Evaluate conflicts of interest both among investigators and IRB members

More public scrutiny is paid to issue

Media attention on research conflicts of interest has made it imperative that IRBs be aware of a wider variety of potential conflicts of interest than what they may have considered in the past, experts say.

Recently, a study published in the New England Journal of Medicine (NEJM) highlighted issues with IRB members having relationships with pharmaceutical companies, notes Heather Fields, JD, a shareholder in the health care department of Reinhart Boerner Van Deuren in Milwaukee. Fields spoke about conflict of interest issues at the 2006 annual Human Research Protection Program Conference of the Public Responsibility in Medicine & Research (PRIM&R), held Nov. 15-18, 2006, in Washington, DC.

One of the challenges IRBs face in managing conflicts is that often IRB members also serve as researchers or have other ties to the research industry.

It would be difficult for many IRBs to make quorum if they were required to find only IRB members who lacked all ties to the research industry, says Elizabeth Bankert, MA, assistant provost, Dartmouth College in Hanover, NH. Bankert also spoke at the PRIM&R conference about conflicts of interest.

Fields and Bankert discuss various aspects of conflicts of interest relevant to an IRB with these examples:

Conflicts of interest among IRB members: Often the individuals most qualified to serve as IRB members are researchers, and they are typically obligated to disclose only those conflicts of interest pertaining to protocols with which they are directly involved, Fields says.

"There is a lack of federal guidance for addressing and managing IRB conflicts of interest," Fields says. "There are guidelines and standards for investigators and the National Institutes of Health guidelines, but very little specific to IRB members."

When asked to disclose their conflicts of interest, IRB members think about the type of conflicts that would impact their ability to be impartial when reviewing a certain protocol, and often do not think about other industry financial ties that may create a conflict, she adds.

The recent study in NEJM found that 36 percent of IRB members had one or more relationships with industry within the past year.1

Of the nearly 900 IRB members surveyed from 100 academic institutions, 85.5 percent said they never thought that these types of relationships with industry affected an IRB member's protocol review decisions inappropriately.1

About 15 percent of those surveyed said they had reviewed a protocol within the past year that was sponsored by a company with which they had a relationship or with that company's competitor, and close to 60 percent of these IRB members said they always disclosed this relationship to an IRB official.1

Of the IRB members who disclosed the potential conflict, nearly 65 percent said they never voted on the protocol.1

The study concluded that relationships between IRB members and industry are common.1

Conflicts of interest among investigators: Most academic and research institutions do not require investigators to report conflicts of interest more than annually, and this annual reporting process may not be linked to the conflict reporting process that occurs at the time information is submitted for a grant or a protocol is submitted for IRB review, Fields notes.

"Many institutions have a separate conflict of interest committee to evaluate conflict disclosures provided in connection with an IRB submission," she says. "But, no universal standard exists with respect to disclosure thresholds, and institutions are increasingly aware that the federal disclosure requirements may create an inadequate reporting threshold to safeguard subjects and preserve the integrity of the IRB review process."

Larger organizations typically have some kind of organized process for medical staff members to report annually their financial interests. When the investigator submits a protocol to the IRB, he or she checks on the box for financial interests, and the conflict of interest committee reviews the conflicts of interest to decide whether the interest needs to be managed, Fields explains.

"Then the conflict of interest committee forms a management plan which is communicated to the IRB," she says. "It is typically the responsibility of the IRB to determine what language should go in the informed consent form regarding an investigators' relationship with the sponsor of the study."

The drawback to most policies is that they only require disclosure of financial conflicts of interest, Fields notes.

"Most institutions don't have a process to identify and track non-financial conflicts of interest, such as promotions and tenure dependent on a person having x number of papers to publish or family relationships, like having a husband on the head of a company's board," Fields says.

The Association of American Medical Colleges has published guidelines suggesting that the informed consent form have some disclosure on it when the principal investigator has significant financial conflicts of interest, she adds.

A study of academic medical centers and their financial conflicts of interest policies found that 58 percent included verbatim language regarding conflicts of interest to be included in informed consent documents.2

The same study found three chief goals for disclosure of conflicts of interest, which are as follows:

1. Providing research participants information: This goal is to give people sufficient disclosure to allow them to make an informed decision about participating in a trial.2

2. Meet regulatory/legal requirements: Regulations do not require informed consent documents to disclose financial conflicts of interest, but there is precedent for investigators and institutions being sued when there is insufficient disclosure.2

3. Deter significant conflicts of interest: Having a conflicts of interest policy requiring disclosure to research participants might discourage investigators from having conflicting interests.2

Another recent study found that research participants want to know about financial interests, but they do not always view them unfavorably.3

Some research participants said they felt a great financial interest would make the investigator do a better and more ethical job.3

How IRBs can assess conflicts of interest: "IRB members are so conscientious they sometimes won't vote on a protocol if they're unsure about their own conflict of interest," Bankert says.

"They might say, 'My son works for the company that provides the analysis of the x-rays for the study,' and I tell them, 'That is not a conflict,'" Bankert says.

Part of the problem is the ambiguity in federal regulations. For example, the FDA form that is completed when an investigational new drug is submitted for IRB review asks the investigator to list all of the people who might be part of the treatment team, Bankert explains.

"This could involve the whole oncology department if you're a small place," she says.

If all of the people listed were to recuse themselves from voting, there might be no oncology experts left on the IRB to review the protocol, Bankert adds. "So you can't recuse everyone who is listed on the 1572 form," she says.

It's a challenge for institutions to come up with a conflict of interest standard that works for all cases, Fields says.

"There's no one-size-fits-all," Fields notes.

When Fields visits research sites, she asks about additional conflicts of interest, including non-financial conflicts, such as family relationships, in order to see how sensitive an IRB is to the issue.

"I look to see if they have procedures in place to address various types of conflicts," Fields explains. "And if they do, I look to see if they follow their standards."

For example, at Dartmouth College the process is to remind IRB members at the beginning of the meeting: "Please recuse yourself if you have a potential conflict and leave the room when we vote," Bankert says. "We have been working on guidance and have made some recent progress."

One of the goals is to come up with a standard that doesn't require IRB members to complete a disclosure form every time they meet, but to have clear guidance in place to remind members of the obligation to disclose potential conflicts of interest," Bankert says.

"It's something we're all thinking about right now," she says.

The lack of regulatory guidance on this issue means that each IRB and institution will have to find its own balance.

"You need people with the expertise and knowledge in the room to make decisions about studies, but at the same time you want a process that minimizes the potential for inappropriate bias," Fields says.

References

  1. Campbell EG, et al. Financial relationships between institutional review board members and industry. N Engl J Med. 2006:355:2321-2329.
  2. Weinfurt KP, et al. Policies of academic medical centers for disclosing financial conflicts of interest to potential research participants. Acad Med. 2006:81(2):113-118.
  3. Weinfurt KP, et al. Views of potential research participants on financial conflicts of interest. J Gen Intern Med. 2006;21:901-906.