Thursday, September 26, 2013

Phun Phacts about Pharma Phraud Phines

Thanks to my most recent issue of the newsletter of the Physicians for a National Health Program (my full disclosure regarding my socialist pinko leanings), I was guided to the Nov/Dec 2012 newsletter of Public Citizen, which features on p. 8 an article by Jake Parent:

The major news in this article is how much criminal settlements and fines against major drug companies have gone up in recent years, to the extent that states going after drug firms for criminal behavior (usually overpricing) are almost assured of eventually recouping all of the costs of the investigation.

A statistic that I have had trouble tracking down in many instances when I’ve blogged about these big settlements is just what proportion of drug revenues the company had to pay in fines, so that from the company’s point of view, there is simply no financial incentive not routinely to skate as close to the legal thin ice as you can. Parent, in reviewing the total of $29.38B paid in fines by the “worst offender” major drug firms between 1991 and 2012, helps us out with this fact:

“Although some of these settlement amounts seem astronomical, many drug companies may consider the settlements a cost of doing business; the total amount paid in fraud cases by pharmaceutical companies over the past 20 years represents just two-thirds of the profits made by the 10 largest drug companies in 2010 alone.”

Public Citizen has added its voice to those calling for criminal prosecution of responsible company execs, as one of the only ways of reining in this persistent corruption. (See our earlier post for why misdemeanor charges against company execs might actually work better for this purpose than felony charges:


Wednesday, September 25, 2013

How to Tell Good from Bad Guidelines, and More on Conflicts of Interest

A recently released paper in the BMJ (subscription will soon be required but apparently it’s openly available for a limited time):
--features an all-star cast of authors, all of whom we’ve had occasion to praise in earlier posts: Jeanne Lenzer, Jerome Hoffman, Curt Furberg, and John Ioannidis.

The gang tells us that it would be really nice if the medical profession would police the guideline-writing process so that practitioners could be sure that any published guideline was a high-quality review of solid evidence and as free as possible from distorting biases. This is what the Institute of Medicine and others have called for, and so far we’ve done a rotten job of responding. So the burden is on the docs to be critical readers of guidelines, and editors of journal to be pickier about which ones they publish and how much disclosure to demand.

The authors then address the counter-attack we’ve considered here in the past, that financial conflicts are not really important because they are just another form of bias, and bias is everywhere and cannot be eliminated from science. Their reply to this assertion is two-fold. First, they note that other forms of bias tend to be multidirectional; some docs for instance are biased in favor of surgery for a condition while others are biased in favor of drug therapy, and so forth. But when there’s money in play, the bias tends to be unidirectional; all the bias tends to line up on the side that has the deep pocket.

Their second reply is a version of something I wrote in an earlier post:
Since that was a longish post, the specific point could have gotten buried, so I now take the liberty of reprinting my own comment on the subject:

As an individual academic-medicine investigator, I may have a strongly held belief that the earth is flat. This gives me a strong and pervasive bias. When I do a study, I will selectively seek out evidence showing that the earth is flat and tend to dismiss data showing that it isn't. Given a choice of things to study, my interests will gravitate toward flat-earth issues. My published papers, if the editors allow them to get through, will contain a variety of statements tending in a flat-earth direction. And so on.

There are also many things that won't happen. I cannot assure anyone will give me funding for flat-earth research. I cannot assure that if I get funding, I won't be the only one; there will be a whole stable of investigators all studying flat-earth matters. I cannot hire expert science writers to draft all of my published papers for me to aid them through the editorial review process and to assure that things about flat-earth are slipped in at every possible point in the manuscript. I cannot afford to buy tens of thousands of dollars of reprints of my published articles, making it more likely that journal editors will be swayed to print them. I cannot afford to hold international "consensus" conferences at glitzy five-star hotels, in which all the high rollers in the field are paid big bucks to come and proclaim how flat-earth thinking is the new best thing in medicine. I cannot donate millions of dollars to medical specialty societies to assure that when they write their guidelines on a clinical subject, they'll be sure that paid consultants to flat-earth thinking dominate the panel and write flat-earth-friendly clinical practice guidelines, which will then be imposed on practitioners as "evidence-based." And so on and so on.

There is a big difference, in short, between investigator bias, and well-funded investigator bias.

The authors of the BMJ paper then go on to address two other ways that guideline panels can be inappropriately biased. The first seems initially counterintuitive: filling a guideline panel with experts in that medical specialty. What could possibly be wrong with having heart surgeons, for example, write a guideline on heart surgery? The problem is that there is a peculiar overlap here between intellectual/professional bias and financial conflict. Heart surgeons as a group have one way of looking at the world, that tends to involve a scalpel. In addition to looking at the world that way, they tend to make more money when more patients seek out their particular ways of solving problems. These combined intellectual and financial biases are very hard to self-detect and eliminate.

Who else could be on guideline panels if not content area experts? This is where we need methodologists who understand study design and critical appraisal of the medical literature, who often gravitate toward primary care specialties. An ideal guideline panel would have a majority of method experts and a minority of content area experts.

The final “red flag” to warn of a badly constituted guideline panel is panel stacking. This is likely to happen when the chair of the committee, or many members of the committee, have financial conflicts of interest, or when the sponsoring organization itself as a huge financial stake in industry funding. It’s relatively easy for a few key panelists to cherry-pick other panelists whom they know will agree with their favorite viewpoint, whether or not those individuals personally have financial conflicts.

As a final touch, the authors review several recent guidelines and rate them according to their red-flag list. Not surprisingly, they rate recent guidelines on cholesterol drugs, treatment of depression, and heart stents as pretty crummy, while giving the U.S. Preventive Services Task Force high marks for their stop-using-PSA guidelines.

Lenzer J, Hoffman J, Furberg C, Ioannidis J. Ensuring the integrity of clinical practice guidelines: a tool for protecting patients. BMJ 2013; 347:f5535 doi: 10.1136/bmj.f5535 (published 17 September 2013)

Monday, September 16, 2013

Science vs. Trade Secrets: Can Pharma Tell the Difference?

Dr. Roy Poses at Health Care Renewal first called this matter to my attention, but Dr. Poses in turn cites two posts from the “1 Boring Old Man” site, so I’ll link there straightaway:

Background: The European Medicine Agency decided some time ago that it was high time that the detailed information on the research studies performed by drug companies to justify the market approval of their products be made public, and no longer treated as the companies’ proprietary information. An American firm, AbbVie, which spun off recent from Abbott Labs, has filed suit to stop this, and has won a preliminary ruling from a European court to block the release of information.

In his first post, “1 Boring Old Man” embedded a 1-hour video of a meeting held in Brussels with both industry representatives and European regulators in attendance, at which one of the panelists was Neal Parker, an attorney for AbbVie. The blog proceeded to talk about the way several regulators jumped on Parker for his failure to understand that he was talking about drug safety and ultimately, people’s lives—and directs the viewer who doesn’t have a full hour to spare to the part of the video where the “fireworks” occur. I watched the fireworks but then reeled back a ways to try to get a sense of Parker’s full presentation.

The lawyer for AbbVie had basically this to say about the idea that regulators should be transparent with the public about Pharma-conducted scientific studies:

  • Drug companies serve an important public health interest in discovering useful new drugs.
  • Both “extreme” positions—that you disclose nothing and that you disclose everything—are bad; a “balanced” position is good.
  • Drug companies already release a ton of information about their scientific research. The question is how to approach what is now “left over” and not currently disclosed.
  • Each company is the proper decision maker as to what to do with its own “left over” information.
  • AbbVie agrees that some of this left-over information can have public health value and move science forward. But (to have “balance”) there has to be reasonable controls preventing the release of this information to other companies, who would enjoy a “tremendous competitive advantage” if they had access to it.
  • One can roughly divide information into two stacks—there’s the “objective” scientific information which is routinely released openly; but then there s the “subjective” or “tactical” information about how the company solves problems related to the research, how it chooses to take the information forward to the regulators, etc. It is the latter that ought to be protected as confidential and as giving other companies unfair advantages if released to them.

“1 Boring Old Man” draws two conclusions from this presentation and the ensuing Q&A:

  • What companies like AbbVie most want to hide is how much they are doing drug promotion under the guise of scientific research
  • People who talk like this simply cannot be trusted to negotiate in good faith; all they care about is competitive advantage, and if screwing the public provides competitive advantage, so be it

There is a third lesson highlighted by a BMJ News account from which the blog draws some of its information—the drug firms themselves are divided over this issue with other firms not wanting to go as far as AbbVie. Other firms seem to have decided that with public trust in them now down in the toilet, the only “competitive advantage” they might enjoy is tied to coming clean.

So what do I make of all this? Well, I agree at least in part with our fellow blogger, but I would add a further lesson.

First, I agree that when a guy starts a discussion by announcing that if I disagree with the position that his company takes, then I am opposed to both the public health and to “balance,” I would want to grab for my wallet and head for the door. That guy is just way too slippery for me to spend time with. So yes, whether such people could ever negotiate in good faith is a serious question.

But there is another issue here as well. I want to give Neal Parker just a little more credit than others apparently were. For all his slipperiness, he had decided that there were a couple of things at stake—preserving the public health and advancing science on the one hand; preserving his company’s competitive advantage on the other. In his own head he thought he had a formula for “balancing” these two goals. But what I think he proved is that the people in the audience who reacted with shocked disbelief to some of what he said, and Parker himself, were bound to misunderstand each other because they were speaking different languages. If you spoke Parker-ese, or Pharma-ese, then everything he said was perfectly logical and indeed irrefutable. Which shows to me one more reason why we must find a way to detach the scientific research enterprise from Pharma funding (as I argued in HOOKED). There is no way we can square the true goals of science and the public health with the clearly commercial agenda of the drug industry.

Saturday, September 7, 2013

An Update on KOLs

In the previous post I mentioned a collection of essays on institutional corruption in Pharma. One of the essays:
--by our old acquaintance Sergio Sismondo at Queen's University in Canada, provides something of an update on the status of KOLs, who were discussed here last with:

Trying to hit the high points, I note that Sismondo is engaged in an ongoing study of KOLs and their influence that includes having attended a number of industry conferences on KOL identification and management, and interviews with a number of highly paid KOLs and Pharma insiders. He agrees with earlier posts here that the drug firms are increasingly outsourcing KOL management to firms specifically devoted to that enterprise. I have previously tended to stress the KOL who's usually a big fish in a small pond, the physician who's supposedly being paid to talk to other docs, but in reality is being paid bribes for her own high rate of prescribing of the company's drug. Sismondo is concerned more about the other end of the spectrum, the big-pond fish who truly can exert influence across large numbers of docs and are being paid especially to do that. The small-pond types typically command $500 to $1000 per lecture, Sismondo tells us, while the big-pond KOLs can draw down $2500.

One interesting and suggestive observation is that as one moves up the food chain to the truly influential docs, the industry treats them more as partners and with kid gloves, because (as one experienced industry consultant told Sismondo): "the number-one requirement specified by KOLs is: 'protect my reputation.' He goes on to reiterate that KOLs desperately want to avoid the 'appearance of...being an industry 'sell-out.'" This seems extremely important because it suggests that the efforts of us pharmascolds over the past decade has actually had an impact. Since KOLs are, indeed, industry sell-outs, this suggests to me at least that a serious campaign within medicine and biomedical science to thus label them publicly could have a significant impact on the general level of professional behavior. On the other hand, Sismondo is skeptical about transparency alone as a vehicle for positive change, and argues that the new U.S. Sunshine Act will have relatively little impact on KOL activity. If anything, the industry is betting on the continued thriving of KOLs; Sismondo notes that currently 15 to 25 percent of total marketing budgets go to speaking events.

I just now suggested that a possible strategy to reduce the number and the influence of KOLs would be to shame them more. Sismondo seems unsure that this would work: "...the medical profession has been corrupted because a small number of companies with well-defined and narrow interests have inordinate influence over how medical knowledge is produced, circulated, and finally used by physicians to make decisions concerning their patients....Most physicians see the companies as playing legitimate roles when the companies promote products in clinics, when they create and distribute medical research, and when they fund and provide continuing medical education." That is, even if KOLs personally wish to avoid looking like sell-outs to industry, Sismondo claims that the larger profession is quite blasé about whether or not these folks have actually sold out. I'm not sure I totally agree with Sismondo on this pessimistic take on general professional values; see for example:

OK, so what do we do about all this, if Sismondo is unsure that shaming KOLs gets us any traction? The big-enchilada solution, for Sismondo, is to break up the industry, separating the research-and-development portion of pharmaceuticals from the selling-and-marketing part. One set of firms would discover new drugs, and once those drugs had been shown to meet high standards of efficacy and safety, those firms would auction off licenses to make and sell the drugs to other firms. This would, Sismondo thinks, remove many of the perverse financial incentives that arise from marketing getting mixed up with research.

Sismondo agrees that this grand solution won't happen anytime soon, so his temporary backup plan is: ban physicians speaking on behalf of drug companies. He argues that nothing is served by this and while firms have every right to market, they could just as well have sales reps give the talks. Of course this ban is just as likely to happen anytime soon as the other proposal, unfortunately. But the point for medical ethics and professionalism is that it could effective happen tomorrow--if only physicians would grow an ethical spine and simply refuse to attend company-sponsored talks.

Friday, September 6, 2013

Special Journal Issue, “Institutional Corruption and Pharmaceutical Policy”

I’m happy to turn the podium over to Professor Marc Rodwin, who a while back sent me the message below, which I managed to put aside at the time without posting, and am now making amends. The topic his symposium addresses—note the free access to the papers—should be of great interest to readers of this blog:

I thought you and the readers of your blog might be interested in a forthcoming symposium on Institutional Corruption and Pharmaceutical Policy that will be published in the forthcoming issue of the Journal of Law, Medicine & Ethics, 2013: Vol. 14 (3).

Below I list a bit of information about the symposium.  I have also attached a list of the articles with URL links on SSRN which has free access.  Also, these items can also be obtained through the Edmond J. Safra Center Lab on Institutional Corruption Web page,

The goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption — that is, widespread or systemic practices, usually legal, that undermine an institution’s objectives or integrity. The pharmaceutical industry’s own purposes are often undermined.  In addition, pharmaceutical industry funding of election campaigns and lobbying skews the legislative process that sets pharmaceutical policy. Moreover, certain practices have corrupted medical research, the production of medical knowledge, the practice of medicine, drug safety, and the Food and Drug Administration’s oversight of pharmaceutical marketing.

I invited a group of scholars to analyze these issues, with each author taking a different look at the sources of corruption, how it occurs and what is corrupted. The articles address five topics: (1) systemic problems, (2) medical research, (3) medical knowledge and practice, (4) marketing, and (5) patient advocacy organizations.

Advanced copies of the 16 symposium articles are now available through SSRN online.  []

For a summary of each article and the key themes in the symposium see, Marc Rodwin, Institutional Corruption and Pharmaceutical Policy

Marc A. Rodwin, J.D., Ph.D.P
Professor of Law, Suffolk University Law School
Lab Fellow, Edmond J. Safra Center, Harvard University


Tuesday, September 3, 2013

Gene Patenting: What Did the Supreme Court Rule in Myriad?

I forget what I was doing back in the late spring when the US Supreme Court issued a couple of major rulings on issues of interest to this blog. I did not have time just then to post about these rulings but made a mental note to get back to them as soon as possible. Right…Anyway, last week’s New England Journal of Medicine has forced my hand (main article for subscribers only).

In Association for Molecular Pathology v. Myriad Genetics, Myriad’s claim to have patented the gene sequence for the BRCA1 and BRCA2 cancer-causing locations, and hence their exclusive right to offer a genetic test for those conditions, was at issue. The article mentions one major downside of one company having this exclusive right to a genetic test—its price. Myriad charges about $4000 and one competitor firm is promising to market a test for $1200. The article omitted to mention an issue that is even more serious regarding medical science and practice. Myriad has been able to sequester data on the effectiveness of its genetic tests as proprietary information. That means any physician counseling a patient on whether or not to be tested, and what a test means, is dependent on the company profiting from the test to say how well its own test works, and that is rather obviously a bad situation.

Lower courts had thrown out first all, then only some of the Myriad patents. The Supreme Court basically split the difference. Some patents involved the actual DNA that makes up the genes. The court said that exists in nature and you cannot patent that. But some patents involve complementary DNA which the company manufactures off messenger RNA that is taken from those genes. That cDNA does not exist in nature, so the court said the company could patent that. (Plaintiffs had alleged that cDNA is really the same as native DNA because what matters is the information in it, not its physical form, and that is the same as the native DNA; the court did not buy that argument.)

Patient advocates such as the ACLU trumpeted the decision as a big win because it does now open the door to competing gene tests. Let’s take a step back, akin to the discussion of patents in HOOKED, and see what basic issues are involved.

First let’s do Patent Law for Dummies. The noise made these days by corporate apologists about “intellectual property rights” obscures the basic fact that a patent is a monopoly. The government is supposed to break up monopolies, not create them. So the whole idea behind patents is that it’s a tradeoff. The government grants temporary monopoly rights. In exchange it’s supposed to get useful innovation that’s in the public good. No patents, no firms willing to invest their cash in bringing new inventions to market, no innovation to benefit the public. Too many or too burdensome patents, prices go way up, public interest is harmed, and in extreme cases (like arguably today’s biotech sector), innovation is actually squelched.

The law says that patents should be granted only if some basic conditions are met. The Supreme Court in Myriad issued a very narrow ruling. It decided one issue only—whether naturally occurring things can be subject to patents—and decided “no,” in keeping with many earlier rulings. The Court refused to review the Myriad patents on other grounds, such as whether they met the conditions of being novel, useful, and non-obvious. Those other grounds are important to most patents relating to Pharma. The argument against the present patent system for drugs is that firms are allowed to patent all different aspects of a drug, even those that are non-useful and obvious. This simply puts barriers in the way of generic competition, and does nothing to spur innovation.

(As I argued in HOOKED, following Marcia Angell, the Patent Office could squelch these nuisance patents without any need for a court ruling, simply by enforcing its own rules. Alternatively, the FDA could refuse to list any such nuisance patents in its reference book that states the conditions for drug approval and generic equivalence. But both Federal bodies are more interested in cozying up to industry, apparently.)

The authors of the NEJM paper provided a bit of good news in that regard—they report that in recent years the Patent Office had issued many fewer patents for naturally occurring gene sequences because they had tightened up their criteria and insisted that biotech companies could not simply patent genes wholesale, they had to make a plausible case that they knew how to do something useful with the discovery. (Presumably the Myriad decision will raise the bar still higher by ruling out all such patents anyway.)

As a bonus, the New England Journal threw in two historical essays:

These address events leading up to the passage of the Bayh-Dole Act of 1980, that opened the floodgates to universities patenting all manner of scientific discoveries, including those paid for with federal research dollars. They make a case for not regarding Bayh-Dole as carved in stone, but as needing review and updating as conditions have changed so much since its creation.

Kesselheim AS, Cook-Degan RM, Winickoff DE, Mello MM. Gene patenting—the Supreme Court finally speaks. New England Journal of Medicine 369:869-874, Aug. 29, 2013.

Sunday, September 1, 2013

Why There's No Such Thing as Conflict of Interest

A good deal of this blog is about conflicts of interest at the interface between medicine and the pharmaceutical industry, and we occasionally encounter those who deny that such conflicts of interest represent any serious problem, for instance:

I have also alluded to the ideology that I and some others have termed economism:
--about which, if anyone is interested in more discussion, they are welcome to peruse my other blog:

All that is a lead-in to a new book, Never Let a Serious Crisis Go to Waste, by a professor of economics at Notre Dame, Philip Mirowski (New York: Verso, 2013). Mirowski explains at a much deeper level why it is that critics of the position taken in this blog, and among the community of pharmascolds, insist that conflict of interest really doesn't exist.

First, on nomenclature--while I offer reasons to prefer the term 'economism' on my blog and in my own book, The Golden Calf, Mirowsky follows the practice of most of our colleagues in history and the social sciences in using the term 'neoliberalism.' So rather than get tangled in who calls it what, I will refer to this ideology henceforth as 'E/N'.

E/N starts off with the claim that the supposedly "free" market is the single most important institution in society, so much so that we ought to regard virtually all of human life as one big market and as following the rules of the marketplace. You might think this is just because a market is such a neat place to buy and sell stuff. But Mirowsky shrewdly notes that one of the great founders of E/N, the Austrian economist Friedrich Hayek, had another reason to glorify the market.

Hayek saw the market as the most perfect information processing system available to human society. If he were writing today, Hayek would probably use the metaphor of the computer. The market is a supercomputer that instantly receives input data from billions of sensors, which are the individual "rational agents" as orthodox neoclassical economics conceives of such a thing.

Now, since all of society ideally ought to be governed by the rules of the market, it follows that the only data worth knowing about anything is its current market price. The market price captures precisely the value of that commodity; the very idea that the market might overvalue or undervalue anything simply does not compute within E/N. The supercomputer of the market takes in all the data from all those who might like to sell a commodity--how much of it they have, and what price they are willing to accept for it. It takes in all the data from everyone who might buy that commodity--how badly they want it, what they might be willing to pay for it, what else they might be willing to forgo, or not, to get some of it. And the computer crunches all those numbers each millisecond to come up with the ever-changing fact, the true market value/price of that commodity.

This is E/N's picture of how society ought to run; and from that picture you can see that there are a number of flies in the ointment, called natural scientists. These folks persist in adhering to a hackneyed, obsolete idea-- that there is another source of valid facts that has nothing to do with how the market functions. These scientists actually think they can consult the body of evidence in their own field, and go into the labs and do experiments, and emerge with data that they view as reliable and true about how the world works.

If these scientists were ever to be taken seriously, all hell would break loose. For the proper role of government, according to E/N, is to stand out of the way and allow the unregulated "free" market to run itself. But so long as these scientists tell politicians that they know some facts--such as, that climate change is a real threat to the human future--then these politicians would be tempted to try to regulate the market to bring about the ends that they desire (like reducing carbon pollution). And that would simply never do. As Hayek famously explained, just let the government think it could regulate even one small thing, and we'd all instantly and permanently lose all of our freedoms.

(As a side issue, whether that was what Hayek really said is quite questionable, and on my other blog I go into some detail about why what today's E/N enthusiasts claim in Hayek's name may actually be a far cry from what Hayek actually wrote:
But for now we can ignore that fine point.)

Now, what in heck does all this have to do with conflict of interest? The point is that the entire ethical argument about conflict of interest assumes, well duh, a conflict of interests. Presumably a scientist has an interest (actually a moral duty) to discover and explain the truth according to the best scientific evidence and methods. If the scientist then proceeds to line his pockets with industry money, he acquires a second interest, in making those industry folks happy and telling them what they want to hear--such as their favorite new drug is extremely safe and effective.  The conflict between those two interests is what creates the ethical problem.

How does E/N see this situation? E/N cannot fathom the duality of interests. Since the market is the only reliable source of truth about value, then if the scientists accepts payment on the open market for his opinions, the market value of those opinions, not some silly body of scientific evidence, is what determines their truth. So the scientist creates no conflict of interest by becoming a corporate shill.

Mirowski looks at his fellow academics and notes spectrum of opinion on conflicts of interest. At one extreme end he places the biomedical folks. They have gotten their knickers more in a knot than anyone else over conflicts in their field, and have created this new cottage industry of COI guidelines and rules. Maybe that has something to do with the idea that some of them actually care about whether patients live or die after being given the newest drugs and devices.

At the far other end of the spectrum are the economists. As Mirowski characterizes the field of orthodox neoclassical economics (which has both taken over virtually all university departments of economics, and has also been fully captured by the E/N ideology, to hear his account of it), the typical econ professor takes a ton of money from various corporations, especially banks and financial firms, believes that nonetheless he's a completely neutral arbiter of fact, and discloses none of those financial involvements in his journal articles and other scholarly work. Plaintive calls among a few disgruntled folk after the start of the recent great recession, that the field of economics needed a code of ethics, were ignored.

When we understand what E/N teaches, we can see why the economists have figured out exactly what conflict of interest is all about, and why from their point of view the biomedical scientists are clueless. And that further explains why those within the biomedical community, who have been most sneering and dismissive of conflict of interest as an ethical concern, seem to be among those most committed to the E/N ideology.