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Insights – Document Management and Archiving Requirements for Observational Studies

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The TMF Reference Model’s specially designed Study Master File will not have an impact on the regulatory requirements for conducting real world research studies in the country of interest…but if used…it will make your real world research studies much easier to manage and less resource intensive (and less frustrating!).

5 NOVEMBER 2021 – Did you know that there is a DIA TMF Reference model for observational studies? 

  • [Lean Version] Real-World Studies Document Index Provides a proposed Document Index for use on real-world studies, based on the TMF Reference Model for clinical trials (v1.0 Approved 29-July-2020) [1]
  • [Detailed Version – with guidance notes] Study Master File [2]

For years, those of us who have been running observational studies (also known as non-interventional studies) have been the ‘poor relation’ with regards to document management tools and offerings.  We’ve had to ‘bootstrap’ existing clinical trial tools to fit the significantly different document requirements for observational studies.  This is why, in 2018 a group of frustrated experts got together with the blessing of the TMF Reference Model Steering Committee…and the rest, as they say…is history…

Why is a Stand Alone Study Master File Needed?

Those of you who are involved in Real World Studies (RWS) know that trying to file your documents using the existing TMF Reference Model (TMF RM) based on ICH E6 can be challenging.  Your study isn’t a clinical trial and as a result, at least 40% of the artifacts in the index are irrelevant.  The result?  You start from the beginning every time you set up a new study and  ‘switch off’ the tabs that aren’t applicable. Alternatively, you may be required to use the existing TMF RM in accordance with your organisation’s policy and disregard tabs that aren’t relevant. Additionally, you hope that an auditor of your ‘real world study TMF’ understands your study and doesn’t penalize you for missing documents (or documents that were never generated, because your study is not a clinical trial).

Real World Studies are increasingly being used to support drug development, product licensing, label claims and reimbursement. Consequently the need for an audit-ready framework has become a critical requirement to effectively collect and manage the documents that evidence integrity in relation to study conduct and study data.

Designing a Solution

To address this, a working group of RWS experts* convened in March 2018 to develop a framework for filing essential documents for non-interventional and observational studies. In designing the Real World Study-Document Index (RWS-DI), the group took into account the ethical standards, regulatory requirements, guidelines and industry best practices applicable to non-interventional studies (NIS). The group developed the RWS-DI based on a prospective study design to provide maximum coverage of the potential documents (or artifacts) across the range of real world study designs, from non-interventional studies, retrospective chart reviews, to prospective product registry studies.

The result is a listing of core and recommended artifacts relevant to Real World Studies (which are not clinical trials) while remaining  as consistent as possible with the TMF-RM format and structure. The RWS-DI adapted the TMF RM removing artifacts specific to clinical trials such as Investigational Product Dossier (IMPD) or Investigator’s Brochure (IB) and replaced terminology such as ‘trial’ with ‘study’ and ‘subject’ with ‘patient’.

The RWS-DI was sanctioned under the auspices of the DIA TMF Reference Model Steering Committee throughout its development. It was endorsed by the DIA TMF Reference Model Steering Committee as a ‘stand-alone’ deliverable for launch to the wider research community. It is anticipated that, as the RWS-DI becomes widely adopted, it will evolve to reflect user community requirements. Feedback, enquiries, and suggestions for enhancements for incorporation in future versions can be made using the e-mail address

The Real World Studies Working Group comprised of the following members, all of whom work within the Real-World Study environment and contributed their expertise throughout the duration of the project.

Shelley Brigstock Study Project Manager, Novo Nordisk

Kath Firth Head of Quality Operations, GSK

Tara Isherwood               Senior Director, Regulatory Advice and Delivery, Syneos Health

Russell Joyce Director and Principal Consultant, Heath Barrowcliff Consulting

Jeff Kirsch* Senior Director, Quality & Risk Management and Governance, GSK

Stuart McCully               Founder, Phoenix RWR

Linda Rudolph               Principal Consultant, Quality Werx, LLC


*Currently-Director and Founder, Jeff Kirsch Consulting, Ltd

Want to Learn More?

Speak to the Master Architect – Russell Joyce.  Russell is one of the founders of the TMF Reference Model and the chair of the Study Master File working group (Real World Study Document Index)





1. Real-World Studies Document Index Provides a proposed Document Index for use on real-world studies, based on the TMF Reference Model for clinical trials (v1.0 Approved 29-July-2020)


2. Study Master File


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