I think to add to the discussion of significant risk (SR) versus non-significant risk (NSR) it is useful to read about the considerations that the FDA suggests to the IRB for SR and NSR determination. I got the below information from a guideline from the FDA. Below are the three main considerations listed in the document.

1. Risk determination is based on the intended and proposed use of the device and not the device itself.

Ex. Daily wear contact lenses that are worn regularly are considered NSR by the FDA. A study for extended wear contacts that are worn overnight is considered SR. This change in intended usage results in a “potential for injuries not normally seen with daily wear lenses”.

2. SR studies are necessary for any device in which the intended usage can “present a potential for serious risk to the health, safety, or welfare of a subject”.

Ex. Pacemakers are necessary to sustain human life. Therefore any changes to a pacemaker that is already commercially available, whether it be “new leads, batter pack, or software”, is SR.

3. If an additional procedure is needed as a part of the investigational study such as a surgical procedure, the potential harm of the procedure must also be considered.

Ex. “An investigatonal stud of a sensor pad that can detect the electrical activity of the spinal cord may be NSR if the following are true: it is done at the “same time as an already planned surgical repair of the spinal cord”, the sensor does not “present a potential for serious risk to the health, safety, or welfare of a subject”
, “the sensor pad is not implanted”, and “the pad is not of substantial importance in diagnosing, curing, mitigating or treating disease”.

Overall, I found the consideration process for determining SR versus NSR helped clarify to me some set guidelines between the two and I thought it would contribute to the overall understanding in this forum. However, in the sensor example it stood out to me that the pad is SR if it is “of substantial importance in diagnosing, curing, mitigating or treating disease”. Upon further thought, it is apparent that it is risky to do a study to prove something can treat a disease because people rely on that to treat them then.

However, this made me wonder what the difference between a SR and NSR study is and what additional considerations must be taken into account in a SR study. Does anyone know anything about this?

Resource: https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf