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 conducted an investigation into research conducted by Dr. Scott S. Reuben, who was - at that time - the chief of their acute pain service. As the phrase "at that time" suggests, the results of the investigation did not exonerate Dr. Reuben. Anything but, in fact. In late January, Baystate sent out a letter to a number of journals recommending the retraction of articles, and Dr. Reuben is now reported to be on "medical leave".
I'll tack the full list of affected articles on the end of this post for those who are interested, but the problems go well beyond just those 21 papers. The extent of the revealed fraud will necessarily call into question all of the work that Reuben has ever published. Any other work - clinical protocols, published articles, ongoing research - that relies on the veracity of Reuben's articles will also need to be re-examined.
All academic misconduct is bad, but this particular case is particularly destructive. Dr. Reuben's work has served as the basis for the use of what's known as "multimodal anesthesia" - using a combination of NSAIDs and neuropathic pain medications after orthopedic and spinal operations instead of narcotics. This practice has become very common in the field, and the vast majority of the evidence-based support for these protocols no longer exists.
Anesthesiology News' report on the case provides a good description of the extent of the problem:
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."In light of the situation and economic concerns, UPMC has stopped giving celecoxib and pregabalin to surgery patients "until we have some very formal evidence that we should do something else," Dr. Chelly said. "In this day and age, doing multimodal [therapy] is expensive. Any institution is going to look at evidence-based clinical decisions, and unless we have very strong data, it is a problem."
It appears that whatever Dr. Reuben's motives might have been, he may have received some financial benefits as a result of his work. Much of his research focused on the use of celecoxib and pregabalin instead of opiates. These two drugs are better-known as Celebrex and Lyrica, and both are manufactured by Pfizer. Pfizer provided Reuben with research grants from 2002 to 2007, and he was a member of their speakers' bureau.
Money - whatever the source - is a potential corruptive influence in science. Researchers who receive funding will have an incentive to make sure that the money keeps coming, no matter what the source of the funding might be. Most researchers - I hope and believe - will be able to resist any urges they might have to falsify their results in order to make themselves more attractive to funders. A few - hopefully, only a very, very few - will not. Fortunately, science is self-correcting - eventually.
Peer review, as it stands now, is not equipped to catch fraud. Reviewers necessarily start their work assuming that the actual data presented in the paper is real and accurate. There's no way they can reasonably be expected to do anything else. Any pre-publication attempt to catch fraud would require physically replicating some of the study, and that's expensive and time consuming.
As a result, it's not all that difficult to get a fraudulent paper through peer review. Fraud detection usually happens later, and for different reasons.
As most liars know - and the rest will learn - the more involved and complicated a lie becomes, the harder it is to keep from getting caught. Research lies are rarely simple, and that's certainly true of a series of long series of lies. In this particular case, Reuben got caught apparently because someone at Baystate got curious about discrepancies in his Institutional Review Board paperwork and started digging.
In other cases, fraud is detected because of the nature of science. Scientific fraud involves lying about reality, and reality is always around for other people to look at. Sooner or later, other researchers are going to find that their work doesn't make sense if the fraudulent papers are accurate. One (or more) of them will start to dig, and the fraud will be detected.
The self-corrective nature of science is cold comfort in a case like this, but it's still good to know that science can detect fraud. Even if it does take too long.
Papers in Question:
1. Reuben SS, Connelly NR. Postarthroscopic meniscus repair analgesia with
intraarticular ketorolac or morphine. Anesth. Analg. 1996;82:1036-9.
2. Reuben SS, Connelly NR, Maciolek H. Postoperative analgesia with controlled-
release oxycodone for outpatient anterior cruciate ligament surgery. Anesth
Analg. 1999;88:1286-91.
3. Reuben SS, Reuben JP. Brachial plexus anesthesia with verapamil and/or
morphine. Anesth Analg. 2000;91:379-83.
4. Reuben SS, Connelly NR. Postoperative analgesic effects of celecoxib or
rofecoxib after spinal fusion surgery. Anesth Analg. 2000;91:1221-5.
5. Reuben SS, Vieira P, Faruqui S, Verghis A, Kilaru P, Maciolek H. Local
administration of morphine to bone following spinal fusion surgery.
Anesthesiology 2001;95:390-4.
6. Reuben SS, Fingeroth R, Krushell R, Maciolek H: Evaluation of the safety and
efficacy of the perioperative administration of rofecoxib for total knee
arthroplasty. J Arthroplasty. 2002;17:26-31.
7. Reuben SS, Steinberg RB, Maciolek H, Manikantan P. An evaluation of the
analgesic efficacy of intravenous regional anesthesia with lidocaine and ketorolac
using a forearm versus upper arm tourniquet. Anesth Analg. 2002;95:457-60
8. Reuben SS, Gutta SB, Sklar J, Maciolek H: Effect of initiating a multimodal
analgesic regimen upon patient outcomes after anterior cruciate ligament
reconstruction for same-day surgery: a 1200-patient case series. Acute Pain
2004;6:87-93.
9. Reuben SS, Rosenthal EA, Steinberg RB, Faruqi S, Kilaru PR: Surgery on the
affected upper extremity of patients with a history of complex regional pain
syndrome: The use of intravenous regional anesthesia with clonidine. J. Clin
Anesth 2004;16:517-522.
10. Reuben SS, Makari-Judson G, Lurie SD: Evaluation of efficacy of the
perioperative administration of venlafaxine XR in the prevention of
postmastectomy pain syndrome. J Pain Symptom Manage. 2004;27:133-9.
11. Reuben S. The effect of intraoperative valdecoxib administration on PGE2 levels
in the CSF. J Pain 6, Supplement 1:S21 (Abstract 649)
12. Reuben SS, Ekman EF. The effect of cyclooxygenase-2 inhibition on analgesia
and spinal fusion. J Bone Joint Surg Am. 2005;87:536-42
13. Scott S. Reuben, Srinivasa B. Gutta, Holly Maciolek, Joseph Sklar, James
Redford. Effect of initiating a preventative multimodal analgesic regimen upon
long-term patient outcomes after anterior cruciate ligament reconstruction for
same-day surgery: A 1200-patient case series. Acute Pain 2005;7: 65-73.
14. Reuben SS, Pristas R, Dixon D, Faruqi S, Madabhushi L, Wenner S. The
incidence of complex regional pain syndrome after fasciectomy for Dupuytren's
contracture: a prospective observational study of four anesthetic techniques.
Anesth Analg. 2006;102:499-503
15. Reuben SS, Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of
celecoxib, pregabalin, and their combination for spinal fusion surgery. Anesth
Analg. 2006;103:1271-7
16. Reuben SS, Buvenandran A, Kroin JS, Raghunathan K. Analgesic efficacy of
celecoxib,pregabalin, and their combination for spinal fusion surgery.
Anesthesiology 2006;105:A1194.
17. Reuben SS, Buvanendran A, Kroin JS, Steinberg RB. Postoperative modulation
of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after
vascular surgery. Anesthesiology 2006;104:411-6.
18. Reuben SS, Ekman EF, Raghunathan K, Steinberg RB, Blinder JL, Adesioye J.
The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain
after spinal-fusion surgery. Reg Anesth Pain Med. 2006;31:6-13.
19. Reuben SS, Ekman EF, Charron D. Evaluating the analgesic efficacy of
administering celecoxib as a component of multimodal analgesia for outpatient
anterior cruciate ligament reconstruction surgery. Anesth Analg. 2007;105:222-7
20. Reuben SS, Ekman EF. The effect of initiating a preventive multimodal analgesic
regimen on long-term patient outcomes for outpatient anterior cruciate ligament
reconstruction surgery. Anesth Analg. 2007;105:228-32
21. Reuben SS, Buvenandran A, Katz B, Kroin JS. A prospective randomized trial on
the role of perioperative celecoxib administration for total knee arthroplasty:
improving clinical outcomes. Anesth Analg. 2008;106:1258-64
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My grandmother takes Lyrica. What (in general) would this mean for her? Does this invalidate Lyrica as a pain medication or just certain uses of Lyrica?
It shouldn't mean anything for your grandmother. The findings do not affect Lyrica in general, just its use in certain postoperative situations.
Thanks for clearing that up for me.
The Bernie Madoff of science! Looks like the greatest strength of science is also it's greatest weakness - namely, that scientists R people too.
I appreciate the concern for the 'integrity of science" on this and some of the other science blogs, but really "science" in this sense is an abstraction. What makes the difference is integrity of individuals. It comes down to whether any particular person claiming to be a scientist is ethical or has integrity, not whether "science" does.
And that's the rub. You can say all you want about "science," but you'll never be able to predict or control what individuals are going to do.
I wouldn't take that stuff, nor would I recommend it to anyone. Opiates are addictive, but that can be managed better than the potential side effects of NSAIDs. See this FDA warning:
"We are requesting that manufacturers of all marketed prescription NSAIDs, including Celebrex, a COX-2 selective NSAID, revise the labeling (package insert) for their products to include a boxed warning and a Medication Guide. The boxed warning will highlight the potential for increased risk of cardiovascular (CV) events and the well-described, serious, and potentially life threatening gastrointestinal (GI) bleeding associated with these drugs."
That's the FDA for you - won't allow medical cannabis on the market, which has never caused any deaths by myocardial infarction or GI tract bleeding, but won't pull the NSAIDs from the market.
And yes - your grandmother would be better off smoking pot for pain relief, or using a THC inhaler, than if she was on NSAIDs:
http://www.netdoctor.co.uk/medicines/100005038.html
"Lyrica: Use with caution in elderly people, kidney failure, severe heart failure"
"Lyrica: This medicine is not recommended for children and adolescents under 18 years of age, because the manufacturer has not studied its safety and efficacy in this age group."
This is true for celecoxib as well as for pregalin - namely, Lyrica and Celebrex.
The Pfizer PR rep said this in response, by the way:
"Independent clinical research advances disease treatments and improves the lives of patients,â said Raymond F. Kerins Jr., a Pfizer spokesman. âAs part of such research, we count on our paid researchers to spin their research results in our favor, and to attend conferences where they promote these drugs. It is thus very disappointing to learn about Dr. Scott Reubenâs alleged actions, as they are certainly going to prompt another FDA review of our highly profitable NSAIDs, and might even lead to a Congressional review of Bayh-Dole legislation governing public-private relationships between taxpayer funded institutions and Pfizer, which we really do NOT want to see."
That's public relations today: providing more opportunities for comic relief. Who has Pfizer these days? Burson-Marstellar? Or is it Edelman? Hill & Knowlton? Come on, you can be honest. :)
While I find Dr Reuben's actions reprehensible, I must say I have to ask, just what motivated "credibility problem" to change the quote of Pfizer spokesman Raymond F. Kerins Jr? I will not contemplate that here, I will simply post the ~real~ quote and my sources.
"Independent clinical research advances disease treatments and improves the lives of patients," Raymond F. Kerins Jr., a Pfizer spokesman, told the paper. "As part of such research, we count on independent researchers to be truthful and motivated by a desire to advance care for patients. It is very disappointing to learn about Dr. Scott Reuben's alleged actions."
http://www.fiercepharma.com/story/influential-doc-faked-pain-studies-ho…
http://www.nytimes.com/2009/03/11/health/research/11pain.html?_r=4&scp=…
Hey, I know the drug companies look out for themselves first but changing a quote like that is simply ridiculous. Noone working for Pfizer would say something as inciminating and preposterous as posted above.
Get real...
Thanks for this very interesting article.
I have seen academic fraud in action at close quarters over the past couple of years, a post doc just up the corridor basically fabricated a whole load of data and ended up with 5 retractions. This was a real bummer for me as I did some work with the guy's supervisor back in 2000 - this was included as one panel of a figure in one of the papers and so I now have a retraction on my CV. Not good.
My experience of this incident leads me to suggest that the phrase "As most liars know - and the rest will learn - the more involved and complicated a lie becomes, the harder it is to keep from getting caught" is completely, totally and utterly wrong.
I would say that the reverse is true - simple lies can be revealed simply, complicated lies take time to sort out, incredibly complicated and convoluted lies are just about impossible to sort out, particularly by a faculty commitee with an eye on possible legal procedings in the future. Remember that coming to the wrong conclussion will reflect badly on the University so there is a great reluctance to probe too deeply.
In the situation I am refering to *everybody* working in the department knew what was going on. That is everyone, not most people but *everyone*. The head of Dept was warned multiple times and responded by asking the guys supervisor what was going on. They were mates, the publications made the dept and the supervisor look good so that was as far as it went.
Even once the lid had finally been prised off (no way could the process be described as "blowing the lid"), the University responded by setting up a commitee which interviewed one person and one person alone - the supervisor. Their attitude was that they wanted him to help them sort out this problem that they had been given. Universities are generally reluctant to admit that they have appointed, supported and promoted the wrong person. This reluctance builds a huge amount of slack into the system and, in effect, this lets people get away with almost anything.
The post doc in question basically spent the whole day at his computer and was very rarely seen to do any experimental work. He actually refused to led anyone see what he was doing on his computer and would go into a panic and turn the power supply to his monitor off if anyone came within a few yards of his desk and tried to look over his shoulder. His supervisor and our head of department saw nothing unusual in this behaviour.
His published papers included blatently fabricated blots, descriptions of experiments that were essentially impossible (expression of heterologous protein in bacteria using mammalian vectors), reported the results of experiments that would have involved far more isotopes that had ever been purchased. You name it it was all in there.
The bottom line is that nobody in authority was in the slightest bit interested in stopping this as they would not accept what was going on. Several people tried to whistle blow - nobody was interested. Even after the University had investigated, there was no attempt to clear up the mess and certainly no pressure put on anyone to retract papers. Were it not for one or two individuals within this University the articles would still be there.
What I have learned from this is that if you are going to commit academic fraud then I would propose sticking to the following guidelines:
(i) be completely blatent about it, very few people will be interested and even fewer prepared to rock the boat. Time spent trying to conceal what you're doing will be time wasted.
(ii) Do not bother wasting time on professional looking forgeries - crude fabrication that anyone can see through in seconds will do just as well. If people actually interupt conference talks to point out that the data are blatently fabricated (as happened in this case) adopt a haughty attitude and dismiss them as a light weight. It is extemely doubtful that the matter will be taken any further and, even if it does, you will be protected by the reluctance of the University to believe that fraudulent work is going on in their labs.
(iii) rubber stamp as many possible names from as many countires as possible, this adds credibility and makes the mess harder to sort out.
(iv) Make the story you are telling so covoluted and complicated that people working in the field will not have the faitest idea what you are talking about. Peer review is notoriously fickle and very few people will challenge you. People outside the field will simply look at how many publications you have.
(v) Finally and most importantly - do not get too greedy. Fabricate only enough data to get a healthy looking CV.
I suspect that the these factors all contributed to the incident described above.
Now if they would just go after the lies and deceits built by Johnson & Johnson's foundation, the ones who PAID for the smoking bans with grants to orgs and universities to do their bidding to fit their agenda. Why would they do this? One good reason, for starters: They make and SELL the no smoke products. Profits!
I am glad you shed some light on this subject