|ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)
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Two Cases of Massive Fraud--Anesthesiology--Psychiatry
Two major cases of medical fraud have undermined patient safety and the integrity of the medico-scientific literature: But how each specialty responded is a study in contrast.
CASE 1. Anesthesiology News reports (below) that a leading anesthesiology researcher, Scott S. Reuben, MD, Director, Acute Pain Service, Associate Professor of Anesthesiology, Baystate Medical Center, Tufts University School of Medicine, is accused of falsifying data and other fraud in potentially dozens of published studies.
"Dr. Reuben, a pioneer in the area of multimodal analgesia...particularly as an advocate for its use in minimally invasive orthopedic and spine procedures, whose 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...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 ).
A cornerstone of Dr. Reuben’s approach has been the use of the selective cyclooxygenase-2 inhibitor celecoxib (Celebrex) and the neuropathic pain agent pregabalin (Lyrica), both manufactured by Pfizer. Dr. Reuben has received research grants from the company and is a member of its speakers’ bureau.
In light of the evidence uncovered, 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....you really don’t have any evidence that the combination is working".
Experts are calling this one of the largest known cases of academic misconduct.
A source told Anesthesiology News that Pfizer recently alerted its speakers to remove any reference to Dr. Reuben’s data from their presentations. The company has not been accused of wrongdoing in the matter.
Companies may provide financial incentives to physicians--but it remains the physicians' responsibility to be honest and to uphold professional and ethical standards.
CASE 2. Across the Atlantic, psychiatrist, Tonmoy Sharma MD, a prominent psychiatrist and senior lecturer at the prestigious Institute of Psychiatry at King’s College in London, who conducted pivotal drug studies for the major pharmaceutical companies, co-authoring ***frequently appeared on as an "expert" on the BBC, had gained an international reputation, particularly in the United States, for the research he was doing--was stripped of his medical licence by the British General Medical Council ( GMC) in April 2008, after an eight year investigation.
Until a recent post by Dr. Bremner--"Don't Squeeze the Sharma"-- we were unaware of the case.
News reports from the UK--including the Times of London, the Telegraph, NRI Internet, and a report by the investigations editor of The Observer--describe the Sharma's gross misconduct, which was first uncovered by the pharmaceutical company Sanofi (2001). That charge resulted in his temporary suspension by the Institute of Psychiatry, prompting the GMC investigation. However the prestigious Institute reinstated Dr. Sharma in Aug. 2001--demonstrating the unreliability of academic in-house investigations.
Two years later, the Association of the British Pharmaceutical Industry asked the GMC to examine Dr. Sharma's conduct after concerns were raised about his failure to obtain proper approval from ethical committees to conduct the tests on human subjects.
Dr. Sharma worked as a consultant psychiatrist for the South London and Maudsley NHS Trust and recruited patients in Kent and parts of the capital for the research, according to reports. His position at the institute helped him to secure funding, said to be almost £1 million, from five drug companies. Most of the money was channeled through a private company that he had set up called Psychmed.
From 1996, Sharma was paid by leading drug companies such as Novartis and Sanofi to conduct trials of antipsychotic drugs on patients with schizophrenia and Alzheimer’s.
According to the General Medical Council, he recruited people in unsolicited telephone calls without contacting vulnerable patients' psychiatric nurses; he failed to obtain proper approval from ethical committees to conduct a number of major studies; he used the same patients as subjects for a number of different studies--thereby invalidating the studies for which he had been paid hundreds of thousands of dollars.
NRI Internet reports that the GMC representative stated:
* Dr Sharma had put mentally unwell patients at risk and ethical
rules had been willfully flouted.
* He gained an international reputation, particularly in the
United States, for the research he was doing.
* In spring 2001 he was suspended from the Institute of Psychiatry
after a complaint from drug maker Sanofi over a study Dr Sharma was undertaking into schizophrenia. He was reinstated in August 2001.
* After the suspension, a picture emerged of a doctor who knew the rules understanding medical research but deliberately took short cuts. He was guilty of gross breaches of the research standards.
* He made untrue statements and eventually the picture which I submit before you was a man who paid little more than lip service to ethical rules in research.
* He failed to give details about the tests to the patient or their carers, it is claimed.
Dr. Sharma is accused of attempting to get data in a drug trial changed as well as of obtaining a free supply of the psych drug Clozaril for a study which he subsequently then sold for tens of thousands of pounds.
The GMC panel found Sharma to be responsible for conducting research without appropriate human subjects approvals, improperly presenting himself as having a PhD, and selling drugs he got for free from drug companies for his research to hospitals. Someone described him as being only interested in making money. He made hundreds of thousands of dollars in outside consulting and speaking work for drug companies over the past decade or so.
Andrew Popat, chairman of the BGMC panel, told Sharma: “Your persistent and wide-ranging dishonesty and untruthfulness, spanning a number of years, together with your lack of insight, is so serious that it is fundamentally incompatible with your continuing to be a registered medical practitioner.”
The GMC found that he acted unprofessionally in relation to five major studies involving four different pharmaceutical companies. Indeed, Tonmoy Sharma's publications have contributed toward corrupting the integrity of psychiatry's drug literature.
Tonmoy Sharma was a member of the Eli Lilly HGDH Research Study Group: many of his journal reports were co-authored by prominent psychiatrists in the HGDH group--including several Lilly employees. The authors of these Lilly-sponsored publications invariably claimed superiority for Lilly's so-called 'atypical' neuroleptic, olanzapine (Zyprexa): "A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol." (2003)
The evidence contradicts the published reports claiming superiority of the so-called 'atypical' antipsychotics:
"systematic reviews indicate that modern antipsychotic agents are not consistently superior to conventional drugs in efficacy or tolerability and that reported advantages are variable and often minor." 
“the side effect outcomes [of patients on atypicals] are staggering in their magnitude and extent and demonstrate the significant medication burden for persons with schizophrenia.… Sky-high drug discontinuation rates were seen, suggesting rampant drug dissatisfaction and inefficacy.” 
But publications such as those co-authored by Tonmoy Sharma have led to the widespread use of the drug: Zyprexa sales reached $39 billion since its approval (1996) and 2007.
OF NOTE: In sharp contrast to the anesthesiology journals whose editors pulled at least 21 publications authored (or co-authored) by Dr. Scott S. Reuben--none of the tainted reports by Tonmoy Sharma have been retracted.
1. David M. Gardner, Ross J. Baldessarini and Paul Waraich. Modern antipsychotic drugs: a critical overview, Canadian Medical Association Journal, June 21, 2005; 172 (13).
2. Carol Tamminga, "Practical Treatment Information for Schizophrenia" Editorial, AJP, April, 2006, vol. 163:563-565.
Sample list of PUBLICATIONS by Tonmoy Sharma:
Olanzapine and haloperidol in first episode psychosis: two-year data. Green AI, Lieberman JA, Hamer RM, Glick ID, Gur RE, Kahn RS, McEvoy JP, Perkins DO, Rothschild AJ, Sharma T, Tohen MF, Woolson S, Zipursky RB; HGDH Study Group. Schizophr Res. 2006 Sep;86(1-3):234-43. Epub 2006 Aug 2.
Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation. Sharma T, Reed C, Aasen I, Kumari V. Schizophr Res. 2006 Jul;85(1-3):73-83. Epub 2006 Jun 21.
Insight in first-episode psychosis. McEvoy JP, Johnson J, Perkins D, Lieberman JA, Hamer RM, Keefe RS, Tohen M, Glick ID, Sharma T. Psychol Med. 2006 Oct;36(10):1385-93. Epub 2006 Jun 2.
A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia. Postma P, Gray JA, Sharma T, Geyer M, Mehrotra R, Das M, Zachariah E, Hines M, Williams SC, Kumari V. Psychopharmacology (Berl). 2006 Mar;184(3-4):589-99. Epub 2006 Feb 2.
Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Zipursky RB, Gu H, Green AI, Perkins DO, Tohen MF, McEvoy JP, Strakowski SM, Sharma T, Kahn RS, Gur RE, Tollefson GD, Lieberman JA. Br J Psychiatry. 2005 Dec;187:537-43.
Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study. Kumari V, Aasen I, ffytche D, Williams SC, Sharma T. Neuroimage. 2006 Jan 15;29(2):545-56. Epub 2005 Sep 21.
Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Keefe RS, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Rock SL, Woolson S, Tohen M, Tollefson GD, Sanger TM, Lieberman JA; HGDH Research Group. Biol Psychiatry. 2006 Jan 15;59(2):97-105. Epub 2005 Sep 2.
Effects of rivastigmine on sustained attention in schizophrenia: an FMRI study. Aasen I, Kumari V, Sharma T. J Clin Psychopharmacol. 2005 Aug;25(4):311-7.
Antipsychotic drug effects on brain morphology in first-episode psychosis. Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, Keefe RS, Green AI, Gur RE, McEvoy J, Perkins D, Hamer RM, Gu H, Tohen M; HGDH Study Group. Arch Gen Psychiatry. 2005 Apr;62(4):361-70.
Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders. Perkins D, Lieberman J, Gu H, Tohen M, McEvoy J, Green A, Zipursky R, Strakowski S, Sharma T, Kahn R, Gur R, Tollefson G; HGDH Research Group. Br J Psychiatry. 2004 Jul;185:18-24.
Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Keefe RS, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Lewine RR, Yurgelun-Todd DA, Gur RC, Tohen M, Tollefson GD, Sanger TM, Lieberman JA. Am J Psychiatry. 2004 Jun;161(6):985-95.
Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Lieberman JA, Tollefson G, Tohen M, Green AI, Gur RE, Kahn R, McEvoy J, Perkins D, Sharma T, Zipursky R, Wei H, Hamer RM; HGDH Study Group. Am J Psychiatry. 2003 Aug;160(8):1396-404.
Contact: Vera Hassner Sharav
Fraud Case Rocks Anesthesiology Community
Mass. Researcher Implicated in Falsification of Data, Other Misdeeds
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.
Dr Scott Reuben 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.
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. Dr. Shafer called the scandal “a tragedy” for the profession, for patients and for Dr. Reuben personally. “I cannot begin to comprehend why a person would take this course,” he said ofthe research fraud. Efforts to reach Dr. Reuben were unsuccessful.
Internal Inquiry Revealed Sweeping Misconduct
The retractions came after an internal investigation by Baystate turned up evidence of widespread fraud in Dr. Reuben’s research. Jane Albert, a spokeswoman for Baystate, said the inquiry was undertaken after an internal reviewer at the medical center had raised questions last year. Ms. Albert said the hospital’s investigation raised “no allegations concerning any patient care. This was focused on academic integrity.”
Dr. Reuben is on medical leave from his position as chief of the acute pain service at Baystate, Ms. Albert said.
Dr. Reuben, who was educated at Columbia University and received his medical degree from SUNY at Buffalo School of Medicine, is well-known among anesthesiology researchers for his studies of multimodal analgesia, the practice of combining several forms of pain relief to better control postoperative discomfort and promote faster recovery from surgery.
Rumors of a problem with Dr. Reuben’s research have been circulating among academic anesthesiologists for a year, according to people familiar with the matter. "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.”
A recent PubMed search for Dr. Reuben’s name turned up 72 citations, the most recent an article in the December issue of the Journal of Cardiothoracic and Vascular Anesthesia on preventing the development of chronic pain after thoracic surgery.
“Massive” Breach of Trust
Josephine Johnston, an attorney specializing in research integrity at the Hastings Center, in Garrison, N.Y., called the scope of the Reuben fraud “massive.” "It’s usually just one article, not a body of work,” Ms. Johnston said.
What’s particularly surprising given the dimensions of the case, Ms. Johnston said, is that Dr. Reuben’s research managed to raise no alarms among peer reviewers. However, she added, “the peer review system can only do so much. Trust is a major component of the academic world. It’s backed up by the implication that your reputation will be destroyed if you violate that trust.”
House of Cards?
A cornerstone of Dr. Reuben’s approach has been the use of the selective cyclooxygenase-2 inhibitor celecoxib (Celebrex) and the neuropathic pain agent pregabalin (Lyrica), both manufactured by Pfizer. Dr. Reuben has received research grants from the company and is a member of its speakers’ bureau. However, a source told Anesthesiology News that Pfizer recently alerted its speakers to remove any reference to Dr. Reuben’s data from their presentations. Pfizer was unable to comment by the time this article went to press. The company has not been accused of wrongdoing in the matter.
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.”
One of the pillars of support for combining celecoxib and pregabalin was a 2006 study in Anesthesia and Analgesia—for which Dr. Reuben has been a reviewer—by Dr. Reuben and colleagues that found the approach effective in patients undergoing spinal surgery. That paper has been withdrawn. “If we take out [those] data in spinal,” Dr. Chelly said, “you really don’t have any evidence that the combination is working.”
BBC psychiatrist Tonmoy Sharma is struck off
By Lucy Cockcroft
1 Apr 2008
Tonmoy Sharma has been struck off the medical register. Tonmoy Sharma was found guilty of serious professional misconduct.
A psychiatrist who regularly appeared as an expert on the BBC has been struck off the medical register after he lied about his academic qualifications and performed unethical drugs tests on mentally ill patients.
Tonmoy Sharma, who was a senior lecturer at the Institute of Psychiatry in London, has been exposed as a fraud who repeatedly referred to himself as a "professor" when records show that he had never completed a PhD thesis.
Despite this, Sharma, who was registered at the Clinical Neuroscience Research Centre in Dartford, Kent, regularly used the letters PhD after his name and managed to deceive the NHS and some of the world's largest pharmaceutical companies.
He also appeared on the BBC2 series Mind of a Murderer in 2000 and was often used as an expert commentator on BBC News Online stories.
A General Medical Council panel yesterday found Sharma guilty of "serious failings of personal integrity" after hearing that he recruited mentally ill patients to test drugs without seeking proper approval.
Andrew Popat, chairman of the panel, told Sharma: "Your persistent and wide-ranging dishonesty and untruthfulness, spanning a number of years, together with your lack of insight, is so serious that it is fundamentally incompatible with your continuing to be a registered medical practitioner."
Mr Popat said Sharma, the author of several books on mental illness, had "contributed significantly towards the advancement of medical science" and was highly regarded by his colleagues.
However, after a 10-month hearing, the GMC Fitness to Practise panel found Sharma guilty of serious professional misconduct and struck him off the medical register.
The 42-year-old, who trained in India, was found to have acted unprofessionally in relation to five major studies between 1997 and 2003, involving four leading pharmaceutical companies including Eli Lilly and the Janssen Research Foundation.
He also misled the companies when he chose to use identical patients in different studies, subjecting them to MRI scans and tests that had not been approved by an ethics committee. In 2003, he recruited mental health patients in unsolicited telephone calls and without consent from their doctors. He then failed to give them proper information about the trials - one schizophrenic was simply handed a leaflet.
His misconduct was first uncovered by the drugs company Sanofi, and a complaint resulting in his temporary suspension was made to the Institute of Psychiatry in 2001, prompting an investigation.
Sharma, who represented himself at the hearing, denied the claims and insisted that he "believed in ethics in medicine".
Additional NEWS REPORTS
Re: Tonmoy Sharma case:
1. The Times, Doctor Tonmoy Sharma faces the sack for unethical tests on patients, March 29, 2008
2. NRI, Tonmoy Sharma NRI psychiatrist accused of being a fraud of conducting unethical drug tests on mentally ill patients. Kuldip Ahuja, March 28, 2008
3. The Observer, Professor in drug study fraud claim by Antony Barnett, investigations editor Sunday 28 May 2006
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