The IRB evaluation should consider all the risks the interventions pose, including physical, psychological, social, and economic risks. Are risks to subjects necessary and minimized? But minimizing risks can undermine social value and raise concerns of fairness.

Are risks justified by benefit to individual subjects and/or the importance of the knowledge to society? To evaluate the risks of research, it is important to have reliable information on existing care for the participants.

A trial may be risky in some places and potentially beneficial in others. Are benefits enhanced?

Risk and benefit judgments rely on comparison to some baseline. For example, does a phase II study of a treatment that has been shown safe and offers a small chance of helping subjects qualify as prospect of benefit? Most commentators argue that IRBs should consider only the clinical or 'direct' benefits of research, not any indirect, inclusion, or financial benefits.