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  • 1.  Protocol Amendment vs. New Protocol

    This message was posted by a user wishing to remain anonymous
    Posted 22-May-2017 12:21
    This message was posted by a user wishing to remain anonymous

    Dear Community-

    I am new with providing regulatory support to clinical.  We currently have a study in process, and we need to modify the protocol (significant changes).  Would it be best to amend the current protocol or create a new protocol – what factors should I consider while offering guidance to my clinical colleagues?

     Any insight or advice is greatly appreciated.  Thank you for your help.



  • 2.  RE: Protocol Amendment vs. New Protocol

    Posted 22-May-2017 15:54

    (I posted one before anonymously but for some reason the post did not appear on the discussion board. Below is a third attempt with different wording. This one is not anonymous, hope this appears on the discussion thread.)

    Since you said that the study is in progress under an active IND, please submit an amendment to the protocol rather than a new protocol. Any changes including significant ones like inclusion/exclusion criteria, endpoints, efficacy/safety evaluation etc…to the protocol require only an amendment to the protocol. I am just curious to know why you did think of a new protocol option?

     

    Let me share a hypothetical scenario (i.e. complex and not likely scenario) for which a new protocol should be considered assuming that the dose/dosage form is same for both situations:

     

    The IND and the protocol in progress are studying for Parkinson indication. Now the team proposes to change the Parkinson patient population solely to a subset of Parkinson disease and wish to study only the MSA patients. I.e. you no longer wish to enroll general Parkinson patients but only the subset of Parkinson disease patients (MSA) requiring new inclusion/exclusion criteria, endpoints etc…

    Then the above scenario will require a new protocol.



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    GRSAOnline
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  • 3.  RE: Protocol Amendment vs. New Protocol

    This message was posted by a user wishing to remain anonymous
    Posted 22-May-2017 16:45
    This message was posted by a user wishing to remain anonymous

    If you have a protocol already submitted to the IND and the study is ongoing, please submit an amendment to the protocol, regardless whether they are significant or non-significant changes. For some reason you thought about a new protocol, can you explain why?

    Let me give you a hypothetical scenario when you should consider a new protocol vs. Amendment to the protocol:

    Just an example of an amendment to the protocol with dosage form being same for both situations:
    Original active IND: Parkinson Disease, original protocol on file with the active IND: typical Parkinson disease patients.

    Proposed amendment to the protocol: Any changes to the above protocol like inclusion/exclusion criteria, efficacy or safety evaluation or any changes with the same population as above requires only an amendment to the protocol

    New Protocol:
    New patient population for Parkinson disease such as MSA only patients (a subset of Parkinson disease).

    However, if your proposed change is to add a cohort of MSA patients to the above original Parkinson disease patient population then you can get away with an amendment to the protocol.


  • 4.  RE: Protocol Amendment vs. New Protocol

    This message was posted by a user wishing to remain anonymous
    Posted 23-May-2017 09:17
    This message was posted by a user wishing to remain anonymous

    The scenario is going from Single Dose to Repeat Dose and changing the population from all male to male and female.  Clinical wants to amend the protocol and call it Part 2, but I'm leaning towards a new protocol.

    Do you agree that it would be a new protocol based upon the above scenario?


  • 5.  RE: Protocol Amendment vs. New Protocol

    Posted 23-May-2017 09:52
    "The scenario is going from Single Dose to Repeat Dose and changing the population from all male to male and female.  Clinical wants to amend the protocol and call it Part 2, but I'm leaning towards a new protocol.

    Do you agree that it would be a new protocol based upon the above scenario? Absolute "No", assuming that the study is still considered ongoing per the original protocol?

    Single dose to repeat dose = Amendment to protocol

    All male to both male & female = Amendment to protocol.

    The above come under an amendment to the protocol not a new protocol. Assuming you are not changing the proposed indication requiring different inclusion/exclusion criteria, efficacy/safety evaluation, dosing regimen etc & the study is not considered completed........


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  • 6.  RE: Protocol Amendment vs. New Protocol

    Posted 23-May-2017 17:02

    If you need further guidance on other issues please send me a message privately. For whatever reason, It seems like there was a pause in your initial protocol design to focus first on the single dose before you jump to multiple dosing. Your clinical group proposal is reasonable to amend the protocol for this and other changes.
    Good luck!



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  • 7.  RE: Protocol Amendment vs. New Protocol

    Posted 24-May-2017 08:55
    I agree with this suggestion for a new protocol.  Although, it does make sense to do an amendment as many of our colleagues have suggested, even for substantive changes, I think you are doing a different kind of change.  The things that I would consider is that it sounds like this is a Phase 1 first in human single to repeat dosing scenario.  To me, the most important thing is to be able to present your development to regulatory reviewers in the most transparent way possible.  If the single dose study has an objective related to safety and PK of a single dose it is likely that the protocol title reflects that objective.  If you are changing the objective, the inclusion/exclusion, monitoring, PK sample collection, etc., you are making such significant changes that I would think a new protocol would be the most transparent.

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    Glen Park
    Scynexis, Inc.
    Jersey City NJ
    United States
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  • 8.  RE: Protocol Amendment vs. New Protocol

    Posted 22-May-2017 17:07
    Dear A,

    As for new protocol, please refer to 21 CFR 312.30(a) - a study not covered by a protocol in your ongoing IND.

    Regarding (non)significant changes in a protocol via protocol amendments, please refer to 21 CFR 312.30(b)

    Thank you.

    s/ David
    ______________________________________________
    Dr. David Lim, Ph.D., RAC, ASQ-CQA 
    REGULATORY DOCTOR
    Phone (Toll-Free): 1-(800) 321-8567

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  • 9.  RE: Protocol Amendment vs. New Protocol

    Posted 24-May-2017 08:59
    Dear Anonymous,

    I agree with the other respondents that the proposed changes should be incorporated as an amendment to the existing protocol rather than submitting a new protocol.  This decision would potentially have other implications such as how the IRB would process an amendment to a protocol vs. a new protocol and your company's internal SOPs for implementing amendments to a protocol vs. a new protocols.  FDA regulations 21 CFR Part 312.30 allow for implementation provided that two conditions are met: 1, the protocol amendment has been reviewed and approved by the IRB and the protocol amendment was submitted to FDA.  Some companies have policies that for "new protocols" they will delay implementation until the two conditions are met but also wait 30 days  from the protocol was submitted to FDA (similar to when the original IND was submitted) for additional assurances that they are OK to proceed.  Hope this helps in your decisions.

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    Michael Trapani
    Senior Consultant
    Biologics Consulting Group, Inc.
    Monroe Township NJ
    United States
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