Thursday, April 30, 2009
I’m a French GP and editor with the continuing education journal Prescrire (French and English edition), and I’m a regular visitor at your blog. My CME organization publishes comparative effectiveness reviews, see the 2008 review of new drugs for instance http://english.prescrire.org/spip.php?article882. Prescrire is totally funded by subscribers and accepts no advertising, grants or outside support of any kind.
Best, Christophe Kopp
Prescrire editorial team
I admit to being slow off the starting block on Prescrire. Based on all the international e-mail traffic I am aware of, this is a truly excellent source of evidence-based, non-commercially-biased drug information, that I believe few US users are aware of. I am pleased to add the Prescrire-English link to this blog, and thank Dr. Kopp for writing.
Wednesday, April 22, 2009
Dr. Lewin's points appear to be very moderate and reasonable on the surface:
- The Bloomberg article mentions the ACC and its involvement with an organization called Partnership for Improving Patient Care, hinting that PIPC is nothing but a Pharma front and that by joining PIPC, ACC is promoting the industry's cause with regard to comparative effectiveness (CE) research
- Dr. Lewin thinks it wrong to suggest that just because the drug industry is part of anything, that automatically makes it bad
- ACC agrees with the drug industry on the need for CE research--it is good
- ACC disagrees with the drug industry on the need to take costs into account in relation to CE research, and holds that cost effectiveness is indeed a central duty of organized medicine
- Nevertheless, within PIPC, groups that have slightly different stands on these details can all promote better patient care
- ACC is firmly behind CE research and also is behind cost-effectiveness research, but believes that the two should be separate but parallel efforts
So if all this is reasonable and moderate, why do I think that something here does not pass the sniff test? Several reasons.
One reason is past history. Over the years, ACC has been one of the major medical organizations whose published practice guidelines have tended to be viewed by my evidence-based-medicine friends as among the lowest on the based-on-evidence scale--and just by coincidence, ACC has been happy to pocket major cash from the drug industry. So if the ACC has suddenly turned into a drug industry skeptic, that's a fairly recent development. Also don't forget that when critics of American medicine show you good-quality evidence that roughly one-third of tratments administered to U.S. patients are medically unnecessary, and somebody asks you for some examples, cardiology procedures always show up near the top of the list. So putting the ACC in charge of cost-effectiveness research is sort of like the old adage about the fox and the henhouse.
A more pertinent reason is: just what is being claimed in the guilt-by-association game? It is not simply that if Pharma joins a club, that club must be bad, even if its other members are all good. It is rather that over the years, Pharma has proven to be amazingly adept at joining a club, and then turning that club toward its own interests and advantage, regardless of who else the members are. When you have the deep pockets that Pharma has it is relatively easy to hijack other people's organizations and bend them to your will. (Assuming that PIPC really is somebody else's organization and not Pharma's own creation, which is certainly possible and indeed likely; I personally have not done the research. Pharma has created many organizations, as I explain in HOOKED in my chapter about "astroturf", that are deliberately made to look as independent from Pharma as possible.)
The final and perhaps most serious reason is to be found in this statement from Dr. Lewin: "Cost effectiveness has to be a critical issue for the nation, but it should be a parallel process, as PIPC members believe. " The claim appears to be: Both ACC and PhRMA can be members of PIPC because they believe that CE research is very important, and also that CE research should be kept separate from cost-effectiveness reserch. ACC differs from PhRMA's position in claiming that cost-effectiveness research is very important too, but only so long as it is parallel to, not combined with, CE research.
I cannot claim to be a research methodologist but I think I know something about what counts as a good cost-effectiveness study. (We know what bad ones look like--the major drug firms sponsor a ton of them. They all seem to come out showing that even though their drug costs 10 times as much as the rival treatment, once you make a set of highly questionable assumptions, the drug still turns out to be cost-effective.) A good cost-effectiveness study addresses both whether a treatment is better or worse than some rival treatment, when cost is not an issue; and then adds cost estimates to see whether the treatment is still a good deal when costs are taken into account. A good study is very explicit in making its assumptions about costs as well as any other variables. A good cost-effectiveness study also addresses the range of values over which its conclusions hold--so for instance, if the cost of the drug were reduced by 50%, would a non-cost-effective drug then become cost-effective, or not?
Suppose that some scientists did a high-quality cost effectiveness study and the results showed that while drug A was somewhat better than drug B, drug A also cost a good deal more than drug B. And suppose that insurance companies then used that study to say that they would not cover drug A but would only pay for drug B. Further suppose that patient advocates disagreed with the insurers, and claimed that the advantages of A over B were so substantial that it was worth the extra cost, and it was a violation of patients' rights to be denied access to A. My point is simply that if the study was a good study, there would be no hidden data. The data needed to carry out this debate would all be included and fully transparent within the research study itself. You'd have no need for a "separate but parallel" CE study; the CE study was built into the cost-effectiveness study and is there for all to see.
So if that's what a good cost-effectiveness study is like, what do you mean when you say that this is all very well, but it should be kept separate from "real" CE research? You could mean two things in my view. One is that you are in favor of good cost-effectiveness studies but not lousy ones. That'as very nice if ACC feels that way, but in that case, why is it jumping into bed with the organization that funds more lousy ones per square inch than anyone else alive?
The second thing you could mean to say is that really, truly, you are against CE research if it makes any mention at all of costs, or in short, limits your chance to make a buck. But you know you'd look unscientific or socially irresponsible if you said so out loud, so you need a cover--and your cover is this nonsense about "separate but parallel." Sort of like how Jim Crow schools were supposed to be separate but equal, maybe. The "separate but parallel" formula, in short, allows you to oppose CE research while all the time claiming that you do not really oppose CE research.
That's why Dr. Lewin's smooth talk does not pass the sniff test, in my humble opinion.
Monday, April 20, 2009
So my esteemed colleague Marilyn Mann is surely onto something by passing along this news report: http://www.bloomberg.com/apps/news?pid=email_en&sid=aHjr0BP1zvgo, which basically shows how several big companies are hurriedly adding more lobbyists to fight against the Obama administration's plans to include comparative effectiveness research of pharamceuticals as a part of the economic stimulus package. We might ask: Just what is it about comparative effectiveness research that so frightens Pharma?
Some previous opinion pieces and news reports have distinguished between comparative ("head to head") trials which simply try to establish the superiority of one treatment over another, as opposed to those that explicitly take cost into account. Then the industry opposition is focused on the latter. From that example, it would seem that the industry is deathly afraid that we might figure out that some very slight improvements in outcomes are being purchased only at huge increases in cost. They'd much rather, for example, that we know that a new chemotherapy drug prolongs the life of the average cancer patient by 2 months; but not that it costs $150,000 to get that extra 2 months of life.
Now the argument against comparative effectiveness research (with or without costs explicitly taken into account) is based on one possible use of the resulting data, which we have to admit might actually occur. The sequence would go as follows:
- Comparative effectiveness research is carried out on drugs A vs. B.
- The research shows that drugs A and B are roughly equivalent in outcome, but B costs less.
- If you look very carefully at the research findings, you'll see that the average outcomes obscure a good deal of individual variability. A sizeable minority of patients actually do better on drug A.
- However, the payer for care (the government in the most-feared scenario; private insurers in today's scenario) seizes upon the uncritical reading of the data from the trial, and issues guielines that demand that physicians use drug B and that essentially eliminate any payments for drug A.
- Bottom line--a significant number of patients are denied the drug that would most help them, just so the skinflint insurers can save a few bucks.
Against the drug company orchestration of outrage are the moderate voices of good sense. Physicians today are starved for good data on what treatments work better than others--since more than 80 percent of trials of drugs are industry sponsored, and industry overwhelmingly chooses to compare drugs to placebo and not to already effective treatment. Everyone (except maybe the pharmaceutial industry) agrees that we can only have a sustainable health system in the future if we can rein in costs. If we want docs to help us to save money, it makes a heckuva lot more sense to ask them to save us money by doing less of what doesn't work, instead of trying to deny them the data about what works better or worse.
Against these voices of reason, drug companies are reduced to doing much what the AMA had to do in the 1960s when it tried to fight the Kefauver-Harris amendments that gave the FDA the responsibility to test the effectiveness and not just the safety of new drugs. The AMA was forced in that instance to act like scientific Neanderthals. They had to claim, for all intents and purposes, that the average physician in the boondocks was just as capable of deciding what drugs are effective as the scientist conducting a multicenter clinical trial. They had to claim that anecdotal evidence was just as good as any randomized controlled study. Similarly, today the drug industry has to stress how different everyone is from everyone else, so that the average results of comparative effectiveness trials are sure to be misleading. This of course, taken to its logical conclusion, undermines any reliance on evidence-based medicine.
I conclude from this sorry spectacle that the drug industry--which shouts so loudly that when it markets its drugs to physicians, it's really engaged in "education"--is in fact deathly afraid that we will someday find out how effective its expensive new drugs really are. That bodes very poorly for what we haven't yet found out amidst the marketing smoke screen that the industry has managed to proliferate around its products.
Sunday, April 19, 2009
We have covered the earlier report of the Robinson saga in our post about the JAMA editors' hissy fit: http://brodyhooked.blogspot.com/2009/03/jama-editors-need-to-come-down-off.html
Drs. Leo and Lacasse set off that comic opera by sending their own Rapid Response to BMJ, in which they pointed out how Dr. Robinson had failed to disclose speakers' fees from a drug manufacturer in a study he published in JAMA, contrary to that journal's editorial policy. Dr. Robinson then proceeded to respond by accusing Leo of his own conflict of interest, having been a board member of an organization that is critical of the overuse of psychiatric medications, which Leo did not disclose in his own letter. (All letters are in the same Rapid Response thread at the above link.)
Now, let's put these purported conflicts of interest, and the non-disclosures of same, side by side.
Leo and Lacasse, in their own reply to Robinson, note several important points. In their own letter they did not impugn any of Robinson's motives, but merely noted that his nondisclosure had violated JAMA policy. The organization they are both members of argues (they say) not for a blanket rejection of psychiatric drugs, on any ideological basis, but rather for the judicious, evidence-based use of those drugs, which does not seem a highly controversial position. They ask reasonably if authors are supposed to disclose not only who pays them, but also all organizations they happen to belong to.
Contrast the purported nondisclosure of the purported COI of Leo's with the Robinson case. If Leo and Lacasse are to be believed (and no one yet in this controversy has called their basic facts into dispute), they did not go out looking for COIs in Robinson's case just on a whim. After Robinson's research was published in JAMA (showing that post-stroke patients had less depression if they had either counseling or antidepressant medication), Robinson was widely quoted in the popular media making claims that seemed to go well beyond the research data, basically calling for all patients to be put on an antidepressant immediately following a stroke. In short, Robinson drew their attention because he was acting like a company shill. When Leo and Lacasse went on the internet, they report it took them only a few minutes to locate traces of financial ties between Robinson and Forest Labs. So it was not as if they had to hire a private detective to follow Robinson around for months before some obscure COI was uncovered.
Put those two side by side and then tell me that the COI problem in Leo and Lacasse's case somehow cancels out whatever Robinson might possibly be accused of; and also tell me that Robinson, by pointing his finger at Leo, has not simply tried to divert attention from the discussion of his own accountability and responsibility, or lack thereof.
The ploy du jour for those who wish to deny or to distract attention from the fact that the drug industry has a near-stranglehold over the medical literature regarding pharmaceuticals seems to be "you're another."
Example: Here's a posting on the "Placebo Journal" blog, which purports to be a humorous site, though I am missing the humor in this particular situation: http://placebojournal.blogspot.com/2009/04/right-way-to-influence-someone.html
This post cites with approval the "Pharmascold" article by Shaywitz and Stossel that I recently skewered: http://brodyhooked.blogspot.com/2009/04/pharmascolds-strike-back-latest-from.html
The writer of the post then somehow manages to turn into a semi-justification for not getting excitedabout conflicts of interest with Pharma the following news account of political COI:
The politics story reveals that Gov. Ed Rendell (D-PA) received campaign contributions from a big Houston law firm, and then handed that firm a juicy contract to try a civil suit on behalf of the state against Janssen regarding their drug Risperdal. This looks very fishy because the contract with the Houston law firm somehow was handled through the guv's office directly, bypassing the state AG who you think would be expected to handle such business. Of course there was the routine denial that the campaign contributions had anything to do with this.
All right, so we agree that this stinks. What are we supposed to conclude? The article about Rendell and his shenanigans notes in passing that the substance of the lawsuit against Janssen was not the point (of the motion filed in PA court by Janssen to protest the way the lawyers were appointed). The substance involves the claim we have investigated at length in a number of previous posts--that Risperdal and its fellow "second generation" antipsychotics were heavily marketed as being safer than older drugs in that class; and that when we actually run the real numbers it turns out that these drugs are not safer, and that the companies engaged in all sorts of underhanded stuff to conceal the actual adverse reactions associated with the drugs. No company could have pulled this off without the active participation of medical investigators beholden to them who willingly did the bidding of the marketers, and who proceeded to conceal the true risk profile of these drugs from their fellow physicians and thus subjected millions of patients to undue and inappropriate risks. These are all physicians who presumably once swore an oath to do what would benefit the patient rather than what would advance their own careers or line their own pockets.
According to this post we are supposed to give these docs a free pass and stop berating them for their conmflicts of interest, all because Ed Rendell is reportedly a scumbag. To which I reply that I utterly fail to see the logic of that so-called reasoning.
We received several submissions (read the comments to that post) and the winner is:
Thanks to "David" for the submission!
What's down this year is the total payment amount--$2.9M compared to $3.1M in 2007. The significance of that change, if any, is very hard to determine, because what's up this year is the percentage of reports that have been labeled by the companies as constituting "trade secrets," and thus acccording to the law immune from reporting in detail--now making up 80% of all reported payments.
If companies consider 80% of all payments to prescription writers in Vermont to be trade secrets, they basically must be claiming that all such payments are trade secrets, which is another way of saying they do not intend to comply with the law requiring public disclosure of such payments. That in turn is a warning to other states and to the federal government now considering "sunshine" legislation--be sure not to include this trade secret loophole. A bill is pending in the Vermont legislature to close the loophole. Interesting enough, the Vermont medical Society and the Vermont Psychiatric Association both support the new bill; PhRMA, no surprise, opposes it.
Friday, April 10, 2009
The newspaper then added its own opinion calling for stricter guidelines: http://www.jsonline.com/news/opinion/42293802.html
There is not much new for regular readers of this blog, but the reporters came up with some pretty blatant cases. Exhibit A was an online course sponsored by UW on smoking cessation. It talked up the drug Chantix as the ideal way to get smokers to quit. The course was bankrolled by Pfizer, Chantix's maker, to the tune of a cool $12.3M, of which UW received $3.5M. Chantix is currently under FDA investigation and is held responsible for 112 deaths since its release in 2006. The online course conveniently leaves out any mention of Chantix's adverse effects. The spokesperson for UW could only come up with the incredibly lame statement that it was all right to leave out these unfriendly facts because "such courses are rarely comprehensive and and designed to meet selected learning objectives."
The fact that UW-Madison has done so little to rein in these excesses is especially sad in light of the Wisconsin medical society's commendably straightforward policy statement on Pharma entanglements, previously posted: http://brodyhooked.blogspot.com/2008/10/wisconsin-medical-society-avoid-drug.html.
Thursday, April 9, 2009
Usually Dr. Stossel is sufficiently entertaining, and also wrong in an instructive way, to make taking his writing apart a worthy exercise. So here goes.
"Relationships between university researchers and medical product companies are under relentless attack by critics who portray these associations as a morality play in which noble academics struggle to resist the dark, corrupting influence of industry." Hmm. Some of thought that rather than attacking industry associations, we were trying to figure out a way that these relationships could move forward to benefit the public health without being encumbered by financial conflicts of interest. What has been "relentless" in recent months has not been the work of academic critics, but rather the flood of press releases listing which drug company has just had to pay which huge fine, or is being indicted in which court for claimed fraudulent or illegal behavior. Makes it a lot harder on those of us who prefer to claim that our beef is not with industry but rather with the unethical behavior of our own medical peers.
"The answer is that by prioritizing the needs of patients, these medical philanthropies [that are eager to partner with industry] remain keenly aware of something academic critics of industry may have forgotten as they've scaled the university ladder. The goal of medical research is not to publish papers, but to develop new treatments for people suffering from disease." Nice point. In the same vein, industry might be reminded that the goal of medical research is to develop new treatments for people suffering from disease, and not to maximize their own revenue by marketing the hell out of ineffective or unsafe drugs.
"And translating laboratory research into new therapies ... is something "academics are really not good at.'" This needs some unpacking. It is quite true that no academics can go into their garage and stir up a batch of a new drug and hand it out to patients, no matter how groundbreaking the basic science discovery. But it is also true that whenever a study is done that looks at where new drugs came from, the role of government- or publicly-funded labs is huge, and the contributions of industry labs, until you get to the mass-production stage, is often marginal--a fact that is routinely reversed in the industry's own PR.
"Given the vital role of medical products companies and the magnitude of their challenges, one might imagine that this industry would be admired. ... But this enlightened view of industry is not widespread. This is largely because of the disproportionate influence of a coterie of prominent critics we have previously dubbed 'pharmascolds,' who routinely vilify the medical products industry and portray academics working with it as traitors and sellouts." I missed the "previously" so am just now being introduced to the term "pharmascold." A cute term. I'll now announce a contest to come up with an equally cute term for people like the authors of this paper, who apparently never met a drug industry dollar they wouldn't pocket. It is getting a bit repetitious to call them "shills." We bloggers need something fresh.
"These critics are pious academics, self-righteous medical journal editors, and opportunistic politicians and journalists. Their condemnation of anyone's legitimate profit -- it's all 'corruption' in their book -- has in fact materially enhanced their own careers." A fresh diagnosis from Dr. Stossel. In previous writing he has accused us pharmascolds of being motivated principally by envy--meaning presumably that Stossel was making the big bucks while our own careers were stagnating. So it is nice to hear that from his vantage point we are making headway. Apparently his own stock portfolio is losing value these days.
"In response to these attacks, drug company spokespeople seem content to offer up measly press releases. When challenged by reporters, most academic consultants to industry refuse to comment or offer a meek explanation, instead of retorting that industry pays them because they add critically important value. This evasion has only emboldened industry critics, disheartened company employees, and caused even allies to wonder if there really is something to hide." Well, of course there is something to hide--see the deluge of press releases of company malfeasance, or at least half the previous entries on this blog. But the larger point is interesting. Pharmascolds like me notice that the usual response we generate from the industry is silence. The industry seems to view us as fleas of such a puny species that we are not even worth the energy to scratch. By contrast, an actual academic scientist who starts to criticize a popular drug--a Nancy Olivieri-type figure--immediately causes the industry to bring out its biggest guns and to try to destroy that individual's career. Given how big those guns are, and how well-funded the ammunition store, most of us pharmascolds are frankly delighted we have been relegated to the sub-flea category.
"For the sake of the many patients whose diseases require innovative treatments ... it's time for the leaders of the medical products industry to take pride in their purpose and start fighting back. And discovering a few important new medicines wouldn't hurt either." Really good advice to the industry, and an amazing attack of frankness at the end of the article. Does anyone really believe that if the truth were as Dr. Stossel likes to portray--that the history of drug development in the past 20 years is the history of one after another highly effective and reasonably safe drug, all aimed at diseases that are truly life-threatening, that there would be as much criticism today against the industry? The industry has brought on its own criticism by forgetting the insight that one of its earliest turncoat-insiders, Dr. Dale Console, former medical director of Squibb who became a star witness before the Kefauver congressional committee in the 1960s, shared with that hearing panel:
Q: [Isn’t it true that the costs of research for the pharmaceutical industry are high because so many initially promising drugs turn out to be failures?]
A (Dr. Console): “This is true, since it is the very essence of research. The problem arises out of the fact that they market so many of their failures.” (Hooked, Ch.6)
Friday, April 3, 2009
The commentary appears in the current week's JAMA (subscription required to access), and one of the co-authors is Catherine DeAngelis, JAMA's editor-in-chief. This juxtaposition renders especially ironic JAMA's recent tantrum (http://brodyhooked.blogspot.com/2009/03/jama-editors-need-to-come-down-off.html). If I may digress for a minute, there has been to my knowledge utter and complete uniformity of opinion on JAMA's ill-advised attempt to impose gag orders on anyone who reports an undisclosed auctorial conflict of interest to them. Not a single party has yet agreed with the JAMA position. When are the editors going to admit that they have no leg to stand on and back down?
Back to present business. In keeping with their general stance on conflicts of interest in medicine, the authors argue for a policy of divesting from industry funding in most of the essential functions of professional medical associations (PMAs). The exception that they would permit is the sale of journal advertising and exhibit space at meetings. These exceptions are defended because they can be seen clearly to be advertising, and because any physician who wishes can simply avoid those pages of the journal or that part of the exhibit hall. I will list some specific proposals first (worth detailing because if previous publications from this group are any indication, this paper will be widely cited in the future) and then return to the authors' overall proposal, because I am concerned that there may be a serious discrepancy.
Specifically Rothman et al. urge:
- No direct industry sponsorship of any part of the CME program
- Strict conflict-of-interest (COI) guidelines for members of CME program committees
- No promotional gifts distributed at meetings (such items are presumably already banned by PhRMA anyway under new guidelines)
- No assistance to industry to publicize or provide for sponsored satellite symposia that accompany regular meeting (e.g., no sales of attendee list to industry)
- Strict safeguards for any acceptance of research funding by PMA from industry
- No strings of any sort attached to industry-funded fellowships, etc. awarded to physicians-in-training
- Zero tolerance for COI among members of guideline writing committees
- No product endorsements (criticism is heaped on the American Academy of Dermatology for charging high fees to endorse sunscreens)
- Same strict rules to apply to affiliated foundations attached to PMAs
- Zero tolerance for COI among officers and board
Here I would challenge the proposal. Had the authors read HOOKED (they don't cite it) they would have been aware of the estimates I was able to provide for my own professional society, the American Academy of Family Physicians. I was fortunate to be able to provide these estimates as a result of personal aquaintanceship with an AAFP official; most societies see no reason whatever to share these figures publicly. Out of an annual budget of roughly $60M in 2002, AAFP earned $13.6M from journal ads and another $3M from all commercial support of its CME programs. Let's for now guess that half of the CME support was exhibit hall rental. That puts the total income that Rothman et al. would allow as unproblematic at about $15M or already 25% of the total operating budget. If AAFP were allowed to receive 25% of its budget from industry not counting these sums, it would have been allowed actually to increase its total level of dependence on industry funding in 2002 (to 50% from its actual level of 37.5%).
The analysis I suggested in HOOKED noted that there are two ways industry can unduly influence a PMA--through specific items of funding, and through the total level of reliance on industry funding. The latter is critical because the internal budget process of a PMA is almost completely fluid. If AAFP (to continue to pick on them) needs $60M to operate each year, it hardly matters that some of the money comes in as journal ads and some comes in as "special project" grants. If the industry were to stop buying journal ads but jack up their special project grants by the same sum, it's a wash. However, AAFP is in trouble if the total amount of its industry support falls. Then it has to ask its members for more dues--a move that hardly ever endears a PMA to its membership, and can have the consequence that membership falls off to an extent that outweighs any increase in dues revenue--or it can cut back on its operations and lay off staff (which could also cost it membership). The net result is that when an organization like AAFP depends on industry for 37.5% of its total revenue, it has a very strong incentive to keep industry very happy with its activities. And this happens to the same extent whether all, some, or none of that revenue arrives in the form of journal ads and exhibit hall rental.
If my concern is not yet clear, imagine a PMA that today gets half its operating budget from industry. Let's say that for some reason it now has no ads in its journal and no exhibit hall at its meeting. Industry currently just hands them the money as a special grant each year. The leadership reads Rothman et al. and decide they are in ethical hot water and need to reform. So they go to the industry and beg them to give them only half as much next year as an outright grant, but instead to use the remaining sum to buy ads in the new ad section of its journal, and rent exhibit space in the new exhibit hall that it just opened at its annual meeting. According to Rothman et al. that PMA is now behaving more ethically than it used to. By my analysis it has not changed its spots in any fashion.
Now this is all of no real consequence if the 25% figure is simply a way station before the real goal of $0 funding from the industry, that Rothman et al. repeat numerous times. But if what they mean by $0 is $0 except for ads and exhibit rentals, they have allowed a huge loophole that will nullify a good part of their ambitious goal.
Rothman DJ, McDonald WJ, Berkowitz CD, et al. Professional medical associations and their relationships with industry: a proposal for controlling conflict of interest. JAMA 301:1367-1372, April 1, 2009.