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One Investigator's Fraud Affects the Field of Neurologic Pain Management

ARTICLE IN BRIEF

In response to a prominent pain investigator's admission of scientific fraud, leading neurologists who specialize in pain management discuss the ramifications of that admission on current and future research in the field.

When news broke in March that pioneering pain medicine investigator Scott Reuben, MD, of Baystate Medical Center in Springfield, MA, had retracted 21 of the many studies that had helped establish the field of anesthesiology, admitting he had fabricated much of the data and had never conducted the clinical trials that he wrote about in 21 journal articles dating from at least 1996, it wasn't the first time a medical researcher confessed to fraud. But Dr. Reuben's long-running deception — compared by Scientific American to a “medical Bernie Madoff scheme” — stands out because of its effect on a still-young field.

“Pain management is a new discipline, especially when you compare it with other areas of neurology, such as epilepsy, movement disorders, and multiple sclerosis,” said Miroslav Backonja, MD, professor of neurology, anesthesiology and rehabilitation medicine at the University of Wisconsin School of Medicine and Public Health.

“Pain management was nobody's baby, so to speak, and there really was no research going on prior to about the last 20 years. When you have a field that's new and still defining itself, anything like this becomes a big black cloud that can really overshadow successes.”

Dr. Reuben's studies formed a substantial chunk of the research done in two areas: multimodal analgesia and pre-emptive analgesia. Most experts agree that there are enough data on multimodal analgesia from other, credible sources that the whole house of cards does not fall.

For example, said Charles Argoff, MD, assistant professor of neurology at the New York University Langone School of Medicine and co-director of the Cohn Pain Management Center at North Shore University Hospital, a high-quality 2005 report in the New England Journal of Medicine by Ian Gilron, MD, and his team at the University of Halifax-Nova Scotia, documents the effectiveness of that particular multimodal combination in patients with neuropathic pain. Other studies have looked at oxycodone combined with gabapentin.

“There are data, and new research going on, in multimodal analgesia that don't rely on what Reuben did, and that's very helpful,” Dr. Argoff said. Still, he believes that the retraction of the Reuben data warrants re-examining other studies with a critical eye.

“Perhaps studies that came later would have produced more useful information if they had true data to build on,” Dr. Argoff said. “Even a negative study is useful. What matters most to the field is not that Reuben's studies were positive or negative, but that the studies cannot be counted upon. We build upon what we already know, and we can't build upon this.”

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DR. MIROSLAV BACKONJA: “Pain management was nobodys baby, so to speak, and there really was no research going on prior to about the last 20 years. When you have a field thats new and still defining itself, anything like this becomes a big black cloud that can really overshadow successes.”

AREAS NOW IN DOUBT

Particularly questionable is the area of pre-emptive analgesia using non-steroidal anti-inflammatory drugs (NSAIDs) and Cox-2 inhibitors. “That's more in jeopardy, especially since previous studies of pre-emptive analgesia failed to show the benefit,” said Dr. Backonja. “So you have negative results, as well as positive results that turned out to be fraudulent. So the whole principle really has to be re-examined.”

Given the political hot potato that Cox-2 inhibitors has become because of concerns about associated cardiovascular risks in certain populations, that re-examination may never happen. (Merck's application for its newer Cox-2 drug was rejected.)

“Should the studies be repeated, or should we not do them because we have safety concerns about this class of medication anyway?” Dr. Argoff asked. “From a scientific point of view, we would like to know ‘the real answer,’ so that properly selected patients — those not considered at risk for harm due to this drug — could be evaluated to determine whether or not the use of this type of medication is appropriate from a multimodal analgesic viewpoint. But there may not be funding to repeat this work, now that it's been done and the data can't be trusted.”

CHRONIC PAIN RESEARCH

Fortunately for neurologists in the field of pain management, much of Dr. Reuben's work focused on acute pain, such as post-surgical pain. Since most, if not all, neurologists deal largely with chronic pain, they are likely to be less affected by the fraud case.

“Few neurologists are working in hospitals on acute pain services, and very few are interacting with surgical patients prior to surgery doing some of the pre-emptive work that has been called into question,” said Russell Portenoy, MD, chair of the department of pain medicine and palliative care at New York's Beth Israel Hospital. “The vast majority of the work that has been withdrawn was relevant to the surgical setting. To my knowledge, there's only one consideration with respect to chronic pain, and that is a finding that treatment prior to mastectomy with antidepressant reduces the likelihood of developing post-mastectomy pain syndrome. That finding is no longer to be considered valid.”

That study, Dr. Portenoy noted, is one of many from the past 15 years that have examined reducing the likelihood of prolonged pain through adequate management of acute pain. “It doesn't negate the understanding that acute pain management may forestall chronic pain problems, but in that specific context, that finding cannot be taken as established anymore.”

FUTURE FOR THE FIELD

Where does the field of pain management go from here? “We're working hard to re-examine what happened and prevent it from happening again,” said Dr. Backonja. “Hopefully, this is something that will lead to positive results. There is a lot of work to be done.”

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DR. CHARLES ARGOFF: “What matters most to the field is not that Reubens studies were positive or negative, but that the studies cannot be counted upon. We build upon what we already know, and we cant build upon this.”

He noted that a new neuropathic pain research consortium has been formed by national societies such as the American Pain Society, the American Academy of Pain Medicine, and the American Academy of Electrodiagnostic Medicine. “This is a multicenter, multidisciplinary effort to develop methods of assessment of patients with neuropathic pain disorders,” he said. “The goal is to raise the level of investigation to a much higher level. In that regard, while you should never say something is impossible, a fraud like Reuben's would be much more difficult with multiple investigators and levels of accountability.”

Broadly speaking, the Reuben case should renew researchers' commitment to disclosure, integrity, and scientific rigor — and remind the research community and the public that the potential for fraud is there, the pain investigators told Neurology Today in interviews.

“The notion that we could publish something and have it permanently archived, and yet have it be untrue, is profoundly disconcerting,” said Dr. Portenoy, who edits the Journal of Pain and Symptom Management, and serves on other editorial boards. “At the same time, it's important to remember that peer review and scientific ethics together means that the overwhelming majority of what gets published is done in a way that's scientifically rigorous and represents actual findings.”

REFERENCES

• Gilron I, et al. Morphine, gabapentin or their combination for neuropathic pain. N Engl J Med 2005;352(13):1324–34.