The most massive scientific fraud ever?

Science as it is practiced today relies on a fair measure of trust. Part of the reason is that the culture of science values openness, hypothesis testing, and vigorous debate. The general assumption is that most scientists are honest and, although we all generally try to present our data in the most favorable light possible, we do not blatantly lie about it or make it up. Of course, we are also all human, and none of us is immune to the temptation to leave out that inconvenient bit of data that doesn't fit with our hypothesis or to cherry pick the absolutely best-looking blot for use in our grant applications or scientific manuscripts. However, scientists value their reputation among other scientists, and there's no quicker way to seriously damage one's reputation than to engage in dodgy behavior with data, and there's no quicker way to destroy it utterly than to "make shit up."

True, opposing these forces are the need to "publish or perish" in order to remain funded, advance academically, and become tenured, a pressure that can be particularly intense among basic scientists, who will basically lose their jobs and very likely their academic careers if they cannot cover 50% or more of their salaries through grants. I always remember that I'm fortunate in that, even if I failed utterly to renew all my grants and burn through whatever bridge funds my university might give me, I'd be unlikely to be fired, as I could just go back to operating full time. Indeed, I'd even be likely to generate more income for my department by doing surgery than I could through research. Clinician-scientists are in general a drag on the finances of an academic department.

Despite the pressures, however, I'm still left scratching my head over this recently revealed massive scientific fraud, as reported in Anesthesiology News, the Wall Street Journal, and the New York Times. A bunch of you sent it in to me, and when that happens, I usually conclude that I'd best comment on it. First, the fraud:

In what experts are calling one of the largest known cases of academic misconduct, a leading anesthesiology researcher has been accused of falsifying data and other fraud in potentially dozens of published studies.

Scott S. Reuben, MD, of Baystate Medical Center in Springfield, Mass., a pioneer in the area of multimodal analgesia, is said to have fabricated his results in at least 21, and perhaps many more, articles dating back to 1996. The confirmed articles were published in Anesthesiology, Anesthesia and Analgesia, the Journal of Clinical Anesthesia and other titles, which have retracted the papers or will soon do so, according to people familiar with the scandal (see list). The journals stressed that Dr. Reuben's co-authors on those papers have not been accused of wrongdoing.

In addition to allegedly falsifying data, Dr. Reuben seems to have committed publishing forgery. Evan Ekman, MD, an orthopedic surgeon in Columbia, S.C., said his name appeared as a co-author on at least two of the retracted papers, despite his having had no hand in the manuscripts. "My names were forgeries on the documents," Dr. Ekman told Anesthesiology News.

Dr. Reuben has been an extremely active and visible figure in multimodal analgesia, particularly as an advocate for its use in minimally invasive orthopedic and spine procedures. His research has provided support for several mainstays of current anesthetic practice, such as the use of nonsteroidal anti-inflammatory drugs and neuropathic agents instead of opioids and preemptive analgesia. Dr. Reuben has also published and presented data suggesting that multimodal analgesia can significantly improve long-term outcomes for patients.

It's hard to overstate how serious this revelation of scientific fraud is for the field of anesthesiology and medicine. Dr. Reuben was considered a pioneer in his field, and his work is not only widely cited, but serves as the basis for an amount of anesthesia practice that few academic anesthesiologists can lay claim to. The twenty-one papers now retracted represent a body of work that appeared on its surface to be quite impressive. Indeed, these two quotes gives you an idea of just how influential Dr. Reuben was:

All of that is now in question, said Steven L. Shafer, MD, editor-in-chief of Anesthesia and Analgesia, which retracted 10 of Dr. Reuben's articles. "We are left with a large hole in our understanding of this field. There are substantial tendrils from this body of work that reach throughout the discipline of postoperative pain management," Dr. Shafer said. "Those tendrils mean that almost every aspect will need to be carefully thought through. What do we still believe to be true? Do the conclusions hold up to scrutiny?"

Dr. Shafer said that although he still believes "philosophically" in multimodal analgesia, he can no longer be absolutely certain of its benefits without confirmation from future studies.

And:

Jacques Chelly, MD, PhD, MBA, director of the Division of Regional Anesthesia and Acute Interventional Perioperative Pain at the University of Pittsburgh Medical Center (UPMC), said that the Reuben episode has left multimodal analgesia "in shambles concerning many of the drugs we use"--particularly celecoxib and pregabalin. "The big chunk of what people have based their protocol on is gone."

That's what's so truly unusual about this scientific fraud. Usually, fraud involves a single paper or, at most, a handful of papers. Even Andrew Wakefield only fabricated data for one paper, at least as far as we can tell. The rest of his results derived from his utter incompetence as a scientist, which led to his unwillingness to worry about little things such as controls. Dr. Reuben's fraud appears to eclipse even that of Andrew Wakefield, as hard as that is to believe. Indeed, I've never seen an example involving such a massive body of work so important to a field over so many years. It's truly staggering. A PubMed search shows that Dr. Reuben has over 70 peer-reviewed papers. It's hard not to wonder how many of those are also fraudulent, and, even if they aren't fraudulent, Reuben's other work will be forever tainted by them, regardless of whether the science was good or not.

Whenever I see an example of fraud like this, I wonder: How could he get away with, in essence, making it up for so long? Clinical trials are complex; they inevitably involve statisticians who analyze the data. Many journals these days will not even consider publishing the results of a clinical trial without a biostatistician listed among the authors. Then there is the question of all the other authors on Dr. Reuben's papers. Although it has been emphasized that none of them have been accused of scientific fraud, I find it hard to believe that so many people over so many years failed to notice a whiff of a problem. My guess is that some of them probably did but remained silent because they liked being on papers with Dr. Reuben. It was good for their careers. Alternatively, they just signed on without taking any responsibility for the actual manuscript, something that's far too easy and tempting to do far too much of the time. I used to wonder if I should have managed to get myself on more papers, regardless of my level of involvement, because my publication record, quite frankly, is not as good as it should be at this stage in my career. But, looking at this incident, one thing I can say about my publication record is that there are some damned good papers there, and I either wrote or heavily participated in the writing of each and every one of them.

The other thing I wonder in the case of such massive fraud, and, no doubt so do my readers, is how so many fraudulent papers from one author could get past peer reviewers. One reason is that peer reviewers can only look at the data presented. They are not equipped to identify fraudulent data unless it's obvious. That's not to say that peer reviewers don't catch obvious fraud (they do, the most common examples I've heard of being autoradiographs cropped in funny ways or duplicated or what have you), but there is a presumption of honesty in science. Reviewers don't start with the presumption that the data themselves in a manuscript might be fraudulent. Rather, they are on the lookout for problems in experimental design, analysis and interpretation of the data, and drawing conclusions from that data. Moreover, they only look at one manuscript at a time. Rarely do they have time to read the references cited, and if they do read cited references usually they don't have time to do more than skim them. If an author's other manuscripts are all fraudulent, it's unlikely the peer reviewer would detect it, as he or she in essence works in a vacuum for each manuscript reviewed.

What this incident does reveal is that there are almost always indications. If there's one thing about science, it's often messy. Results rarely always turn out the way one expects or wants. If they did, then science would be pretty useless. Often the results that lead to new discoveries are the anomalous results, the unexpected result. Dr. Reuben's work suffered from what is in retrospect a very suspicious degree of consistency:

"Interestingly, when you look at Scott's output over the last 15 years, he never had a negative study," said one colleague, who spoke on the condition of anonymity. "In fact, they were all very robust results--where others had failed to show much difference. I just don't understand why anyone would do this or how anyone could pull this off for so long."

When you see an outlier, an investigator whose results are always more robust than those of his colleagues, be wary. It may not be scientific fraud, but it's definitely fishy. However, what brought Dr. Reuben to the attention of his hospital were two abstracts that he submitted for presentation. No record of approval for human subjects research could be found:

Dr. Reuben's activities were spotted by Baystate after questions were raised about two study abstracts that he filed last spring, Ms. Albert said. The health system determined that he had not received approval to conduct human research, Ms. Albert said.

Baystate investigators determined that Dr. Reuben had concocted data for 21 studies, and the health system asked the journals in which those studies were published to withdraw them.

What most angers me about this case is the massive betrayal of trust. The public expects that its scientists, at the very least, will be honest about their results. Too much depends on it, especially in medical science, where it is people's health that is at stake. Even worse, much of Dr. Reuben's work was underwritten by the pharmaceutical companies that manufacture the the very nonsteroidal anti-inflammatory drugs combinations of which he studied. What that means for those of us who defend science- and evidence-based medicine is that every crank alt-med site and blog on the Internet is going to be harping on this incident as The Proof That Conventional Medicine Is Hopelessly Corrupt and their favorite woo is being kept down by The Big Bad Pharma Man. Look for Age of Autism and NaturalNews.com to go crazy about this story as proof that they were right all along and The Big Bad Pharma Man has suppressed The Real Proof that vaccines cause autism. Not only has he put a stain on scientific medicine that will be very hard to erase, if it's even possible at all, but that bastard Reuben has made my work here harder, as well as that of every advocate of of science- and evidence-based medicine, as Whale.to, NaturalNews.com, and Age of Autism, not to mention every crank blog and website spread the story far and wide as some form of "vindication."

But even worse than that, he's wasted huge amounts of resources and left a huge mess for his colleagues to figure out. It'll take years for the studies he's done to be either redone or for other investigators to find out if the very concept of multimodal analgesia is even a valid concept. He's screwed every anesthesiologist who, based largely on his work, came to accept this therapeutic modality as the best for their patients.

Come to think of it, he's screwed all those patients too.

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The headlines bring news of another scientist (this time a physician-scientist) caught committing fraud, rather than science. This story is of interest in part because of the scale of the deception -- not a paper or two, but perhaps dozens -- and in part because the scientist's area of research,…
Wow! This is massive! From Anesthesiology News: Scott S. Reuben, MD, of Baystate Medical Center in Springfield, Mass., a pioneer in the area of multimodal analgesia, is said to have fabricated his results in at least 21, and perhaps many more, articles dating back to 1996. The confirmed articles…
Several news agencies are reporting that a massive academic fraud case has surfaced. A single researcher apparently fabricated data used in the publication of at least 21 journal articles published over a 12-year period. After an internal reviewer raised concerns, Baystate Medical Center…
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Often the results that lead to new discoveries are the anomalous results, the unexpected result. Dr. Reuben's work suffered from what is in retrospect a very suspicious degree of consistency

Come to think of it, the Geiers have never published one negative result that I know of. In their case, the confounds they ignore and their errors are so obvious that it's only natural to suspect scientific fraud.

He should go to prison. If those studies were paid for and he didn't do them, that is fraud. If Pfizer paid for those studies, Pfizer needs to get him prosecuted for fraud.

It's going to take a while before we recover from this. Negative results from studies are just not exciting enough to get published.

Yes, every alt-med crank is going to be high-fiving over this. However the med-blogsphere reaction to it shows the difference between alt-med and real medicine.
In the real-medicine world, people like Orac are openly blogging about this, asking "How could it happen? What can be done to stop it happening again? What can be done to repair the damage in trust?"
When fraud is exposed in the alt-med world, however, the reaction is invariably along the lines of "X is innocent! They're lying! It's a Big Pharma/gubmint conspiracy to suppress Teh Truth!"

Not to mention that celecoxib (Celebrex) and rofecoxib (Vioxx, which was withdrawn in 2004) increase the risk of heart attacks. If patients were put on those drugs because of his work, they could have suffered heart attacks as a result. Maybe not if they were only on the drugs for a short period of time, but my experience is that once someone is put on a drug, it's not unusual for the prescription to get renewed over and over. Plus, a study published last year in The Lancet showed that the risk from rofecoxib may have continued for at least a year after the patient stopped taking the drug.

Baron et al., Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial,The Lancet, Volume 372, Issue 9651, Pages 1756 - 1764, 15 November 2008
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61490…

By Marilyn Mann (not verified) on 12 Mar 2009 #permalink

I can see him getting away with changing data, or always getting positive results. It might be a little suspicious, but when do you play the "your results are too good, you must be a quack" card? If someone deletes or changes a few outliers, that's bad enough, and it's almost impossible to detect. But, I don't understand how he got away with making up results for studies he apparently never even performed. How do you do that over 20 times, and how do the co-authors not even know that the studies were never even performed?

"Negative results from studies are just not exciting enough to get published."

Is this a concept purely based in the sciences? The statistics professors I had, undergraduate and graduate school, always stressed that we should look at every (hypothesis testing) result, rejection or not, as an opportunity to learn something about the problem at hand.

I cannot comment on this particular case as it is well outside my area of expertise, although it certainly sounds serious and probably devastating for people using the results.

I'd like to pick up on your comment, of reviewers, that "[r]arely do they have time to read the references cited, and if they do read cited references usually they don't have time to do more than skim them."

When I used to get papers to review, I'd check as many of the references as I could easily locate. It was amazing how many were wrong. In some cases it was merely a mistake in the author's name, the title or the pagination, or a twisting of what had been said in the original (probably changed during the course of rewriting drafts). Too often, however, it was simply wrong. I've seen potassium exchanged for phosphorus, references to data from organisms that were not mentioned in the original, references to claims that were themselves mis-citations and results quoted completely backwards. In the last case, the second author of the cited and the citing paper was the same person.

I did not keep records, but perhaps 1/3 of the papers had errors sufficient to modify at least some of the conclusions of the paper. Some people were always spot on with their citing, but one author managed to make errors in 12 of the 13 references I checked. I rejected the paper on the grounds that if there were so many errors in the references, that I could check, how could I possibly trust the data that I couldn't check?

But as you say, it takes a long time, for which you get essentially no credit, and I've never come across anyone else who made a practice of checking references.

By Richard Simons (not verified) on 12 Mar 2009 #permalink

Imagine how much more difficult it would be to sort fact from fantasy in anesthesiology, if we had the National Center for Alternative and Complementary Anesthesia promoting speedballs, Long Island Ice Teas, peyote, acid, and ecstasy, all "integrated" with halothane; and a few Dr. Ornish types dreaming up their own unique cocktails of six ingredients combined with hypnosis, meditation, and aromatherapy pre-op; and all this combined with advocacy groups more interested in "freedom" than truth.

Delusion and deception have been the rule in medicine for millenia. Science has been the still, small voice in the circus guiding some of us a few steps forward.

The alties view themselves as Davids fighting the Goliath of BigPharma and conventional medicine. In reality, science is the puny David standing up against the far mightier Goliath of human nature.

dean, I think part of the issue is maintaining scientific agnosticism. Too many researchers get emotionally and in some cases even financially interested in achieving specific results. If you've staked your career on the effectiveness of X, and your results start showing the X isn't that effective, then you have quite a conflict on your hands.

@Dr. Benway,

You are easily the most amusing commenter on this blog. Keep it coming.

By Joseph C. (not verified) on 12 Mar 2009 #permalink

Good on ya, Richard Simons.

The issue of lazy vs. quality peer review came up at Science-Based Medicine. I imagined a system of pseudononymous review, which would allow good reviewers a chance to build reputations and a demand for their services, while perhaps weeding out reviewers who make a poor effort.

It's easy to ask "why didn't anyone see it" with the old 20-20 hindsight. If his earlier papers were genuine, then it would be easy for people to skip over fraudulant material because of the severe penalty science hands out to fakes - "Someone with so much to lose would never fake stuff". Also calling someone a fraud in science research is not a thing done lightly in any case.

Religious figures can bounce back after being caught faking things by excuses of 'the devil made me do it'. Politicans just say it was a 'mistake and I'm really sorry', and the woos just mumble about conspiracies and toxins. In science research you get caught even _once_ faking things, and your entire career is stone dead - forever.

It also explains why science does trust researchers a lot to be honest. While generally the rewards when you do the right things are small and scattered, the penalty for fraud is severe (no more grants, other researchers will always know of you as 'that fraud', universities and institutions wont touch you with a 10 foot pole, etc). Faking it is like playing a game of Russian roulette. You may get lucky faking data and win big for a while, but when (not if) you lose, you're gone. And you dont get a second chance.

As for the woo brigade - they will be all over it like a bad rash. Of course they'll neglect to mention it was science which exposed the fraudster in its ranks - something the crystal waving crowd have yet to do, despite having plenty of subjects to expose.

As a graduate student I took some data from a graph and performed regressions and correlations to see how well it fitted a theoretical relationship. The worst (of 3) r^2 was 0.994, while the best from other people's data was about 0.75. Then I noticed I'd made a very common mistake in the equation I used. I asked a couple of the faculty what to do about it but they did not want to address the issue and I had no idea what to do. In retrospect I should probably have informed the editor of the journal and asked the author for a copy of the data.

Further to my comment on faulty citations: I had a letter on it published in Nature. They managed to make two mistakes in my name!

By Richard Simons (not verified) on 12 Mar 2009 #permalink

Just yesterday I was informing a young 'sceptic' that scientists were basically honest in their work because they had so much to lose if they weren't, and generally they could be trusted more than an anonymous blogger. This fraud hurts.

How the science community deals with this will be teling though. For example, is there "We believe in Dr. Reuben" petitions being circulated a la the ones for Wakefield? I doubt it, and should the Reuben item be mentioned we could point out how our responses differed from the antivax/alt-med group.

As painful as it is, we excised the bad studies like a tumour. By contrast, Wakefield and his fraud is still being embraced, protected and declared healthy despite all evidence to the contrary. Science follows the evidence no matter where it leads, whether we like it or not.

Publishing is hard work, lots of 'field' work, rewrites, rejections. Then it seems this fraud just makes stuff up and gets published?! Let's start a petition asking Reuben to run the gauntlet and apologize personally to everyone affected...then we'll put on our steel-toed boots and make him run back through the gauntlet.

By Daniel J. Andrews (not verified) on 12 Mar 2009 #permalink

*telling*--darn type is too small for old eyes

By Daniel J. Andrews (not verified) on 12 Mar 2009 #permalink

Are there any immediate repercussions we regular people need to worry about? My baby needs surgery this summer. Do I need to have a conversation with the surgeon about the method of anesthesia being used, and if so, exactly what should I say?

To expand on daedalus2u:

Follow the money. Orac, you focused on the pressure to publish or perish. That's a biggie, but what I see here is pure greed. Somebody was paying for a study, and it looks like the study wasn't done. What happened to the money? Dollars to donuts it went into somebody's pocket, funding a lavish lifestyle. That, all by itself, could have been a big part of the impetus behind this fraud.

Somebody besides the lead author must have known about this fraud. People who worked with him every day (secretary, research assistant, office manager, whatever) would have had to be involved in the research, but wasn't. The days of doing research all by ones self are gone, if they ever existed in this field at all.

Another scientific fraud this brings up is that of Jan Schoen ( http://en.wikipedia.org/wiki/Jan_Hendrik_Sch%C3%B6n ). He got amazing results in solid state physics until a reviewer noticed a graph being repeated, noise and all. The ultimate ending was not only retraction of the papers, firing, but also the revocation of his Ph.D. Would losing his medical license be appropriate here ? I don't I would want to be treated by a doctor who had lied for profit.

By spudbeach (not verified) on 12 Mar 2009 #permalink

I don't know if this is the most massive scientific fraud ever but certainly is one of the most massive. This sort of behavior is really disturbing. Yet it thankfully appears to be very rare in science. Cases of fraud in science are rarer than fraud in other lines of work.

"Often the results that lead to new discoveries are the anomalous results, the unexpected result. Dr. Reuben's work suffered from what is in retrospect a very suspicious degree of consistency"

Just like Madoff.

Orac,

I chafe at all the politically correct knee jerk reactions to cliches, stereotypes, ethnic putdowns and so on. Corrections and awareness raising was long overdue for much of it but now the pendulum is swinging into the arc of extremism. Clint Eastwood has raised a good point about that recently.

So it is with surprise at myself that I realize I wince inwardly whenever I read a reference to drinking the Kool-Aid. Each mention of that brings up unpleasant and disturbing images of all those poor people, especially the children, lying dead. Many of them were forced to consume and had no way out. They didn't chose that option. Surely there must be some other way to illustrate the intended point of being overly gullible without mentioning that horrific event as an analogy because as an analogy for gullibility it just isn't true.

You've used it a lot so it's probably in your wordbank but if you could substitute something else instead, that would be nice. If you still use it I won't boycott you, picket your blog or virtually throw you rotten tomatoes. I'll always read your blog.

Thanks for the good work you do.

Sally

Unfortunately, a rotten apple, unless you get rid of it early enough, will spoil the whole bunch in the box. And as long as we afraid to point at the bad apple ourselves, hoping that someone else will do it, the rot will spread to all of us. Consider the following comment:

"Interestingly, when you look at Scott's output over the last 15 years, he never had a negative study," said one colleague, who spoke on the condition of anonymity. "In fact, they were all very robust results--where others had failed to show much difference. I just don't understand why anyone would do this or how anyone could pull this off for so long."

Speaking on the condition of annonymity?! Clearly, the asshole who wants to stay annonymous knew something before the story broke and then, just as now, s/he preferrd to stay annonymous. We, as scientists, do not really police ourselves at all, but we absolutely fight tooth and nail against any notion of policing our activities by others. We cannot have it both ways; we either root out the rot ourselves or accept the fact that the criminals among us will hurt us more than a police force watching us in our labs and clinics.

19 comments so far, and not one troll popping up to say,

"No, the most massive scientific fraud ever is Al Gore/Darwin/vaccination/USAF Blue Book/...!!1!"?

Orac's anti-woo fu is strong today.

By Pierce R. Butler (not verified) on 12 Mar 2009 #permalink

Although Orac has been the flag bearer of the fight against woo and alties, the case described in the present post should really force us to look inward. Rather than mock and belittle the alties right now, we must consider very seriously directing much energy and thought at fighting the virus, namely, scientific misconduct, that could infect and kill its host i.e., scientific and clinical research.

Clearly, the asshole who wants to stay annonymous knew something before the story broke and then, just as now, s/he preferrd to stay annonymous.

Or maybe he/she just felt stupid for having failed to catch it.

This just makes a publicly available register of clinical trials even more important. All trials licenced by the national authority should be included on a public register with an abstract of the proposed trial and a reference to the results. all of the trials should be published by law. Negative trials can be 'published' by reporting to the regulatory authority if they cannot find a journal to publish.

This will not only prevent drug companies burying bad news about drugs, and also issueing multiple papers based on the same datasets (or at least it will make it more obvious if they do) but also frauds like this one can be easily detected- if the trial doesn't happen then you don't have a reference to the database.

Surely there must be some other way to illustrate the intended point of being overly gullible without mentioning that horrific event as an analogy because as an analogy for gullibility it just isn't true.

I strongly disagree as far as the adults are concerned. Nobody forced them to go down to Guyana at gunpoint. And there certainly were warning signs, lots of them. Like the fact that Jones had taken to sodomizing a good number of the male members of The People's Temple.

By Joseph C. (not verified) on 12 Mar 2009 #permalink

S. Rilvin,

It is always important to be most critical of ones self before being critical of others, not just when the shit hits the fan. As I mentioned in my own post on the topic, the acts of this physician are not the end of the world, they are merely illustrating the fact that doctors are humans, and some humans are fucking stupid. This isn't even a hiccup for the culture of science - the method works and it will continue to work, so long as we follow it and not let it be influenced by special interests or our fear of "not being famous."

In cases of fraud like this, where the funder of the studies (Pfizer) benefited greatly from the fraud through increased sales of their products, I think it is extremely important to put the funder of the fraud and the perpetrator of the fraud in direct legal conflict so that the truth can come out.

If Reuben simply scammed Pfizer, took their money and gave them studies he made up, that is bad. If on the other hand Pfizer was aware that he was committing fraud and funded him anyway, that is a degree of misconduct on Pfizer's part that is completely different.

The only way to find out if Pfizer and Reuben colluded in this fraud is to put them in direct legal conflict. It is necessary to put Reuben on trial for fraud and facing many years in prision. Only then will he have the incentive to disclose if people at Pfizer knew about it. If Pfizer did know about it, then their fraud encompasses the sales of their products based on the fraudulent studies they hired Reuben to produce.

If Pfizer submitted studies to the FDA by Reuben when Pfizer knew they were fraudulent, then those Pfizer employees should go to jail too. I presume that Reuben would have kept correspondence that would implicate others to protect himself if ever the shit hit the fan.

I'm not a big believer in the death penalty, but if there ever was a case for it, this would be it. Thousands of physicians relied on these studies to treat millions of patients with very serious pain. The depravity exhibited by Dr. Reuben is on par with the most heinous of crimes.

By David C. Brayton (not verified) on 12 Mar 2009 #permalink

Something to note: from what I've seen, Pfizer didn't start funding his research until 2002. The first fraudulent paper was published in 1996, 6 years earlier. I would be hesitant to put blame on Pfizer at this time, unless it can be shown that he was being funded by them previously. However, I haven't done any research into the long-term funding of Dr. Reuben, so don't take my word for gospel truth. Also, the fraud was discovered because he didn't have approval for his latest research - that doesn't mean he didn't do the research, just that it didn't have the proper approvals, so the people working with him may not have known anything was wrong.

We definitely need to find out who knew what, when. I just don't want to see a witch-hunt.

I am hoping that no one at Pfizer was aware of the fraud while it was occurring. I can't help wondering, however, whether any teensy weensy bit of doubt regarding Dr. Reuben's results entered the minds of any Pfizer scientist who had been engaged in development of Celebrex and Lyrica. I just wonder whether any of them asked themselves, based on their own research or other research in the field, whether his results were too good to be true.

By Marilyn Mann (not verified) on 12 Mar 2009 #permalink

@spudbeach: Jan Schoen was never a medical doctor.

@everybody: My experiences with collaborators have made me very hesitant to blame them for not catching fraud. What degree of vigilance is good enough? My closest collaborator is working in another lab a few hours away. I can't look over his shoulder daily and see what he's doing. What I do is look at his results and see that they make sense, that they're not too perfect, and that different experiments look different. But I basically have to trust him on things like whether he used the mutants he said he did. No matter how closely someone is involved with a collaborator, there's always something he or she can hide.

Reuben sounds like a gradual sellout.

As though he did some good early research, and found he was under pressure to continue to produce the goods. He gave in to temptation to "tidy up" the data "just a little bit", and having crossed that little rubicon, it became easier to do it again, and more.

Sometimes peer pressure to be successful is greater than peer pressure to be honest.

Marcus, exactly. If Pfizer doesn't get him prosecuted for fraud then it appears that Pfizer colluded with him on the fraud. If Pfizer does get him prosecuted for fraud, then he has a large incentive to disclose that Pfizer knew his work was fraudulent. That moves the monitary fraud from the millions for the studies to the billions for sales of the drugs.

>>>"...there is a presumption of honesty in science. Reviewers don't start with the presumption that the data themselves in a manuscript might be fraudulent."

Slightly off topic, but:
This is why so many scientists have been fooled by the likes of Uri Gellar when testing his "abilities". Scientists generally are not used to their experimental subjects actively and deliberately try to trick, fool, and deceive them.

By Karl Withakay (not verified) on 12 Mar 2009 #permalink

The main difference between pseudoscience and real science:

Nobody is circulating a petition to "save" Dr. Reuben. (see: http://www.wesupportandywakefield.com/ )

In fact, there seems to be a large (and growing) number of scientists and doctors that want him run out of "town" on a rail. I suspect that Dr. Reuben will not have another job in real science for the rest of his life.

Maybe he can get a job at "Thoughtful House".

Prometheus

Not to mention that celecoxib (Celebrex) and rofecoxib (Vioxx, which was withdrawn in 2004) increase the risk of heart attacks. If patients were put on those drugs because of his work, they could have suffered heart attacks as a result. Maybe not if they were only on the drugs for a short period of time, but my experience is that once someone is put on a drug, it's not unusual for the prescription to get renewed over and over. Plus, a study published last year in The Lancet showed that the risk from rofecoxib may have continued for at least a year after the patient stopped taking the drug.

However, it is now beginning to look like there is cardiovascular risk with most of the NSAIDs, with the exception of aspirin. A large retrospective British study that correlated myocardial infarctions with NSAID prescriptions found an adjusted odds ratio of 1.32 for a roxecoxib (Vioxx) prescription within 3 months, falling to 1.05 after 3 months. For comparison, the odds ratios were 1.27 and 1.09 for naproxen, 1.55 and 1.13 for diclofenac, 1.24 and 1.04 for ibuprofen. The increase in risk for within 3 months was statistically significant for all of the NSAIDs examined except for celecoxib (Celebrex), which had odds ratios of 1.21 and 1.14.

The APPROVe study was of patients who mostly would not have normally been taking NSAIDs, since it was directed toward prevention of colon cancer rather than pain relief. But most people taking NSAIDs long-term in real life are taking it for joint pain, and if they are not taking one of them, they will probably be taking another. So it is increasingly questionable whether the incremental increase in MI risk of Vioxx is sufficient to justify withholding it from patients, particularly considering the greater GI risk of nonselective COX inhibitors. Of course, that is all pretty much moot. Considering potential liability, there is no way that Merck could bring it back. And Celebrex is actually looking rather good.

I am surprised at the lack of data corroboration in this case. Shouldn't this research have been duplicated elsewhere as part of the scientific process?

By Richard Eis (not verified) on 12 Mar 2009 #permalink

"If Pfizer doesn't get him prosecuted for fraud then it appears that Pfizer colluded with him on the fraud."

Full disclosure: I work for a Pharma, but not Pfizer.

What you say is sort of correct, athough it's not that straightforward. What you'll probably see is Baystate Medical Center take action against Reuben, not Pfizer, but that's the only was it'd be workable.

If Pfizer's legal agreements are the same as industry standard ways of working then Pfizer will have agreements with an institution not a person, so in this case they'd have a contract with Reuben only as a named representative of Baystate Medical Center or of a anmed clinical trials group. As such Pfizer can only sue Baystate, not Reuben personally.

It would only be Baystate Medical Center who could take action against Reuben himself as he broke, presumably, his contract and terms of employment with them. At least I hope he broke his employment conditions, otherwise it'd not say much for Bayside's terms and conditions.

Personally this is a rare case where I feel sorry for Pfizer and Wyeth : Reuben appeared to everyone, industry, academia and medics alike to be a "key opinion leader" and they'll have fought like mad to get him to do their trials as they were conned by his fake reputation from prior fraud. Despite the fact his reputation was faked well before they got involved, they'll still be accused of a part in the corruption whereas they are victims as much as the journals and patients involved.

Pierce, I was going to say 'Cyril Burt' for most massive, but you're right, Hansen is a contendah.

The curious thing about Hansen, compared with Reuben, is that Orac is all over Reuben like white on rice, while the dozens of exposes of fraudulent, mistaken, fabricated or just plain silly warming studies have not budged Orac, or many, many others, off the Gore dime.

Why is that?

By Harry Eagar (not verified) on 12 Mar 2009 #permalink

Because there's no scientific fraud there? Not to mention that this is not a climate science site...

In any case, Harry doesn't recognize irony when he sees it, as Pierce was clearly being sarcastic.

But thanks for fulfilling his prediction with such an utter lack of self-awareness.

The curious thing about Hansen, compared with Reuben, is that Orac is all over Reuben like white on rice, while the dozens of exposes of fraudulent, mistaken, fabricated or just plain silly warming studies have not budged Orac, or many, many others, off the Gore dime.

I'll bite. Name one clearly fraudulent AGW study by Hansen or anyone else where fraud has been ignored.

"It is always important to be most critical of ones self before being critical of others, not just when the shit hits the fan."

moneduloides, eventually you haven't read my book and thus you don't know that I was, am and will be critical before and after the shit hit the fan. ;)

It occurs to me there is another subtle but basic anti-woo lesson in this, aside from the contrasting community responses ("burn him!" vs "leave Andy alone!").

The fraud raises the question "why didn't we notice?" not just for the peer-review process at the collaborator, journal and community levles, but also at the doctor and patient level. Why didn't doctors and patients notice that the drugs weren't working as they were supposed to?

The answer, it seems to me, is that in many cases they couldn't. Doctors and patients aren't typically scientists, an they certainly aren't examining their care scientifically. They just want to make better/feel better. Ostensibly they trust that the minority like Orac have filtered the treatment tools available to them so they don't have to worry about it, though I wonder how many actually think about it. The critical fact here is that the reality of a treatment doesn't necessarily inform the perception of it. Unless the difference between the two is large enough, patients and doctors often may not notice.

Which is why we do science and the woo crowd don't. We KNOW everyone can do something that doesn't work (or work well) and think it does. They don't.

Joseph C.

You wrote: "I strongly disagree as far as the adults are concerned. Nobody forced them to go down to Guyana at gunpoint. And there certainly were warning signs, lots of them. Like the fact that Jones had taken to sodomizing a good number of the male members of The People's Temple."

You're absolutely right about their gullibility to go to Guyana. I was only referring to the actual mass murder (yes, and partial suicide). From what I've read only some chose to die of their own free will. The rest had guns pointed at them. Either way, it brings up horrific images to me.

Now some really stupid and decidedly gullible people were the ones who chose to go follow the comet. I've forgotten the details of that event and I don't intend to look it up, but all of those people were willing wackos in their own demise. That event only makes me shake my head in wonder at such foolishness but at least the only images that come to my mind are rows of bunkbeds.

Anyway, my apologies to Orac for veering from his topic.

Sally

Yes, every alt-med crank is going to be high-fiving over this. However the med-blogsphere reaction to it shows the difference between alt-med and real medicine.
In the real-medicine world, people like Orac are openly blogging about this, asking "How could it happen? What can be done to stop it happening again? What can be done to repair the damage in trust?"
When fraud is exposed in the alt-med world, however, the reaction is invariably along the lines of "X is innocent! They're lying! It's a Big Pharma/gubmint conspiracy to suppress Teh Truth!"

As we just saw with the Mercury Militia's closing ranks around Andrew Wakefield when he was shown to have falsified his data.

It occurs to me I should make clear I'm not bashing doctors and patients...just pointing out that we don't expect them to do controlled studies as part of their daily practice/trearment seeking.

@ Karl Withakay

...This is why so many scientists have been fooled by the likes of Uri Gellar when testing his "abilities".

So many? Citation, please?

Couple of guys at Vanderbilt seem to think they've identified the gene's linked to autism. So that should shut them up.

OTOH, there is a great deal of truth that much of medicine has been corrupted by money and profits. People can deny this all they want, but not only was this man exposed, but there is a lot of evidence, mostly testimonial, that big Pharma does tend to cherry pick its studies through running multiple trials then using the most favorable.

Arren,
Let me first clarify, I didn't say that many scientists have been fooled by Uri Geller specifically, though at least 2 have been fooled by Uri Geller specifically in "controlled" scientific testing.
http://en.wikipedia.org/wiki/Uri_Geller#Scientific_testing

I said that many scientists have been fooled by the likes of Uri Geller, as in paranormal frauds like Uri Geller.

If you dispute that over the years, many scientists have been fooled when supposedly conducting controlled scientific tests of persons claiming paranormal powers, I suppose I could take the time to comb together references if you really want.

By Karl Withakay (not verified) on 12 Mar 2009 #permalink

there is a lot of evidence, mostly testimonial, that big Pharma does tend to cherry pick its studies through running multiple trials then using the most favorable.

Isn't that a flaw of the scientific method in general? It's not only Pharma that might be unwilling to publish negative studies. Independent researchers might not be inclined to do so either. Often studies get canceled because the preliminary results were poor. Journals might not find some negative studies worthy of being published.

Statistically, all of that is clearly a problem.

I'm surprised about the utter lack of detail in the accusations. We know, the institution has asked for the papers to be withdrawn. But I can't see any notice if it's for violations of their human research protocols, for sloppy work, overly generous data massage or outright falsification of data. The Cell affair around Imanishi-Kari should be a warning.

I know what people mean about how references are not checked. The internal examiner for my PhD had a well cited paper. In half of the citations his surname was mispelled. We traced it to the original paper to get it wrong. The bet is that the vast majority of people had recycled the reference from that paper and had probably never read the guy's paper.

By Peter Ashby (not verified) on 12 Mar 2009 #permalink

As a scientist I have often been pressured to do things that just aren't right. Being the nice cooperative sheep that I am, I tell people to go to hell. Because of this I've lost one job (my employer claimed I was "difficult"), but as I see it, competent people shouldn't let monkeys control them. Unfortunately sometimes that means quitting and moving on - I much prefer that to lying for money. Incidentally I've also accused many colleagues of doing just that - lying to get money. You can imagine how popular I must be with that lot - but I don't even consider those people to be scientists. The end result is that I don't get as much money as I could if I'd thrown out ethics and played the silly games, but real scientists around the world still respect me and I can still enjoy calling people monkeys and telling them to go to hell.

By MadScientist (not verified) on 12 Mar 2009 #permalink

@ MadScientist

My husband is the same as you. He has moved on from several positions for the same reasons. Unfortunately this has made him probably the world's oldest post-doc.

I was easier to be principled before we had children, and I lost my contract research position, but I hope he never loses his principles...It's one of the things that makes me very proud of him.

By Long time lurker (not verified) on 12 Mar 2009 #permalink

@Andrews:

How the science community deals with this will be teling though. For example, is there "We believe in Dr. Reuben" petitions being circulated a la the ones for Wakefield? I doubt it, and should the Reuben item be mentioned we could point out how our responses differed from the antivax/alt

How about a petition entitled "We believe in Dr Reuben... being a fraud", with the petition being a point-by-point parody of the "We believe in Dr. Wakefield" petition? I'm not sure if it would be effective at getting the point across, but it would definitely be funny.

By Matthew Cline (not verified) on 12 Mar 2009 #permalink

Couple of guys at Vanderbilt seem to think they've identified the gene's linked to autism. So that should shut them up.

On the contrary, they will simply argue that these are genes for sensitivity to mercury, or formaldehyde, or aluminum, or whatever the toxin boogeyman of the week happens to be.

Remember, dead men do bleed

Of course they'll neglect to mention it was science which exposed the fraudster in its ranks - something the crystal waving crowd have yet to do, despite having plenty of subjects to expose.

Do we know that it was science as opposed to an admin irregularity?

As for the co-authors being unaware - unfortunately, despite journal policy that mandates author declaration of involvement, for far too long, it was routine for a string of names to go on a paper where few of those writers had anything to do with the data, the research or the writing. There are authors whom it would be inappropriate to name in this context who had hundreds of publications with their name on in a year.

It was that sort of "put my name on it" publishing that led to calls for the abolition of the notion of authorship and declarations of contributions. There are particular problems, of course, with authorship proliferation and projects that involve multiple international centres.

Fraud in medical research this far reaching astounds me. Surely it has as much potential to affect the health of people the author cares about as it does the rest of us? Shouldn't that thought serve to self-regulate too?

By Astonished (not verified) on 12 Mar 2009 #permalink

Warming of the Antarctic ice-sheet surface since the 1957 International Geophysical Year

Eric J. Steig1, David P. Schneider2, Scott D. Rutherford3, Michael E. Mann4, Josefino C. Comiso5 & Drew T. Shindell6

By Harry Eagar (not verified) on 12 Mar 2009 #permalink

Part of the reason that Dr. Reuben was able to perpetrate such a fraud is that he was doing research in an area where not too many others were working - multimodal analgesia. His "outing" is a good sign that even in the more arcane and esoteric scientific fields, the system works to get rid of bad data and "cheaters".

In hindsight, some people have said "His results were too good to be true.", but I think that a lot of people ignored that because they wanted his results to be good - not for corporate profit but because they wanted to think they had found a better way to relieve post-operative pain.

Although his work emphasized drugs made by Pfizer(especially in recent years), his results were applied clinically using a variety of selective and non-selective NSAID's and neuropathic pain medications. I can't see that he did this to help out a company that funded his research, since it was just a matter of time before his findings weren't replicated and he was "found out" - which, you might notice, hasn't helped him or Pfizer.

I suspect that he thought he was just "tidying up" the data to show what he "knew" was the "truth". This is a terrible temptation for any researcher, since you "know" that anyone repeating your experiment will find the "right" answers, even if your data don't seem to show it. It takes self-discipline to publish data that are ambiuous or contradict your hypothesis - self-discipline that Dr. Reuben apparently lacks.

I am curious about what he did to the data, since the report has been very vague about it. His lawyer's statement makes it seem as though it was "all a big misunderstanding" (but don't the lawyers always say that?). No matter, if he fabricated data - even "just a little bit" - he is finished in the world of real science. No legitimate research institution (not even "Big Pharma") would touch him with a ten-meter pole after this.

Of course, the usual suspects will be crowing about how this "proves" that "mainstream medicine" is corrupt. It will be typical of them to miss the point - that real science and real medicine work to find out how the world (or the human body) really works. For that reason, fraud and error are eventually rooted out and corrected.

I haven't seen anything like this in the worlds of pseudoscience and "alternative" medicine, where the goal seems to be to "prove" whatever the "researcher" already believes is true. Given that human nature is what it is, any deficit of reported fraud and error in "alternative" medicine simply means that it has remained undetected.

Prometheus

@Harry Edgar: So? There are no indications that study is even mistaken, much less fraudulent. There are only accusations.

trrll,

I agree that there is cardiovascular risk with all NSAIDs, except for aspirin. I mentioned celecoxib and rofecoxib because, according to the newspaper articles I have read, Dr. Reuben's research involved those particular drugs.

My understanding from talking to my husband's cardiologist is that naproxen is thought to be safer than ibuprofen. There is an ongoing clinical trial comparing cardiovascular risks of celecoxib, naproxen and ibuprofen.

I would disagree with you that the evidence justifies bring back rofecoxib. The risks associated with rofecoxib are just too high, and there are alternatives available.

By Marilyn Mann (not verified) on 12 Mar 2009 #permalink

This is an ethical dilemma for the entire community of scientists. Clear fraud, yet there is the chance that some of this work was still correct. The fraudulent should be discredited, but it is also equally difficult to throw out theories and claims in their entirety, when the chance exists that they may have some useful truth in them. Perhaps a researcher willing to redo these exact studies would be doing the world a service, even though it is less than fulfilling to revisit someone elseâs lies.

Even quality review can not do much more than detect obvious errors. In some cases it may be abused and used to censor inconvenient results or to protect a reviewers beliefs. There are clearly benefits to peer review, but it does not prove the science behind the paper, and one must be wary of abuse.

Einsteins major theories were never subject to peer review, since peer review did not exist then. In 1936 he had his first paper reviewed and it was rejected, he was furious it was reviewed by anyone other scientist before being published without his permission, and he sent it to another journal which was happy to publish it. Of course, at that time Einstein had taken on the giants of quantum physics and their "spooky" theories, so perhaps one of the reviewers took exception to his skepticism.

I do not where the funding for Reubens studies came from, but in 1961 when Eisenhower gave his last speech warning of the dangers of the MIC, he also mentioned concern with government funding driving science. He was right on both counts. Obviously, corporate funded science can have biases as well.

This expose gives weapons to those skeptical of vaccines and mans role in global warming. We have been asked to trust science and scientists as if they operate at a higher standard than politics or business, and are independent of pressures that could bias their results. It is clear this is not true.

That's why in science all theories or hypothesis must be treated with a great deal of skepticism. The debate should never be closed on anything, especially just because a paper has been published in a peer reviewed journal or because it has not been disproven. Funding for research to disprove popular (political and/or profit in industries tending toward monopoly) theories/hypothesis is in short supply.

That's why in science all theories or hypothesis must be treated with a great deal of skepticism. The debate should never be closed on anything, especially just because a paper has been published in a peer reviewed journal or because it has not been disproven.

If you followed that logic it might render scientific research unworkable. You can't prove a negative, mostly you can only ever state that the preponderance of evidence is such that something is unlikely or even biologically implausible.

Marilyn Mann,

It is my understanding that naproxen is no longer available here in the UK. It was withdrawn on the grounds that it is a higher suicide risk than ibuprofen.

By Peter Ashby (not verified) on 13 Mar 2009 #permalink

I'm not a research scientist, but I have a question for those of you who are: How easy is it to publish/get funding for replications of routine research work?

I had always understood that one principle of good science was the research reports had to include enough information to allow replication of the research being reported, and that until it had been (replicated) it was considered tentative. When did this change? Or has it? Is it possible that the growth of opportunities for original research has so outstripped available researchers that nobody wants to do replication any more?

AK, to my (very limited) knowledge, replicate experiments were performed and got decent results. The average of those replicates weren't as good as the average of Dr. Reuben's, but taken individually, not enough different to sound any alarms. It was the overall pattern that betrayed him. Placing a higher premium on review papers might have caught this earlier. Perhaps.

The really sad thing, to me, is that this seems to speak rather badly about the specific field of medicine in which Reuben practiced, if not the field as a whole. What I mean by this is that any fraud should be readily detected as long as independent corroboration of results is routine.

After all, we have no right to expect that scientists will always be honest and forthright. The best we can hope for is that the system will quickly and efficiently excise these cancerous lumps from our ranks. There will always be some immoral and/or incompetent bastards out there, and if they are allowed to flourish, they will on occasion reach the same degree of respectability as Reuben here. The only really strong check on human failings is independent corroboration of results, which also means consistent reporting of negative results. This type of fraud cannot persist if the research environment is healthy.

And it is precisely for this reason that I was particularly vexed by the following statement:

But even worse than that, he's wasted huge amounts of resources and left a huge mess for his colleagues to figure out. It'll take years for the studies he's done to be either redone or for other investigators to find out if the very concept of multimodal analgesia is even a valid concept.

This worries me because these tests should already have been performed, before Reuben's results became accepted by the community.

I don't know, perhaps I have a somewhat unrealistic view of the degree to which such corroboration is possible, but such independent checks on results is just expected within physics. And we don't even just make sure that results of any one observation are corroborated, but we also go back and make sure that other, independent predictions of the underlying theory are also validated through multiple experiments across multiple completely independent data sets. No fundamental fact about the universe is considered accepted until both types of corroboration have been performed.

I suppose in a sense it's easier to do this with physics, because physicists are dealing with fewer issues, and so each can be examined in more depth, but independent corroboration of individual observations, in my opinion, cannot be sacrificed no matter what: even discounting fraud, human foibles lead to erroneous positive results all the time. In the presence of such corroboration, it becomes vastly more challenging to perpetuate such falsehoods.

This isn't to say that physics is immune to this sort of issue, particularly as later tests are never completely independent if they are aware of the previous result (making confirmation bias a problem). But to not have already redone the experiments? That seems to me to be really unhealthy.

By Jason Dick (not verified) on 13 Mar 2009 #permalink

Joseph, it used imaginary data, exactly one of the errors being held up against Dr. Reuben.

That's not an accusation. That's stated right in the paper.

By Harry Eagar (not verified) on 13 Mar 2009 #permalink

Joseph, it used imaginary data, exactly one of the errors being held up against Dr. Reuben.

That's not an accusation. That's stated right in the paper.

That's just made up. The contention was that the paper was using data from a station with an unusual warming trend. This is how Gavin Smith of RealClimate summarized that little distraction:

In summary, speculation that the erroneous trend at Harry was the basis of the Antarctic temperature trends reported by Steig et al. is completely specious, and could have been dismissed by even a cursory reading of the paper.

Public policy wonks, politicians and quackademics honor the likes of Samuel Hahnemann and Franz Mesmer while mainstream perpetrators of scientific fraud become national disgraces eponymously associated with scandal, e.g. the Darsee affair, the Summerlin affair. The mainstream does a poor job of guarding its own henhouse, but not in the way the general public tends to think.

Peter Ashby said:

It is my understanding that naproxen is no longer available here in the UK. It was withdrawn on the grounds that it is a higher suicide risk than ibuprofen

? ? ? ?

Jason Dick, if medicine tried to meet the evidentiary standards used in physics, our journals would be empty.

I think the FDA require two clinical trials demonstrating efficacy prior to granting an indication.

Clinical trials are very expensive. Sometimes it takes years of monitoring before we appreciate the effects of a new drug, positive or negative. Replication of long-term studies may not appear in the literature for many years.

Replication helps constrain noisy information. Another constraint is prior plausibility. So where replication is difficult, limiting precious research resources to fairly plausible hypotheses is crucial.

That's why we ought not study homeopathy, naturopathy, chiropractic, etc.

Orac:

The other thing I wonder in the case of such massive fraud, and, no doubt so do my readers, is how so many fraudulent papers from one author could get past peer reviewers.

But isn't Peer Review supposed to be just the first stage in confirming a scientific result? What happened to waiting for confirmation by independent groups of scientists? I'll say that depending so heavily on results obtained by one person/group and bypassing that independent confirmation was the real failure here, for which responsibility has to be shared by all the leaders in the field of Anesthesiology.

By Stagyar zil Doggo (not verified) on 13 Mar 2009 #permalink

Joseph, it used imaginary data, exactly one of the errors being held up against Dr. Reuben.

That's not an accusation. That's stated right in the paper.

Since you say that it is stated right in the paper, please provide quotes that you believe make this statement. And yes, that is a link to a .pdf of the paper, so no claims that you don't have access.

But isn't Peer Review supposed to be just the first stage in confirming a scientific result? What happened to waiting for confirmation by independent groups of scientists?

Papers aren't kept out of the journals until a study is repeated by another group.

Peter Ashby said:

It is my understanding that naproxen is no longer available here in the UK. It was withdrawn on the grounds that it is a higher suicide risk than ibuprofen

Hardly, it is now available over the counter!

Since you say that it is stated right in the paper, please provide quotes that you believe make this statement.

I imagine that he's talking about the use of statistical methods to interpolate missing data, a fairly routine statistical approach, and not at all the same thing as fabricating data. Of course, if "it was stated right in the paper," it couldn't be scientific fraud, since scientific fraud means not accurately stating what you did. Reviewers cannot necessarily be expected to know when the author of a paper is lying, but (especially with a high-end journal such as Nature) they generally do a decent job of evaluating the appropriateness of the stated statistical procedures.

"His "outing" is a good sign that even in the more arcane and esoteric scientific fields, the system works to get rid of bad data and "cheaters".

Which system? In this case, it was the hospital administration that 'outed' him, not because they took a good hard look at his study results, but because an administrator noticed that Reuban did not have the proper approvals to do clinical research at the hospital. Only at this point did the hospital begin to question his work.

I would say, that this case shows that a good hospital administrator had more sense to question Reuban, than all of Reuban's peers in anesthesiology. Sadly, this is not a triumph for science and the scientific method. It is a triumph of administrative due diligence.

Whether it's a routine statistical practice or not, they still made up temperatures for which there were no observations.

There are no global surface temperature observations earlier than the 21st century. None.

This is kind of a problem. It would be akin to filling in blood counts. Not a practice my physician follows.

By Harry Eagar (not verified) on 13 Mar 2009 #permalink

This is disturbing, but why only 21 of his studies. On my blog, I list everything available from PubMed, not just the admitted fraudulent studies. Why not the rest, especially the ones where Dr. Reuben is the sole author?

Harry: What you're referring to would be "extrapolation", not "interpolation", which leads me to conclude that you don't know what you're talking about.

Interpolation is absolutely reasonable and accepted and not even remotely controversial in just about any field.

Extrapolation is much more questionable and requires far more analysis to justify.

But, of course, whatever paper you're referring to almost certainly didn't perform unjustified extrapolation, because that would NOT pass peer review. (As to the question of if the justification is valid, well, that depends on the paper, and I've not been able to properly follow the thread of your tangent.)

By Michael Ralston (not verified) on 14 Mar 2009 #permalink

... and a second reading of Harry's comment, as well as a quick reading of the paper, indicates he believes that global temperatures weren't being measured more than a decade ago.

I withdraw my previous attempt at interaction with him, as he is a blatant troll, whose claims aren't burdened by reality.

By Michael Ralston (not verified) on 14 Mar 2009 #permalink

Apparently Dr Reuben didn't didn't care about the great service he was doing the alties, for whom this is all grist to their mill, giving them a wonderful new excuse for rantings against modern medine, such as this one by Mike Adams:

"It is no exaggeration whatsoever to say that if the entire drug industry shut down tomorrow, and all the doctors went on strike, and all the oncologists overdosed on chemotherapy and died, the health of the population would immediately improve."

When fraud is exposed in the alt-med world, however, the reaction is invariably along the lines of "X is innocent! They're lying! It's a Big Pharma/gubmint conspiracy to suppress Teh Truth!"

The quackery is normally exposed by scientists(Big Pharma)/gubmint, so of course it's suppressing Teh Truth! How often do quacks expose or take down other quacks? Even if it's not for quackery, but for, say, tax evasion or other non-quackery crimes. I know quacks do sometimes attack each otherâit can be quite amusingâbut are there any cases of quacks (or an organisation of quacks) taking down a quack?

There are no global surface temperature observations earlier than the 21st century. None.

This claim by Harry Edgar is, of course, complete nonsense.

Harry is spewing AGW denialist rhetoric that he apparently found on the anti-AGW equivalent of Whale.to and NaturalNews.com. It's lame, even by AGW denialist standards.

AGW denialsts have standards???

By Militant Agnostic (not verified) on 14 Mar 2009 #permalink

JennyJo:

Having not died from dehydration caused by a blocked esophagus two weeks ago thanks to the fact that doctors were not on strike, I could only say to Mike Adams that he needs to go **** himself.

Reuben is innocent. He is being FRAMED by Big AltMed!! :)

Theron - What Mike Adams needs is a good case of appendicitis, but I doubt that he really believes his own bullshit.

By Militant Agnostic (not verified) on 14 Mar 2009 #permalink

We have been asked to trust science and scientists as if they operate at a higher standard than politics or business, and are independent of pressures that could bias their results. It is clear this is not true.

But anyone who understands what science is understands that scientists are not "independent of pressures that could bias their results", any more than firemen are invulnerable to fire, or police officers are immune to the depredations of criminals, or any of two dozen other analogies.

People think of scientists as people who generate plausible-sounding hypotheses, but the fact is that scientists and pseudo-scientists alike generate hypotheses. The difference between the two is that scientists then subject those hypotheses to testing, specifically trying to counter or nullify "pressures that could bias their results." Some of these, such as confirmation bias, can be effectively countered by practices such as double-blind testing. Others, unfortunately, are nearly impossible to correct directly -- until someone figures out a means by which scientists don't need money to live and to work, it's going to be near-impossible for any science to be done fully independently of that pressure.

The antivaxxers still claim Dr. Wakefield did nothing wrong even with all he's admitted to doing, because they don't understand why what he did was wrong. To them, it was okay that he took money to try and prove a particular hypothesis because they like that hypothesis. What they don't understand is that even if he took money from Richard Barr to test the pre-existing hypothesis of an MMR/autism link, what he did that was scientifically unconscionable was to conceal the existence of that biasing factor. If he was a true scientist, he would have revealed the existence of his funding source, and what his funding source expected/wanted, so that others reviewing his work could take that potential bias into account. Instead, he concealed it even from his co-authors.

By Antaeus Feldspar (not verified) on 14 Mar 2009 #permalink

I would disagree with you that the evidence justifies bring back rofecoxib. The risks associated with rofecoxib are just too high, and there are alternatives available.

But just how high were the risks associated with rofecoxib compared to the alternatives? The closest thing to a direct comparison was the VIGOR study, which found an incidence of MI of 1 per thousand for naproxen and 4 per thousand for rofecoxib, but the relative risk had a fairly wide confidence interval of 0.1 to 0.7. Risk of death from cardiovascular causes was 2 per thousand in both groups. And of course the risk of GI events (in a population without GI risk factors) was lower in the rofecoxib group. The retrospective BMJ study, which reflects real-world patterns of compliance, dosing, and risk factors, did not find a substantially greater risk for rofecoxib than other NSAIDs.

And while there are alternatives available, not every alternative works equally well for all patients. Individual variability in response to drugs is poorly understood. Overall, rofecoxib seems about as effective against pain as other NSAIDs, but I've had a number of people tell me that no other drug ever worked as well for them, and that they'd take it again if they could get it, even with the cardiovascular risk. A former Merck exec told me that even after the withdrawal of Vioxx, some people at Merck held onto their personal stashes.

Dr. Benway:

Papers aren't kept out of the journals until a study is repeated by another group.

True. But I hope you'll grant that accepting the conclusions as the "Standard Model" of your field should indeed be held up until such is performed.

By Stagyar zil Doggo (not verified) on 15 Mar 2009 #permalink

I just realized why the global warming denialists are so adamant in their belief. The Bible says that after Noah's flood that God promised to never destroy the world in a flood again. Global warming will raise sea level. The Greenland ice sheet is about 7 meters, the West Antarctic ice sheet is also about 7 meters and the East Antarctic ice sheet is about 50 meters. If those do melt, much of the Earth is effectively destroyed by flood, and God's promise to never do so again is broken. That is the mindset of the AGW deniers. They would rather risk global warming and the melting of the ice caps than consider the Bible to be in error.

True. But I hope you'll grant that accepting the conclusions as the "Standard Model" of your field should indeed be held up until such is performed.

LOL. The only standard model I have is, "first do no harm."

We've got a long way to go. In my field, the evidential basis for many accepted treatments is weak. Each individual patient brings so many unknowns to the table, making comparisons to group data difficult.

Where the fund of knowlege is poor, the methods of good science become even more important. Each treatment decision is like an experimental, clinical trial. Target symptoms must be explicit. The definition of success or failure must be explicit prior to any intervention. Daily tracking of target symptoms and other relevant variables is necessary to guard against the biases of human memory.

The next step is figuring out a way to standardize this process among as many clinicians as possible, in order to pool observations and identify trends.

We've got a long way to go.

The pseudo-doctors love to point out the uncertainty in the field. They believe this uncertainty justifies their sloppy thinking and data tracking.

They're not "part of the solution," I'm afraid.

Dr. Benway:
While I don't disagree with any part of you last post, it appears to address my comments only peripherally. I was referring to these parts of Orac's post:

All of that is now in question, said Steven L. Shafer, MD, editor-in-chief of Anesthesia and Analgesia, which retracted 10 of Dr. Reuben's articles. "We are left with a large hole in our understanding of this field. There are substantial tendrils from this body of work that reach throughout the discipline of postoperative pain management," Dr. Shafer said. "Those tendrils mean that almost every aspect will need to be carefully thought through. What do we still believe to be true? Do the conclusions hold up to scrutiny?"

Dr. Shafer said that although he still believes "philosophically" in multimodal analgesia, he can no longer be absolutely certain of its benefits without confirmation from future studies.

And:

Jacques Chelly, MD, PhD, MBA, director of the Division of Regional Anesthesia and Acute Interventional Perioperative Pain at the University of Pittsburgh Medical Center (UPMC), said that the Reuben episode has left multimodal analgesia "in shambles concerning many of the drugs we use"--particularly celecoxib and pregabalin. "The big chunk of what people have based their protocol on is gone."

The implication is that Academic Anesthesiology accepted the hypothesis that "multimodal analgesia" as proposed by Reuben is superior to whatever they were using before and made it a part of standard medical practice more or less on just his say so. No one working independently bothered to try to reproduce his results.

This I think is less than what is required by the scientific process, no matter how difficult the collection of data in that specific field.

By Stagyar zil Doggo (not verified) on 15 Mar 2009 #permalink

Stagyar zil Doggo

I quite agree that replication of everything would be a superior approach. You just have to remember that underneath this discussion of scientific methodology are not electrons. These are patients we're talking about. They are sometimes quite vulnerable people who trust us.

We don't randomise patients to treatment lightly.

When extant clinical trial evidence gives a strong treatment indication there is not a strong rationale for more clinical trials of the same hypothesis/design.

The problem here is fraud. Which when you are a clinical triallist, like me, is a barely speakable evil.

By antipodean (not verified) on 15 Mar 2009 #permalink

Michael, read it a 3rd time. It says there are no global surface temperature observations before the 21st c. That's true. There are not.

But if I'm wrong, please lead me to them.

There are no global observations of any kind before 1979.

By Harry Eagar (not verified) on 15 Mar 2009 #permalink

Sorry I was a bit tangential there, Stagyar.

Prometheus posted something about other groups studying multimodal analgesia and getting positive results, just not as positive as Dr. Rubin's. I'm not sure if that work would count as replication or merely convergence.

I agree with you, independent replication is the best check we have against bad studies.

Perhaps I might waive the need for replication if the outcomes between treatment A and treatment B were dramatically different, and if some independent parties could observe these outcomes directly while the study is in progress --e.g., a tumor completely disappears in one week on treatment A in most patients receiving A but doesn't change on B.

In some areas of medicine, we don't have data regarding "no treatment" for comparison --e.g., behavioral interventions for autism. Doing nothing to help kids with dire problems isn't acceptable.

The ABA people have published some studies showing that ABA techniques seem to help. But even before ABA became a thing, people were using behavioral principles in their work with autistics. So comparisons between groups aren't easy to sort.

The science has to start where it starts.

There are couple of thing that we need to address here;
1)Industry and faculty are very close, and there are very unprofessional relations, results are modified, changed or ignored to make industry happy because they are paying you.
2)There is a system problem, people in academic enviroment are evaluated with how much money they are bringing, money part should be taken out of the academic enviroment.
3)There are number of dishonest people in every part of community, scientists are not different.
4)As everybody suggested no negative results get published, editors and reviewers need to change their way of thinking.

The self-corrective nature of science is evident. Too bad it didn't kick in a little earlier.

Posted by: Dr Benway | March 12, 2009 8:53 AM

Really? Looks more like the question should be asked "Is there a self-corrective nature or not". This situation gives two options;
1: This is an isolated incident.
2: More of this is going on than we know.

If the scientific community wishes to maintain some level of respect with the masses then they are going to have to prove it. After all scientist should have a healthy dose of skepticism before crowning something as scientifically true.

Stella asked earlier and none of you answered, and I'll ask again. I come from a scientific family: I know how angry you are, but this isn't a question that should or can safely wait for you to calm down.
For those of us who aren't medical/pharmocological professionals, what does this mean? Should we walk into our bathrooms and throw away the bottles of ibuprofen and naproxin? Is there a site with recomendations as to actions we can all take? How do we protect ourselves and our families in light of this discovery of fraud? This isn't like the fellow a few years back who claimed he'd cloned dogs when he did no such thing: that didn't affect every family. Something involving NSAIDs does: we all have them in our medicine cabinents.
You think about it: I'm going to go ask some medical professionals I know and trust what I should do, but it would be very responsible and reasonable for a link to a site with basic directions as to what to do for safety's sake to show up where ever this topic is discussed under the general eye.

The fraud involved how to manage post-operative pain. The fraud is not about what is or is not safe for you to use for pain that is not post-operative. This is not about the medications themselves. This is about how they were supposedly studied and used in post-operative pain.

At least that's my understanding.

I've read about 50% of all the blogs and I'm surprised at the absence of references to "Conflict of Interest." Granted Reuben's fabrications started in 1996 and Pfizer's funding started in 2002 but who funded him before 2002? Were his earlier papers part of a scheme to get noticed by Pfizer? The red flags should have started popping up after 2002 when his results were consistently too good to be true.

By opadesala (not verified) on 20 Mar 2009 #permalink

One has to wonder: if it's this easy to fabricate data and publish clinical studies, how many other people are doing the same? The studies may not necessarily involve human research, but it could be about basic science, molecular biology, nanotechnology, cloning, etc.

The onus is on the drug manufacturer to prove that the drug is safe and effective. No one else is sufficiently interested enough to fork over the billion dollars required.

You can't separate drug manufacturers from drug research without ending drug research.

Reuben might have faked data for money. Or for narcissism. Or he bit off more than he could chew and started cutting corners to keep up, for fear of disappointing people.

Getting rid of the money factor won't get rid of biases.

As for funding to replicate routine work, after the Friedhelm Herrmann scandal in Germany, the DFG paid 1 Million Marks to have his research repeated because he had been considered a key oncologist. Aside from this, the group which was to look into Herrmann's research was also to look into how it came to be. It is striking that here, again, we have a case of an MD in a case of academic fraud of a stunning scale. Back then, the group suggested a reform of medical education to put more emphasis on proper scientific method.

I think there is a system in this. It's not to say that MDs are fraudsters, but MDs have a totally distinct motivation. The entire education of MDs is aimed a)at practical activities and b)at healing people. As such, there is a strong motivation even for MD researchers to find a way to heal people. On the other hand, the PhD scientist has his education aimed at creating knowledge. This is not to say that PhD scientists don't commit fraud, but above and beyond financial issues, MDs have a particularly high risk in that a)they have even more lack of understanding of scientific rigour than the PhDs, in whose education scientific method and theory, alas, is also often sorely lacking and b)added motivation.

As for scientists being dead when revealed to have committed fraud, you wish. Herrmann is said to enjoy a position in the industry. Probably not in R&D, yes. But it's not like his existence has been shattered. Especially not since as a professor, he was a civil servant, and since academic fraud isn't a crime, his university had to pay him a hefty sum to actually get rid of him, not being able to fire him.

Please specify the data that Dr. Wakefield falsified with specific references to the data and the proof of falsification.

Thank you.

By Skkepticon (not verified) on 18 Feb 2010 #permalink

Please specify the data that Dr. Wakefield falsified with specific references to the data and the proof of falsification.

Please explain why, if you actually want an answer to this question, you chose to ask the question as a comment on a post that had not seen any activity in almost 11 full months. That actually looks more like the behavior of someone who doesn't want their question answered - perhaps because they know the answer will not support their point of view.

By Antaeus Feldspar (not verified) on 18 Feb 2010 #permalink

I am NOT a scientist, merely a member of the public who was taught to respect science and methodology, which until very recently I did.

With all the hullaballo about Climate Change and fudged figures and data, and now more revealing information about Reuben's fabrication, and the (hint) of possible complicity with Big Pharma, it really does challenge us mere mortals, and makes us ask just who can you trust these days.

YES I KNOW there are many of you who are real, open, honesty with integrity and should feel proud of your achievements, but I feel your pain, so I hope you can feel ours, and please don't label us 'doubters' or 'deniers', we just would like to know who we can trust these days. Is FOLLOW THE DOLLAR an unfair tag - perhaps it is...... only time will tell.

Too bad you didn't learn what you were taught, or you wouldn't make such a braindead remark.

When was the last time you saw an astrologer admit he was wrong, that the alignment of Jupiter with Ceres means fuck-all to your life, after all?

NEVER.

When did you see a YEC-soaked liar say, "You know... Maybe that flud stuff is all bogus?"

NEVER.

But what did you see here?

Scientists agonizing, and asking, and wondering--what do we do to correct this? Where did we go wrong.

You will NEVER EVER see morons who are more arrogant than intelligent do that. You will never see people who have their precious dogmas to defend rather than facing the truth do that.

If you can't appreciate the difference between clinging to stupid and wrong in the face of all conflicting evidence (Ex: OMG I migte haz 2 givs up me SUV so noooo AGW can't be reall NONONONONO!!!!), and honestly, maturely looking at reality and saying, you know, maybe we were wrong, how can I fix it, then there's no help for you. If the latter, you might as well go and hide under your Mama's skirts the rest of your life, or DIAF. The rational alternative is to grow up and face reality.

it's up to you.

Someone on the WSJ Blog re: this matter naively asked why the perp had to pay a fine to BigHarma when they paid him to commit this crimeâ¦.

The reason he paid BigHarma âbackâ the $420,000 is so they can make it look like in their little make believe world of lies that no crime occurred, i.e. he paid us back so all is well.

It is much more serious than this though, please visit http://MercuryJustice.org, an extremely well documented site friends share with each other showing video and original smoking gun documentation including the notorious Simpsonwood Memo, where you can read about how BigHarma is just a seamless continuation from the Anglo-American Eugenicist funded NAZI human death camp experiments clean through to the present. http://MercuryJustice.org In other words, BigHarma is a lie so big most cannot comprehend it.

If most people actually did sit down to read the transcript of the Simpsonwood conference (which is what I assume you're calling "the notorious Simpsonwood memo") they would realize that most of the stories they hear about nefarious conspiracies at that conference are in fact complete lies concocted by the mercury militia.

By Antaeus Feldspar (not verified) on 24 Feb 2010 #permalink

For posterity: Scott S. Reuben was sentenced on June 24, 2010, in federal court to six months in jail plus three years supervised release after he pleaded guilty to one count of health care fraud . In addition he was ordered to repay $361,932 in restitution, forfeit $50,000 and pay a $5,000 fine.

By Scientizzle (not verified) on 26 Jun 2010 #permalink

I have personally experienced two instances of scientific fraud in my career. In both cases I saw what was going on but in neither case was I in a position to do anything. The first one was a PhD student fudging practically everything. As a foreign post-doc I was in no position to finger the guy. I felt really dreadful about not telling his boss who I really liked. The second case was more serious and was actually damaging to my career. I went to do another post-doc in a 3rd country. I was given a students' MSc and told to build upon it. The student had continued his studies and was now doing a PhD in the same lab. Reading his thesis and learning how to use the autoanalyser he used convinced me the work was fudged. Observing him in the lab confirmed my suspicions. PhD students working in the lab knew what was going on and told me so. I proceded to quietly do what needed to be done myself. After one year I was fired for not doing what I was employed to do. The boss was dispicable. A real creep. I did not attempt to tell him what was going on except in an email after I left I advised him to supervise his lab more closely. No reply. I told an old retired director of a CSIRO division my story. He said he had a similar experience as a young man at Roscoff - he was given a PhD to "build upon" and realised it was all bull fritters. He got sent home. The Director of Roscoff sent a nasty letter about him to the Australian Minister for Science.

By Raymond J. RITCHIE (not verified) on 27 Sep 2011 #permalink

An excellent article overall, with exactly what I would hope to hear from someone in your position.

I'm disappointed in your paragraph lambasting -- in cut-and-dried talking points -- the so-called "alt health" community. Painting with such a wide and ignorant brush is exactly what you accuse these people of. It's silly.

As a sometime clinician and a current pain patient, I expect a bit more sense from a practicing pain clinician. It's a matter of what works, not what you believe in. Your belief is moot in the face of events.

Counterfactual positions do not make for good medicine. Lack of scientific data does not mean lack of performance, it means the scientific data haven't been adequately developed. They should be. Preferably accurately, appropriately, and with proper integrity.

As a sometime clinician and a current pain patient, I expect a bit more sense from a practicing pain clinician.

Perhaps you should direct this at a practicing pain clinician, then.