If I had to guess, the rumors that you have heard are based on the question of whether the results of your study are generalizable to the patient population for which FDA is responsible.
This is determined in part by your indications for use and by your inclusion/exclusion criteria. These would be described in your protocol, which would be included in the IND you submitted to FDA. This would give FDA the opportunity to assess whether you are proposing to enroll subjects that will, in fact, be representative of the US patient population.
Generalizability will also be determined by a number of other site-related factors, such as the standard of care followed at the site, and the overall profile of the patients served by the site. (This is an issue in the US as well, where a site located in a central urban area is likely to serve, and therefore enroll, different demographics than a site located in a town in Iowa.) Again, if you submit your sites to FDA, it gives FDA a chance to consider these issues before, rather than after. (But no guarantee that it will actually consider them.)
If your reviewing division is strong on scientific methodology, they will want you to do a pooling analysis. This is a somewhat ham-handed way of assessing these issues after the fact. If the results of the analysis don't support pooling the data across all of your sites, then you may have to delete data from some sites and reanalyze. That's a very exciting experience, in much the same way that volcanic eruptions, forest fires, and tornados are exciting. It will also require rewriting or amending your study report.
How important all of this is to you depends on what is important to your company about the study:
- If your company seriously wants to learn something about the safety and effectiveness of its product, then you need to give all of this serious consideration. And you will need to find someone to help you design your study who understands experimental design and methodology as something more than a number-crunching exercise.
- If your company will be satisfied with data that will be accepted by FDA...maybe, maybe not. The glaring difference between FDA's GCP regulations and its other "good practice" regulations is that its GCP regulations were designed only to assure ethical studies, where its GLP and GMP regulations were designed to assure quality results. An understanding of these issues may be widespread at CDER, or it may be spotty and depend on the level of scientific understanding within the reviewing division or even that of the individual reviewer.
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Julie Omohundro, ex-RAC (US, GS), still an MBA
Principal Consultant
Class Three, LLC
Mebane, North Carolina, USA
919-544-3366 (T)
434-964-1614 (C)
julie@class3devices.com------------------------------
Original Message:
Sent: 10-Jul-2019 12:39
From: Anonymous Member
Subject: Foreign clinical studies
This message was posted by a user wishing to remain anonymous
Hi Michael,
I heard once that there are data analysis implications for studies when some sites are under an IND and others are not. I heard that some sub-analyses of data just from the IND sites may be required, and there may be some complications when it comes to writing the clinical study report. I don't know if there's any truth to this, but are you aware of any potential hiccups or complications down the line when a study is conducted with some sites not being under an IND?
Thanks!
Original Message:
Sent: 08-Jul-2019 07:24
From: Michael Hamrell
Subject: Foreign clinical studies
there is no requirement that sites outside the US need to be under the IND. you can continue to run these sites separately and only put the US sites in the IND.
if the non-US sites are not included in the IND then there is no requirement to collect/submit 1572 for those investigators.
as per the regulations, (314.120) any clinical data from non-US sites not under the IND must comply with GCP, as defined in the regulation. You also need to collect Financial Disclosure forms for ALL investigators, if you intend to include their data in the submission.
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Michael Hamrell, Ph.D., RAC, FRAPS
Huntington Beach CA
United States
Original Message:
Sent: 05-Jul-2019 12:04
From: Anonymous Member
Subject: Foreign clinical studies
This message was posted by a user wishing to remain anonymous
Hello,
We have been running a clinical study in the EU for a year and now plan to open some sites in the US under an IND.
1. Will the studies already being run in the EU now be required to follow IND regulations? If yes, do we have to submit 1572s/CVs from EU investigators and list all non-US vendors in the (Transfer of Regulatory Obligations)?
2. Can only some part of the study be under an IND and the rest non-IND (i.e. EU part of the studies)?
3. What other requirements do we need to comply with?
Thanks,
Anon