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  • 1.  IND Safety Reporting for Blinded Studies: Regulatory Operations Question

    This message was posted by a user wishing to remain anonymous
    Posted 23-Dec-2021 11:02
    This message was posted by a user wishing to remain anonymous

    I am a Regulatory Lead (small Sponsor company) supporting a randomized, double-blinded, placebo-controlled phase 1 study in a patient population with advanced disease.  I also wear clinical development/clinical operations "hats" and need to remain blinded to treatment assignments during study conduct and data analysis.  Unblinded individual IND safety reports will be sent directly from our contracted pharmacovigilance partner to our contracted regulatory submissions partner (I will not have access to these reports).  The plan is for me to prepare and sign a cover letter and Form FDA 1571 for each individual IND safety report (or follow-up report) and send it to our regulatory operations partner for submission with the corresponding unblinded MedWatch/CIOMS I form.  The cover letter will indicate that I do not have access to the treatment assignment/unblinded IND safety report.  Is this reasonable?  It is not feasible for another intramural professional who is not associated with this project to assume this role.  The cover letter will remain "generic" and will not refer to the specific SUSAR, because any reference to subject number in the cover letter would effectively unblind me (since reports are only submitted for subjects receiving active study treatment).  Should I authorize the regulatory submissions partner to sign the cover letter and Form FDA 1571 on my behalf?  Is there a more advisable approach to this entire process?  I can elaborate if someone has additional questions before providing advice.  Thank you in advance for your assistance.



  • 2.  RE: IND Safety Reporting for Blinded Studies: Regulatory Operations Question

    This message was posted by a user wishing to remain anonymous
    Posted 23-Dec-2021 15:54
    This message was posted by a user wishing to remain anonymous

    Little bit confused with your situation! Is it a phase 1 study double blinded for an advance indication? Certainly your regulatory submission partner can sign off on your behalf but I don't think it is necessary and in fact you can sign off the submission yourself. ! You are only un blinding the subject who experiences SAE so you are still blinded to the entire study in terms of assignment and conduct. I think most others would agree with my view point!


  • 3.  RE: IND Safety Reporting for Blinded Studies: Regulatory Operations Question

    Posted 24-Dec-2021 08:52
    There are no hard rules covering your situation. I agree that it is better that you are not unblinded. However, in my experience, clinical study team members know what SAEs occur and when that SAE is considered a SUSAR. Therefore, the event results in a "de facto" unblinding, particularly in a small Phase 1 study. Depending on the study design and randomization, unblinding of an individual subject does not necessarily compromise the blinding overall. 

    That said, I have had a third party sign a cover letter "on behalf of" and I would sign the 1571 as the legally authorized representative of the company. The cover letter can include any details needed to put the event into context and you would never need to see it during the conduct of the study.

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    Glen Park PharmD
    Vice President, Regulatory Affairs and Quality Assurance
    New York NY
    United States
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  • 4.  RE: IND Safety Reporting for Blinded Studies: Regulatory Operations Question

    This message was posted by a user wishing to remain anonymous
    Posted 30-Dec-2021 15:23
    This message was posted by a user wishing to remain anonymous

    Thank you, Dr. Park...greatly appreciated.


  • 5.  RE: IND Safety Reporting for Blinded Studies: Regulatory Operations Question

    Posted 05-Jan-2022 19:51
    Your approach is reasonable considering your role and definitions associated with blinding studies including double blind. Key to the double blind study is that neither participants nor the doctors treating them know which people are getting which treatments. This  avoids the doctors' hopes and expectations influencing the results of the trial.  I wouldn't imagine your role either clinically or regulatory would influence the results of the study.  I would also offer that your SOPs clearly define your role and process for double-blind study such that you comply with the SOP and demonstrate no influence to outcome of treatment.

    Best,

    Dar 


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    Darlene Rosario MBA, RAC
    Principle Consultant
    Ventura CA
    United States
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