Cracking Down on Research Fraud

The ORI is on the case.

By Jerry Helzner, Senior Editor

The recent revelation that an up-and-coming “star” in the field of ophthalmic stem cell research was caught fabricating data on two National Eye Institute grant applications has put the spotlight on the important work of the Office of Research Integrity (ORI), an arm of the US Department of Health and Human Services.

The researcher, Peter J. Francis, MD, PhD, formerly of the Oregon Health and Sciences University (OHSU), had been considered a rising star in the area of using stem cells to treat some retinal diseases.

Though many practicing ophthalmologists may not be familiar with the role of the ORI, the organization has been given significant enforcement powers to carry out its stated mission of “promoting research integrity” and “responding effectively to allegations of research misconduct.”

In the years prior to the case involving Dr. Francis, the ORI had meted out penalties in other high-profile cases of misconduct in ophthalmic research. Penalties for violators can range from supervision of research activities, as is the case with Dr. Francis, or the much stronger sanction of “debarment,” which prohibits the culprit from conducting any publicly funded research for a specified period of time.

Here, with guidance provided by John Dahlberg, PhD, director of ORI's Division of Investigative Oversight (DIO), I will explain the range of the mandate that has been given to the ORI and how it functions to both prevent and police the use of fabricated, falsified and/or plagiarized data in Public Health Service-supported research — data which, if left unchallenged, could be used in ways that would be detrimental to the health and safety of the public.

The ORI and its Range of Activities

Dr. Dahlberg notes that the ORI “defines research misconduct as fabrication, falsification or plagiarism.” Simply stated, fabrication is viewed as making up data and/or results and reporting them as fact. Falsification is seen as manipulating, changing or omitting data and/or results in ways such that the research is not accurately represented in the research records. Plagiarism is the “appropriation of another person's ideas, processes, results or words without giving appropriate credit.”

The ORI emphasizes that research misconduct does not include “honest errors or differences of opinion.”

To prove that research misconduct has occurred requires that three separate conditions have been met. First, there must be a significant departure from the accepted practice of the relevant research community. Second, the misconduct must be committed “intentionally, knowingly or recklessly.” Finally, the allegation of misconduct must be proven by a preponderance of the evidence.

When these three conditions are met, the ORI can enforce a range of punitive actions — and even the mildest of these penalties can put a stain on any researcher's career. The ORI also has the power to correct or retract published research in order to ensure the integrity of the scientific literature. In addition, the ORI protects the confidentiality of its sources, makes sure that its witnesses are not retaliated against and provides educational guidelines for responsible clinic research.

A Limited Focus

The ORI's mission is strictly limited to ensuring, enforcing and promoting research integrity. Dr. Dahlberg points out that the ORI does not get involved in other important issues related to research, such as misuse of human or animal subjects, financial mismanagement, radiation or biosafety hazards, or conflicts of interest.

The ORI also does not have jurisdiction over several other areas of research that often cause controversy. These include differences in interpretation or judgments of data, authorship or credit disputes, duplicate publication, disputes among collaborators and ownership of intellectual property. The ORI does not involve itself in laboratory management, quality control, employment issues, or general disputes over such things as access to equipment or workspace.

Even in the actual performance of clinical research, the ORI steers clear of adverse event reporting, deviations in protocol, failure to obtain informed consent, breaches of patient confidentiality and failure to obtain Institutional Review Board (IRB) approval for changes to protocol. These activities fall within the jurisdiction of the Office of Human Subjects Protection.

By leaving these research-related areas to other regulatory bodies, the ORI can directly focus on the fabrications, falsifications and instances of plagiarisms that it is mandated to investigate.

What Constitutes Research Misconduct

Behaviors in clinical research that are considered research misconduct and that can be investigated by ORI include activities that make a subject eligible for a trial who otherwise would not be. Thus, misconduct encompasses:

► Substitutions of one subject's record for another's.
► Changing a research record to favor the study's hypothesis.
► Altering eligibility dates and eligibility test results.
► Falsifying dates on patient screening logs.
► Falsifying or forging consent forms.
► Not conducting interviews with subjects and creating records of the interview.
► Making up patient visits and inserting that record into the medical chart.
► Recording the results of follow-up visits with deceased subjects.
► Types of data that have been falsified or fabricated in clinical studies.
► Interviews.
► Entry criteria.
► Screening logs.
► Approval forms.
► Follow-up exams/data.
► Consent forms.
► Test scores.
► Laboratory results.
► Patient data.
► Number of subjects.
► Dates of procedures.
► Protocol.
► Study results.

How the ORI Handles Cases

ORI's legal authority rests in large part with the assurance that every institution has to file with ORI in order to obtain research funds from Public Health Service agencies such as the NIH. An allegation of research misconduct may come from a research colleague, the institution where the research is being conducted, from an outside source or from information developed by the ORI itself. The allegation is then assessed as to its likely credibility.

If the allegation is found to be credible, an inquiry and investigation are pursued by the institution(s) where the questioned research took place. If ORI receives an allegation, it conducts its own assessment and, where appropriate, refers the matter to the institution. The institution's findings are then reviewed by the DIO and a recommendation for disposition of the case is made by the ORI.

This can lead to a settlement with the researcher in question, or failing that, charges may be filed that the researcher can appeal by means of a hearing. If ORI prevails in the hearing, the administrative actions determined by the administrative law judge generally represent the final departmental action, although it is possible for the respondent to appeal to a federal court.

Where Research Goes Wrong

The Division of Investigative Oversight cites several key lapses in the monitoring of clinical research that contribute significantly to allowing misconduct. Better oversight of the following problem areas, could prevent much misconduct:

► Inadequate record keeping and lack of guidance from mentors on how to record and retain research data.
► Failure of mentors to regularly review raw data; over-reliance on derivative data such as PowerPoint presentations at lab meetings.
► Unquestioning acceptance of data that others consider “too good to be true.”
► Lack of transparency within the laboratory and among the staff.
► Labs so large that authority becomes diffuse.
► Principal Investigators spread too thin, and thus do not provide adequate training and guidance to students.

The ORI concludes that “the bottom line is that good mentorship and the constant review of raw data can profoundly reduce the likelihood of a mentee committing research misconduct. OM