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Findings and Consequences of Research Misconduct
DEFINING RESEARCH MISCONDUCT
Any institution that applies for or receives Public Health Services (PHS) support for biomedical or behavioral research, research training or activities related to that research or research training are subject to ORI’s guidelines defining and enforcing research misconduct. Activities applicable to ORI guidelines include:
- “Grant applications or proposals;
- Research training or activities related to that research or research training and training programs;
- Activities related to research or research training, such as the operation of tissue and data banks or the dissemination of research information;
- Plagiarism of research records produced in the course of PHS supported research, research training or activities related to that research or research training.” (DHHS
ORI defines “research misconduct” as: “…fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.
- Fabrication is making up data or results and recording or reporting them.
- Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record.
- Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit.
- Research misconduct does not include differences of opinion.”
“To be considered research misconduct, actions must:
- represent a “significant departure from accepted practices”;
- have been “committed intentionally, or knowingly, or recklessly”; and
- be ‘proven by a preponderance of evidence.’”
CONSEQUENCES OF MISCONDUCT
Findings of research misconduct may result in debarment or a voluntary exclusion agreement. In 2005 ORI received 265 allegations of research misconduct; only eight resulted in either a Voluntary Exclusion Agreement or debarment (Weiss). Individuals and institutions may be disbarred or excluded. Debarred individuals or institutions may not participate in any research and supervisory roles involving Federal procurement or non-procurement transactions; debarments are government wide. Debarments are the result of an ORI investigation where ORI determines that there is reasonable evidence to
conclude that research misconduct has occurred. Voluntary Exclusion Agreements are often the result of an agreement between ORI and the alleged individual or institution in lieu of a full investigation; they are, metaphorically speaking, a plea of “No Contest”. Excluded individuals or institutions may also be prohibited from participating in research involving Federal procurement and non-procurement transactions; however, sometimes individuals or institutions may only be prohibited from participating in advisory roles. Individuals and institutions who are debarred or enter into voluntary exclusion agreements are placed on ORI’s public list PHS Administrative Action Bulletin Board for a period of three years. The FDA maintains a separate list of debarment or other administrative actions.
In two complete years of data available on the ORI website for Public Health Services (2006 – 2007),^1 ORI during its oversight review for the U.S. Public Health Services found reasonable evidence to warrant administrative action regarding research misconduct in twenty-four cases. Twenty-one of the twenty-four closed investigations involved data falsification and/or fabrication. One of those twenty-one cases involved the use of images as data. In that case, the investigator, a doctoral student, darkened with a marking device multiple sections of the image including the original autoradiographical film. One of the twenty-four cases involved data destruction and falsification of records to hide the data destruction. One other case involved mail fraud, criminally negligent homicide, and making false statements. In years 2006 and 2007, fifteen of the twenty- four closed investigations involved some kind of student—doctoral students, graduate students, postdoctoral students, medical residents, and even one undergraduate student. Nine of the twenty-four closed investigations involved researchers in other categories.
Consequences for research misconduct depend upon the severity of the misconduct. In the aforementioned years, fifteen closed investigations resulted in a Voluntary Exclusion Agreement and eight in debarment. One individual was excluded for two years, three individuals were excluded for five years, and two individuals were excluded permanently/lifetime; the remaining nine were excluded for three years. Eight individuals were debarred ranging from three to five years. The most severe of those, the criminally negligent homicide, entailed a seventy-one month imprisonment, payment of restitution of over $690,000, and a lifetime government-wide debarment from “participating in any and all Federal agency transactions to protect the public interest overall”. At minimum four—three students and one professor—of the twenty-four closed investigations required the retraction of a published manuscript even if it involved multiple co-authors; one required that data be corrected in the published manuscript.
Individuals who are excluded may sometimes continue to participate in federally funded research. In those cases the individual may not be a PI and the PI or other supervisory authority must submit to ORI a Supervisory Plan designed to ensure the scientific integrity of research conducted by the excluded individual before that individual can participate in the research.
(^1) Detailed data for 2005 is no longer available as of January 2008.
The UAB BioCryst BCX-34 case involved image manipulation in addition to multiple other instances of research misconduct. Peugeot in early study trials traced lesions very loosely making them appear larger than the very tight tracings she performed in later trials, a clear instance of image processing which, in the continuum between best practices and misconduct, falls on the side of misconduct. When numerical data related to lesion size was found to be missing from a patient’s chart, and Peugeot was asked about the data, she wrote in a number claiming to have remembered it from an examination performed over a week earlier. This was judged to be an instance of data fabrication. Furthermore, Peugeot and Sams often disagreed, in front of patients, over the size and redness of lesions. It was Peugeot’s assessments that were recorded on patient charts and not Sams’s assessments, a biochemist and M.D. and the study leader.
Dr. William Cook, hired by UAB to be Snyder’s boss, requested examination of the randomization schedule (the “code key” identifying control and experimental patients) after BioCryst made public announcements regarding BCX-34’s positive efficacy in the early trials for FDA approval. Cook wanted to begin writing the scientific paper. He found that the data results did not match the information supplied to the FDA and NASDAQ. Cook then asked a study coordinator, a subordinate of Snyder, for the printed copy locked in a cabinet. Again the data results neither matched the public data nor the data results from the randomization charts supplied by Snyder. Snyder created a false randomization chart, a clear instance of data falsification as defined by ORI.
The FDA barred Sams for life from testing drugs due to his failure to properly supervise the studies. Peugeot and Snyder were found guilty in criminal court of conspiracy, mail fraud, and making false statements to the FDA.
Subsequent studies not performed by Sams, Peugeot, Snyder, or Bennett revealed that BCX-34 performed at least equally as well as the placebo in 30% of cases and the placebo outperformed BCX-34 in reducing lesions in 70% of cases.
Where did the reasoning go wrong?
The UAB BCX-34 case involves clear examples of data fabrication, falsification, and misrepresentation. Peugeot fabricated data by writing data onto patient charts not based upon clinical examinations. Snyder falsified data by creating alternate randomization schedules. Peugeot misrepresented data, if not falsified and fabricated data, by subjectively drawing lesions to give the impression of positive treatment outcomes.
We may ask two different questions: Why are these actions scientifically wrong? Why are these actions morally wrong? Here we are concerned with the latter question. T-cell lymphoma has no known cure. The BioCryst executives were claiming, based upon falsified data, that BCX-34 provided a potential cure for T-cell lymphoma, a deadly form of cancer. If the falsified data had not been discovered by Cook, BCX-34 may have been on the path towards FDA approval. The health of patients utilizing BCX-34 would have been highly compromised; patients may have forgone other treatments with positive
effects for BCX-34 with no positive effects. As medical professionals Peugeot, Snyder, and others violated their Hippocratic Oath of “do no harm”—their data falsification, fabrication, and misrepresentation entailed a potential for malfeasance. In presumed marketing of BCX-34, if awarded FDA approval, BioCryst would have violated the principle of truthfulness. Once exposed, the misrepresentation of BCX-34’s efficacy would have undermined public confidence in medical testing, health professionals, researchers (some of whom, like Sams, perform dual functions as educators), and the broader scientific community whom the public views as impartial seekers of the truth. Medical professionals and researchers are stewards of public health.
Korea: Hwang Woo-suk’s Cloning and Stem Cell Research
One of the best known cases of research misconduct occurred in 2005; Hwang Woo- suk’s fabricated and falsified data involving the cloning of eleven stem cell lines from 11 patients:
- Digital photographs of two stem cells had been manipulated to make it seem as though they were 11 stem cells from 11 patients cloned.^2
- DNA comparison tests were misrepresented as comparing DNA from the donor and a cloned stem cell when they really compared DNA from the donor and an embryo from the donor.
- There were also problems with the human subjects practices: not describing the consent process consent forms of collaborators in the US were approved by the IRB but not signed participants suffered side effects not listed in the consent form graduate students enrolled as participants describing methods other than those used colleagues were coerced to donate oocytes and without IRB or equivalent approval
According to Donald Kennedy, editor-in-chief of Science as a consequence of this case journals now more closely scrutinize “high risk” papers—research that is of significant public interest, has unexpected or counterintuitive results.
Where did the reasoning go wrong?
In interviews, Dr. Woo-suk stated he firmly believed in the validity of the methods described in the research papers that were not methods actually employed and that one day the fabricated research would be validated by others in the field. His blind faith in the
(^2) Refer to Wade article in the New York Times to see the images and the process used.
Office of Research Integrity, Handling Misconduct - Case Summaries: http://ori.dhhs.gov/misconduct/cases/. Last viewed January 31, 2008.
Office of Science and Technology Policy. 2000. “Federal Policy on Research Misconduct: Preamble for Research Misconduct Policy” Federal Register ; 65(235): 76260-76264. http://frwebgate.access.gpo.gov/cgi- bin/getdoc.cgi?dbname=2000_register&docid=fr06de00-72. Last viewed May 28, 2008.
Turner, E. H., et. al. 2008. “Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy”. New England Journal of Medicine ; 358(3): 252
Wade, N. 2005. “Clone Scientist Relied on Peers and Korean Pride.” New York Times ; Dec. 25. http://www.nytimes.com/2005/12/25/science/25clone.html. Last viewed May 28, 2008.
Weis, R. 2006. “Deception by Researchers Relatively Rare: But the Few Scientists Who Falsify Data Are Difficult to Police, Experts Say.” Washington Post ; Jan. 15: A19. http://www.washingtonpost.com/wp- dyn/content/article/2006/01/14/AR2006011400935.html. Last viewed May 28,
