03/18/2011 08:39 am ET Updated May 25, 2011

Fraudulent Medical Research Could Affect Your Diagnosis

The press has led us to believe that the recall of a medical research paper represents a rare, media-worthy event. Case in point: the week-long blitz announcing the retraction of a single, disputed paper, published in The Lancet in 1998. By comparison, the retraction of more than 100 papers by two medical researchers didn't even make the evening news. The enormity of that recall rattled the entire subspecialty of anesthesiology and pain management. The identification of many more recalled papers exposes the extent of scientific misconduct and the failure of peer review across the entire medical industry.

During the week of March 3, the editors of 16 international medical journals announced the retraction of "unethical" research carried out by German doctor, Joachim Boldt, a leading specialist on intravenous fluid management. Boldt has published more than 200 studies, many on a colloid product called hydroxyethyl starch, or HES.

Anesthesiologists rely on colloids to deliver nutrients to cells and to keep a patient's blood volume high during surgery, thus avoiding the risks that can come with blood transfusions. Boldt is under investigation for allegedly forging up to 90 of his studies, thought to contain bogus, fraudulent, manipulated and/or distorted data. However, an even more serious infraction is that it appears Boldt did not have the approval of an Institutional Review Board (IRB), an ethics body required by law for all clinical research. Investigations done without the oversight of an IRB is a criminal offense.

This was not Boldt's first violation. On October 28, 2010, the editor of Anesthesia & Analgesia withdrew an article entitled, "Cardiopulmonary Bypass Priming Using a High Dose of a Balanced Hydroxyethyl Starch (HES) vs. an Albumin-Based Priming Strategy" under suspicion of scientific misconduct. An investigation concluded that there was no convincing evidence that the study had ever been done.

Scientific Misconduct All Around the World
Breached ethical research standards are not isolated occurrences. A search of online journals for "retracted" papers and reviewing the relatively new, important blog, Retraction Watch, reveals an alarming number of papers retracted for data manipulation and other malfeasances. For example, The American Society for Microbiology (ASM), publisher of Infection and Immunity, recently retracted five papers by researcher Naoki Mori, published between 2000 and 2009. ASM also banned Mori from publishing in any of its journals for 10 years. To date, 16 papers of his have been revoked, including studies published in Journal of Virology, Retrovirology, and Blood.

Last month, The Korean Journal of Otolaryngology-Head and Neck Surgery retracted 17 papers published between 1993 and 2006, with the common theme of 'overlap'. According to Retraction Watch, this is "almost always a euphemism for plagiarism, whether self or otherwise."

Britain has long been plagued by researcher misconduct. In 1996, the British General Medical Council (GMC) took action against Dr. Geoffrey Fairhurst for forging consent forms of patients involved in drug company sponsored research. Fairhurst became the 16th physician to be found guilty of serious professional misconduct by the GMC and to be struck from the medical roster. Ironically, Fairhurst had been the vice chairman of his local medical ethics committee. At the time of his dismissal, The British Medical Journal (BMJ) joined forces with The Lancet, calling on the medical profession to get a grip on research misconduct. "Otherwise," said Richards Smith M.D., then-editor of the BMJ, "government will have to do it, and the doctors' ability to regulate themselves will be thrown further into doubt."

The U.S. has had its own issues with research integrity. One of the most egregious revelations was the 2009 massive scientific fraud committed by anesthesiologist, Dr. Scott Reuben. Reuben, who had revolutionized the way physicians provided pain relief to their patients, was found to have completely fabricated at least 21 papers.

The editor-in-chief of Anesthesia & Analgesia, the journal which had published 10 of Reuben's fraudulent papers, stated, "We are talking about millions of patients worldwide, where postoperative pain management has been affected by the research findings of Dr. Reuben." While all of Rueben's papers have been retracted, one can only wonder how many billions of dollars were paid by insurance companies, Medicare and Medicaid for bogus treatments. Since his research also supported the effectiveness of Vioxx, the pain killer which caused at least 3,400 deaths, he may be indirectly responsible for those outcomes. Reuben, who blamed his actions on mental illness, is now serving a six-month prison sentence for health care fraud.

While the revocation of more than 100 publications in one discipline has enormous impact, the recall of only a few papers from one highly respected researcher can be equally as troublesome. Three studies by well-known researcher Sylvia Bulfune-Paus, recalled from the Journal of Immunology, will have a ripple effect: the studies had been collectively cited as references in 136 other papers.

Only the Researchers?
In light of the flurry of scientific papers that have been retracted in the last year, one has to wonder where quality control standards have gone when it comes to medical journal publications. Investigators may manipulate and then submit fraudulent data, but the study still must pass through scientific scrutiny, called peer review, prior to going to print. There are multiple uses for the term, "peer review," but in this context, it is meant to be a method to critically and systematically examine scientific and medical research prior to publication. Peer review requires a community of qualified experts who are able to perform impartial analysis of the submitted research. Journals with extremely stringent standards reject papers if the editors feel the work is not a breakthrough in the field, even if the research is good. By this process, for example, Nature publishes about 5 percent of received papers, while Astrophysical Journal publishes about 70 percent.

If a paper makes the cut after the first round of review, it is sent to multiple reviewers for evaluation. Different publications have different criteria used for the in depth review. According to Wikipedia, the process where the reviewers know who the authors are, but the authors do not know the reviewer, is called a "single-blinded review." This distinguishes it from a "double-blinded" process where neither party is revealed to the other. In a double-blind review, the authors and reviewers are required to remove any reference that may reveal their identity.

By these definitions, it would appear that the submissions by Boldt, Mori, Reuben and others were subjected to only single-blinded analysis. With so many publications in reputable journals, perhaps the reviewers had been lulled into a sense of complacency, assuming scientific standards had been met previously and, with little oversight, assumed the same standards had been upheld.

What to believe?
Information overload is real in every profession, but especially in the field of science and medicine. 1n 1991, it was estimated there were approximately 10,000 biomedical journals in print globally. No doubt the electronic information, RSS feeds, social media and the immediacy of online journals has made the overload exponential. Sorting out good versus bad research has become nearly impossible, especially since busy physicians generally read only the conclusion of the introductory abstract about the study, not the full study itself.

Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science. Born in 1965 in NYC and raised in Athens, Greece, Ioannidis graduated first in his class at the University of Athens Medical School. He attended Harvard University, specializing in internal medicine with a fellowship in infectious disease at Tufts University. His 2005 paper, "Why Most Published Research Findings Are False" has been the most downloaded technical paper from the journal PLoS Medicine.

Ioannidis has published papers with 1,328 different co-authors at 538 institutions in 43 countries. He speaks with authority when he charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His assessment is that "the field of medical research is so pervasively flawed, and so riddled with conflicts of interest, that it might be chronically resistant to change -- or even to publicly admitting that there's a problem."

According to an article in The Atlantic by David Friedman:

"Researchers head into their studies wanting certain results -- and, lo and behold, they were getting them. We think of the scientific process as being objective, rigorous, and even ruthless in separating out what is true from what we merely wish to be true, but in fact it's easy to manipulate results, even unintentionally or unconsciously. At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded. There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded."

When doctors find patients don't respond to a treatment as well as the literature would lead them to expect, they are taught to subordinate their observations to the findings reported in the medical journals or told to them by pharmaceutical sales reps. If a patient reports a bad outcome to a procedure such as a vaccine, their event is negated by physicians who retort there are "no studies" to support the patient's experience. Or if a holistic practitioner identifies a method or treatment that seems to work exceedingly well with a large number of her patients, it is disparaged for not having peer-reviewed studies to confirm it is anything more than an anecdotal response. Hasn't clinical observation been the cornerstone of the advancement of medicine for centuries?

The recent retractions are putting a crack in the armor of medical infallibility. It appears much of what doctors consider to be "usual and customary" may turn out to be misleading, exaggerated and chillingly, flat-out wrong. Physicians would be well served to take medical publications under advisement rather than believing that just because it has been published, it is accurate and infallible, as gospel engraved in stone. Medicine is both art and science, but with all the questionable "science" coming to light, it is time for healthcare practitioners to once again embrace the art of their trade. Having an open mind and a willingness to listen is a good place to start.