I also think you need to consider that the "quality" of all IRB's is not the same, nor is the experience of all IRB's equivalent. You could easily have a less experienced, less "risk averse" IRB review early on and get a low risk determination. Then when you add an additional site (potentially months or years into the trial itself depending on timing and recruiting) you could have another IRB that is more experienced or more risk averse (maybe even an IRB that has had a risk determination called into question by FDA previously) send back a SR determination. Now you need to go through the agency for final determination. What happens if the agency decides that SR is the real risk categorization? Now, you have an ongoing trial that has patient subjects enrolled that the FDA has now determined needs an approved IDE for conducting....not a good position in my opinion.
While it is not necessarily intuitive that you would WANT the agency to actually determine risk class pre-submission, it certainly seems like anything that could be at the border of minimal versus significant (or at the border of no IDE and IDE required) would be best to discuss with the agency. This becomes especially true in my opinion when there is no cost, the timelines are relatively short (even assuming the 120 day long period that David noted) and the fact that FDA has made a determination is dispositive of the issue so all of your IRB's should review under the same level of risk categorization which leads to significant potential efficiencies, and there is no reason in my mind not to use this option.
And while it is not to say the FDA can't change its mind once they give you a determination, especially if it is changing its mind based on data from the trial(s), it is far less likely that FDA will change their minds than it is that you will get a different classification of risk from any one of multiple IRB's reviewing the conduct of your trial.
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Victor Mencarelli
Sr. Manager - Regulatory Affairs
United States
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Original Message:
Sent: 12-14-2014 12:20
From: Melissa Walker
Subject: Study Risk Determination Requests
Julie,
Besides the circumstance that David has noted, there is also an occasion when the Sponsor is not confident that every IRB (multiple sites) will reach the same NSR conclusion. If one IRB disagrees with an NSR designation, the decision will go to FDA. This is especially awkward if the study is already ongoing at two sites as NSR, but the IRB at a third site decides the study is SR.
By using this type of pre-sub meeting, Sponsor avoids the uncertainty by getting FDA's opinion up front. Of course, the FDA may decide the study is SR, too. In which case, the Sponsor proceeds with an IDE.
Melissa
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Melissa Walker RAC
President & CTO
Graematter, Inc.
Saint Louis MO
United States
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Original Message:
Sent: 12-14-2014 01:47
From: Julie Omohundro
Subject: Study Risk Determination Requests
Melissa and David,
I have been curious about this pre-sub option. The guidance says that "FDA is available to help the sponsor, clinical investigator, and IRB in making the risk determination." I can't think of any reason a sponsor would want to refer this question to FDA instead of to an IRB. Are there circumstances that I haven't encountered, where this option is useful? I feel like I'm missing something here...
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Julie Omohundro RAC
Durham NC
United States
Original Message:
Sent: 12-13-2014 16:25
From: Melissa Walker
Subject: Study Risk Determination Requests
Has anyone had direct experience with making a Study Risk Determination Request under the CDRH Pre-Submission Feedback Program? There is no specific time frame for response listed in the guidance, so I am particularly interested to know long the process is actually taking.
Thanks in advance for the help!
Cheers,
Melissa
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Melissa Walker RAC
President & CTO
Graematter, Inc.
Saint Louis MO
United States
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