Comment from David Strong

It would be helpful to have additional guidance on identification and reporting of certain types of deviation. As mentioned in the guidance, deviations can occur at different levels and for a variety of reasons. It seems, for example that deviations which occur at the “study level” or due to issues that effect multiple sites should be reported by the sponsor and not by individual sites. For example, if there is an omission in the protocol, or conflicting instructions leading to a protocol deviation, individual sites can not write a meaningful corrective action plan or provide insight into why the mistake occurred. This information would need to come from the sponsor level. Currently, this situation is being handled differently by each sponsor, but frequently the reporting is being pushed back onto the sites which can not provide any meaningful input on root causes of the issue or develop an effective action plan for corrective action. As outlined in line 234-239, sponsors should be responsible for a priori identifying which deviations are considered important and must be reported to the IRB. Sites have no meaningful way to identify when a missed data point for one subject might significantly affect the completeness, accuracy, and/or reliability of the study data as a whole. There needs to be a mechanism to evaluate how effectively sponsors are accomplishing the goals outlined in lines 273-298 Regarding lines 355-356, do these deviations need to be reported by sites to the IRB at all? If they fall into this category, it seems the sponsor should be able to evaluate their frequency with regard to the protocol requirements and determine whether mitigation steps need to occur to reduce the frequency or impact of the deviations. Regarding lines 199-201, this point deserves a more nuanced approach. Is it really necessary to report to the IRB if a site needs to schedule a participant visit 1 day out of window because the participant is not available during their visit window?