Data used in clinical studies of treatments for traumatic brain injury were falsified by a prominent researcher, according to the Office of Research Integrity.1 Such widely publicized research scandals raise ethical concerns indicating the general public will lose trust in research or be less likely to participate in a clinical trial.
“That’s one reason why it is so important to promote research integrity in clinical trials,” says David B. Resnik, JD, PhD, a bioethicist at the National Institutes of Health.
There is not much IRBs can do to spot misconduct or fraud in clinical trials. IRBs do not typically review data. “However, IRBs should promote compliance with legal and ethical requirements, and deal with suspected noncompliance in a fair, reasonable, and timely fashion,” Resnik asserts.
Resnik recommends IRBs make it easy for researchers and others to report noncompliance, including suspected fraud. For example, IRBs could establish a hotline that allows for anonymous reporting in case people are afraid of retaliation.
Resnik offers this hypothetical case: A data manager for a clinical trial reports suspected fabrication to the IRB chair, based on irregularities found in the information collected so far. The IRB chair is required to immediately contact the institution’s research integrity officer, who, in turn, informs the lead investigator of the allegation. At that point, a research misconduct inquiry may be initiated.
“The IRB chair should also contact the investigator to inform them of the allegation and take appropriate steps to protect research subjects from harm, if necessary, depending on the situation,” Resnik says.
IRBs and study investigators might conclude it is necessary to suspend the study, initiate an audit of the clinical trial, or both.
Most clinical trials undergo continuing review annually. Implausible trends are a red flag for IRBs. For instance, it is suspicious if there are no protocol deviations or adverse events for a large study where at least some of those issues would be expected.
Unusually fast recruitment is another red flag. IRBs also should look for research interim findings that are difficult to believe, according to Resnik. For example, scrutiny probably is warranted if an investigational drug is found to be 10 times more effective than standard therapies or a placebo.
If anyone notes these red flags, the IRB and research integrity officer must coordinate their efforts. This ensures all potential noncompliance is investigated and addressed. “Confidentiality would need to be protected. But this can be difficult,” Resnik admits.
For example, an institution cannot guarantee anonymity if a complainant is asked to testify in a misconduct inquiry or investigation.
If an investigation reveals egregious research misconduct, trust in research in general takes a hit. “Public trust is a big worry. Those kinds of stories do stay with people; it is really a big part of the damage that results from these cases,” says Monika S. Markowitz, PhD, executive director of research integrity and ethics and research integrity officer at Virginia Commonwealth University.
Egregious cases of research fraud make headlines, but there is not much coverage of the aftermath. Thus, people do not realize the often-monumental efforts the institution and the scientific community are taking. The goal is to correct the scientific record and prevent the fraudulent research from affecting the development of future studies. “Addressing misconduct from start to finish can take a while, which is frustrating for many,” Markowitz says. “But the goal is to clean up the scientific literature.”
The general public may wrongly assume the misconduct put human participants at risk. However, many of the highly publicized misconduct cases are in the preclinical realm, involving basic science or animal research.
“There are certainly exceptions. But many misconduct cases don’t necessarily involve human research participants being in direct risk,” Markowitz notes.
The misconduct still could affect human participants in other studies. “Research builds on other research,” Markowitz explains.
Therapeutically based human subjects research has to provide evidence indicating the intervention has been investigated in a preclinical setting. “Basic science and preclinical research build until it’s at a point where introduction into human research is a possibility,” Markowitz says. “That’s really where it could become quite dangerous if it were fraudulent.”
For research staff who are recruiting for clinical trials, it is challenging to reassure wary people. Education is one way to do that. “It is important for the public to understand that these concerns are taken very seriously,” Markowitz says.
For instance, study participants might want to know IRBs review study protocols using strict criteria. IRBs must ensure the investigators’ research questions can be answered, based on the study design. “That kind of assurance is something that could be offered to people during recruitment, if they have concerns about participation,” Markowitz offers.
Participants also can be informed on how the intervention has been tested before their enrollment (i.e., whether with human participants, or only with animals). “This kind of information is generally in the informed consent form. But really emphasizing it so that participants understand how they fit into the research could be quite meaningful,” Markowitz says.
Giving people enough time to think about participation also is important. Research staff should make it clear that it is OK to ask questions — not just at the initial point of contact, but even days later. “We are really just talking about making sure there is good communication between the research team and the prospective participant,” Markowitz says.
Explaining up front what is expected from the participant, and what the participant can expect from the research team, is essential. On the IRB side, researchers can expect scrutiny on these points. Informed consent documents should specify who study participants can call. It is not enough just to list contact information; a member of the research team must be available and respond.
“Sometimes, IRB members themselves will call the number listed on the informed consent document to make sure that someone responds who is acquainted with the study or can appropriately refer the question or concern,” Markowitz warns.
REFERENCE
1. [No authors listed]. Findings of research misconduct. Fed Regist 2023;88:43363-43364.
There is not much IRBs can do to spot misconduct or fraud in clinical trials. IRBs do not typically review data. However, IRBs should promote compliance with legal and ethical requirements, and deal with suspected noncompliance in a fair, reasonable, and timely fashion.
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