Meeting Date: / Wednesday September 26, 2012 / 11am-12pm Eastern
Meeting Title: / Stage II
Location: / Telecon: 1-770-657-9270, code: 7485962
Webconnect: https://collaboration.fda.gov/stageii/
Meeting Recorder / Crystal Allard
Attendees: /
First Name / Last Name / Affiliation / E-mail Address /
Crystal / Allard / FDA /
Michael / Brennan / J&J /
Jay / Levine / FDA /
Clyde / Ulmer / NCTR /
Armando / Oliva / FDA /
Mead / Walker / Mead Walker Consulting /
Amy / Malla / FDA /
Julia / Zhang / Genzyme /
Helena / Sviglin / FDA /
Dave / Genzig
Fred / Miller / Regulatory Informatics Consulting /
Mitra / Rocca / FDA /
Lise / Stevens / FDA /
Syed / Haider / FDA /
Eric / Tavela / 5AM solutions with NCI /
Rashmi / Srinivasa / 5AM solutions with NCI /
Hon-Sum / Ko / FDA /
Kannan / Bhanu / FDA /
Name Change
Crystal / o RCRIM voted to revise the name of the RCRIM-CDISC listserv to RCRIM-Study-Data. The work group thinks this is more reflective of the topics discussed on the listserv.
o Email sent to RCRIM Group on 9/25
o Will be changed Monday, October 1, 2012, 8am
o NOTE: if you send an email to the old listserv name the messages will not be forwarded to the new address and there will be no notification.
o Will we have to re-subscribe or will the current list be automatically added to the new listserve? Crystal will ask Ed Tripp.
Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of
Meeting; Request for Comments
Crystal / · Meeting:
o DATES: The meeting will be held on November 5, 2012, from 10 a.m. to 4 p.m.
o ADDRESSES: The meeting will be held at FDA White Oak Campus, 10903 New
o http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm
o Webcast?
Study Participation Testing Results
· Sharing of results of Study Participation xFormTesting
o Michael Brennan
o Initially attempted to auto-populate from internal databases, but information required on the form came from diverse places. (clinical databases, other databases) Extent of metadata went beyond what’s typically on the 1572. e.g. investigator credentials. This is typically a yes/no, access to license, stored in a study file. E.g. effective dates, etc. not captured now.
o Key process questions – would like to reach consensus regarding signature on the 1572 form.
o Related work with pharma – moving away from web signing would save in excess of 80% of cost of managing 1572 forms. Estimate from 2005, eliminating wet signatures partial cost of 1572 can be reduced by ~$4.7 million
o Very positive response to finally moving to electronic workflow implemented by firebird is extremely valuable to sponsors.
o Not anticipated by form: is the information being provided new or amended? Under what conditions would the information be submitted. How is this tracked? Identify new vs. updated information in the form.
o Unique ID for a PI: only unique within a sponsor or can there be a unique ID that would apply to an investigator that might participate in multiple studies with multiple sponsors.
o Drop-down list for service providers – given complexity of trials, likelihood of ‘other’ is very high. Makes sense to expand to include EGC readers and other specialized services? Expectation of agency regarding information that’s needed and wanted. Consider expanding the list?
o Need to engage more industry testers – add as limitation to testing report.
o Michael willing to informally present and share testing results.
o Fred Miller
o Same comment regarding this would be a combination of inforomation from a clinical system and a regulatory tracking system. Would assume a regulatory information management system would have to collect information from all systems to generate messages.
o 1 investigator per site, not study
o Investigator by name, title only
o Not possible to specify ‘none’ for sub-investigators
o May have multiple addresses for a site – different address for drug delivery on 1572?
o Sub-investigators selected by last name which might not be unique across a study.
o Many questions about status codes in drop downs. Few, well-defined codes would be ideal. Otherwise, there’s likelihood of confusion.
o Hon-Sum Ko
o Use of xForm in relation to 1572?
o 1572 requires title of study, which is missing in the xForm.
o Xform appears to be more focused on sponsor/study than investigator
o Regulations only mention investigator, not principle investigator – discrepancy, needs definition
o Xform is for one study, so may need multiple for different studies for the same investigator.
o Addresses: xForm uses addresses for US address format. Foreign addresses don’t conform to the same format.
o Questions/comments: is the purpose to generate a 1572 or transmit information that would otherwise have been transmitted in a 1572?
o Who would create this file? – assume it would come from the sponsor? 1572 has signature of the investigator. Do we need investigator to digitally sign this transmission? It is the sponsor’s responsibility to obtain a signature from the investigator. It is the sponsor’s responsibility to submit to FDA. But holding investigator responsible for non-compliance requires signature from investigator.
o Somewhere within the context of form, want proof that the investigator has accepted the information as complete and correct = signature and date – best to avoid printed .pdf, if possible.
o Hope that this would replace the .pdf version of 1527 submission in IND/NDA, etc. 1572 was created to conform to regulation. Not the other way around.
o Assumption is that we’re using ISO codes for countries and such, but this isn’t readily apparent when entering data. This needs to be explicit.
o What’s submitted is the xml file containing the information. Xform is a tool to aid in creation of xml file.
o Is xForm necessary? Or would it be easier for sponsors/investigators/CROs to create their own programs to generate the xml file?
o Xform allows attachment of pdf of cv or license. Is this necessary? If provide all metadata about credentials, can the submission be simplified by eliminating .pdf files?
o Required to submit CV? Or evidence that the investigator is appropriately credentialed? – regulations require only credentials, not cv. Cv is submitted for convenience.
o Don’t Need 1572 for sub-investigators, is general practice to identify sub-investigators.
o Definition of investigator/principal investigator/sub-investigator = BRIDG harmonization: generally accepted terms need to be clarified and checked with Regulations. Term needs to be consistent and aligned with clintrials.gov
o Rashmi Srinivasa and Eric Tavela
o Producing xml output that conforms to study participation schema from NCI application, OCR (formerly firebird) allows investigators and sponsors to enter 1572-type information – workflow to submit to sponsor, digitally sign, request changes or accept form and supporting documents.
o Took data stored from that workflow and generated xml output that conforms to schema.
o Some technical findings in regards to schema. These were sent with test results.
o Unique Identifiers – across multiple organizations/sponsors, potentially multiple studies
o Ideally for BIMO, globally unique ID for investigator would be very useful.
o Is anyone working on creating unique IDs associated with Investigators? Hever?
o Ideally, information can be collected and submitted once, then re-purposed.
o NCI stores and retrieves all investigators from a separate CTRP (poe) repository of investigators and persons related to clinical trials – has its own unique IDs. NCI may use these (for now). These are unique but only from NCI source – relevance to other users? Globally unique ID?
o How should schema be best represented: investigators at study level or site level in xml file. = what’s best?
o Have investigators only at the site level, but site is not exactly mapped to a practice site on the 1572, but to a study (virtual) site.
o CBER BIMO: site level information may be most meaningful
o Questions/comments:
o Repository of investigators: can there be alignment between related initiatives – work emerging from Hever that would be moving toward a shared investigator database.
o In repository, retain credentials like cv or license that may obviate need to attach pdf files. OCR = Online Credentialing Repository
o Look up OMB statement regarding anticipated man hours required to complete, send, review the 1572 form.
· Up next
o Document Study Participation test results
o Share Study Participation test results
o Make changes to xForms, schema, IG
o Recruit more testers
Patient Narrative Testing
Armando / · Demo of Patient Narrative xForm
· Next meeting, 10/10
· Planning for Patient Narrative xForm Testing
· Next meeting, 10/10
Action Steps / Responsible Party / Description
Crystal / Ask Ed Tripp if the members of the RCRIMCDISC listserve will be automatically added to the newly-named RCRIMStudyData listserve.
Crystal / Find out if the November 5th meeting at FDA will be webcast.
Next Meeting Date: / October 10, 2012 / Time: / 11 am – 12 pm
Previous Topics
Discussion Points: / § Kick-Off Meeting scheduled for May 25, 2012, 10-11 AM EST
Study Design Structured Document IG R1 Scope
Discussion Points: / § Armando sent a Study Design Structured Document IG scope for version 1. Comments/Questions/Additions/Removals?
§ Scope document available on wiki page:
http://wiki.hl7.org/index.php?title=File:Study_Design_Structured_Document_IG_R1_Scope.doc
Study Design Test standard from Mead
Discussion Points: / § Available on Wiki:
http://wiki.hl7.org/index.php?title=File:StudyDesignTest.zip
§ First: read description of RMIM where biggest changes are.
§ Then look at model – Mead’s updates are linking timepoint events directly to planned study
§ It’s now a structured document, so there’s a document header, etc.
§ We have 3 weeks to make changes before submission to HL7. Draft material already sent to Becky by Mead
§ Please bring comments to March 14th Stage II meeting.
§ Otherwise, please send all comments to Mead and Crystal by March 16th.
bridg mapping for study design
Discussion Points: / § Mead to send BRIDG to listserve for discussion
§ Link to BRIDG to Study Design mapping to be included in Study Design Model Ballot Package
Study Participation Question – Mead
Discussion Points: / § In the StudyParticipation RMIM, there’s an identifier on Study, which is in the event mood, while in StudyDesign, there’s an identifier on PlannedStudy. In conversation with Jean, you’d indicated that these are separate.
The BRIDG SCC wants to know what the use-case is for having a distinct identifier on the “study execution”, because in their experience, a given PlannedStudy only ever has one execution – i.e. one “event” and therefore doesn’t need its own identifier. Does HL7 have use-cases where this situation doesn’t hold? I.e. Where the same PlannedStudy might have multiple Study executions, each with their own id?
§ Is there any distinction between ID for study and ID for protocol/study design that the study refers to?
§ Have a planned study, but might have multiple instances of a planned study. Does this still make sense?
§ Does BRIDG need to add PlannedStudy ID?
§ A single protocol may have multiple studies or multiple phases, but don’t need new IDs for each study, just refer to the protocol ID.
§ This caused confusion during testing of XForms. Removed protocol ID and used only a single study ID. In practice, it appears that IDs are the same.
§ On IND study reports, there have been different IDs. The document ID is different, but the study ID is the same. AE reports, instead of using study ID, the form completer used the protocol ID. Was difficult to search for protocol ID in database to figure out which study ID it was associated with.
§ Best to stick with 1:1 associate between protocol ID and study ID?
§ For Study Participation, only use StudyID?
§ In BRIDG there’s no distinction between the ID of the study and the ID of the protocol. Study Report document ID is different.
§ For BRIDG harmonization, these should not be the same ID.
§ Should the protocol number be equivalent to the study ID?
§ Would it make sense to propose that study ID should be unique (within the sponsor’s namespace, not globally) and equivalent to the protocol ID, then ask for situations in which this may not be the case?
§ Mead will respond to BRIDG SCC
§ Lise will bring questions to CBER and provide their responses to Mead.
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