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Clinical study "start date" under MDR

  • 1.  Clinical study "start date" under MDR

    Posted 24-Jan-2019 05:49
    Edited by Simona Ioana Ulea 25-Jan-2019 08:13
    ​Hi all,

    What is considered to be the clinical study "start date" according to MDR? Is it the moment where the EC and CA approval are obtained or the moment when the first patient is enrolled? Please see article below:
     

    Art. 120.11. "Clinical investigations which have started to be conducted in accordance with Article 10 of Directive 90/385/EEC or Article 15 of Directive 93/42/EEC prior to 26 May 2020 may continue to be conducted. As of 26 May 2020, however, the reporting of serious adverse events and device deficiencies shall be carried out in accordance with this Regulation".

    Also, if you have any source you can point out to that would be great! 



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    Kind Regards,

    Ioana Ulea
    Regulatory Affairs Professional

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  • 2.  RE: Clinical study "start date" under MDR

    Posted 24-Jan-2019 16:40
    I have always understood "start dates" to be the date of initial enrollment for the study.  You can get approval for a protocol through the CA and EC and never initiate the study - correct?  If that is true then why would these be the "start dates" for anything?  Just logically looking at the way the statement is made in 120.11 it implies that the study must have "started" and the only way to start the study is to enroll and treat the first patient in the study in my opinion.​

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    Victor Mencarelli
    Director Regulatory Affairs
    United States
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    Original Message


  • 3.  RE: Clinical study "start date" under MDR

    Posted 25-Jan-2019 01:28
    ​Hi Victor,

    Thank you, that makes sense.

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    Best Regards,

    Ioana Ulea
    Regulatory Affairs Professional
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    Original Message


  • 4.  RE: Clinical study "start date" under MDR

    Posted 25-Jan-2019 07:48
    ​It makes sense to me, too, but I can tell you that this topic has been subject to ongoing debate among the clinical research crowd for about as long as there has been a clinical research crowd.  That's in part because, in some situations, deciding that study "start date" equals date of first subject enrollment then leads you to the question of what "enrolled" means. 

    Typically these discussions have been inspired more by concerns over the point at which patient protections (consent, IRB approval) should kick in, rather than adverse event reporting, which seems simpler.  It's hard to see how a product might cause an adverse event before any subjects have been exposed to it.  On the flip side, the fact that a subject has been "enrolled" in a trial doesn't necessarily mean they've been exposed to the investigational product.

    I would suggest documenting the definition you decide to use in the absence of a definition in the MDR (or the IND or IDE regulations, ISO 14155, the ICH GCP guidance, or any other authoritative source, as far as I know), along with rationale.

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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Durham, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


  • 5.  RE: Clinical study "start date" under MDR

    Posted 25-Jan-2019 08:13
    Many thanks Julie, appreciate your feedback.

    I agree that "start date" is a bit in the grey area and it is a unfortunate that MDR does not provide a clear definition on this. In absence of any other formal references, if I would look at the definition given by clinicaltrials.gov, the "study start date" is also seen as the date when first patient is enrolled.

    "Study start date: The actual date on which the first participant was enrolled in a clinical study. The "estimated" study start date is the date that the researchers think will be the study start date"
    Glossary of Common Site Terms - ClinicalTrials.gov

    Regards,

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    Ioana Ulea
    Regulatory Affairs Professional
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    Original Message


  • 6.  RE: Clinical study "start date" under MDR

    Posted 25-Jan-2019 08:37
    I fundamentally agree with Victor and Julie about the "start date" being the first time a patient is enrolled in the study, i.e. once the informed consent has been signed.  Logic holds true that an unanticipated/anticipated adverse event can not be made if no patient is every exposed to the product, therefore the start date would be first enrolment, even first use of product.  There are other sources as Julie mentioned like ICH E6, ISO 14155 that have some description that completely agree to clearly define this within your documentation system so there is no confusion on when reporting is done.

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    Richard Vincins RAC
    Vice President Global Regulatory Affairs
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    Original Message


  • 7.  RE: Clinical study "start date" under MDR

    Posted 25-Jan-2019 14:44
    ​Thanks to you, Ioana!  I consider ClinicalTrials.gov to be a solid authoritative source, and I wasn't aware its glossary included this definition.

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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Durham, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


  • 8.  RE: Clinical study "start date" under MDR

    Posted 26-Jan-2019 07:37
    Hi Julie,

    You know this: while a patient may not have been exposed to investigational product, they certainly will have been put through screening for inclusion/exclusion.  I know someone who had to have an invasive biopsy as part of screening, which collapsed a lung. Yikes!

    I have heard BIMO investigators state trial initiation can be as early as when you put up flyers recruiting patients, so as you say, it depends.  I have not found it to be as late as when patient is exposed to investigational product. Adverse events can be caused by more than investigational product.

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    Ginger Cantor, MBA, RAC
    Founder/Principal Consultant
    Centaur Consulting LLC
    River Falls, Wisconsin 54022 USA
    715-307-1850
    centaurconsultingllc@gmail.com
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    Original Message


  • 9.  RE: Clinical study "start date" under MDR

    Posted 26-Jan-2019 11:28
    Hi Ginger,

    Sounds like you've done your time with the ACRP crowd, as these are the types of scenarios they muddle over routinely in their forum  However, they mostly do US-based studies, both pharma and devices.  When the question is limited to studies conducted to meet the requirements of the MDR, I think the simple definition will serve.

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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Durham, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


  • 10.  RE: Clinical study "start date" under MDR

    Posted 26-Jan-2019 12:17
    Julie,

    This was not a hypothetical case, it was a relative.  Not cool.  Initiation starts early.

    But yes, while I was not a certified study monitor, I have spent time monitoring, auditing CROs, and writing IBs, protocols, and reports.

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    Ginger Cantor, MBA, RAC
    Founder/Principal Consultant
    Centaur Consulting LLC
    River Falls, Wisconsin 54022 USA
    715-307-1850
    centaurconsultingllc@gmail.com
    ------------------------------

    Original Message


  • 11.  RE: Clinical study "start date" under MDR

    Posted 26-Jan-2019 23:58
    ​Very not cool.

    To be clear, the scenarios discussed in the ACRP forums are not hypothetical, either.  They discuss actual studies, which they are conducting or planning to conduct, although someone might post a hypothetical to clarify a point.

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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Durham, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


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