Clinical Trials Hurdles Session 4: Trial Master Files (2015)

In this series, we will discuss how to successfully support and manage clinical trials.

Regulatory Science

Course Syllabus/Topics

  • Phlexglobal Company Overview
    • Dedicated to trial master file 
    • Works with sponsors to provide compliant electronic trial master files (eTMFs)
  • What is a Trial Master File (TMF)
    • Comprised of essential documents that allow for the evaluation of the conduct of a trial and the quality of data produced 
    • Demonstrate compliance with GCP standards
    • Must be able to stand on its own regardless of ICH, European Directive definitions 
    • High quality TMF is necessary for quality clinical trials 
  • The relationship between the TMF and drug/device approval
    • Stages of drug discovery and development
    • Impact of inadequate TMF
    • Defining the TMF
      • ICH GCP chapter 8 has the minimum list of essential documents
      • Other trial-related records that permit evaluation of the conduct
      • Business records and supporting files are not included
      • TMF content-reference model
        • Standard contents, standard naming, standard structure, and standard metadata
        • Unofficial industry standard of how to compile a TMF and what documents to include and naming conventions
        • Not every company follows this model
          • The reference model consists of:
            • 11 zones based on clinical function
            • Pick a zone, find the artifact, and place document into the artifact
              • Ex. IRB zones include IRB and IRB-associated documents
  • The clinical research professional role in TMF management
    • TMF contributors/consumers- 
      • Sponsor
        • Red= largest contribution and use of TMF project manager and clinical manager, make sure TMF is complete 
        • Green = regular contributions (ie. documentations of new sites) 
        • Blue = infrequent contributors or consumers 
      • Site
        • Obligated by federal regulations to maintain records at site for 3 years post-marketing
        • Documents per trial stage
          • Start-up (15%), conduct (75%), and close-out (10%)
          • Start-up and close-out is well defined
          • Conduct is when data may get muddled
          • Essential documents per study phase- start-up
            • Protocol
            • Informed consent 
            • Plans
            • Master file plan 
            • 1572s.
          • Essential Documents per study phase- study conduct
            • Present challenges: no idea about number or protocol amendments
            • Credibility issues
          • Essential documents per study phase – close-out
            • Final clinical study report
            • Final country visit reports 
            • Close-out visit report
  • The challenges of TMF management
    • The number of documents in a TMF vary depending on type of study, number of sites, number of countries, and study duration
    • Impact of a clinical event
    • Protocol amendment etc. cause changes of documents 
    • Best to start collecting and storing documents properly from the beginning rather than wait until the end or before audit 
    • Timeliness
      • Maintain the TMF to know which sites to include for the next trial
      • Consistent data accrual means that a site is responsible and reliable and no one has to come out as often to check on them 
    • Everything in the TMF is subject to audits
    • Completeness
      • Systematic checks
      • Establish processes to react with conduct period 
      • Make sure everything required for the study is available
  • Regulatory agencies (FDA, EMA, MHRA) expectations


Accompanying text created by Annie Ly | Undergraduate Research Associate and Provost's First Generation Research Fellow |

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