By Ted Agres and Adam Marcus

Scott S. Reuben, MD, former chief of the acute pain service at Baystate Medical Center in Springfield, Mass., and implicated in one of the largest cases of publishing fraud, has agreed to plead guilty to one charge of fraud in connection with falsifying and fabricating research studies involving Pfizer Inc.’s painkiller Celebrex.

In court documents released yesterday by the U.S. Attorney’s office in Boston, Dr. Reuben has agreed to pay nearly $362,000 in restitution to Pfizer, Merck & Co., and Wyeth/Rays of Hope and forfeit an additional $50,000. Although the charge to which he has agreed to plead guilty (health care fraud, 18 U.S.C. section 1347) allows for a maximum sentence of 10 years in prison and twice the amount of restitution, prosecutors agreed to recommend a sentence “at the low end” of the guideline range followed by supervised release of two years, according to the plea agreement signed on Jan. 12. Dr. Reuben’s attorney will be permitted to seek an alternative form of sentence not involving prison when the case is brought before a judge.“Although the plea agreement has been filed, it has not been accepted by the Court,” said Christina DiIorio-Sterling, a spokeswoman for the U.S. Attorney’s office. “There has to be a plea hearing, and the judge needs to accept the plea for it to be binding,” she told Anesthesiology News.

Dr. Reuben is scheduled to appear in federal court on Feb. 22. As part of the agreement, Dr. Reuben will voluntarily enter into a disqualification agreement with the FDA. Debarred or disqualified investigators cannot engage in certain activities related to clinical research.

According to an Information document filed in the U.S. District Court of Massachusetts on Jan. 14, Dr. Reuben in September 2005 entered into a $73,512 clinical research grant agreement with Pfizer to compare Celebrex to placebo in 100 patients undergoing multimodal analgesia therapy. Dr. Reuben published articles in Anesthesia & Analgesia (2007;105:222-227 and 2007;105:228-232) claiming positive results in treating 200 patients with multimodal analgesia therapy, 100 with Celebrex and 100 with placebo. In fact, Dr. Reuben did not enroll any patients into that study and fabricated the results.

In addition to Pfizer, Dr. Reuben also made proposals for research funding to Merck & Co. (Vioxx). The Information document does not elaborate on those other proposals, but the plea agreement requires restitution payments of $361,932 to Pfizer; $49,375 to Merck; and $16,000 to Wyeth/Rays of Hope.

Pfizer did not respond to requests for comment today. But in a statement to the Wall Street Journal in March 2009, the company said: “It is very disappointing to learn about Dr. Scott Reuben’s alleged actions. When we decided to support Dr. Reuben’s research, he worked for a credible academic medical center and appeared to be a reputable researcher.”

Jane Albert, a spokeswoman for Baystate, said the medical center was not seeking restitution from Dr. Reuben, nor would it pursue any legal action against him.

Steven L. Shafer, editor in chief of Anesthesia and Analgesia, the journal most victimized by the fraudulent research, said he was pleased to learn of the charge against Dr. Reuben. “I hope they throw the book at him,” Dr. Shafer said.

“It is a sad case,” said Paul F. White, MD, PhD, distinguished chair of anesthesiology at the University of Texas Southwestern Medical Center at Dallas. “This case does nothing but make it even more difficult to perform clinical research. It is very analogous to the effect of terrorism on airline travel. Clinical researchers like myself will become dinosaurs before long,” he told Anesthesiology News. Dr. White is a leader in the field of multimodal anesthesiology, the area of research in which Dr. Reuben was particularly active. He is also a member of the advisory board of Anesthesiology News.

Allegations of rampant fraud involving Dr. Reuben’s research and the retraction of papers were first reported by Anesthesiology News (March 2009) after Baystate Medical Center officials uncovered evidence of wrongdoing following a routine audit. Falsified reports involved at least 21 articles dating back to 1996. The articles were published in Anesthesiology, Anesthesia & Analgesia, Journal of Clinical Anesthesia and other titles, which have since retracted the papers. The journals stressed that Dr. Reuben’s co-authors on those papers have not been accused of wrongdoing.

Separately, in late October 2009, Dr. Reuben signed a voluntary agreement not to practice medicine in Massachusetts, which was approved by the Massachusetts Board of Registration in Medicine on Nov. 4. Under the terms of that agreement, Dr. Reuben will cease treating patients while the board investigates an ethics complaint against him stemming from the case. The practice agreement will become void when the board either disciplines Dr. Reuben or dismisses the complaint, according to the document.

The federal case against Dr. Reuben was conducted by the FDA, FBI, and the Health and Human Services’ Office of Inspector General.