Professionalism/Scott Reuben and Research Fraud

Introduction
The falsification of research results can be tempting for researchers who wish to get ahead in their fields. They may falsify data because they feel pressure to publish papers, want to boost their reputation, or are being incentivized monetarily. Even though the peer review process is effective at preventing many of these cases, some instances can slip by undetected.

A professional, however, has the responsibility to uphold the integrity of his or her work. Professionals are transparent and honest, and they are concerned more with their professions than the honors or money that may come with impressive research results. Similarly, if a professional notices unethical behavior, they point it out and try to stop it.

Scott Reuben, an anesthesiologist, managed to commit research fraud for 13 years before he was caught. Fortunately, a few individuals prevented this fraud from going on longer when they raised suspicion that something was wrong. In this chapter, we discuss Scott Reuben's research fraud, the impact of his actions, and the researcher's ethical dilemma.

Scott S. Reuben
Scott Reuben obtained his medical degree in 1985 from the State University of New York at Buffalo. Following his residency at Mount Sinai Medical Center in New York, Reuben moved to Massachusetts where he was employed as an anesthesiologist by Baystate Medical Center in Springfield from 1991 until 2009. At Baystate Medical Center, he served as chief of acute pain and provided anesthesia services and post-surgery treatment for surgical patients. Reuben was also a professor of anesthesiology and pain medicine at Tufts University in Boston. 

Research Interest in Multimodal Analgesia
Reuben was interested in pursuing post-operative multimodal analgesia strategies, the study of using various analgesic drug therapies instead of opioids. He theorized that “multimodal analgesia therapy would be as effective for pain, promote long term healing and avoid some of the side effects associated with opioid therapy”. In particular, Reuben focused on the role of COX-2 inhibitors in post-operative pain management. Multimodal analgesia was controversial due to questions regarding the safety of the drugs used; however, Reuben reported that his studies confirmed the safety and efficacy of COX-2 inhibitors.

In 2005, Reuben began a clinical study titled Perioperative Administration of Celecoxib [Celebrex] as a Component of Multimodal Analgesia for Outpatient Anterior Cruciate Ligament Reconstruction Surgery. Reuben proposed to treat 100 patients (50 with placebo and 50 with Celebrex) to study the efficacy of multimodal analgesia using Celecoxib (a COX-2 inhibitor drug manufactured by Pfizer). In 2007, he published two articles regarding this proposed study in the journal Anesthesia & Analgesia. In these publications, he reports that 200 patients (100 with placebo and 100 with Celebrex) were treated. Furthermore, he documents that multimodal analgesia therapy was shown as successful by his clinical study. 

This was not Reuben’s only clinical study. Throughout his career, Reuben conducted many clinical studies related to COX-2 inhibitors for post-operative pain management (published in journals such as Anesthesiology and Anesthesia & Analgesia) that influenced the standard of care in anesthesiology. Reuben is listed as an author on 72 papers, 39 of which are clinical studies. Between 2002 and 2009, Reuben's papers averaged approximately 200 citations per year; in total, Reuben's papers have accrued over 2600 citations.

Relation to Pfizer and Merck
According to court documents, Reuben was funded in part by Independent Research Grant Agreements with Pfizer. In the study mentioned from 2005, Reuben received $73,512.00 from Pfizer. In fact, between 2002-2007, Pfizer financed much of Reuben's research. 

How was Reuben Caught?
In 2009, during a routine audit, Baystate's chief medical officer Hal Jensen noticed that Reuben's abstracts had never been approved by the hospital review board. These audits, which should have verified the validity and assured the quality of Baystate's publications, were only performed for about 5% of the total publications each year, allowing Reuben's fraud to slip by undetected. After noticing the inconsistency, Jensen launched an investigation into Reuben's research, and Anesthesia & Analgesia put his papers on hold.

Independently, orthopedic Evan Ekman began to have his own suspicions on Reuben. Ekman was given one of Reuben's papers to review for a journal, but when he asked Reuben for information regarding the orthopedic surgeon listed in the paper, Reuben ceased all communication with Ekman. Later that year at a conference, Ekman was handed a copy of the same paper, and he was surprised to see that his name was listed as a co-author. Reuben had forged Ekman's signature and listed him as a co-author without his knowledge. 

Outcome of the Court Case
In January 2010, Reuben pleaded guilty to Health Care Fraud for fabricating data and patients; he was also accused of forgery for adding the names of uninvolved co-authors without their permission. He was charged by the United States District Court for the District of Massachusetts in June 2010. At the time of his sentencing memorandum (June 2010), Reuben was found guilty of "publishing six fraudulent articles which generated in excess of $360,000 in research funds." In addition to having his license for practicing medicine revoked, Reuben was sentenced to 6 months in jail and ordered to pay over $400,000 in fines and restitution. Additionally, the FDA banned Reuben from participation in future research. According to Reuben's sentencing memo, "there is no possibility that Dr. Reuben will ever engage in research again, and so there is no possibility that his misconduct will ever recur." 

Since the exposure of Reuben's fraud, many of his publications have been retracted. In 2015, Retraction Watch (a blog dedicated to reporting retractions of scientific papers) reported that 25 of Reuben's papers had been retracted. However, a search conducted in April 2018 on PubMed Central's archive of biomedical and life sciences journal literature found a minimum of 30 retracted papers on which Reuben is listed as an author:

Surgical Patients
Millions of patients were prescribed COX-2 inhibitors based on Reuben’s fraudulent claims, thus risking patient health. Despite animal studies indicating COX-2 inhibitors correlated with impaired bone healing, Reuben presented research that showed COX-2 inhibitors such as Pfizer’s Celebrex to be beneficial. Merck’s Vioxx, a specific COX-2 inhibitor deemed safe and effective by Reuben, has caused nearly 3,500 deaths and was recalled in 2004 due to increased risk for heart attack and stroke. Celebrex was also believed to carry risk for cardiac events; however, Reuben had downplayed such negative side effects in his papers. Ongoing studies have been performed to determine long term effects of drugs recommended by Reuben's studies.  In the words of Steven Shafer, editor-in-chief of Anesthesia & Analgesia, “We are talking about millions of patients worldwide, where postoperative pain management has been affected by the research findings of Dr. Reuben.”

Reuben’s falsifications also had financial impact. According to Paul White, billions of dollars worth of COX-2 inhibitors were sold based on Reuben’s studies. 

Field of Anesthesiology
According to 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), Reuben 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.” Steven Shafer made similar comments about the impact of Reuben's fraud on the field of anesthesiology: “We are left with a large hole in our understanding of this field".  Since Reuben's work had significant influence on how anesthesiology was conducted, the revelation that his findings were entirely faked means that anesthesiology practices have been based on unsubstantiated claims. This has generated uncertainty and mistrust in how anesthesiology is performed and how researchers in anesthesiology should move forward.

Propagation of False Data
Reuben's research fraud exemplifies circular reporting--a phenomenon in which information that appears to be substantiated by multiple credible sources actually propagates from one original source, which often makes unsubstantiated claims. In circular reporting, misinformation is propagated due to failure to check the validity of the primary source and lack of awareness of where information originates. For example, the Korean Knee Society (KK Society) used Reuben's retracted papers to form guidelines for pain management throughout total knee arthroplasty. A paper published by the KK Society states that "preoperative oral administration of a COX-2 inhibitor can facilitate pain relief, reduce the need for opioids and related complications, and improve patient satisfaction. Furthermore, the efficacy of COX-2 inhibitors for postoperative pain management have been well established." The claim that COX-2 inhibitors have been "well established" as effective relies predominantly on Reuben's fraudulent claims and others who have cited Reuben's faked data.

Research conducted by Science and Engineering Ethics shows that "even 5 years after their retraction, nearly half of Reuben's articles are still being quoted and the retraction status is correctly mentioned in only one quarter of the citations."  '''The importance of knowing the sources from which information originates and tracing information back to the primary source is reiterated by the observations of circular reporting in the case of Scott Reuben. Professionals must routinely practice fact checking.'''

Conflict of Interest
From as early as 1999, Reuben signed contracts with pharmaceutical companies (particularly Pfizer and Merck) to procure funding for his research. Pfizer and Merck claimed to be unaware of Reuben's fraudulent practices and were ruled innocent; nevertheless, the case of Scott Reuben highlights dangers posed by conflict of interest. As a result, it is now standard practice to disclose conflicts of interest in publications and presentations. Reports have shown that bias for favorable outcomes, even without intention to mislead, exists when industry funding is involved. In order to avoid being subjected to biases, professionals must evaluate what interests are at play and how conflicts of interest may distort the lens through which information and situations are assessed.

The Researcher's Ethical Responsibility
A researcher's goal is to uncover new truths about the world. Thus, he or she has a commitment to honesty and the integrity of the research process. Failure to uphold this duty can result in endangering others. In Reuben's case, he risked the health of billions just to get ahead in his field and support the drugs he was being funded for researching.