Weigh risks/benefits under component analysis model
SACHRP recommends its use in pediatric studies
IRB members and researchers are beginning to hear more about a new model for weighing risks and benefits in human subjects research. Called component analysis, it requires IRBs to weigh individual procedure risks and benefits against themselves.
"Component analysis is an idea that has been worked on and forming since the early 1990s," says Charles Weijer, MD, PhD, an associate professor, philosophy and medicine and the Canada research chair in bioethics at the University of Western Ontario in London, Ontario, Canada. Weijer has promoted component analysis and spoke on the topic 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.
"My colleagues and I have been doing a lot of work on this concept," Weijer says. "The aim of component analysis is provide a procedure for deciding when it's acceptable and when it's not acceptable to expose human subjects to risk for scientific ends."
Typically, IRB members engage in collective analysis when they weigh the risks and benefits of a study.
"Collective analysis allows you to look at all the risks in total for the study and all the benefits in total, and if the potential risks are at least balanced by some of the potential benefits, then you can say the risk-benefit relationship of the research is acceptable," explains Ernest Prentice, PhD, an associate vice chancellor for academic affairs and the chair of the Secretary's Advisory Committee on Human Research Protections (SACHRP) for the U.S. Department of Health and Human Services. Prentice also spoke at the PRIM&R conference about component analysis.
With component analysis, it's not the overall risks and benefits that are weighed, it's the individual risks and benefits. In other words, each procedure or intervention included in a trial protocol is weighed for its own risks and benefits.
SACHRP has recommended that component analysis be used in pediatric research so that different procedures in a single trial maybe approved or disapproved under different subpart D categories, Prentice says.
One of the reasons why IRBs increasingly are using component analysis is because it provides a clear ethical model for thinking through risks and benefits, Weijer says.
"IRBs struggle with how to think through whether there are acceptable benefits or harms in studies, and a major challenge in IRBs has been achieving consistency in reviews across IRBs," Weijer says. "It's hard to see how it can be consistent in a structured approach, and component analysis provides just such a structure, so it has been fairly widely accepted."
Prentice offers this example of how component analysis would work in the review of a protocol for studying two different drugs in a pediatric population:
- First, IRB members would break down the trial's procedures into separate units. One unit would be the administration of either drug A or drug B to diabetic children, ages four through 12 years.
- The IRB discussion might entail reviewing the prospective benefits of these drugs for the ill children, versus the risks of side effects and discomfort. IRB members likely would find that the potential risks balance with the potential benefits with regard to the drugs.
- Next the IRB would look closely at the protocol's add-on procedure of pharmacokinetic (PK) testing, which would require an indwelling, intravenous (IV) catheter, serial blood sampling, and an overnight hospitalization of the child.
- The risks of the PK testing might appear greater than minimal because of the hospitalization and the IV catheter. There would be no potential of direct benefit to the children because the procedure was added to the protocol purely to gain additional scientific knowledge about this population of patients.
Under component analysis, the risks of the PK testing must be balanced by the potential benefits of the same procedure.
"It's very clear that we would say that the risks of the testing are greater than minimal, and there is no direct subject benefit," Prentice says. "So the PK component of the research cannot be approved under the 45 CFR 46 category."
The PK component could be considered under the more stringent category of 46.406 in which the IRB has to find that the risk represents a minor increase over minimal risk and that the procedure represents experiences to the subjects that are reasonably commensurate with experiences expected in medical, dental, psychosocial, etc. interventions, Prentice explains.
"Is sticking a kid with a needle and indwelling intravenous catheter and taking blood samples and hospitalizing overnight really commensurate with the experiences of a child from ages four to 12?" he says. "Some IRBs will say kids get shot, get blood taken, and end up in the hospital, so some would say 'Yes,' and some would say, 'No.'"
The PK intervention is likely to yield general knowledge about the subject's disorder or condition, which is of vital importance to the understanding of the condition Prentice notes.
So a key point in analyzing this scenario under component analysis is that the children have a medical problem, Prentice says.
"A totally normal, healthy child involved in this protocol would not qualify because you could not meet the condition of their having a disorder or condition under the regulations," Prentice says.
The IRB could not approve the PK procedure under 45 CFR 46.405 because the potential benefits don't offset the potential risks, he says.
However, under 46.406, the IRB might find that the PK procedure's risks represent only a minor increase over minimal risk, and the pediatric participants are sick, and so if assent and informed consent are adequately obtained, it could be approved, he says.
"I personally think that when using component analysis in this example the study could be approved under 46.406," Prentice says. "One would then have to judge whether or not whatever data they get from the PK testing is of significant importance, and how important it is to do this test on children."
IRB members and researchers are beginning to hear more about a new model for weighing risks and benefits in human subjects research. Called component analysis, it requires IRBs to weigh individual procedure risks and benefits against themselves.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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