In 2009, Baystate Medical Center (Tufts University School of Medicine) in Springfield, MA, made public the results of an inquiry into fraudulent research practices by Scott S. Reuben, MD, a Professor of Anesthesiology at the institution. Baystate Medical Center notified affected journals of its conclusion that 19 peer-reviewed articles and 2 abstracts contained fabricated data. After this notification, these publications were retracted from the peer-reviewed literature, including 10 published in Anesthesia & Analgesia.1 We have previously reported some of the scientific and clinical implications of these retractions,2 particularly with respect to the reduction of chronic pain by perioperative administration of nonsteroidal antiinflammatory drugs. Some of the retracted clinical trials are now being replicated.3 In addition, Marret et al.4 examined the impact of Reuben's papers on the conclusions of published systematic reviews, and determined that only 1 of the 6 quantitative category III reviews would have come to a different conclusion if Reuben's data were eliminated. Exclusion of these data made no difference when reports by Reuben's group contributed fewer than 30% of the patients in the final analysis.
Dr. Reuben published an additional 12 papers and 2 letters to the editor in Anesthesia & Analgesia. Baystate Medical Center did not find substantive evidence that these 14 publications contained fabricated data. The lack of a disposition on the remaining publications presents journals, and their readers, with a quandary: what should one make of the nonretracted papers?
These nonretracted publications contain some potentially important findings, the validity of which must now be questioned. For example, Reuben et al.5 reported that rofecoxib 50 mg administered before arthroscopic knee surgery resulted in a longer duration of analgesia, smaller postoperative opioid requirement, and lower pain scores than administration of the same dose at the end of surgery. Reuben et al.6 reported similar findings when they compared the intraarticular injection of morphine 3 mg before and after arthroscopic knee surgery. Prospective studies by other investigative groups,7–9 and a systematic review of the literature,10 have raised serious questions about the existence of the “preemptive” analgesic effect described in these 2 articles by Reuben's group.5,6 More importantly, these findings have not been duplicated by any other investigative groups. Therefore, our Editorial Board thought it important to assess the validity of Dr. Reuben's nonretracted articles published in Anesthesia & Analgesia.
In the interest of providing an accurate scientific record, the Editorial Board of Anesthesia & Analgesia asked the authors of this editorial to contact Dr. Reuben's coauthors and collaborators to request their assistance in evaluating these nonretracted articles. The investigation at Baystate had previously concluded that Dr. Reuben was solely responsible for any data fabrication. It appears that coauthors were deceived, just as the reviewers, editors, and readers were deceived. There is no evidence that these individuals were in any way complicit. We therefore asked the coauthors if they could give us reasonable assurance that the findings in these nonretracted articles5,6,11–22 could be trusted.
It is generally impossible to prove a negative assertion. Therefore, we did not expect to be able to “prove” that the data were not tainted. However, we rejected outright retraction of these papers because of the appreciable costs associated with retraction of valid research. Retraction of valid research removes a finding from the literature, a finding that might have been helpful in improving the care of patients. Retraction without specific evidence is disrespectful to the patients who contributed their data with the intent of helping future generations of patients. Retraction of valid research also diminishes the work of coauthors who were attempting to promote scientific understanding and improve patient care.
Our goal was therefore to draw reasonable conclusions based on the information provided by these coinvestigators. For this reason, we believe it is important to present the detailed findings of our investigation.
Not surprisingly, none of Dr. Reuben's colleagues could state that they remembered all of the subjects enrolled in any given study. However, each coauthor gave us a good sense of his/her confidence regarding various aspects of the clinical research process. Neil Roy Connelly, MD, the current Director of Anesthesia Research at Baystate Medical Center, provided substantial confirmatory evidence that 4 of the original articles11,15,17,22 and 1 Letter to the Editor20 were valid reports. Robert B. Steinberg, PhD, MD, is a coauthor on 5 additional original articles. Dr. Steinberg reassured us about these findings in 2 of the articles because he participated in the data collection process.18,21 Dr. Steinberg was only peripherally involved in 3 additional studies and was not comfortable “vouching” for data reported in those manuscripts.14,16,19
Wandana Joshi, DO, vouched for 3 original articles on which she was listed as either the primary author11,13 or one of the coauthors.5 Joseph Sklar, MD, an orthopedic surgeon at Baystate, recalled enrolling his orthopedic patients in the 2 preemptive analgesia studies.5,6 However, he did not participate in the data analysis. Therefore, Dr. Sklar did not feel comfortable vouching for either of these manuscripts. Dr. Sklar could not remember the details of a third trial and could not vouch for the data.13
Holly Maciolek, RN, was the research nurse associated with primary responsibility for collecting data in several studies, including the studies on preemptive analgesia.5,6 She recalled collecting the data for these patients, including seeing each subject before discharge, obtaining contact information, and making follow-up phone calls. She is confident of the data collection.
Charles Gibson, RN, a research coordinator, performed much of the data analysis for Dr. Reuben and was a coauthor on 3 of the original articles.14,17,19 He had clear recollection of entering data from original data collection sheets for these studies. For the studies on preemptive analgesia,5,6 he recalled receiving completed spreadsheets from Ms. Maciolek, the research nurse.
Anyone looking for a decision to retract, or not retract, based on “hard evidence” will be disappointed by our rendering a decision based on admittedly “soft evidence” of coauthor recollections. If hard evidence of fraud had existed for any of these papers, Baystate Medical Center presumably would have found it in their internal or subsequent external inquiries of Dr. Reuben's publications. We admit that the recollections of the coauthors might have been swayed by their own conflict of interest regarding their publications. However, Baystate Medical Center believed the coauthors to be honest investigators, and our discussions with the coauthors were consistent with this assessment. Additionally, the consistency in the accounts and recollections among the coauthors, as shown in Table 1, suggests that their recollections were reasonably accurate.
1. A Letter to the Editor by Dr. Reuben12 referenced a previously retracted article by Reuben and Connelly.23 It is therefore retracted.
2. For the 12 research publications and 1 letter to the editor, at least 1 coauthor or colleague was willing to vouch for the authenticity of subject enrollment, data collection, and/or the data analysis, as shown in Table 1. Based on these good faith assertions by the coauthors, and the fact that Baystate Medical Center's analysis did not identify substantive evidence of fabrication concerning them, these publications will not be retracted and will remain part of the unimpeached medical literature.
3. As stated previously,1,2 time and additional investigation will ultimately determine the “truth” of all these studies. Hopefully, Reuben's coauthors will consider repeating the studies5,6 questioned by other investigative groups7–10 to either verify or reject the more controversial findings in the remaining publications.
4. As for Anesthesia & Analgesia, we hope that the Scott Reuben saga has come to an end.
We appreciate the assistance of Dr. Connelly, Dr. Steinberg, Dr. Joshi, Dr. Sklar, Mr. Gibson, and Ms. Maciolek with our assessment. We also appreciate the help of Anita Sarro, RN, MS, JD, Research Integrity Officer at Baystate Health, Inc.
a Verbatim quotation from Wikipedia, http://en.wikipedia.org/wiki/Scott_Reuben. Accessed September 10, 2010 Cited Here...
1. Shafer SL. Tattered threads. Anesth Analg 2009;108:1361–3
2. White PF, Kehlet H, Liu S. Perioperative analgesia: what do we still know? Anesth Analg 2009;108:1364–7
3. Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg 2010;110:199–207
4. Marret E, Elia N, Dahl JB, McQuay HJ, Møiniche S, Moore RA, Straube S, Tramèr MR. Susceptibility to fraud in systematic reviews: lessons from the Reuben case. Anesthesiology 2009;111:1279–89
5. Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J. The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002;94:55–9
6. Reuben SS, Sklar J, El-Mansouri M. The preemptive analgesic effect of intraarticular bupivacaine and morphine after ambulatory arthroscopic knee surgery. Anesth Analg 2001;92:923–6
7. Kokki H, Salonen A. Comparison of pre- and postoperative administration of ketoprofen for analgesia after tonsillectomy in children. Paediatr Anaesth 2002;12:162–7
8. Sun T, Sacan O, White PF, Coleman J, Rohrich RJ, Kenkel JM. Perioperative versus postoperative celecoxib on patient outcomes after major plastic surgery procedures. Anesth Analg 2008;106:950–8
9. Fong WP, Yang LC, Wu JI, Chen HS, Tan PH. Does celecoxib have pre-emptive analgesic effect after Caesarean section surgery? Br J Anaesth 2008;100:861–2
10. Møiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia. Anesthesiology 2002;96:725–41
11. Joshi W, Connelly NR, Reuben SS, Wolckenhaar M, Thakkar N. An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management. Anesth Analg 2003;97:35–8
12. Reuben SS. Ambulatory anesthesia for knee arthroscopy. Anesth Analg 2001;92:556
13. Joshi W, Reuben SS, Kilaru PR, Sklar J, Maciolek H. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or morphine. Anesth Analg 2000;90:1102–6
14. Reuben SS, Steinberg RB, Lurie SD, Gibson CS. A dose-response study of intravenous regional anesthesia with meperidine. Anesth Analg 1999;88:831–5
15. Reuben SS, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine. Anesth Analg 1999;88:729–33
16. Reuben SS, Steinberg RB, Lurie SD. Is there a place for meperidine in intravenous regional anesthesia? Anesth Analg 1998;87:1215–6
17. Reuben SS, Connelly NR, Lurie S, Klatt M, Gibson CS. Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery. Anesth Analg 1998;87:98–102
18. Steinberg RB, Reuben SS, Gardner G. The dose-response relationship of ketorolac as a component of intravenous regional anesthesia with lidocaine. Anesth Analg 1998;86:791–3
19. Reuben SS, Steinberg RB, Cohen MA, Kilaru PA, Gibson CS. Intraarticular morphine in the multimodal analgesic management of postoperative pain after ambulatory anterior cruciate ligament repair. Anesth Analg 1998;86:374–8
20. Reuben SS, Connelly NR. Local analgesia effect of nonsteroidal antiinflammatory drugs. Anesth Analg 1997;84:1168–9
21. Reuben SS, Steinberg RB, Kreitzer JM, Duprat KM. Intravenous regional anesthesia using lidocaine and ketorolac. Anesth Analg 1995;81:110–3
22. Reuben SS, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995;80:1154–7
23. Reuben SS, Connelly NR. Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine. Anesth Analg 1996;82:1036–9
24. Reuben SS, Duprat KM. Comparison of wound infiltration with ketorolac versus intravenous regional anesthesia with ketorolac for postoperative analgesia following ambulatory hand surgery. Reg Anesth 1996;21:565–8
As reported in the press, and summarized in Wikipedia: “On June 24, 2010, Reuben was sentenced in Federal Court to six months in jail (after pleading guilty to one count of health care fraud on February 21, 2010) to be followed by 3 years of supervised release. Further, a five-thousand dollar fine was imposed and he was ordered to provide restitution of more than three hundred sixty thousand dollars.”a