Wednesday, November 27, 2013

The Next Vioxx? Disease-Mongering "Low T"

Natasha Singer in the New York Times:
--writes about the campaign to convince all men over the age of maybe 25 that if they ever once felt tired or run-down or in any way lacking in manly vigor, they probably have testosterone deficiency and need one of the various products to supplement their testosterone--now a $2B annual industry. It seems that the brilliance of deciding that testosterone deficiency should be called "low T" was a major breakthrough in the public acceptability of this new supposed disease state. Two executives from AbbVie, the maker of AndroGel, were named by the trade magazine Medical Marketing & Media as "the all-star large pharma marketing team of the year" for their low-T promotional campaign.

Singer makes two major points in her article--first, that Pharma has successfully skated around the FDA by pushing the idea of "low T" through unbranded promotions. If you run an ad telling the public that low T is real and serious and they should see their doctors to find out if they have it, but don't at the same time mention your drug by name, you can get away with pushing your drug for all sorts of conditions for which it has not been granted FDA approval. (The FDA, it seems, is quite old-fashioned and still thinks that testosterone replacement products should be used for medically diagnosed cases of significant hormonal deficiency.) The second point is the widespread use of questionnaires where virtually anyone will answer "yes" to at least one question, which is then supposed to suggest that you probably have low T and could benefit from treatment.

Singer mentions along the way that the risks of taking testosterone long-term when you don't have serious hormone deficiency are essentially unknown. So why does "low T" sound like the next Vioxx waiting to happen, where drug firms convince the entire world that they all need to take a drug, and only later find out the substantial increase in adverse reactions that they have now inflicted on thousands if not millions of people? (This is what a while ago Don Light and I labeled the "Inverse Benefit Law":

Monday, November 25, 2013

New Cholesterol Guidelines, Part Two

When I first posted on these guidelines:
--I figured that others would soon chime in who understood the technical details much better than I did and who could therefore make clearer what the problems were.

One such contribution is now up on the Health Care Renewal blog, courtesy Dr. Roy Poses:

In a long post, Dr. Poses adds two important things to my earlier comments. First, he drills down a good deal into why the new risk calculator attached to the guidelines is flawed and premature. Second, courtesy the Pharmalot blog, he fills in more details about conflicts of interest among the guideline panelists, showing that I was too optimistic when I stated that COI was at least somewhat kept under control or at least acknowledged more. (For example, it’s nice, according to the IOM guidelines for writing good guidelines, that the chair of the panel had no financial ties to industry. But does it matter that in order to become guideline chair, he had to divest himself of a whole pile of financial ties that he previously enjoyed? Divestment: good; lots of things that needed to be divested:  perhaps not so good.)

Nevertheless, while more details are being filled in, it is still challenging to keep the big picture in view. The media accounts I’m seeing in the newspapers seem calculated to reassure patients that it only appears that the cardiology crowd is in disarray over the guidelines; actually everything is just fine, so if your doc says to take a statin, you should have full confidence that it’s good advice. In short, if the drug industry could have written the script, it would be saying what most people are now saying.

So to restore a sense of perspective, let me go back to a theme I have tried to raise on a number of occasions, for example:

The old narrative, that has led to so many millions of Americans being placed on statin therapy, at great cost and at huge risk of serious side effects, is: if your bad cholesterol is high, you’re at greater risk for heart disease and stroke. Statins lower your bad cholesterol. So you need to go to the doc, get a blood test to check your cholesterol, and if it’s an eentsy bit high, start taking statins for the rest of your life.

If you carefully ask the right questions of the research that’s been done in recent years, you learn that there is a shrinking amount of evidence that supports this narrative, and a lot that says it’s in fact just plain wrong. To the extent that statins reduce your risk of future bad stuff, as they seem to, a little, in people with existing heart disease, there’s now many reasons to believe that they don’t do it by lowering cholesterol in the blood. The new guidelines, as I said in my previous post, sort-of-kind-of admit this by eliminating the need to check cholesterol levels routinely and the idea of target levels of cholesterol to shoot for.

So if the guidelines were true to the evidence, what message would emerge? The message would certainly be: the grounds on which we used to prescribe statins were all wet; there are a bunch of folks now taking statins who probably don’t need them; we need to be much more refined in selecting the smaller subsets of people who might actually benefit from taking statins.

What message is actually being disseminated? It seems to be: If you took statins under the old guidelines, have faith and keep taking them. If you were not on statins previously, don’t worry, because our new, flawed risk calculator will probably say that you too need to be on statins.

As I said, if the drug industry had been allowed to write the script for this, it would have said exactly the same thing.

Sunday, November 24, 2013

Yet More on the Markingson Case at U-Minn

It has been a while since I commented on the tragic Dan Markingson case at University of Minnesota, for example:

For some time, my colleague in bioethics, Dr. Carl Elliott, at U-Minn, was alone in pressing for a full investigation of this case that led to a young man committing suicide while enrolled in a university-conducted, industry-sponsored clinical trial of psychiatric drugs, when his mental state would have appeared to preclude the possibility of his giving proper informed consent to participate in the trial. More recently, however, as a recent piece in Minnpost summarizes:
--Dr. Elliott has been joined by his U-Minn colleague in bioethics, Dr. Leigh Turner, and also by Dr. Trudo Lemmons at the University of Toronto, in approaching the University administration and demanding a thorough investigation and accounting. (Full disclosure: I am a signatory to the petition that Dr. Lemmons circulated.)

You might wonder why I continue to call attention to this case, which the University insists is old news, was previously investigated and they were found blameless, and these are just malcontents trying to stir up trouble. Besides all the important ethical issues about the ethical conduct of research and informed consent and protection for psychiatric patients, there is what happens when a University decides to get into bed with Pharma and accept big research grants--and then to decide that the faculty who attract those grants, by doing Pharma's bidding, are their best faculty and should be properly rewarded for the largesse they are bringing in. There is further the question of what happens when something ethically questionable is alleged in one of these studies; and whether the University will then remember that it is supposed to be about good science and about the public interest, or whether the instinct of self-preservation takes over and the response is stonewalling and obfuscation.

Dr. Turner in the Minnpost interview is commendably noncommittal over whether any actual wrongdoing occurred, and in calling solely for more information to be disclosed. I would say that enough is known so far to show that Drs. Elliott, Turner, and Lemmons are fully justified in demanding more answers and in saying that the so-called investigations that have taken place so far are woefully inadequate. People who really care about the reputation of the University of Minnesota would be listening to them rather than continuing to attack them.

Monday, November 18, 2013

Generic Prescribing and Conflicts of Interest

The great investigative reporting team at ProPublica did a good job on money wasted in Medicare through failing to prescribe generic drugs:

Now, the price of drugs, and generic prescribing, is not a hot topic on this blog, so the main thing I wanted to point out is one fact from the article. The authors note that a relatively small number of Medicare prescribers are responsible for a hugely disproportionate excess of brand-name prescriptions and hence unnecessarily high costs. They then  proceeded to check out their Dollars for Docs tool and noted that these same docs also seemed disproportionately represented among those receiving payments from drug companies. When ProPublica reporters visited some of the offices of these docs, they could hardly get in the door for all the drug reps waiting in line to handout free samples and other goodies.

As was nicely summarized in the excellent review article by Spurling and company from Healthy Skepticism:
--all the available evidence shows that taking money and information from the drug companies is associated with irrational prescribing and more expensive prescribing. I can think of few things more irrational than routinely prescribing brand-name drugs when a generic equivalent is available; and that certainly leads to higher costs.

New Cholesterol Guidelines—The Devil in the Details

I had been holding off on commenting on the cholesterol treatment guidelines recently issued by the American Heart Association and the American College of Cardiology:
--because I know that many of the friends that I have previously quoted here, the thoughtful naysayers in the put-everybody-on-statins campaign, were sharpening their statistical knives to go after the new document, and I hoped to be able to link to a truly scholarly dissection of the issue.

I am perhaps jumping the gun a bit egged on by today’s All Things Considered on NPR, which had a lead story on the critics of the risk calculator that’s part of the guidelines, a debate that apparently blew up at the Heart Association’s big annual meeting. So with apologies for my own inability to drill down with any statistical acumen, I will offer a preliminary read.

If you just looked at the guidelines quickly, you’d say that the guideline writers had had a sudden attack of brilliance. Some of the basic points that this blog has been carping on for several years now are reflected in the document:

  • Treatment with statins should be based on the patient’s heart-disease-stroke risk level and not on a blood level of cholesterol.
  • There’s no evidence that shooting for any specific target level of cholesterol is better than simply placing the patient on a reasonable dose of a statin and keeping them there.
Not only that, but the guideline panel seems actually to have taken on board some of the criticisms of conflicts of interest. The chair of the panel reports no conflicts, and while a few of the panelists have seriously long lists of industry funding, many do not. And there’s quite detailed disclosure. (I admit that I did not check to see if any of the people reporting no COI actually could be found to be on the industry payroll.)

So—what’s not to like? Well, a number of things. What the panel giveth, they then taketh away, usually in the fine print of the document.

The panel realizes that there’s no good evidence to recommend a particular target level of cholesterol. But they are impressed (as we’ll see) with the studies that show that lower LDL cholesterol is associated with lower risk. They then urge the physician to prescribe a “moderate” or a “high” intensity dose of their favorite statin, with the idea that the end result will be a certain percentage drop in the LDL level—with the additional proviso that if you don’t achieve that level of drop, you will need to up the dose. So the idea of treating to a target level went out the front door and snuck back in the rear window.

Where did this panel get the idea that you need to reduce LDL by a certain percentage? Well, it turns out that they were quite enamored of one particular study, the CTT meta-analysis in Lancet in 2012. I tried to explain at some length:
--why that study was deeply flawed because it answered the wrong question. Moreover, that was not an independent clinical trial; it was a re-analysis of data from many previous trials, and when analyzed by people who are not on the statin bandwagon, all those previous trials yielded much less optimistic results in favor of prescribing statins. Yet if you look at the evidence table that the current panel relies on, “CTT” jumps off the page at every turn.

Next we come to the point that NPR addressed today—the risk calculator. If you no longer treat with statins based on level of blood LDL, but based on the patient’s level of risk, then it becomes critical that you have a reliable measure of that risk. The critics are shouting today that the calculator that the panel favors way overestimates heart-disease risk. Before I get into that discussion I will wait to see one figure that I think is critical—how many additional people will be prescribed statins in the US based on this risk calculator? There are no doubt some people that could benefit from statins who are not now getting them. But there are a whole bunch more IMHO who are currently on statins because their blood tests looked bad and yet they have no diagnosed heart disease and are at reasonably low risk. So if the calculator leads to a net increase in statin prescribing, we know it has to be a move in the wrong direction.

But wait, as those TV ads say, there’s more. Two things are almost completely absent from these guidelines, that ought to be front and center in any practical approach to evidence-based prescribing of statins today. First is the concept of NNT. I didn’t see anywhere where the guidelines stated an actual NNT. The assumption is that if a study shows that statins offer any benefit for any particular group, then you should prescribe the statin—never mind if you have to give a statin to 400 people to prevent 1 cardiovascular event. (If you had an NNT, then you could talk further about shared decision making, giving the patient the facts and letting them decide if they wanted a statin—another concept curiously lacking from these guidelines.) Finally, what’s massively missing is any significant discussion of the downside of statins. According to these guidelines, a vanishingly small number of patients have any serious side effects. The possibility, for example, that as many as half of all patients on statins have some muscle aches or weakness, or the emerging worry that dementia may be more common in statin users, gets no mention whatsoever.

Bottom line—it looks worrisomely like what I concluded with CTT—even if these guidelines were not written by people in the pay of the drug industry, they could just as well have been. And somehow, while important new evidence against the routine use of statins, and suggesting that we really don’t know much about the true mechanism by which these drugs work in the cases where they do, crept into the guidelines for the first time, the bottom line is largely unaffected by such enlightened thoughts. We’re back to putting statins in the water supply.

NOTE ADDED 11/20: I can now cite a comment by some real experts, Drs. John Abramson and Rita Redberg, in the New York Times:
These two estimate that the new guidelines would increase the number of people considered candidates for statin therapy by 70 percent, with 18 percent of these at risk for the adverse effects of statins, with no evidence of fewer deaths from heart disease or stroke as a result. (They mention what most statin advocates ignore, that even the most successful clinical trials tend to show that statins reduce the risk of heart attack or stroke, but still have no impact on overall mortality.)

Saturday, November 16, 2013

Welcome to the Harm/Hope Ratio: An Alternative to Industry Brainwashing

I have been mulling over several new posts, including one on the recently issued cholesterol treatment guidelines, and have come to the realization that underlying all of the messages I most want to convey is one basic point.

In keeping with the recent post:
--I have become increasingly impressed with the overall epidemiological picture painted by recent data on the harm caused by prescription drugs. We have reviewed Donald Light's data:
--showing that people taking their drugs as prescribed (not errors; not overdoses) is currently the 4th leading cause of death in the U.S. Just to up the ante a bit, we more recently encountered Peter Gøtzsche's statement that this should be elevated to the 3rd leading cause of death:

So the worrisome bottom line is that all this time, as we have been sold a bill of goods from the drug industry about how if we do one single thing to get in the way of their excessive profiteering, we'll suffer a screeching halt to medical progress, we have ignored the fact that the real "progress" in recent years is how many prescription drugs the average American is already taking and the harm done to them in terms of both mortality and morbidity from this over-drugging.

My friends in the evidence-based medicine movement have tried to chip away at this industry brainwashing particularly by attacking the commonly heard phrase "risk-benefit ratio." They point out quite reasonably that this term, which seems totally objective on the surface, actually hides a serious bias. We talk about "benefits" as if they were assured (no "risk" of benefit) but we only allude to harm as something that might or might not happen. The EBM gurus now say that we should always be precise and talk about the "harm-benefit ratio," unless we want to get really wordy and talk about the "probability of harm-probability of benefit ratio."

This leads me to one of my periodic modest proposals. I suggest, in light of the recent epidemiologic evidence, that we should now begin to talk about the "harm-hope ratio." I propose this term because:
  • As above we have solid epidemiologic evidence that the American public is killing ourselves by ingesting way too many prescription drugs.
  • When we do the usual studies, we are generally shocked by the high number-needed-to-treat (NNT) attached to commonly used drugs. The really great drugs like metformin for Type 2 diabetes usually run an NNT of around 10-30--that is, 10 to 30 patients have to take the drug for a certain length of time to achieve the hoped-for therapeutic benefit. The crappy drugs like statins for primary prevention of heart disease run NNT's typically in the several hundreds.
  • Therefore, the usual situation when we take prescription drugs--we can be almost certain that at least on the population level, harm is being caused; and we accept the harm given our hope that we might be the lucky soul who's the 1 out of 30, or the 1 out of 400, who will actually derive some significant therapeutic benefit, like not dying of a heart attack in the next few years.

Maybe if we were more honest and started talking widely about the harm-hope ratio, instead of the highly misleading risk-benefit ratio, we'd start to turn the proverbial ocean liner around.

Monday, November 11, 2013

J&J's Recent Settlement: For the Record

Once again, nothing new here for regular readers; but just to be sure that we are keeping up to date for the record, we should note yet another huge (more than $1B) legal settlement involving a major drug firm. A comprehensive account can be found over at our friends, Health Care Renewal:

Let's return to our standard form for such matters:
Company: Johnson & Johnson
Drugs involved: Risperdal, Natrecor, Invega
Allegations: Off label marketing, kickbacks
Amount of settlement: $2.2B
Settlement equals what percent of annual drug sales: Approximately 87% as best as I can estimate for all 3 drugs, making this one of the heftier settlements on record
Did company admit guilt? Supposedly J&J admitted "accountability" but not wrongdoing, whatever that means

In what appears now to be the formulaic response to any such settlement, J&J spokespeople deny that the company is guilty of any wrongdoing, but say that the settlement was paid simply so that the company can move on and put this unpleasantness behind them. I can sort of understand this; if you paid me $2.2B, I can imagine a good deal of moving on that I would be able to accomplish, and I would certainly put a lot of unpleasantness behind me.

Dr. Roy Poses, as usual, noted that magically, J&J managed to do this bad stuff without any individual human being doing anything wrong and requiring punishment, and opines that until individuals start doing jail time, we should not expect any changes in industry behavior. For a confirming opinion, recall our recent post:
--and the quote therein: “I dedicate this book to the many honest people working in the drug industry who are equally appalled as I am about the repetitive criminal actions of their superiors and their harmful consequences for the patients and our national economies. Some of these insiders have told me they would wish their top bosses were sent to jail, as the threat of this is the only thing that might deter them from continuing committing crimes.”

Sunday, November 10, 2013

Catching Up: Recent Articles of Interest

Once again I'm indebted to my friends Rick Bukata and Jerry Hoffman at Primary Care Medical Abstracts for pointing out papers that I missed when first published in the last 6 months or so (subscriptions may be required to access articles).

First off is a review by authors from London, Australia, and Stanford U. (the latter being our old pal John Ioannidis). Nothing really new here for regular readers of this blog, but the article is a nice update on the most compelling recent evidence for the various ways that undue industry influence distorts medicine. Those wanting to be sure to cite the most recent and comprehensive evidence will want to have this handy.

Next is a study out of UCSF, co-authored by Lisa Bero, another name familiar to our regular readers. At question here is what conflict-of-interest guidelines govern the activities of the 51 state Medicaid boards that decide what drugs should be covered by these tax-supported plans for low-income patients. The authors were able at first to get only 14 of these guidelines off websites or other easily available sources, and by further correspondence and begging and pleading they eventually got a total of 27 guidelines. Only 4 of the 27 guidelines seemed really strict on banning COI with industry, and in many cases they were told that the guidelines are not for public disclosure. Excuse me? A taxpayer-supported public program, and the guidelines to govern COI are secret??? What the heck is going on here? The overall situation is obviously highly unsatisfactory.

Stamatakis E, Weiler R, Ioannidis JPA. "Undue Industry Influences that Distort Healthcare Research, Strategy, Expenditure and Practice: a Review." European Journal of Clinical Investigation 43:469-475, 2013.

Nguyen NY, Bero L. "Medicaid Drug Selection Committees and Inadequate Management of Conflicts of Interest." JAMA Internal Medicine 173:338-343, March 25, 2013.

Sunday, November 3, 2013

Trial Registries, Again--Non-publication of Large Trials

I have blogged in the past--
--about the hope that mandatory registration of clinical trials would end some of the lack of transparency that currently surrounds industry-sponsored drug studies. In general, the previous studies indicated a lot of problems despite the registry, including frequent changes in study end-points, for example.

The BMJ recently published a new study:
--by a group primarily based at University of North Carolina, that looked only at one outcome--how likely was a trial that included at least 500 subjects to publish results within about 4 years of completion? Note that they did not look at whether anyone juggled the trial design or methods, just whether any results at all were published in peer-reviewed journals or on the registry website itself. The authors chose only large studies because they judged that common excuses for non-publication--we got too busy; or we submitted and the editors rejected the manuscript--would be much less likely to hold for trials of this size.

Basically the authors found that 29% of these large trials remained unpublished. Of that 29%, an additional 22% had some results available through the trial registry itself. The authors commented that this latter is not an optimal result, as the journal peer review process is presumably valuable for identifying possible flaws and gaps in study methods. Industry-sponsored studies were more likely than others not to be published (32% vs. 18%). Put another way, industry-sponsored trials accounted for 88% of all the unpublished trials.

The present authors highlight an ethical concern that I mentioned in HOOKED. When people volunteer as subjects in a research trial, they believe that they are doing something in the service of science. If the results of the trial are never published, their "contract" with the investigator is thereby violated. Hence investigators have an ethical duty to do their best to publish research results, quite apart from whatever other obligations they may also be under.

This study, as noted, merely looked at whether any results were published in peer-reviewed journals; they did not ask whether the methods reported in the final paper matched what had been entered into the registry. So we still could have had, among the trials that were published, cases of industry-sponsored trials changing the endpoints or otherwise adding unscientific spin to make the company's drug look better, as noted in previous research. In short, the present study probably underreports by a considerable extent the continuing problems with the commercial control over pharmaceutical research. Even so, it highlights the fact that merely creating a mandatory trials registry has been far from solving the basic problem.

Friday, November 1, 2013

Pharma Issues at the American Society for Bioethics and Humanities Annual Meeting

I began writing this post from Atlanta where I was (as usual this time of year) attending the annual meeting of the American Society for Bioethics and Humanities. In past years there has been maybe one session per year on something directly related to Pharma issues, so I was impressed to see at least three sessions on this year’s program. Here I report on a panel, “Bioethics Capacity Building in a Corporate Setting: One Pharmaceutical Company’s Experience,” presented by two folks from Eli Lilly and two distinguished academic bioethicists who have served for 15 years on the company’s bioethics advisory panel. The panel moderator was Luann E. Van Campen, PhD, head of the Bioethics Program at Lilly, and one of the panelists was Donald G. Therasse, MD, VP for Global Patient Safety and Bioethics at the firm, to whom Dr. Van Campen reports.

I gather from the presentation that Lilly has had an advisory committee on bioethics for 15 years, but that the internal bioethics program was inaugurated in 2008. You can find out more at:
The two academic bioethicists on the panel were indeed heavy hitters—Tom Beauchamp, PhD of the Kennedy Institute of Ethics at Georgetown, co-author of what most regard as the canonical textbook in the field, Principles of Biomedical Ethics; and Robert Levine, MD, of Yale.  I’ll focus mostly on what Dr. Beauchamp said as Dr. Levine indicated he endorsed almost all the former’s comments.

The academics reminded us that the bioethics advisory board at Lilly has so far concentrated its work in only one area—the ethics of research on human subjects. (The case study Dr. Levine discussed had to do with clinical trials in a poor country of a drug that might then be unaffordable to the population of that country.) Organizational or business ethics related to Lilly as a corporation was simply not on the agenda. Therefore, the academics said, apparently with justification, that they saw very little difference between being a paid consultant for Lilly and consulting on any bioethics body within their own university or in the academic world.
In response to an audience question, Dr. Therasse made an interesting comment. He said that perhaps in a few years, the bioethics program at Lilly would branch out and start to address these wider ethical issues. However, Lilly right now, like many of the large drug firms, is under a corporate integrity agreement with the U.S. Department of Justice. Until that agreement expires, the staff people who might work on that wider ethical inquiry have their hands completely full doing all the required compliance tasks with the corporate integrity. When the agreement expires, those people will presumably be freed up.

Dr. Therasse did not tell the audience what the corporate integrity agreement was triggered by, so I can’t be sure that it relates to this previous post:
But consider what’s apparently being said. Lilly was forced by a legal settlement to improve its corporate ethics behavior. They now say that they don’t have enough staff to attend to a full bioethical inquiry into their company’s activities because they are too busy complying with that settlement. But as soon as the settlement ends, then they can take the time and trouble to think more about ethics. Everybody got that? (I’m pretty sure that Lilly monitors this blog, so if I’ve been unfair to you guys, tell me, OK?)

My main concern, however, was not with Lilly but with my academic bioethics colleagues. Dr. Beauchamp began his talk by noting that some in our field criticize him for consorting with industry in this fashion. He then characterized their criticism using a series of straw-man arguments, such as they thought it was bad to make profits. He failed to address a single substantive argument made against close relations with Pharma based on actual patterns of industry behavior. So far as Beauchamp was concerned, there simply was all upside and no downside to consulting with drug firms. We recently reviewed the new book by Peter Gøtzsche that was highly critical of the industry:
If you were to listen to Dr. Beauchamp’s talk, you’d have no idea that such a book ever could have been written.

What was embarrassing about this presentation was that if a physician/scientist had given such a talk, explaining why he was a paid consultant to Eli Lilly, anyone with any familiarity with the industry would have labeled the talk as the typical rationalization that people with their hands in the till give when in denial of their actual conflict of interest. Here we have one of the bright lights of the field of bioethics imagining that he is giving a presentation that defends his role as a paid industry consultant, apparently not even realizing that he is merely giving that much more ammunition to critics of current financial entanglements.
To elaborate further on a theme that I have stressed repeatedly here, I want to contrast the positions of my academic colleagues with that of Dr. Van Campen. I may agree or I may disagree with her ethical thinking on a variety of issues, but at least we know fully where her loyalties lie. She’s a paid Lilly employee, and we must imagine that the minute that her activities were judged by Lilly to be bad for business, she’d be out the door. My concern rather is for people like me who imagine that we are independent, objective scholars, but that we can accept a role as a paid consultant to Lilly or any similar company while still adhering with full integrity to our independent stance. This panel, if anything, further demonstrated the fallacy of that view.

Deadly Medicines: Over the Top or Overdue Wake-up Call?

I promised a while back:
--to provide a book review of the new volume by Peter C. Gøtzsche, Deadly Medicines and Organized Crime: How Big Pharma Has Corrupted Healthcare (New York: Radcliffe Publishing, 2013).

The book features Forewords by two heavy hitters, Richard Smith, former editor of BMJ, and Drummond Rennie, long-time deputy editor of JAMA. If you read between the lines, the two editors both convey more or less the same message—this guy comes across as a raving lunatic, but it would be a shame if you were put off by that tone, because he actually has something important to say.

By way of the lunacy quotient, I append a representative list of quotes:

  • “In the United States and Europe, drugs are the third leading cause of death after heart disease and cancer.”(1)
  • “The main reason we take so many drugs is that drug companies don’t sell drugs, they sell lies about drugs. Blatant lies that—in all the cases I have studied—have continued after the statements were proven wrong.”(2)
  • “The book addresses a general system failure caused by widespread crime, corruption and impotent drug regulation in need of radical reforms. Some readers will find my book one-sided and polemic, but there is little point in describing what goes well in a system that is out of control. If a criminologist undertakes a study of muggers, no one expects a ‘balanced’ account mentioning that many muggers are good family men.”(2)
  • “I dedicate this book to the many honest people working in the drug industry who are equally appalled as I am about the repetitive criminal actions of their superiors and their harmful consequences for the patients and our national economies. Some of these insiders have told me they would wish their top bosses were sent to jail, as the threat of this is the only thing that might deter them from continuing committing crimes.”(3)
  • “[Industry] clinical trials are rarely research in the true sense of the word…it is marketing disguised as research. The trials are often flawed by design, additional flaws are introduced during data analysis, and the misleading results are spun to make sure that whatever an honest trial might have shown, the trial concludes something that is useful for boosting sales.”(87)
  • “We should ask our politicians to forbid marketing of drugs, as it is harmful, just like marketing of tobacco is, which is why we have prohibited tobacco advertisements…. There is no need for drug marketing, as the products should speak for themselves.”(94, 275)
  • “Anyone of us will need to consider the pros and cons of taking a drug, and our doctor isn’t always the best person to ask, as most doctors have been brainwashed and many have been bribed by the drug industry.”(129)
  • “We cannot trust industry trials at all and the reason is simple. We don’t trust a person who has lied to us repeatedly, even though that person may tell the truth sometimes.”(265)

Throughout the book, Gøtzsche uses the organized crime motif to characterize the drug industry. This is quite deliberate and measured. He argues that something counts as organized crime when:

  • They kill people
  • They lie about what they do
  • They routinely break the law as a part of their business practices
  • They use their ill-gotten gains to corrupt the government regulatory apparatus so as to be allowed to continue to operate

Gøtzsche is a physician, epidemiologist and research methodologist, and has achieved prominence as head of the Nordic Cochrane Center, a part of the Cochrane Collaboration which is generally recognized as the most reliable and independent assessor of medical data—a sort of gold standard if you want to know: how good is the evidence that any treatment works for any disease? So this guy is not one to fly off the handle and make charges that he cannot document with solid evidence. (I give him some credit for solid evidence since he several times cites HOOKED.)  I have not always agreed with Gøtzsche in the past—he’s co-author of a widely cited meta-analysis in the New England Journal (2001) purporting to show that the placebo effect, one of my own pet research interests, probably doesn’t exist. But while some of the evidence he brings forward in this volume is new to me, and much is worth reading simply to get the European perspective on the issue, very little of what he says would be of any real surprise to anyone who has read HOOKED and/or kept up with this blog.

In a minor way, the evolution of this blog parallels what Gøtzsche is up to. If you take the trouble to go back and look (I don’t advise it), check out how long it took me to use the actual words bribery and corruption in describing Pharma behavior. I now use those words unabashedly because I am quite secure in knowing that the behavior is accurately described by such terms, and there is no point in pussyfooting around the real and serious problem the behavior poses. If we get overly obsessive about not appearing intemperate, we pay the price of failing to endorse the really basic and drastic reforms that are needed to clean up the current mess.