A group of us found ourselves asking this very question after a monitoring visit…what is the difference 
between a compassionate use subject and a subject who is enrolled in a study without meeting all the inclusion/exclusion criteria (planned protocol deviation)? In both cases the subject does not meet inclusion/exclusion criteria.
As always, we took it to the Federal Regulations/Guidances to see what they said.
- It is the use of an unapproved device in a single patient or small group.
- It is not considered research; if there is a clinical study using the device, the patient would not meet inclusion criteria.
- The patient’s condition must be serious and there must be no other alternative treatment.
What is a planned protocol deviation?
- A Sponsor provides a memo allowing the site to enroll a subject who does not meet inclusions/exclusion criteria.
- 812.150 (a) (4): Deviations from the investigational plan
- Prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights of the subjects, IRB approval is also required
- 812.35 (a) (1): Changes in the investigational plan requiring prior approval
- A sponsor must obtain IRB approval prior to implementing a change to the investigational plan
What did the FDA say when asked? (gcp.questions@fda.hhs.gov)
The compassionate use provision allows access for patients who do not meet the requirements for inclusion in the clinical investigation but for whom the treating physician and sponsor determine that a patient who is not eligible for the study has a clinical need for the investigational device and should receive the device, they should utilize the Compassionate Use (CU) or Emergency Use (EU) pathways. Subjects treated under CU or EU are generally not considered part of the study cohort and data related to those subjects are reported separately.
So, although in both cases the subject did not meet inclusion/exclusion criteria if the Sponsor wishes to include the subject’s data with the other study data the subject would be enrolled with a planned protocol deviation. Compassionate Use subjects are not part of the research study.
Do you have any experiences with this? We would love to hear them!
