Prescrire Now Has English Edition

I was delighted to receive this e-mail:

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
Website: english.prescrire.org

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.

Not Passing the Sniff Test: ACC, PIPC, and CE Research

In my previous post, http://brodyhooked.blogspot.com/2009/04/why-is-industry-so-scared-of-finding.html, I provided a link to a Bloomberg News article on foes of comparative effectiveness research, which had been called to my attention by Marilyn Mann. Marilyn has also very kindly called my attention to two subsequent posts by Dr. Jack Lewin, CEO of the American College of Cardiology:

http://lewinreport.acc.org/post/Clinical-and-Cost-Effectiveness-The-Bloomberg-Boo-Boo.aspx
http://lewinreport.acc.org/post/Committed-to-Comparative-Effectiveness.aspx

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.

Why Is Industry So Scared of Finding Out What Really Works?

In a previous post: http://brodyhooked.blogspot.com/2008/08/massachusetts-gift-law-industry-took.html, I suggested that the way to find out what the drug industry really is thinking is to find out what they are fighting the hardest to avoid. (At that point, it was about how the Massachusetts state house was overrun with Pharma lobbyists when it considered a bill to require open reporting of and strict limits on payments to physicians.) This would sound terminally paranoid were it not for the fact that the drug industry is so slippery--they have become so used to never saying what they really mean, that you have to search for all sorts of indirect clues as to what might be on their minds.

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.

As I say, this could happen, and occasionally has. But we need to notice that there are a number of intervening steps between the actual conduct of the comparative effectiveness trial, and the result that we find so upsetting. If the drug industry was focusing its lobbying efforts on those intervening steps, we could have more sympathy for them. But it's noteworthy to me that they are aiming all their big guns at the very first step in the process--long before anyone has drawn inappropriate or simplistic conclusions or constructed straitjacket clinical guidelines.

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.

"You're Another," Part II

Another example of the "you're another" riposte when a physician is caught with his hands in the Pharma cookie jar was provided by Dr. Robert Robinson of Iowa in the "Rapid Response" column of BMJ:
http://www.bmj.com/cgi/eletters/338/feb05_1/b463#212337

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.

"You're Another"--Not a Very Good Answer to Pharma Influence

This is getting tiresome.

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:
http://online.wsj.com/article/SB123914567420098841.html

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.

And the Winner Is--Pharmapologist

In a previous post: http://brodyhooked.blogspot.com/2009/04/pharmascolds-strike-back-latest-from.html, I announced a contest to come up with a new term for pundits who consistently defend the pharmaceutical industry and its ways, to determine what would be the opposite of the "pharmascolds" alluded to in the article discussed there.

We received several submissions (read the comments to that post) and the winner is:

Pharmapologists

Thanks to "David" for the submission!

Latest Vermont Report--It's a Trade Secret

The state of Vermont, the pioneer state to require public reporting of all drug company payments to physicians above a threshold amount, has now released its latest annual report (for 2008): http://www.boston.com/business/healthcare/articles/2009/04/16/vt_doctors_get_29m_cash_gifts_from_drugmakers/
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.