Departmental and Institutional Strategies for Reducing Fraud in Clinical Research

Abstract

In recent years the anesthesia community has learned of major fraud in clinical research committed by Scott Reuben and Joachim Boldt. In November 2011, Donald Poldermans, an even more prominent perioperative investigator, was fired by Erasmus University for fraud. And most recently, 8 of Yoshitaka Fujii’s publications were retracted after more than a decade of controversy. The extent of malfeasance and fraud in clinical research is unknown, but it is likely that data selection, incomplete blinding, undeserved authorship, and post hoc designation of primary outcomes are relatively common. In contrast, the most egregious types of fraud, such as outright fabrication or deliberate manipulation of results, are presumably rare. But even occasional episodes do enormous damage to confidence in clinical research results and patient trust, to say nothing of degrading the reputation of involved institutions. And most importantly, incorrect results may be incorporated into clinical practice with consequent harm to countless patients. Any degree and amount of fraud in clinical research is thus unacceptable. The purpose of this commentary is to discuss departmental and institutional strategies to reduce the risk of fraud in clinical research. Consider the way clinical research was typically done in the past, and still often is. A single investigator develops a protocol, applies to the IRB, identifies qualifying patients, obtains consent, randomizes and provides treatment, evaluates outcomes, manages study data, does the statistical analysis, and writes a manuscript. This approach is acceptable if allocation is fully concealed until randomization, blinding is complete (i.e., identical-looking treatment and control drugs are provided by the pharmacy), and blinding is maintained throughout data analysis. Principal investigators have legal and moral responsibility for their studies, and nothing we propose in any way diminishes this ultimate responsibility. We nonetheless believe that it is risky for a single investigator to control every aspect of a study. Instead, we advocate a central structure that distributes specific research functions among individuals or teams. A distributed approach not only provides substantial protection against malfeasance and fraud, but can also be the most efficient way to structure research with the highest degree of compliance and regulatory oversight. Some support for this approach is provided by Nath et al. who reviewed all retracted MEDLINE papers between 1982 and 2002 and found that papers retracted for fraud were nearly twice as likely to have a single author, and had significantly fewer authors. The perspective for our recommendation are the systems that we have implemented in the Department of Outcomes Research at the Cleveland Clinic and how they integrate with institutional controls. All anesthesia-related clinical research at the Cleveland Clinic is coordinated by the Department of Outcomes Research, 1 of 6 departments in the Anesthesia Institute. Major steps in prospective research include (1) approval by the Anesthesia Institute Research Committee; (2) approval by the Clinic’s IRB; (3) patient screening and consenting; (4) randomization; (5) enrollment and protocol procedures; (6) measurements and outcomes evaluations; (7) data management; (8) statistical analysis; and (9) manuscript preparation. We generally delegate responsibility for these functions to separate teams. Retrospective studies undergo a similar process except that steps 3 to 6 do not apply, and step 7, which includes retrieval of appropriate data, is handled by one of our registry teams. A single person is responsible for all communication with the IRB, including original applications, renewals, amendments, and reports of protocol deviations and adverse events. This coordinator also confirms that every study being done in the department is currently approved. Patient consent is usually obtained by a separate team, with each member specifically trained for each study. Every consent is evaluated by an independent monitoring team that confirms that (1) the approved and current version was used and signed appropriately; (2) a note was inserted into the medical record (to alert clinicians and other investigators); and (3) the patient was entered into the clinic’s clinical trials management database (to alert clinic-level research regulators). We recently switched to a Web-based randomization system, which provides considerable advantages and protections in comparison with sealed envelopes and similar techniques. For example, the Web-based system permits From the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. Accepted for publication March 28, 2012. Funding: Supported by internal funds only. The Department of Outcomes Research is supported by the National Institutes of Health, the Canadian Institutes of Health Sciences, and numerous companies. The authors declare no conflict of interest. Reprints will not be available from the authors. Address correspondence to Daniel I. Sessler, MD, Michael Cudahy Professor and Chair, Department of Outcomes Research, Cleveland Clinic, 9500 Euclid Ave., P77, Cleveland, OH 44195. Address e-mail to DS@OR.org. On the world wide web: www.OR.org. Copyright © 2012 International Anesthesia Research Society DOI: 10.1213/ANE.0b013e3182580cbb