This is the third post in the unfortunate series about conflicts of interest.

You must be kiddin’! That’s all Scott Reuben, MD, the doctor Scientific American calls “a medical Madoff“, had to say after putting the last two handful of nails into the coffin of the scientific peer-reviewed process? You see, Dr. Reuben is responsible for what may turn out to be one of the greatest cases of scientific fraud of the last 50 years?

In truth the quote is from one of his attorneys. Dr. Reuben, a world-famous anesthesiologist and former chief of acute pain management at Baystate Medical Center, Springfield, Mass, one of the campuses of Tufts University School of Medicine is accused to have fabricated over 13 years at least 21 medical studies (and perhaps many more among the 72 papers written by the good doctor) that claimed to show benefits from painkillers like Vioxx and Celebrex, 2 drugs since withdrawn from the U.S. and worldwide market due to safety concerns of an increased risk of cardiovascular events (including heart attack and stroke).  Most, if not all, of these articles are in the process to be retracted. The wonderful Dr. Reuben also wrote to the Food and Drug Administration, urging the agency not to restrict the use of many of the painkillers he studied, citing his own fabricated data to prove their safety and effectiveness.

In addition to allegedly falsifying data, Dr. Reuben seems to have also 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 and in fact being in part responsible for pointing to inconsistencies in Dr. Reuben research.

Even better Dr. Reuben published fabricated studies showing the great effectiveness of a combination treatment using 2 drugs from Pfizer, Celebrex and Lyrica. No one paid attention to the fact that, like Dr Robinson and Dr. Ridker et al. Dr. Ruben was regularly paid by pharmaceutical companies. In fact he was active as a member of Pfizer speakers bureau until recently and received, from 2002 to 2007, 5 research grants from that company. Besides the evident culture of greed that has infected a lot of the medical research activities, there must be something even deeper that can convince doctors that it is OK to put many lives at risk by falsifying results.

Flummoxed? Wait, there is more! Dr. Reuben’s attorney also said there were extenuating circumstances! I kid you not. As usual no one is really talking. Dr. Reuben is on extended medical leave. Tufts University doesn’t seem to know him anymore. I guess everybody is trying to get the story to disappear under some heavy duty carpet. But this story cannot disappear. For multiple reasons:

• Together with some of the other stories we have mentioned lately we are starting to have a painful thread showing one of the worst reasons why authoritative papers are dead: conflicts of interests are rampant and no one knows the extent of the problem.
• The peer-reviewed process, presented as the gold-standard of the publishing world because it guarantees high-quality work is not working! How can 21 main articles from a major fraudster pass muster and never raise an eyebrow? As a doctor said “when you look at Scott’s output over the last 15 years, he never had a negative study. In fact, they were all very robust results—where others had failed to show much difference. I just don’t understand how anyone could pull this off for so long“
• The fraud didn’t stop at the published articles but was also used in multiple letters in response to valid scientific articles to destroy the scientific findings of honest researchers. I found this letter to show how it worked.
• It is high time to ask hard questions: who benefits from this fraud? Do we have to demand that Congress get involved with yet one more layer of regulations to limit the corrupting impact of pharma-sponsored medical research?

If you think this is just another rant, think again!  Granted, Dr. Reuben was one of the great experts in multimodal analgesia . But the scientific method requires the ability to duplicate results. With a fraud this vast, how come no one raised flags earlier, based on the inability of many clinicans to recreate his positive results?  The clinical impact of the fraud will be profound. 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 fraud has left multimodal analgesia “in shambles”. He added

“the big chunk of what people have based their protocol on is gone. we have stopped giving celecoxib and pregabalin to surgery patients until we have some very formal evidence that we should do something else.  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. Since most of evidence is now unreliable you really don’t have any evidence that the combination is working.”

I think this post should be followed by one describing the issues we see with the peer-review process. What do you think?

Here is the list of fraudulent medical studies authored / fabricated by Dr. Scott Reuben

Preventing the development of chronic pain after thoracic surgery.
Reuben SS, Yalavarthy L.
J Cardiothorac Vasc Anesth. 2008 Dec;22(6):890-903. Epub 2008 May 7.
No abstract available.
PMID: 18834790

A prospective randomized trial on the role of perioperative celecoxib administration for total knee arthroplasty: improving clinical outcomes.
Reuben SS, Buvenandran A, Katz B, Kroin JS.
Anesth Analg. 2008 Apr;106(4):1258-64, table of contents.
PMID: 18349203

Update on the role of nonsteroidal anti-inflammatory drugs and coxibs in the management of acute pain.
Reuben SS.
Curr Opin Anaesthesiol. 2007 Oct;20(5):440-50. Review.
PMID: 17873597

The effect of initiating a preventive multimodal analgesic regimen on long-term patient outcomes for outpatient anterior cruciate ligament reconstruction surgery.
Reuben SS, Ekman EF.
Anesth Analg. 2007 Jul;105(1):228-32.
PMID: 17578979

Evaluating the analgesic efficacy of administering celecoxib as a component of multimodal analgesia for outpatient anterior cruciate ligament reconstruction surgery.
Reuben SS, Ekman EF, Charron D.
Anesth Analg. 2007 Jul;105(1):222-7.
PMID: 17578978

Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.
Reuben SS, Buvanendran A.
J Bone Joint Surg Am. 2007 Jun;89(6):1343-58. Review.
PMID: 17545440

The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain.
Madabhushi L, Reuben SS, Steinberg RB, Adesioye J.
J Clin Anesth. 2007 May;19(3):226-9.
PMID: 17531734

Chronic pain after surgery: what can we do to prevent it.
Reuben SS.
Curr Pain Headache Rep. 2007 Feb;11(1):5-13. Review.
PMID: 17214915

The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery.
Reuben SS, Buvanendran A, Kroin JS, Raghunathan K.
Anesth Analg. 2006 Nov;103(5):1271-7.
PMID: 17056968

Acute post-surgical pain management: a critical appraisal of current practice, December 2-4, 2005.
Rathmell JP, Wu CL, Sinatra RS, Ballantyne JC, Ginsberg B, Gordon DB,
Liu SS, Perkins FM, Reuben SS, Rosenquist RW, Viscusi ER.
Reg Anesth Pain Med. 2006 Jul-Aug;31(4 Suppl 1):1-42.
PMID: 16849098

Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery.
Reuben SS, Buvanendran A, Kroin JS, Steinberg RB.
Anesthesiology. 2006 Mar;104(3):411-6.
PMID: 16508386

The incidence of complex regional pain syndrome after fasciectomy for Dupuytren’s contracture: a prospective observational study of four anesthetic techniques.
Reuben SS, Pristas R, Dixon D, Faruqi S, Madabhushi L, Wenner S.
Anesth Analg. 2006 Feb;102(2):499-503.
PMID: 16428550

The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain after spinal-fusion surgery.
Reuben SS, Ekman EF, Raghunathan K, Steinberg RB, Blinder JL, Adesioye J.
Reg Anesth Pain Med. 2006 Jan-Feb;31(1):6-13.
PMID: 16418018

Interscalene block superior to general anesthesia.
Reuben SS.
Anesthesiology. 2006 Jan;104(1):207; author reply 208-9. No abstract
available.
PMID: 16394719

High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion.
Reuben SS, Ablett D, Kaye R.
Can J Anaesth. 2005 May;52(5):506-12.
PMID: 15872130

More on current issues in pain management for the primary care practitioner. Acute pain: a multi-modal management approach.
Carr DB, Reuben S.
J Pain Palliat Care Pharmacother. 2005;19(1):69-70. No abstract
available.
PMID: 15814519

The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion.
Reuben SS, Ekman EF.
J Bone Joint Surg Am. 2005 Mar;87(3):536-42.
PMID: 15741619

The prevention of post-surgical neuralgia.
Reuben SS.
Pain. 2005 Jan;113(1-2):242-3; author reply 243-4. No abstract
available.
PMID: 15621388

Surgery on the affected upper extremity of patients with a history of complex regional pain syndrome: the use of intravenous regional anesthesia with clonidine.
Reuben SS, Rosenthal EA, Steinberg RB, Faruqi S, Kilaru PA.
J Clin Anesth. 2004 Nov;16(7):517-22.
PMID: 15590255

Preventing the development of complex regional pain syndrome after surgery.
Reuben SS.
Anesthesiology. 2004 Nov;101(5):1215-24. Review. No abstract
available.
PMID: 15505459

Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome.
Reuben SS, Makari-Judson G, Lurie SD.
J Pain Symptom Manage. 2004 Feb;27(2):133-9.
PMID: 15157037

Analgesic effect of clonidine added to bupivacaine 0.125% in paediatric caudal blockade.
Joshi W, Connelly NR, Freeman K, Reuben SS.
Paediatr Anaesth. 2004 Jun;14(6):483-6.
PMID: 15153211

The perioperative use of cyclooxygenase-2 selective nonsteroidal antiinflammatory drugs may offer a safer alternative.
Reuben SS, Connelly NR.
Anesthesiology. 2004 Mar;100(3):748. No abstract available.
PMID: 15109000

An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management.
Joshi W, Connelly NR, Reuben SS, Wolckenhaar M, Thakkar N.
Anesth Analg. 2003 Jul;97(1):35-8, table of contents.
PMID: 12818939

An evaluation of the analgesic efficacy of intravenous regional anesthesia with lidocaine and ketorolac using a forearm versus upper arm tourniquet.
Reuben SS, Steinberg RB, Maciolek H, Manikantan P.
Anesth Analg. 2002 Aug;95(2):457-60, table of contents.
PMID: 12145071

Preoperative administration of controlled-release oxycodone for the management of pain after ambulatory laparoscopic tubal ligation surgery.
Reuben SS, Steinberg RB, Maciolek H, Joshi W.
J Clin Anesth. 2002 May;14(3):223-7.
PMID: 12031758

Intravenous regional anesthesia with clonidine in the management of complex regional pain syndrome of the knee.
Reuben SS, Sklar J.
J Clin Anesth. 2002 Mar;14(2):87-91.
PMID: 11943518

Preemptive multimodal analgesia for anterior cruciate ligament surgery.
Reuben SS, Sklar J.
Reg Anesth Pain Med. 2002 Mar-Apr;27(2):225; author reply 225-6. No
abstract available.
PMID: 11915075

Evaluation of the safety and efficacy of the perioperative administration of rofecoxib for total knee arthroplasty.
Reuben SS, Fingeroth R, Krushell R, Maciolek H.
J Arthroplasty. 2002 Jan;17(1):26-31.
PMID: 11805921

The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery.
Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J.
Anesth Analg. 2002 Jan;94(1):55-9, table of contents.
PMID: 11772800