OASIS eTMF Interoperability Committee Discusses Digital Signatures

oasisThe latest meeting of the OASIS eTMF Interoperability Technical Committee convened yesterday (3rd March). The main topic on the agenda was signatures and how these should be exported from one system to another. A number of interesting – and perhaps controversial – issues were discussed. The meeting began with an overview presentation of some of the regulations pertaining to electronic and digital signatures, one of the key ones highlighted being 21CFR11. The guidance from the FDA suggests that export of records should be in common file formats such as PDF, XML or SGML. The benefits of digital signatures was highlighted by Peter Alterman from SAFE-BioPharma.
We pointed out that whilst digital signatures might be seen as “the gold standard”, 21CFR11, the FDA and EMA all permit the use of simple electronic signatures and these are widely used across industry within eTMF systems currently. It is important therefore that any eTMF interoparbility standard should not exclude this type of signature manifestation. Similarly, the discussion focussed heavily on the EMA and FDA requirements for digital signatures on documents included in submissions but these only make up a small part of TMF component (typically 45 artfacts out of the 245 in the TMF Reference Model).
There was even a question raised regarding what documents needed to be signed. It is clear this is outside the remit of the OASIS Technical Committee! It is for industry to decide what documents to sign – referring to relevant regulations – and to use whatever technology is appropriate to them. The OASIS TC then needs to ensure the standard accommodates common industry practice. In fact, the Committee did recognise that wet-ink signatures are still used widely across industry and the metadata model for interoperability needs to recognise the fact that some scanned images in eTMF systems will bear a wet-ink signature and the related file attributes are important for interoperabilty and data exchange.
On the topic of export format for documents, perhaps the Technical Committee is going ‘off piste’ again? The reference to the FDA guidelines is not referring to export of TMF content from one systen to another. The reference actually relates to the provision of TMF content for inspection purposes. Ideally, the original TMF content would be provided but the guidance note 3.4 from the FDA confirms that export of content using automated means to common file formats such as PDF, XML and SGML is permitted. Surely, when transferring TMF content from one eTMF system to another (i.e. TMF interoperability) the ideal scenario is to retain content in its original format? So if the the source eTMF system creates and maintains records in Microsoft Word, the target eTMF system would accept the content in Microsoft Word, and not in a different file format. This is not to preclude file format conversion but simply to state that an interoperability standard should not dictate the source or target file format.
If you have a view on this topic, or any other topic related to TMF interoperability, please make sure you sign up as an OASIS member and join the Technical Committee.

TMF Reference Model (TMF RM) Steering Committee Statement on the OASIS Interoparability Initiative

The TMF Reference Model Steering Committee (SC) has been discussing eTMF interoperability in the light of recent announcements from OASIS following the establishment of an eTMF Standard Technical Committee within OASIS. Overall, we are supportive of this initiative, but with caveats as detailed below.
The TMF Reference Model provides sponsors and CROs with a reference point to help them define the content of their TMFs with recommended content definition, vocabulary and taxonomy that meets their business needs. We have considered whether the TMF Reference Model should be developed into a standard but there are significant concerns with this proposal, including the need for individual sponsors to retain flexibility in their approach to TMF content management across varying regulatory requirements globally and the absence of a definitive TMF inventory from any regulatory agency. For the time being then, the SC will not be recommending development of the Reference Model as a standard though will review the decision again in the future. This is in line with the survey done at the end of 2013 where although 97% of the respondents felt that an interoperability standard was needed, 34% of respondents felt that the TMF Reference Model itself should not be a standard. However, we confirm that industry is facing significant difficulties arising from the inability of eTMF solutions to easily exchange content with each other. In this respect, we agree that a globally recognized interoperability standard would be helpful. This should be an open source technical standard that facilitates the exchange of TMF content between eTMF systems whilst allowing a dynamic content definition, taxonomy and vocabulary.
With respect to the OASIS initiative, we have significant concerns that the TMF Reference Model is not being used as the starting material for the OASIS Technical Committee. We do not support the use of the CareLex Reference Model taxonomy and vocabulary as the starting material for the interoperability standard. We are also concerned that the activities of the OASIS Technical Committee should not be unfairly biased towards any one vendor, CRO or organization. In addition, the development of a standard with an organization that is more closely aligned with Life Sciences/Healthcare may have been more appropriate. However, we firmly believe that the initiative within OASIS provides an acceptable opportunity for the clinical community – including sponsors, CROs, vendors, sites and other interested parties – to develop a technical interoperability standard and we therefore support development of such a standard via the OASIS Technical Committee.
We believe that a usable and valuable eTMF interoperability standard would be consistent and harmonized with the TMF Reference Model and we acknowledge that the Model may require changes in the course of developing the interoperability standard. For this reason, we believe it is important for our TMF Reference Model community to be appropriately represented on the OASIS Technical Committee. As an organization, we are unable to provide official representatives for the Technical Committee but we encourage individuals to join the OASIS Technical Committee as employees of the companies they work for, particularly those who have experience and technical expertise in the management of electronic TMF documents and/or data exchange systems.
If your company is already an OASIS member, you may obtain an OASIS login and once you have a login you then join the eTMF Standard TC. If your company is not yet an OASIS member and there are multiple people who wish to participate, your company will need to join OASIS ($3,520 – $8,825, depending in the size of your company) and then each individual obtain an OASIS login and then join the eTMF TC. If you are the only employee likely to participate in your company, you may join OASIS with individual/associate membership ($1,315). Finally, if you are unemployed or a self-employed consultant, you may join as an individual ($325).
The public web page of the OASIS eTMF Standard Technical Committee can be found here.
Karen Redding (Chair), Steve Scribner (Vice-chair), Eldin Rammell (Secretary)

EORTC Adopts Reference Model

The European Organisation for Research and Treatment of Cancer (EORTC) have recently published an article in Science Omega Review which outlines how it is using IT resources to shape the future of cancer therapy. EORTC Headquarters has developed a comprehensive and integrated suite of software to manage its multicentre international clinical trials.
The article goes on to say:
“It is very important to stay current with the latest documentation standards. The EORTC now implements the Drug Information Association (DIA) Reference Model for all new trials, and the EORTC electronic Trial Master File (e-TMF) has been built on the Microsoft® SharePoint platform”.
Great to see a well-regarding organisation like EORTC recognising the value that the Reference Model will bring to their operations!

How does your TMF / ISF compare? Take the 2013 survey!

One of the things I enjoy about attending conferences and meetings is to hear how other organizations are tackling the same issues. When you hear of others struggling with the same issue, there’s a sense of being “all in it together”. Equally, when you hear of other successes, it is great to be able to join in the congratulations.
And so it is in this spirit that the 2013 TMF/ISF survey is launched. This will enable us as an industry group to gather some really useful benchmarks on where the industry is in the area of TMF document management. The data may help you with an eTMF business case. It may help you to secure additional resources. But of course, the data will only be valuable if people contribute!
So this is a last call to action! The survey closes May 16th so you only have a few days left to complete it. Please TAKE THE SURVEY NOW.

Meeting Minutes – 15th April 2013

  • Introductions – there were 60 people on the call
  • Currently 320 people from around 180 companies

 DIA DRM SIAC

  • Please submit abstracts by 18th April to European DIA Annual meeting
  • Need to get abstracts to DIA eCTD conference in October – call not open yet
  • Focus efforts to expand the DIA SIAC projects on AP audience
  • DRM Community meetings starting monthly – 3rd Thursday of every month, 11am.
  • DIA Connex is a challenge – Lisa taking that to DIA

 Recent and future TMF relevant Conferences (discount vouchers available for CBI and eXL):

  • CBI Clintech in Dublin – 11/12 June http://www.cbinet.com/conference/pc13140
  • DIA in Boston – 24-26 June
  • eXL inspection readiness & eClinical in Philadelphia – August
  • DIA Document Management/eSub – October
  • ARMA conference in Las Vegas – 28-30 October
  • eXL TMF Summit in London – 23/24 October
  • DIA EDM in Dublin – 20-22 November

Usability Group

  • Eric Rubinson, Steve Bioty, Annika Dansson, Sherry Marsh, Lisa Mulcahy, Fran Ross, Adair Turner, Thuy Tran, Sharon Ames, Chan Linh, Michele Atherton, Jamie O’Keefe, Subhayen Das, Kathleen Kirby, Lisa Goines, Jamie Toth, Jennifer Choi, Ellen Liedl Sargent, Karen Redding, Rosalie Phelan, Tamika Jackson, Leah Rose, Kim Fowler, Sarah Silvers.
  • Leader – Ellen Liedl Sargent
  • Goals
    • User manual – by June 2013, with case studies on how people have used the model.
  1. Karen Redding          Phlexglobal
  2. Martin Thorley          Pfizer
  3. Stacy Hitchman          Biogen
  • Webex of model introduction by end of 2013
  • Keep presentation of TMF Reference Model current
  • Final draft in place – some content needs to move to QC group, some to case studies
  • Need plan for communication of manual to community
  • Meeting – first Friday of the month
  • Two pathways for citing TMF Reference Model in publications.
    • Use content published in the TMF Usability guide, found here: xxx.  The content can be amended for verb tense or other readability edits, but otherwise may not be changed.
    • Send article draft to co-chairs Karen and Lisa.   They will comment only on Model history/background/contact details.  If you deliver with the appropriate section(s) in highlight, they will turn around the comments within three working days.

QC group

  • Members: Sharon Ames, Billie Graci, Francisca Darmer, Robin Rimsky, Sam Mowaswes, Karen McCarthy-Shau, Barry Milton, Bruce Pfannenstiel, Michelle Ingraham, Cynthia Pinto, Jodie Salisbury, Eldin Rammell, Andrea Achatz, Sarah Hitching; Rosalie Phelan, Marie Falvo, Pam Monds, Amanda Harring-Abbott, Carlton Clark, Lisa Rakebrand, Sarah Tucker, Lisa Mulcahy, Shah Ashraf, Michele Atherton, Marie-Christine Poisson-Carvajal, Monica Chiotti, William Kiniklis, Donna Vilines, Kathie Clark, Lisa Pabion, Sherry Marsh, Patrick Zhang, Ziyad Abushima, Wendy Beeby, Shah Ashraf, Stacy Hitchman, Suellen Bigaj, Michelle Green, Jane Twitchen, Tricia Fryer, Mike Czaplicki, Maria Shabe
  • Lead – Michael Agard from Paragon
  • Four groups with leaders appointed
    • Best practice for TMF processes e.g. filing, scanning (lead Tamika Jackson)
    • Best practice for TMF content e.g. correspondence, translations, requiring QC (lead Michael)
    • Best practice for working with a CRO e.g. eTMF (Lead Karen & Marie Christine)
    • Metrics and Reporting (lead Fran)
  • Charter completed
  • Monthly Meeting for team leads only
  • Sub-team groups in addition


Australia / Asia Pac
Leader – Fran Ross from Paragon

    • 25 members as of Jan 1; many from trial sites
    • Strong Australia participation;  Looking to increase Japan and China members
    • Piloting the use of the TMF Reference Model at sites – sites identified.
    • Looking for other countries to pilot the template
    • Looking for companies to volunteer to use the index
    • Meet 2 days after the main group, 6pm pacific time, 6am India

 
Communication group

  • Lead: Maryanne Quinn
  • Members – Karen Redding, Fran Ross, Chih-Wu Chang, Jennifer Choi, Eldin Rammell, Ellen Liedl-Sargent, Michael Zwetkow, Lisa Mulcahy, Paul Fenton, Francie Rawlings, Sam Mowaswes, Kathleen Kirby, Rose-Emily Calo, Dean Gittleman, Ivan Walrath, Jan Bettina
  • Applied Clinical Trials article in final draft
  • No Longer a separate group – part of the main meeting

Survey Team

  • Lead: Fran Ross
  • Survey live for 2013
  • Members: Karen Redding, Kathy Moore, Jonathan Burd, Virginia Morhan, Kelley Robinson, Rahul Ganur, Jennifer Gaskin, Shah Ashraf, Suellen Bigaj
  • Communication – TMF RM Linked in group, Other Linked in groups, MAGI, SOPRA, emails, twitter, eNCAP, ACRP
  • Use this – Join your industry colleagues in making your voice heard by taking the 2013 TMF Survey. This is the 3rd generation industry-wide survey sponsored by the TMF Reference Model initiative. Our aim is to collect valuable insight into both paper and electronic Trial Master Files, at sponsor and at site; to identify trends, assess changes in practice and reveal opportunities for improvement. The survey takes less than 10 minutes to complete and closes on May 16, 2013. To thank you for your participation, you will receive a free copy of the survey results to inform you of trends in TMF / ISF practices. ———————– Survey link:  https://www.surveymonkey.com/s/YLL78Z5

Metadata group

  • Leads: Karen Redding and Lisa Mulcahy
    • Team: Karen McCarthy Shau, Mark Shiner,  Martin Thorley (volunteered!), Joanne Ritchie, Sam Mowaswes, Sharon Ames, Janet McDougall, Karin Schneider, Don Palmer, Mary Durham, Kathie Clark, Eldin Rammell, Andrew Mitchell, Scott McGrail, Jan Bettina, Denise Desmond, Anne-Mette Varney, Lisa Ballanco, Francisca Darmer, Kathy Moore, Jonathan Burd, Janet McDougall; Lisa Potanovich, Todd Tullis, Colleen Maude,
      • Define the purpose of the metadata in the TMF Reference Model – Finding (search/navigation)
      • Define the scope of the metadata – i.e. document vs system
      • Identify the common metadata across the model
      • Identify the metadata for types of documents e.g. communications, plans
      • Identify specific metadata per artifact
      • Compliance requirements
      • Interoperability/linking
      • Agency requirement
  • Next meeting to booked

Other discussion topics:

  • TransCelerate – 5 areas of focus – risk based monitoring, data standards, portal, comparative drug supplies. Goal for portal team is to build a portal from a site perspective, currently in RFP. Gateway to sponsor systems. Will grow to full portal with TMF capability. Challenging initiative. Requirements do mention TMF RM for eTMF.
  • MHRA GCP forum – TMF thread – will publish FAQs on there.

 

  • Discussion Points
  • How we can share materials? Q&A on the Reference Model – how can we centralize?
      • Blog could move to a different technology
        • FAQs
        • Library of resources
        • Need people – Andrew, Eldin, Jamie, Maryanne, Karen.

 

    • EU Directive on retention of TMFs
      • Lengthy process – vote in next 2 weeks, then months to go to parliament
      • New regulation to standardize a variety aspects
      • Revised regulation stipulates indefinite retention period for TMF documents (Sponsor and Investigator)
      • Proposes archiving in EU database, which was proposed for subject data
      • No formal mechanism for feedback to be submitted. Member of European Parliament can be contacted. The EU Regulation is being sponsored by the Environment, Public Health and Food Safety Committee. The Secretariat can be contacted at:

envi-secretariat@europarl.europa.eu
The Rapporteur is Glenis Willmott glenis.willmott@europarl.europa.eu. The proposed regulation can be downloaded here:
http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-%2f%2fEP%2f%2fNONSGML%2bCOMPARL%2bPE-504.236%2b01%2bDOC%2bPDF%2bV0%2f%2fEN

  • EMA Position paper on TMFs
    • Closing 29th April

 Next Meeting

  • 3rd June  11am ET, 4pm GMT
    • Please join at least 4 calls a year, as we will be limiting membership to people who take part.

Highlights of the 2012 Metrics Survey

An overview of the 2012 metrics survey has recently been made available.
The data indicates a significant growth in the number of organizations transitioning to eTMF.  32% of survey respondents maintain inspectable TMF’s in paper, down from 50% in the corresponding 2010 survey.  While there is only a modest increase in the number of respondents maintaining inspectable electronic TMFs (8%), the increase in the number of respondents maintaining a combination of paper and electronic was significant – 48% in 2012, compared to just 27% in 2010, indicating a continuing transition to eTMF in the industry.  The data on the current status of eTMFs in the industry also supports a trend to implementing eTMFs.  The 2012 survey reveals that 28% of respondents are currently using an eTMF, and 57% are in the process of planning, building or evaluating eTMF.  (In 2010, only 45% of respondents reported active building or evaluating of an eTMF.) Meanwhile, only 3% of respondents said they are not considering eTMF.
Adoption of the TMF Reference Model is also changing the landscape of trial master file management, especially for new trials just being launched.  Most respondents working with the reference model have updated their SOPs, guidance documents, and file structures to align with industry best practice.  Implementation of the TMF RM and alignment on SOPs and guidance documents may significantly ease the administrative burden in regulatory inspections, industry partnerships, collaboration between sponsors and CROs or acquisitions.

TMF Reference Model Group Meeting – 14-JAN-2013

There were 65 people on today’s call! There are currently 320 members from around 200 companies. Notes from meeting:
DIA DRM SIAC

    • New leadership committee – Chairman and core team
    • Goals to expand SIAC enrollment to other regions (Asia Pac critical)
    • Other goals to be defined across the groups (EDM RM, TMF RM, Content reuse, Framework for destruction and Cloud computing (possible))
    • Requesting showcase abstracts – 30 min presentations. TMF RM to submit one for usability, QC and metadata
    • Looking for European co-chair – any volunteers?
  • Future TMF relevant Conferences (discount vouchers available):

·         eXL TMF Summit in Arlington, USA. Will get together for dinner. Ana Ramirez, Lisa Mulcahy, Fran Ross, Bruce Pfannenstiel, Amanda Harring-Abbott, Wendy Beeby, Karen Redding attending. Who else?
http://www.exlpharma.com/TMF
·         CBI Clintech in March USA
http://www.cbinet.com/conference/pc13077
·         DIA in Boston in June
·         ARMA conference in Las Vegas – ARMA now has a UK and European chapters
·         DIA EDM in Dublin in December
 

·         Usability Group

·     Members: Eric Rubinson, Steve Bioty, Annika Dansson, Sherry Marsh, Lisa Mulcahy, Fran Ross, Adair Turner, Thuy Tran, Linda Rizzo, Wendy Toney; Sharon Ames, Chan Linh, Michele Atherton, Jamie O’Keefe, Subhayen Das, Kathleen Kirby, Lisa Goines, Jamie Toth, Jennifer Choi, Ellen Liedl Sargent, Karen Redding, Rosalie Phelan, Tamika Jackson, Leah Rose.
·         Leader – Ellen Liedl Sargent
·         Goals
·   User manual – by June 2013, with case studies on how people have used the model
·   Webex of model introduction by end of 2013
·   Keep presentation of TMF Reference Model current
·         Good draft for next meeting
·         Need plan for communication of manual to community
·         Next meeting Friday 8th Feb (will be first Friday of the month)
 

 ·         QC group

·         Members: Sharon Ames, Billie Graci, Francisca Darmer, Robin Rimsky, Sam Mowaswes, Karen McCarthy-Shau, Barry Milton, Bruce Pfannenstiel, Michelle Ingraham, Cynthia Pinto, Jodie Salisbury, Eldin Rammell, Andrea Achatz, Sarah Hitching; Rosalie Phelan, Marie Falvo, Pam Monds, Amanda Harring-Abbott, Carlton Clark, Lisa Rakebrand, Sarah Tucker, Lisa Mulcahy, Shah Ashraf, Michele Atherton, Marie-Christine Poisson-Carvajal, Monica Chiotti, William Kiniklis, Donna Vilines, Kathie Clark, Lisa Pabion, Sherry Marsh, Patrick Zhang, Ziyad Abushima, Wendy Beeby, Shah Ashraf
·         Lead – Michael Agard from Paragon
·         Four groups with leaders appointed
·   Best practice for TMF processes e.g. filing, scanning (lead Eldin)
·   Best practice for TMF content e.g. correspondence, translations, requiring QC (lead Michael)
·   Best practice for working with a CRO e.g. eTMF (Lead Karen & Marie Christine)
 

·   Metrics and Reporting (lead Fran)

·         Charter completed
·         Meeting 3rd Monday of each month – next 28th December
·         Australia / Asia Pac
·         Leader – Fran Ross from Paragon
·         25 members as of Jan 1; many from trial sites
·         Strong Australia participation;  Looking to increase Japan and China members
·         Site level focus – piloting the use of the TMF Reference Model at sites. Draft model will be open for comments
·         Anyone on team want to be involved? Karen Redding, Michael Agard, Mike Czaplicki
·         Meet 2 days after the main group, 6pm pacific time, 6am India
 

·      Communication group

·         Lead: Maryanne Quinn
·        Members – Karen Redding, Fran Ross, Chih-Wu Chang, Jennifer Choi, Eldin Rammell, Ellen Liedl-Sargent, Michael Zwetkow, Lisa Mulcahy, Paul Fenton, Francie Rawlings, Sam Mowaswes, Kathleen Kirby, Rose-Emily Calo, Dean Gittleman, Ivan Walrath, Jan Bettina

    • Applied Clinical Trials article in draft
    • Survey results attached. Need people to volunteer for 2013 survey. Will be old team plus Kathy Moore
    • The Comms team is going to take on the current challenges of communication:

·   Where to host the TMF Reference Model
 

·   Where to host supporting information, articles, webinars etc

 

·   Q&A on the Reference Model – can we hold in a DMS or blog or website?

 

·   Add in how to present the different groups at conferences

 

    • Next Meeting – to be decided

 

·         Metadata group

 

·       Lead: Karen Redding

 

·           Team: Karen McCarthy Shau, Mark Shiner,  Martin Thorley (volunteered!), Joanne Ritchie, Sam Mowaswes, Sharon Ames, Janet McDougall, Karin Schneider, Don Palmer, Mary Durham, Kathie Clark, Eldin Rammell, Andrew Mitchell, Scott McGrail, Jan Bettina, Denise Desmond, Anne-Mette Varney, Lisa Ballanco, Francisca Darmer, Kathy Moore

 

o   Define the purpose of the metadata in the TMF Reference Model – Finding (search/navigation)

 

o   Define the scope of the metadata – i.e. document vs system

 

o   Identify the common metadata across the model

 

o   Identify the metadata for types of documents e.g. communications, plans

 

o   Identify specific metadata per artifact

 

o   Compliance requirements

 

o   Interoperability/linking

 

o   Agency requirement
Target February 2013 start

 

  • TransCelerate – 5 areas of focus – risk based monitoring, data standards, portal, comparative drug supplies. Goal for portal team is to build a portal from a site perspective, currently in RFP. Gateway to sponsor systems. Will grow to full portal with TMF capability.
  • MHRA guide has a chapter on TMF, available as an ebook on Amazon (Kindle)
  • MHRA GCP forum – TMF thread – will publish FAQs on there. We can submit questions to Andy. Please send to Karen Redding!

 

Next Meeting

    • February 11th  11am ET, 4pm GMT
    • Please join at least 4 calls a year, as we will be limiting membership to people who take part.