Kathie Clark

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  • in reply to: Financial Documentation #3668
    Kathie Clark
    Participant

    Filing in the TMF and making available to an auditor/inspector are not necessarily the same thing. In the TMFs I have been responsible for in the past, we have been able to flag these documents as financially sensitive and not make them available out of the box to an inspector. [And by the way there are probably many other people who should not see them.]

    We were also able to change this on the fly if the inspector demanded access (although I never heard of them happening).

    Most of my clients agreed that their position was not to provide access unless access was specifically requested. But I would say it’s a good practice to include in the TMF if your technology supports how you want to handle them.

    in reply to: Document content referencing multiple studies #3667
    Kathie Clark
    Participant

    One more point to keep in mind is that you need to ensure your processes and technology support this properly. For example, say you have an Investigator Brochure linked to Study A and Study B:
    * If Study A is finished and the TMF locked, what happens if there is a new version of the IB? Will it cause a change to locked Study A’s TMF?
    * If you have a practice of storing your TMF in an external archive, and you remove Study A from the system, will it cause any change to Study B?
    * If study A is one week from finishing and you update the IB, will it cause an inappropriate update to Study A (as you would not distribute a new IB at that point in the study)?

    If you look at something like an unblinded safety document, there may be even more issues (what if the blind is lifted in Study A but still in place in Study B)?

    in reply to: CSV files #2965
    Kathie Clark
    Participant

    MHRA discourages “live date” (Excel, SAS, etc.) from being stored exclusively as “flat files”.

    However I would look to find a better archival medium than flash drives as these are not considered reliable or stable over the long term, and are subject to viruses, leading many organizations to ban their use.

    in reply to: CSV files #2964
    Kathie Clark
    Participant

    MHRA discourages “live date” (Excel, SAS, etc.) from being stored exclusively as “flat files”.

    However I would look to find a better archival medium than flash drives as these are not considered reliable or stable over the long term, and are subject to viruses, leading many organizations to ban their use.

    in reply to: CSV files #2963
    Kathie Clark
    Participant

    MHRA discourages “live date” (Excel, SAS, etc.) from being stored exclusively as “flat files”.

    However I would look to find a better archival medium than flash drives as these are not considered reliable or stable over the long term, and are subject to viruses, leading many organizations to ban their use.

    in reply to: Archiving eTMF with no in house eTMF solution #2962
    Kathie Clark
    Participant

    Taking a step backward, you also need to have a good understanding of your data quality as part of the archiving process. Of course, some organizations do a better job than others in their TMFs, and that becomes obvious when an archive is created.

    For example, if you do not have reliable data for every record for its artifact, study, country and site, it will be difficult to create an organized artifact. I have seen exports where site level documents were missing site numbers, and instances where the originating organization has assured the recipient that all information was coded into a file name, which proved not to be true.

    So no matter the archive used, you will need to ensure that your data and documents are organized in a manner that will facilitate retrieval and inspection.

    Also, quoting from MHRA GCP:

    Minimum requirements for an eTMF system should enable appropriate
    security to be in place, which would include role-based permissions for activities being undertaken through the use of secure passwords. Accounts should be created and deleted within a formal approval process and in a timely manner. This is analogous to the paper system where the TMF is kept in a secure location, with retricted access.

    and from EMA Guidelines:

    An external archive providing retention of paper documents or electronic media or electronic storage (e.g. cloud data centre) may be used for archiving of the TMF. When an external archive is used by the sponsor or
    nvestigator/institution, they should undertake an assessment of the suitability of the facility prior to use and continue quality assurance measures once the organisation has been contracted. There should be a formal agreement in place between the sponsor/investigator/institution and the external archive. In cases the external archive has several storage locations, the sponsor and/or investigator/institution should ensure they are informed about the actual storage location of their TMF and notified if this changes. The agreement is recommended to include provisions for the situation of
    the sponsor or external archive going out of business.

    in reply to: Document Receive Date #2931
    Kathie Clark
    Participant

    A couple of points to add:
    * Receipt Date can indeed be valuable in TMF Metrics, but of course it’s difficult to prevent users from “gaming the system” here. We know that Receipt Date must be greater than or equal to Document date, and less than or equal to upload/submission date. But it’s a sort of honor system as to when the document was received for filing in many cases. So it is then worth looking at the difference between document date and receipt date to see how long it is taking to receive a document after it is finalized.
    * Certain document types, such as CVs, lab normals, etc. could have a document date that is a long time before receipt date and this is legitimate. For these documents, receipt date is actually more important in reconstructing the trial than document date.

    in reply to: Best Practice: Wet-Ink Signatures & Certified Copies #2812
    Kathie Clark
    Participant

    See http://paperdestruction.org/ “FRAMEWORK FOR THE DESTRUCTION OF PAPER” for a very detailed treatment of this topic. The short answer is that if you have a validated process to certify copies, you do not need to retain the paper. In fact the MHRA made the following interesting comment at a recent TMF Summit”

    “11. Can you destroy paper if a certified copy has been created?
    A certified copy can replace an original paper which can then be destroyed. If the original has not been destroyed, the MHRA may ask why. If you certify copies and then don’t destroy the originals, are
    you confident you have a certified copy because what is rationale for keeping the paper? Not necessarily a finding, but would need explanation on why you would still be keeping the paper originals.
    Inspectors may want to look at the paper. ”

    See https://tmfrefmodel.com/wp-content/uploads/2018/12/UK-MHRA-q-a-TMF-Summit-2018-12.pdf for the summary of this MHRA Q&A session.

    in reply to: IBC TMF Filing #2797
    Kathie Clark
    Participant

    Wouldn’t these fall under committees? There are a number of artifacts in this zone and section:

    01 Trial Management 01.03 Trial Committee 01.03.01

    For example, the Committee Process artifact says:

    To describe the purpose and mode of operation/manner of working of the Independent Trial Committee, which may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data and the critical efficacy endpoints and to recommend to the sponsor whether to continue, modify or stop a trial. To describe in advance the decision-making process of the Committee that will evaluate key trial events (e.g. endpoints).

    Committee Types may include but not limited to: DMC, DSMB, National, Steering, Scientific, Internal DMC, Device, Dose Escalation, Safety Evaluation, Adjudication, Clinical Events Coordination. These may be used as sub-artifacts or metadata. Applies to all Committee artifacts

    in reply to: CSR Filing Options in eTMF #2787
    Kathie Clark
    Participant

    There are a few points to consider here:
    * In the US, CSRs are generally submitted in the granular format using the study tagging file. As a result, a monolithic report may not exist, but the granular format is not very digestible for users of the eTMF (nor for transfer back to the sites, which I believe is a requirement). I know several of my clients took time to produce a somewhat condensed single file report that was then filed in eTMF.
    * some CSR appendices (protocol, sample CRF) already exist in eTMF. It would probably be confusing to re-file these.
    * other items listed as appendices (investigator curricula vitae, ethics committee approvals, informed consent forms, and batch numbers per subject) are in the TMF or clinical supply database and should generally not be included in the CSR appendices.

    So I think either a condensed CSR or the body, synopsis and certain selected appendices would be filed. (interestingly, the synopsis is actually smack dab in the middle of the report even thought it is a separate component in the STF). If you didn’t file the CSR but only a cover letter, then you would have to explain how people that need access to the actual CSR would get it (they may not have access to the submission system).

    • This reply was modified 6 months, 3 weeks ago by Kathie Clark.
    in reply to: IP Related Docs #2779
    Kathie Clark
    Participant

    Brad, I can’t lay my hands on anything in writing at this time pertaining to IP specifically, but Andy Fisher’s very detailed 2015 presentation mentions guided access to similar systems as being acceptable. I do not think that the HAs would want to have to train on more than a few systems (preferably one) and it’s my recollection that MHRA mentioned that systems storing data could be accessed with an expert to assist. Maybe someone else who attended MHRA’s TMF day a few years ago would have something in writing.

    Pertaining to the requirements on storage, EMA says:

    “The TMF should be managed securely at all times to ensure completeness and to prevent accidental or premature loss, unauthorised alteration or destruction of documents. Access to the TMF should be based on a role and permission description that is defined by the sponsor and/or investigator/institution.”

    So the system of record (whether part of the core TMF or not) should be subject to these controls and should also be subject to validation/UAT. If you are transferring records electronically, that transfer should also be controlled/validated. If this is really the system of record for batch records or MSDS, one would expect that anyway.

    • This reply was modified 6 months, 3 weeks ago by Kathie Clark.
    in reply to: Financial Agreement in eTMF #2770
    Kathie Clark
    Participant

    One more point – if you do keep these in your eTMF, there probably needs to be a way to restrict access to people with a “need to know” – as financial information is often considered sensitive and access may be limited to a subset of eTMF users.

    in reply to: IP Related Docs #2764
    Kathie Clark
    Participant

    Hi Brad,

    I would appreciate the opinion of others, but I think that many of the document types you mention aren’t literally part of the TMF. For example, if you consult MHRA GCP, p. 333, there is a diagram that shows IMP documentation as part of “Supporting documentation” and not part of the TMF.

    That doesn’t mean it’s not inspectable, but that the expectation would not be that it is filed in a TMF structure.

    I also see the following in an MHRA presentation on GCP.
    •Essential documents (E6 section 8) can reside on a single system, but the MHRA extended expectations include access to material residing on different systems:
    –GMP data (e.g. batch records) not needed by clinical staff
    –Regulatory documentation (e.g. applications to MHRA)

    Would be interesting to hear from those with inspection experience on this point.

    Kathie

    in reply to: TMF Document Naming Convention #2739
    Kathie Clark
    Participant

    Hi Maria,

    It’s good to keep in mind that the goal of naming is to 1) allow a user to find a document quickly by keyword search 2) accurately identify the content of the document and 3) allow a user (including a health authority) to understand what is in a document without having to open it.

    Hopefully it is possible for your eTMF to produce automatic names for your documents that include key elements of metadata. I once had someone tell me there were 14 different ways of naming protocols in their organization! Obviously that is not helpful. On the other hand, simply identifying the document as a protocol (or amendment) is probably sufficient in an eTMF as there are not a significant number of these in a given study.

    However, there are other cases where document type, site, etc. are not sufficient. For example, when naming IRB submissions and approvals, the system probably does not have enough metadata to assign a unique name. Having a dozen “IRB Submissions” only distinguished by date does not help an inspector know which one to look at.

    In this case, there should be a variable part to the title in addition to the standard part. Submitters should be given guidance on what information to include in the variable part to accurately identify the document.

Viewing 14 posts - 1 through 14 (of 14 total)