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.