On 26th March On 30th July 2021 a team of experts from Industry, CDISC and FDA came together to discuss the topic of 'Technical Conformance Guide & Test Data Integration and Submission ChallengesSubmission to the eData FDA Team'. You can watch the recording here. The panel actively sourced questions prior to the event from the SDTM/ADaM Implementation FAQ project, as well as a 'call out' to our community members who were given the opportunity to submit questions ahead of the event. In addition, on the day questions came in via the Q&A chat from the audience. Many questions were answered 'live' so we encourage you to listen back to the recording, but those that the panel didn't have time to address have been curated and captured below. The following blog shares highlights of the event and additional links. |
| Questions | Team Response | |
| For ADaM, can external data (not SDTM) be used – like an Excel file? How do you submit the external data to the FDA – in the original Excel file, or an SAS file? | I would suggest two potential strategies: (1) if it is a small table, you could include it as an appendix to your ADRG; (2) convert the spreadsheet into an SAS dataset (transport file) and place it in the MISC folder. In both cases you should include text in your ADRG explaining this data and how it was consumed to support your analysis. | |
| If CBER does not accept a test submission, what should unexperienced sponsors do instead if they plan a BLA at CBER? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Thanks to the FDA for setting up this process in place. Does the FDA review the data submitted in sample submissions? In some cases of ongoing Phase studies, there will be less data in test submissions and new scenarios may come in the final submission, which should not be of concern to the FDA. | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Should big companies also follow the sample submission process if that’s helpful for the FDA? Does the FDA support/recommend it, to avoid any last-minute surprises? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Can the FDA share a platform where sponsors can just upload and test their package as it is technical and not a composite review? | The FDA (CDER) uses Pinnacle 21 Community version to test study data. This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Having submitted many filings to the FDA (without having an RTF), we often wonder to what level of quality the FDA found our eSub Dataset packages. Is there a way that we can obtain feedback from the FDA on the quality of the data packages submitted? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
Is Technical Rejection Criteria validation applicable to Emergency Use Authorization submission? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| For the Phase I eSUB with a PK-oriented submission, we do not provide an aCRF. We plan to explain this in the cSDRG. What would be your recommendation for submitting Define-XML without an aCRF? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Could this test data be dummy data? Should it be the live study data since they are only interested in seeing the structure of the data? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Did the panellist say that Technical Rejection Criteria cannot be checked during the test submission process? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
Do you have any suggestions for submitting macro programs and any about their programming standards? Are there any to define that don’t currently exist? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Is a TS file required for new clinical/nonclinical studies under 4.2 and 5.3 and what should it include? | Please refer to the Technical Rejection Criteria and the Technical Conformance Guide. | |
| At the beginning, there was an announcement about the Working Groups’ needs. Could you show the names of these groups again or provide a link about this? Thanks. | Details on the Working Groups can be found on the Advance Hub. | |
| Thank you. I have a few more questions regarding the TCG. If the unique ATC code is not assigned in SDTM/ADaM, what will happen in the gateway or the FDA database? Will the data package be rejected? Or will it be requested to be modified? | The format and content of your CM domain/ADCM analysis dataset is not subject to FDA Technical Rejection Criteria, so it should pass through the gateway successfully. You will likely get feedback from your review division if they expect ATC codes as part of your analysis. This would be a good topic for a Type C meeting or your PreNDA/PreBLA meeting. | |
| Should the sponsor explicitly indicate the version of TCG in any documentation? For example, in the cSDRG or ADRG of each individual study or in the SDSP? | This was covered during the live session. Please listen back to the recording on the PHUSE Engagement Hub. | |
| Do we need to submit the metadata datasets (intermediate datasets) as part of the submission package used to create the ADaM/TFLs? | ||
| Questions | Team Response | |
| What's FDA preference? Integrating ADaM from individual ADaM seems a good option if ADaM at study level were well "curated". But still would it be a plus for FDA having one single source with data from all studies contributing for example to an ISS? i.e. iSDTM. | From individual ADaM to integrated ADaM is a good option and is recommended. However, there are multiple approaches discussed during the EAtCQ event which the Sponsor can consider. Sponsors should discuss ISS content and approach during the pre BLA or pre NDA meeting with their review division. | |
| Are there any initiatives taken to align the data standard requirements (versions) across different regulatory authorities?. | There is no formal initiative to use the same data standards requirements across the different authorities. | |
| We have a couple of situations where FDA have asked us to provide integrated SDTM - do different divisions have different expectations?. | It's not uncommon for different divisions to have different expectations when it comes to how the standard data is integrated. The language is continually updated in the Study Technical Conformance Guide to further establish a consistent request and requirements across the divisions. This will evolve based on industry approaches and existing code, and each individual divisions have adopted and grown accustomed to over time. | |
| What is the input from FDA representatives on submitting ADaM programs only or submit both (ADaM & TFL's programs)?. | We require from SDTM to ADaM and then other requests will be based on division. | |
| What is the strategy to be followed for submitting aCRF for ISS studies?. | There is no expectation to have an aCRF for ISS. The data is collected for the individual study and so the aCRF at the study level is what is expected. | |
| What about an oncology compound that continues to submit for each unique indication/tumour type. We re-use the same studies in our ISS again and again. | The approach of adding newer studies to the existing ISS is valid. | |
| For integrated SDTM and ADaM datasets used for ISS/ISE, is there a need to run the SDTM/ADaM conformance validation checks on the datasets, in the same way we do at study level?. | Yes. Even though conformance or validation rules does not exist from CDISC and FDA for integrated data, it is necessary to ensure the data/metadata is compliance just like individual study. Of course, some of the validation checks may not apply for integrated data. The upcoming iADRG and iCSDRG template do have provision to provide conformance issue summary just like ADRG and cSDRG template. | |
| Integrating legacy studies (started prior to December 2016) and studies in SDTM format directly into an iSDTM (eg., we skip conversion at study level, we do it directly in the pool), provided that is fully traceable (documented), it's an acceptable option provided that this is discussed upfront (we did with a couple of projects where we had to pool several old legacy studies). | The sponsor may be required to integrate studies that have been completed using different versions of the SDTM IG or may have legacy data in a non-standard format. Older studies may have been finalised suing custom SDTM domains that, in later versions of the SDTM standards, have become standard SDTM domains. This would require some amount of harmonisation activity to take place. The Sponsor should determine whether to implement this legacy data conversion in individual studies, as intermediate datasets used in the integrated SDTM dataset generation, or within the code to generate the integrated SDTM dataset itself. Please refer to the White Paper for further details. (See section 3.2). | |
| If individual study SDTMs are up-versioned/harmonised (but not integrated) and then used to create ADaM integration, what should be submitted to fulfil the traceability requirements?. All the original study SDTMs/SDPs in addition to the set of up-versioned SDTMs/SDPs for each study used for the ADaM integration. | For traceability purposes, we do recommend that the Sponsor submits the up-versioned/harmonised SDTMs from the individual studies if they are used for integrated ADaM. If those up-versioned SDTMs are stacked/integrated to generate iSDTM, then our recommendation would be to submit iSDTM only. We strong recommend to document this in the Study Data Standardisation Plan (SDSP) and discuss ISS content and approach during the Type C or pre BLA/pre NDA meeting with their review division. | |
| For new studies, we have ADaM datasets and for the legacy studies we have SDTM and so we were hoping to use combination of ADaM and SDTM as a source to generate integrated ADaM. What is your recommendation?. | This scenario is not common. We strongly recommend to document this in the Study Data Standardisation Plan (SDSP) and discuss ISS content and approach during the Type C or pre BLA/pre NDA meeting with their review division. | |
For Integrated SDTM, how to populate trial design datasets?. | The recommendation is not to integrate the trial design domains. Please reference the White Paper for further details. |