Survey finds physicians often dismiss complaints about drugs' side effects. Washington Post, August 28, 2007: HE04.
Wednesday, August 29, 2007
The Inside Scoop on Reps: Who's Right?
When I saw the article by Ahari and Fugh-Berman in PLoS Medicine, in which the first author describes his fomer career as a drug rep (see my posts on the article dated April 26, 2007), I was pleased to see a general confirmation of what I had written, along with additional details as to the precise psychological profiling techniques that reps use to size up each physician and to select the sales approach that works best for each.
Now, Kevin O'Reilly, writing in American Medical News, has dug out (rather belatedly one would think) the Ahari-Fugh-Berman paper, and provides a summary of their report along with denials from a couple of former drug reps. (I am quoted at the end of the article as supporting Ahari's account.)
The former reps who took issue with Ahari's characterization (I should add that Ahari has an MPH and is now doing health services research at UCSF) are:
- Pam Marinko: "the very kind of thing that gives drug reps such a bad reputation"... Ahari "cherry-picked" certain sales practices and "served it all up in a negative light"..."It's absurd to suggest that a physician would make a prescribing decision based on whether he liked a drug rep."
- Sarah Taylor: "My experience wasn't anything like that"
Just what do these former reps do today? Marinko is CEO of Proficient Learning LLC, a drug rep training firm in Wilmington, NC. Taylor is author of The Secrets of Successful Pharmaceutical Salespeople. I will let you decide whether those people sound suficiently free of bias to commment fairly on Ahari's allegations.
(Incidentally, another former drug rep, now an academic, who paints a picture of the rep business in terms very similar to Ahari's is Michael Oldani, now a professor of anthropology--see HOOKED for references to his publications.)
Just a nice extra touch--Marinko is so convinced that detailing is the best way for docs to get the latest drug information, that she refuses to go to any physician who has a won't-see-drug-reps policy. I wish her well.
O'Reilly K. Professional issues: Drug rep creates stir with details on tricks of his trade. American Medical News, Sept. 3, 2007.
Sunday, August 26, 2007
Student, Resident Members Urge Family Medicine Academy to Get Strict with Pharma
Meeting August 2-4. the congresses encouraged more study of the results of pharmaceutical company interactions with family physicians; and the residents called for the AAFP to explore more ways to fund its annual conferences without pharmaceutical funding and commit to a pharm-free conference by 2012.
Comment: As a long-time AAFP member I applaud this action by the students and residents. I am about to attend what is strangely my first AAFP annual scientific assembly, in Chicago in October, where I am supposed to participate in two panels on the role of the pharmaceutical industry. The rumor mill has always held that the exhibit hall at AAFP is one of the most extreme displays of commercialism at any medical organization meeting, though reportedly there have been serious efforts to rein in the excesses in more recent years. I hope to have a report following the meeting.
Champlin L, Porter S. Residents, students wrestle with health system reform, other issues. AAFP News Now, Aug. 10, 2007;
Saturday, August 25, 2007
Industry CME Spending Increases; What Does It Signify?
HOOKED explains that in 2003-4, two events occurred that would have appeared to make CME a less attractive investment for the drug industry. First, the Office of the Inspector General, DHHS, issued a stern report warning the industry that if they did not create secure firewalls between their marketing activities and CME support, they might be in violation of Federal anti-kickback laws. Second, the group that oversees CME, ACCME, introduced strict new rules to prevent speakers from parroting the industry message at conferences.
It was an open question what the response of industry would be to these changes. Some predicted a major falling-off in commercial support for CME. Others wondered if the industry, as it always had before, would simply find the seams in the new rules and continue on its merry way. My conclusion in HOOKED: too soon to tell.
The announced increase in industry CME support might at first glance persuade the paranoids that the new "strict" guidelines must after all not be working. My own conclusion at this point is the same as before--too soon to tell. Some factors mitigate the possibility that the industry is again in the CME driver's seat. The low 2005 funding figures might simply represent that the industry was holding back, waiting to see what action DHHS planned to take on the anti-kickback front. The slight increase in 2006 vs. 2005 might show that the industry is now confident that it has figured out the legally safe ways to invest in CME. MM&M notes that the venues seeing the largest increase in 2006 were medical schools and medical societies. The industry may have reasoned that supporting CME in those institutions was safest overall in terms of showing the Feds that a real firewall was in place, and that marketers were not controlling CME content. (This does not mean that CME at medical schools and medical society meetings is free of commercial bias; but it may mean that at least, the industry continues to live in fear of the DHHS Inspector General.)
Iskowitz M. Pharma pursued safe haven for its CME spend last year. Medical Marketing & Media On-Line, July 19, 2007; http://www.mmm-online.com/Pharma-pursued-safe-haven-for-its-CME-spend-last-year/article/24565/
Friday, August 24, 2007
Epstein vs. Relman: A Debate to Overlook
I have not read Epstein's book, and based on HOOKED you can presume that I would tend to disagree with most of what he says. Epstein also wrote a paper published last winter in Perspectives in Biology and Medicine on conflict of interest, and I disagreed with most of what he said in that paper. All of which is beside the point here, as the question is rather what one might learn from this exchange of views.
Alas, it is disappointing. Relman beats up on Epstein for two cardinal sins. First, Epstein is a frequent consultant for the drug industry and is also an economic disciple of Milton Friedman. Second, Epstein is a lawyer writing about health care matters. Both sins show that he is an idiot and that he cannot possibly therefore be correct about anything further.
Epstein replies in kind. Since Relman is a physician without any additional training, he clearly knows nothing about law, or economics, or corporations, so he's incompetent to pass judgment on any of these issues. And since Relman rejects Friedman, he must be an unreconstructed New Dealer (proof: he was born in 1923!) and is therefore completely unreliable on anything related to either economics or government.
Just how this pissing contest is supposed to enlighten the rest of us is never explained by either party.
Because Epstein assumes that Relman is an ignoramus, he proceeds to teach Relman (and the weary reader) a course in Econ 101 as he sees it. Industry must make a profit or else it will have to shut down. Regulation has costs as well as (purported) benefits. Advertising lets consumers know that there is a product out there that they might wish to consume. Drug companies spend a lot on research. Gee, thanks for all of these insights.
If we are going to keep score, I give the win to Relman. He accuses Epstein of being an unabashed apologist for the industry, citing all the arguments that support the industry position, selectively remaining silent on any point that is not in the industry's favor. Epstein, in his Econ 101 course, basically acts in such a way as to verify Relman's description of him. As my printout of his rebuttal runs 16 pages, single spaced, I can give only one example. Epstein says that as a consumer who has no special training in drugs, he naturally goes out and hires a professional--a physician--to advise him on medical matters. But in the next paragraph, he says that if he had a serious or terminal illness, he would not wish to wait for the randomized controlled trials to be finished. For such a person, he says, "the fetish over clinical trials is a death sentence." He goes on to praise the Abigail Alliance for demanding a legal right to access to any experimental drug that the patient and physician think might be life-saving.
Now, what Epstein never explains, and seems completely unaware of, is the contradiction between saying that he would hire a doctor to give him the good advice he needs on drugs, and depriving that same doctor of what is today considered the best possible evidence of what drugs work and for whom (that is, the randomized clinical trial). How is the doctor that he prudently hires supposed to get the information on which to base his advice--tea leaves?
Fortunately this is not about keeping score. It is about figuring out these thorny policy issues, and we cannot do so if we have a cardboard caricature of free-market worship on one side, and a cardboard caricature of anti-free-market attack on the other.
Instead, read two different books. First read Medicine and the Market by Callahan and Wasunna. You will find a careful analysis of both the ethics and the facts related to markets as a means of organizing medical care. Among other things you will read that in most of the civilized world, it is simply a given that we need both private markets and government regulation, and that regulation helps markets run well by leveling the playing field. Only in the U.S. do we find the ideological fervor that insists that we worship at the altar of the "pure" free market and the government be damned.
Next, read Leonard Weber's Profits Before People? Weber (an esteemed colleague of mine, who taught at University of Detroit-Mercy) has taught and written about business ethics in health care. His book on the pharmaceutical industry could be viewed as an ethics consultation, as if the industry had noted its poor PR lately and asked Weber for his ethical advice. Weber tries to give them the advice that he thinks a good business ethicist would. And his advice is markedly different from the Milton Friedman school. In fact, Weber ends up saying just about the same bad things about the drug industry as do its more strident critics like Angell (and me for that matter). I'd like to hear Epstein explain how it is that Weber knows nothing about corporations and markets and the realities of business.
Relman AJ. To lose trust, every day. The New Republic, July 23, 2007: 36.
Epstein RA. Cambridge v. Chicago: an answer to0 Dr. Arnold Relman's New Republic review of Overdose. August 22, 2007; http://www.pointoflaw.com/columns/archives/004194.php
Callahan D. Wasunna AA. Medicine and the Market: Equity v. Choice. Baltimore: Johns Hopkins University Press, 2006.
Weber LJ. Profits Before People? Ethical Standards and the Marketing of Prescription Drugs. Bloomington, IN: University of Indiana Press, 2006.
Wednesday, August 22, 2007
Pharma Goal: "Expand the Druggable Universe"
In Boston early this month was held the Drug Discovery and Development of Innovative Therapeutics conference. Senior executives from the big firms showed up to tip their hands on their future research agendas.
Dr. Melvyn Turner, senior VP of external research at Merck, indicated that one of his company's prime goals was the oncology drug sector, particularly the new area of RNA interference compounds. He said Merck found this area attractive because of the technology's ability to "expand the druggable universe."
I am sure that Dr. Turner meant nothing sinister by this phraseology. Nevertheless, for paranoids like me, it does seem to capture rather nicely what seems to be the overall agenda of Big Pharma.
The old joke had it that what kept the puritan awake nights was the abiding fear that somewhere, somebody was having fun. I assume by the same logic, what keeps pharma execs awake at night is the abiding fear that somewhere in the world, somebody is not taking drugs.
Breaking news on drug discovery.
Prominent Cancer Scientist: Stop Evergreening
Joining the voices condemning evergreening and related patent shenanigans is Brian Druker, the scientist (at Oregon Health and Science University) generally given the major credit for the discovery of the cancer drug, Gleevic (or Glivic outside the U.S.), which ushered in a new generation of less-toxic "designer" anti-cancer drugs.
Druker reviews the history of the development of Gleevic, noting that it involved an extended collaboration between academic and industry scientists. He recalls also how the drug developers had to overcome continued skepticism about the value of their discovery. (His story is rather at odds with the standard Pharma history of the same events. The Pharma side now seems not to recall how skeptical the money managers were, and also believe that almost all the major discoveries were made by in-house industry scientists.)
Druker goes on to complain about the high price now being charged for Gleevic or Glivic. (HOOKED explains how the price chosen had nothing to do with the actual cost of producing the drug, and was for all intents and purposes simply what the market would bear. Within a year or so Gleeevic sales reimbursed its maker, Novartis, for all the costs of research and development.) He complains about the games played with patents and monopolies that result in these high drug prices, that put needed drugs outside the reach of too many patients. He argues that he and his fellow scientists never planned to discover important new treatments for dread diseases like cancer, just to see the drug priced so high as to be unavailable to so many.
In HOOKED, Gleevic is presented as a showcase industry success story. It's a genuinely novel drug, based on a novel biochemical concept, that produced near-magical results in its early trials for patients with a couple of relatively rare sorts of cancer. Further experience with the drug appears to date to have confirmed both its effectiveness and its low side-effect profile--a huge breakthrough in cancer chemotherapy. So, if one wanted to pat the drug industry on the back, it is hard to find a better case to do so than Gleevic. It is therefore especially sad to see even this "wonder" drug drawing this severe criticism, and for good reason.
Druker B. Don't abuse patents: scientists. http://www.livemint.com/Articles/PrintArticle.aspx
Something Rotten in Minnesota, Disclosure Law Reveals
Now, the Associated Press has brought forth the news that two members of the Minnesota Medicaid Drug Formulary Committee, that decides important questions as to which drugs will be reimbursed by the Medicaid system, have both received big bucks from the industry. A psychiatrist earned $350,000 (most presumably in speakers' fees) over a 2-year period; a pharmacist earned $78,000 during that time.
Both of them, plus the committee chairman, stated that these payments did not affect their work on the committee. I guess they have to say that, as unbelievable as it must sound to anyone with half a brain. However, the Committee is now thinking about (!) instituting some new rules to deal with conflicts of interest.
I admit that for a while I was rather skeptical about the value of gift disclosure laws such as Minnesota's. The goal is to stop these conflicts of interest in medicine, not to disclose them. But given the way that publicity is being used in the right hands to stimulate change, I am becoming convinced that this is at least a necessary intermediate step, however much work still remains to be done.
Associated Press. Financial ties link docs, drug companies. August 21, 2007; http://www.msnbc.msn.com/id/20379563/
Tuesday, August 21, 2007
Pharma Loses Crucial Court Battle in UK
The second post reports that the court threw out 5 of the 6 charges against NICE, leaving NICE "guilty" only on a small technicality that it can easily address.
The reason the court found in favor of NICE, in hindsight, is simple. All the scientific evidence goes to show that these drugs, which have precious little effect on Alzheimer's at any stage, are especially ineffective when given early in the course of the disease. The Datamonitor article notes that Alzheimer's is a terrible disease; and that it is becoming more common with the aging of the population. Both true. But neither means that the drugs work, as much as we might wish they did.
This victory is a very important one because my colleagues who study "evidence-based medicine" view NICE as the single most important body in the world for trying to bring rational cost control to medicine. The agency basically looks at the scientific evidence about both the benefits and the costs of treatment and then issues a ruling about whether the benefits are great enough to be worth it. (Many people think if we are ever going to have meaningful control of medical costs in the U.S., it will only be because we manage to invent NICE's U.S. equivalent.) The reason why no court challenges like this (or at least few) have occurred till now is that NICE has been very nice to the drug industry. Most treatments, even some thought to be questionable, have previously been approved. The mild Alzheimer's case is one of the relatively rare instances of NICE digging in its heels. (Which means that had the court overruled it here, it would have been especially unfortunate.)
Datamonitor made a big deal of "patient power" in the form of the Alzheimer's Society, which joined the two drug makers, Eisai and Pfizer, in the court suit. The Society's presence proved that this was all about patients getting the drugs that they have a right to, and not about greedy companies making more money. It was considered unimportant that the Alzheimer's Society receives generous funding from the two drug companies. The Society primly pointed out that it used funds from other sources to pay its court costs. (See HOOKED for a more extensive discussion of "astroturf," or how the industry creates supposedly "grass roots" action that happen to favor its products by laundering its money through PR middleman firms and through these patient advocacy groups.)
How Is Merck Faring in Vioxx Lawsuits? Very Well, Thank You
So now it's three years down the road. And, as Alex Berenson reports in the New York Times, the liability risk once estimated to be as high as $25 billion has shrunk to $5 billion. And after Merck stock plunged at the first adverse jury award, it has since regained 80 percent of its value.
How has Merck done it? It has simply decided to use its financial muscle ($1 billion so far spent on legal fees) to fight each case individually, and to appeal every adverse ruling all the way up. The courts have helped by insisting that each case be tried separately and opposing any class action suits.
The medical facts work in Merck's favor in such a setting. We can know, on a population basis, that there may have been as many as 140,000 excess heart attacks in the U.S. during the five years that Vioxx was on the market after the risks were clear. The problem is to translate that number into the reasonable certainty that John Doe of Podunk, East Dakota was one of those heart attacks--that he had his particular heart attack when he did because he took Vioxx, and that his high blood pressure, high cholesterol, or other risk factors had nothing to do with it. So far, in most cases that have come to court, Merck lawyers have managed to create reasonable doubt that Vioxx was the cause of the heart attack. And, in the case of Robert Ernst, where the jury found against the company and demanded $253 million, the case is still tied up in appeals and the Ernst family lawyer predicts that if they see any money at all, it won't be until 2010.
I'm no legal expert, but it seems from this vantage point that if you want to have your day in court in the U.S., having an extra billion or so dollars in your pocket does not hurt.
Berenson A. Plaintiffs find payday elusive in Vioxx cases. New York Times, Aug. 21, 2007.
Monday, August 20, 2007
Some Discouraging News about Training Pharmacy Residents
A recent study looking at pharmacy residents is discouraging even on this count.
Ashker and Burkiewicz reported on a web-based survey of 496 pharmacy residents (estimated to be about a third of potential responders). One-quarter of the residents who responded had received some sort of training regarding interactions with industry, and 60 percent said their institutions had policies regarding such interactions--though over half of that subset reported that the policies did not change their interactions.
The group, by overwhelming margins, viewed as appropriate education gifts, free samples, and attendance at dinners and meals. They balked only at "noneducational" gifts which 69 percent viewed as somewhat or very inappropriate.
Interestingly, residents at institutions that had policies, or that had received training, were less likely to believe that they or their peers were influenced by industry marketing. They did, however, receive fewer gifts (as self-reported) and were more likely to view noneducational gifts as inappropriate.
There are a number of limitations for this survey and its methods, but if we take the results at face value, it certainly is not very reassuring that educating residents (in this case, pharmacy residents, who if anything ought to be more skeptical about the industry's message than medical residents) produces the changes in behavior that I would see as desirable. I would argue that this is one more bit of evidence that it is vain to imagine that the status quo in interactions between medicine and the industry is a given, and so the best we can do is educate our trainees to act more appropriately in this environment. The only effective activity is something that changes the status quo.
Ashker S, Burkiewicz JS. Pharmacy residents' attitudes toward pharmaceutical industry promotion. Am J Health-Syst Pharm 64:1724-31, August 15, 2007
Thursday, August 16, 2007
Avorn: Give FDA Committees Some Credit
Dr. Jerry Avorn of Harvard, author of Powerful Medicines and a well-known critic of the pharmaceutical industry and regulatory system, writes in this week's New England Journal that it is not as bad as all that. He reviews several recent decisions from FDA scientific advisory committees that show considerable backbone in standing up for drug safety and protecting the U.S. public. He compares the recent drug action to an action on a similar drug within the past decade, and shows that for the drugs Arcoxia (anti-inflammatory) and rimonabant (weight loss), the recent decision was much more scientifically defensible and hard-nosed than was the previous one. The one disappointment he admits to is Avandia, noting that its advantages as a drug for diabetes are so meager that it is hardly defensible to keep it on the market in light of fears of increased heart risks.
Avorn has basically given up on the FDA or Congress cleaning up its own messes and so calls on the scientists who serve on the external advisory committes to shoulder the burden of standing up for the facts. He reminds us that when we compare the regulation of the drug industry with the energy, defense and finance sectors, we have it head and shoulders above them in our ability to bring rationality and science to bear on the problems, even with our present flawed system.
Avorn J. Keeping science on top in drug evaluation [perspective]. New England Journal of Medicine 357:633-35, Aug. 16, 2007.
New England Journal Study: DTC Ads Increase
Specifically, DTC ads fell off a little in 2002 but then rebounded from 2003 to 2005 (the last year for which data are available). In 2005, the industry spent $4.2B on DTC, which was 14 percent of total promotional spending. By contrast, in 2004, the industry spent $7.6B on detailing (26 percent); the next year this figure dropped to $6.8B (22.6 percent), all figures being converted to 2005 dollars.
Total spending for promotion in 2005 was $29.9 B, which increased from $11.4B in 1996. That represented 18.2 percent of total industry sales revenues.
While DTC ads expanded, the ability and/or willingness of the FDA to police them dropped off. In 1997, the FDA issued 142 notification letters for violation of regulations in advertising; this had fallen to 21 in 2006. The authors note data from the FDA that make it much more likely this drop was due to lack of personnel than to improved compliance.
The authors also provide data to show that the DTC budget is skewed toward a few heavily advertised drugs. The list of leading drugs for DTC is headed by Nexium, Lunesta, Vytorin, Crestor, Advair, and Nasonex. Nexium, as the top drug, had $224M spent in DTC ads. By contrast, drug #7, Flonase, had only $111M, and drug #20, Prevacid, got only $71M.
Comments: The total promotional spending figure of almost $30B is news; previous articles had tended to repeat the earlier figure of around $21B. According to the analysis offered by Marcia Angell in her book, The Truth about the Drug Companies, the true figure is still higher than this and probably tops $40B, due to so many of the true promotional costs being hidden. I also believe that this figure is low because of the author's claim that companies spend only 18 percent of revenue on promotion; for reasons explained in HOOKED, I think the better estimate is nearer 30 percent.
It had been widely predicted in recent years that DTC spending had topped and was about to drop, due to the public apparently having become saturated with ads so that they were losing effectiveness. The makers of that funny stuff called "Head On" seem to have figured out that annoying the heck out of you with their ads is actually a good way to sell theior product, and maybe Pharma is reading out of the same playbook.
While noting that DTC still represents a small slice of promotional costs compared to detailing and "free" samples, it is proportionately growing, especially now that costs of detailing have actually dropped-- apparently due to recently announced layoffs in sales force as the reps trip over each other all trying to see a limited number of physicians. If so we might see even lower figures for detailing costs when 2006 and 2007 numbers become available.
Donohue JM, Cevasco M, Rosenthal MB. A decade of direct-to-consumer advertising of prescription drugs. New England Journal of Medicine 357:673-81, Aug. 16, 2007.
Monday, August 6, 2007
Excellent Series in LA Times on Pharma's Influence
See this article and click the several links for "related articles." Disclosure: Yours truly is prominently featured in the last in the series.
Here are some fact-updates from a couple of the articles:
According to Dartmouth marketing professor Scott Neslin, the return on investment for $1 spent on the following marketing techniques by the drug industry are: advertising in medical journals, $5.00; meetings or continuing education, $3.56; direct to consumer ads, $1.37; average detailing of drugs to physicians, $1.72; detailing of aggressively marketed drugs, >$10. (This shows why the industry is starting to sour on DTC ads, and continues to surprise us as to how great the payoff is from the old-fashioned journal ad.)
Data on drug reps: Healy estimates there are still about 100,000 of them despite recent talk of layoffs; they earn on average $81K annually (she does not say if this is before or after bonuses).