June 28, 2012 | eCliniqua |  

By Maryanne Quinn and Fran Ross | GUEST COMMENTARY    

In June 2010, an industry coalition, under the auspices of the Drug Information Association, published version 1.0 of the Trial Master File Reference Model (TMF RM).  The Trial Master File (TMF) contains those essential documents that individually and collectively permit the evaluation of the conduct of a clinical trial and the quality of the data produced. Until this version of the TMF RM was released, there was no comprehensive common industry model for the TMF.    

The TMF RM presents a consensus position on the content that supports the evaluation of the conduct of a trial and the quality of the data produced, in accordance with industry opinion and best practices.  By design, the TMF RM is a guidance and not a regulatory standard.  The team that developed the TMF RM is composed of approximately 275 representatives from more than 165 biopharmaceutical companies, contract research organizations (CROs), consultancies, vendors, industry groups, healthcare, academia, non-for-profit / NGO and regulatory agencies.    

Within the coalition, a subgroup developed the first industry benchmark TMF surveys.  The intent is to gather data on industry’s current TMF processes and to develop benchmarks for quality and effectiveness improvements, both in paper and electronic TMFs.  The first survey was completed in the fall of 2010, and a second survey followed in the spring of 2012.  The 2012 survey provides valuable data from 168 respondents (57% of which were sponsors) on current TMF practices for both paper and electronic trial master files.  

Electronic Trial Master Files  

The 2012 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.    

The 2010 survey provided compelling data on eTMF benefits, showing that the ability to implement and validate the eTMF processes against established SOPs in a predictable and consistent manner provides process efficiencies, such as the ability to control TMF costs and quality.  This data is supported in the 2012 survey – 47% of respondents indicate that an eTMF eases the burden of internal and regulatory audits and inspections, while only 5% responded negatively.  

Electronic Investigator Site Files  

Although the 2012 data indicates a trend to eTMF, the data collected on electronic Investigator Site Files (eISF) looks dramatically different.  Not previously polled, the 2012 data reveals that most trials (59% vs. 23%) do not currently have the capacity for the site to manage their trial files electronically.    

Reasons for not implementing eISF

A majority of respondents (55%) have not yet considered using eISF in their trials, although significantly, no respondent cited site refusal as a rationale for not using eISF.  Many respondents commented on planning for eISF in the future (similar to the 2010 data on eTMF).  Based on the trend towards eTMF, we anticipate that there will be a similar trend toward eISF implementation as organizations refine and mature their eTMF processes.  

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.  

Conclusion 

Our 2012 survey data confirms that eTMF uptake continues to grow, eISF is entering the clinical trial landscape, and the TMF RM continues to inform best practices.  V2.0 of the TMF Reference Model, which includes content update feedback from adopters and has been expanded for device and investigator-initiated trials, was released on June 25, 2012.   

A free copy of the TMF RM can be downloaded at:  http://www.diahome.org/en/News-and-Publications/Publications-and-Research/EDM-Corner.aspx  

TMF RM activities can also be followed on LinkedIn by joining the TMF Reference Model group.  

Maryanne Quinn is President, Integrated Submission Strategies and can be reached at ISS.Quinn@Verizon.net  

Fran Ross is Principal Consultant, Paragon Solutions and can be reached at fross@consultparagan.com