FDA Validation Rules – Webinar Q&A
- Is the CLI still being developed in the OpenCDISC community version?
Yes, Command Line Interface (CLI) is still available in OpenCDISC Community v2.0 for Validator and Data Convertor tools. - Would we need to annotate the output of the validation rules and submit along with submission?
All data and metadata issues that were not resolved should be explained in section 4 of the Study Data Reviewer’s Guide. - Does OpenCDISC community 2.0 include all FDA validation rules at the time of first release?
Yes, OpenCDISC Community v2.0 implements all FDA validation rules published at the time of the release. - Is the severity aligned between FDA rules and OpenCDISC?
Yes, OpenCDISC Community 2.0 provides an executable version of FDA validation rules using the published Severity, Messages and Descriptions. - Are there any cross domain checks in FDA rules?
Yes, there are many cross domain checks. For example, FDAC208/ SD0080 “AE start date is after the latest Disposition date”. - What will be the next release of Community version with FDA rules referenced?
It depends on FDA publishing activity for validation rules. A new OpenCDISC Community “Auto Updates” functionality allows you to receive new validation rules and tool updates as soon as they are published and released. - It was mentioned that FDA configs will "replace" SDTM configs. Will SDTM configs disappear completely from the OpenCDISC community version?
Yes, the FDA configs replace the old SDTM configs. - Could you describe the algorithm used to differentiate each subject in rule FDAC041, Duplicate USUBJID: "The value of Unique Subject Identifier (USUBJID) variable must be unique for each subject across all trials in the submission"?
FDA041/SD0083 check algorithm is looking for records with duplicate USUBJID values in DM domain. - In trials, we do often collect AEs after the last disposition date, especially when the trials are ongoing. Is OCV looking for the last date in the DS data set?
Yes, SD0080 check is looking for the last DSSTDTC value in DS domain. - Are FDA rules required immediately after they are published? For example, if I'm scheduled to submit data to the FDA, and two weeks prior to that date the FDA releases new data rules, must we comply with these new data rules?
At this point FDA does not explicitly have any specific requirements on usage of published validation rules for SDTM data. In the document Supplementary Information section FDA says: “Submitters of clinical study data can use this information to understand how FDA validates the data”. Sponsor is responsible for quality of submission data, which is not limited to a set of any validation rules.
FDA business rules for SDTM data are based on well-known Standards and FDA Guidance documents. Majority of FDA rules are based on already existing OpenCDISC checks that are referenced on FDA Study Data Standards Resources web page. Most of the new rules are around Trial Summary dataset, which contains study metadata and can be easily created or fixed.
Therefore our recommendation is to do your best to comply with FDA requirements. - Say sponsor is doing a submission one month from now. This means that majority of the work is already done including data guide documents. The data guide would have used OpenCDISC Enterprise Rule IDs (i.e. no FDA Rule IDs in enterprise version used currently). Since FDA rules are official now, would FDA be expecting to see FDA rule ID in data guide a month from now?
At this point FDA does not explicitly specify that FDA Rule IDs are the only option to use in Reviewer Guide. You are safe using OpenCDISC check IDs instead. - In context of protocols allowing that individuals within a given study are re-screened after initial screening failure: SDTM IG on first glance seems to be quite clear: "dm.xpt, Demographics Version 3.2. One record per subject, Tabulation" However, a PhUSE CSS Working Group is currently drafting a Best-practice-doc which understands the word subject in two different concepts: USUBJID, an identifying variable assigned to a person who participates in one or more clinical studies within an application; and SUBJID, the topic variable in the SDTM DM domain, uniquely assigned to each participant in a study, iow, for each screening attempt. The working group's paper recommends to create a new record in the DM domain for each screening attempt, with a new SUBJID. This results in possibly several SUBJID per individual. Each SUBJID record is unique within DM domain, but links to 1 USUBJID only, so that per USUBJID more than 1 record can occur within DM. Is this approach considered / reflected by OpenCDISC?
As you correctly pointed out there is no established standard guidance on how to handle re-screen subjects. Currently, OpenCDISC Validator has a check for uniqueness of USUBJID records in DM domain. - What exactly is define.xml as I’m new to SDTM and CDISC?
Define.xml is a special file with metadata describing your study data. It’s developed and managed by CDISC as Define-XML standard. See more details at http://cdisc.org/define-xml. - Who defines the severity of the rule? Can they be modified to suit local conditions?
FDA defines severity as it applies to submission. Sponsors can modify severity for their internal use if necessary. - Do you have the plan to introduce configuration file for PMDA check?
Yes, OpenCDISC will have separate validation configurations for PMDA business rules, if and when they are published. - What are edit checks?
“Edit checks” are manual or computer checks applied on the data to ensure that database is accurate and consistent. See Good Clinical Data Management Practice for details. - Are you detecting any differences in the same rule area from different publishers (eg FDA vs PDMA )?
PMDA has not published validation rules yet, but we’ll compare and summarize differences when they do. - Is it planned to support WhoDRUG dictionary?
Yes, support for WhoDRUG dictionary will be available in 2015. - Should warnings be explained in the Reviewer's Guide?
Yes, all identified issues including warning and informational messages should be addressed in Reviewers Guide. - How will the rules catalog be governed going forward? Is there a process for submitting new rules or proposing changes to existing rules? Also is there a proposal for how rules will be versioned and harmonized with previous versions/ new SDTM versions?
FDA validation rules are governed by internal FDA change control board (CCB). Industry can submit rule changes to the eDATA team at cder-edata@fda.hhs.gov. - Will there be rules for SDTM that do not include/inbed the FDA rules?
Since CDISC hasn’t yet published SDTM validation rules there is no way of knowing if all or just some will be included in FDA validation requirements. - We have a series of studies to be submitted end of next month frozen following SDTMIG 3.1.2 plus amend. 1 (slightly differnt from 3.1.3). Will there be a config file for "SDTMIG 3.1.2 plus amend. 1 FDA"?
FDA says to use SDTM IG 3.1.3 business rules to validate SDTM IG 3.1.2 Amend 1 data. - Is it 21 CFR part 11 compliant? What kind of IQ oQ PQ testing performed?
OpenCDISC Community is an open source project and is not officially validated for compliance with 21 CRF Part 11. However, it is validated and tested as part of OpenCDISC Enterprise. Users who need validation (IQ, OQ, PQ, etc.) package can get it as a part of commercial support from Pinnacle 21. - If a person downloads OpenCDISC how does he upgrade? What kind of communication been sent since it is open tool?
OpenCDISC Community has “Automatic Updates” feature. If enabled, the software will automatically update when new releases are available. If the feature is disabled, the software will notify the users that an update is available and provide instructions on how to upgrade. - Are there classes available for OpenCDISC software and who provides the classes?
Pinnacle 21 provides training and other commercial services for OpenCDISC. - If MedDRA version is specified in Define.xml do you have to select it when you run the validation?
In previous versions of OpenCDISC Validator MedDRA version provided in define.xml file took precedence over MedDRA version specified in Validator Graphical Users Interface (GUI) or Command Line Interface (CLI). However we saw too many incorrect implementations of define.xml and decided to change the algorithm for MedDRA version in OpenCDISC Community 2.0 to make it more reliable and easy for users. Now the Validator uses only MedDRA version specified in GUI or CLI and ignores MedDRA version in a define.xml file. - Will the Rule ID currently in OpenCDISC change in new version?
We will keep original OpenCDISC Rule IDs in addition to new Publisher ID. - MedDRA - that is a great feature added to OpenCDISC
Actually MedDRA validation has existed since version 1.3 released in 2011. - Will the new OpenCDISC include an option to 'turn off' some checks? Though we will use all checks for our FINAL data, we like to run OpenCDISC in mid study but know that there will be some issues and would like to tell OpenCDISC to not check those things.
Yes. There is an attribute Active="Yes"/"No" in validator specification XML files. By changing its value from “Yes” to “No” you can deactivate a check assignment to particular domains. - Will it be possible to inactivate the FDA check when we are doing a study for another agency?
When submitting data to another agency please follow their specific validation requirements. Currently only FDA publishes the requirements. - FDA posts the exact configuration file names currently being accepted. Will the new "...(FDA)" config files be listed?
FDA recommends that sponsors use the most recent validation configurations available. - Does FDA still use WebSDM validation tool? If yes, how is OpenCDSC 2.0 better than WebSDM?
FDA has stopped using WebSDM for validation about 4 years ago. At first FDA switch to OpenCDISC Validator and now they are using DataFit, which is the agency’s implementation of OpenCDISC Enterprise. - Will these new rules apply to EU studies that are not been submitted for FDA?
“FDA validation rules for SDTM data” is a new document. At this moment we do not have any information about its usage by EMA. - Do you have any guidance document for custom domains for different therapeutic areas?
CDISC published several Therapeutic Area (TA) Implementation Guides. See details on http://cdisc.org/therapeutic.
OpenCDISC Community Validator does not have any TA specific validation profiles because CDISC TA Implementation Guides are rather sets of good examples than enforcement documents. However if Sponsor have their own TA specific standards they can be easily implement new custom validation specifications. - Will FDA accept "Error" as it is?
The decision on acceptance is handled by the FDA reviewers for a given submission. So we can’t say with any certainty if Errors will be accepted. Therefore, we recommend that sponsors try their best to resolve all fixable issues and provide reasonable and detailed explanations for issues that could not be resolved.
