Risk-benefit assessment: One size doesn’t fit all
IRB’s review worksheet is useful tool
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Assessing risks and benefits is an evolving process in the human research protection world — especially for IRBs that handle social-behavioral, as well as biomedical, studies. One size in risk-benefit assessment definitely does not fit all. For instance, IRBs sometimes over-emphasize risks in studies involving social-behavioral topics without considering protections that researchers have put in place, IRB experts say.
At Baruch College in New York City, the IRBs previously would send automatically any study involving sexual content or deception to the full board, notes Keisha Peterson, coordinator of the Baruch College human research protection program office. Baruch College is part of the City University of New York (CUNY) organization.
"In the past four to five years, the mindset has changed regarding these risks in research," Peterson says.
Now, the IRB office assesses whether identifiers are collected and whether researchers have communicated clearly that answering any of these types of sensitive questions is entirely voluntary, she explains.
"If investigators are providing an [opt-out] to subjects and are decreasing and minimizing the risk, protecting data, and making sure subjects are fully informed of the research purposes, then the risk level is lowered," Peterson adds.
IRBs have moved further away from the locked cabinet mentality of previous generations. The way they envision confidentiality risk now involves encryption software, more complex questions about how confidentiality and privacy are protected, and how electronic systems are protected from breaches, says Jean Larson, MBA, human research protection program education and community outreach manager at Yale University in New Haven, CT.
The key question from an IRB standpoint is: "Are the risks to subjects minimized?" As IRBs adjust their risks and benefits assessments, they should start with the elements of informed consent and then broaden their consideration of what might be achieved, Larson suggests.
For instance, studies might have variable risks depending on which population is enrolled in a study, she notes.
"A good example would be split findings for children’s studies, where the risk to one group may be different from the risk to another group," Larson explains. "You might have a protocol where there is one group of children with a condition and one group without the condition, so the children’s risk findings would be different from one group to another."
In the biomedical field, some researchers are questioning conventional wisdom about risks and benefits involving some vulnerable populations. For example, one researcher asks how IRBs might arrive at a decision about risks and benefits involving pregnant women, as technology and cutting-edge research provide opportunities for greater benefits to fetuses or the women.
"We have recognized that research potentially beneficial to pregnant women has not been carried out because of concern about injuring the fetus. There now seems to be increased interest in testing medications during pregnancy to benefit either the pregnant woman or fetus," says Carson Strong, PhD, a retired professor of bioethics in the department of internal medicine at the University of Tennessee Health Science Center in Memphis. Strong also is an IRB member at the university.
"This increases the importance of having discussions about how to balance risks and benefits between the pregnant woman and fetus, given that the federal regulations leave a number of questions in this area unanswered," Strong says.
"In my view, IRBs generally do a good job of protecting vulnerable subjects," Strong says. "However, there are exceptions, which can occur in situations in which the assessment of risks is controversial or the regulations do not provide sufficient guidance."
The Yale University HRPP’s protocol review worksheet includes questions that help the IRB assess whether risks are minimized adequately. Larson developed the worksheet in consultation with the IRB chairs and IRB manager. They created it to provide IRB members with a handy tool to use when conducting a protocol review, she explains.
"We also included it with the protocol minutes, further supporting the fact that the committee has looked at these issues," Larson says. "We were looking for a way to support our members in their approach to reading a protocol or thinking about the review criteria or informed consent criteria as it applies to the individual study they were looking at."
The protocol review worksheet is completed before the IRB discussion of a study. The reviewer who used the worksheet can use it as a guide during his or her oral presentation, Larson says. (See story about Yale reviewer worksheet, page 99.)
IRBs primarily are concerned that studies’ risks and benefits are clearly stated to participants in the consent form, and sometimes there are issues with investigators not clearly stating their risks and benefits, or with consent forms and IRB review applications not matching, Peterson says.
But there often are other issues involving risks and benefits. For instance, IRBs in the CUNY system often assessed risks based on their individual campus’ culture, Peterson says.
When CUNY reorganized in 2011, the multi-campus institution eliminated local IRBs and moved to a centralized IRB structure. Instead of having 19 IRBs, the institution has four full boards. This has affected how risks and benefits are handled, Peterson says.
"We used to assess risks based on campus culture," she adds.
Since moving to a centralized IRB system, CUNY increasingly has used non-research and exempt determinations, which previously were rarely used, Peterson says.
"When we had 19 IRBs, every IRB was run differently; everyone had their own rules," she explains.
The centralized review system ensures quality and that every review is conducted according to the institution’s policies and procedures, she adds.
As a result, the number of studies taken to the full board because of their perceived risks has declined by an estimated 75%, Peterson says.
Instead of sending all studies with sexual content or deception automatically to the board, the HRPP office conducts pre-reviews to determine whether a study qualifies for a review exemption or whether the study can be expedited, Peterson says.
"We have a separate board solely tasked with expedited protocols," she says.
Studies with risks that are not mitigated still might be sent to the full board, but these full board reviews are much rarer than they were before the centralized IRB process was created, she adds.
"Now, more attention is paid to the federal definition of research; does the study meet that definition? Does the project meet exemption criteria?" Peterson says.
This change has resulted in a more streamlined and fair review process that gives researchers more options than they had previously, she says.
"I’ve seen a shift where people are starting to trust the IRB more, and more research is being done," she adds.
Strong has called for new federal guidelines for handling risks and benefits in studies involving pregnant women to clarify risk and benefit assessment.
"There have been minor modifications in the regulatory guidance for research involving pregnant women and fetuses, but there still is a need for specific guidance in a number of areas," Strong says. "There have been risk-benefit discussions in the literature, mostly focusing on how to interpret the regulatory concept of minimal risk. We need more discussion concerning how to understand minimal risk in research involving pregnant women and fetuses."