The Trial Master File Reference Model (TMF RM) group has announced the results of their 2019 TMF survey, which was launched in November 2019. The purpose of the TMF Survey is to gather industry-wide insights of TMF/eTMF management and knowledge of the reference model. The data collected is used to identify new TMF trends, measure the impact of the RM, and analyze changes in the industry. As in years past, there were some very interesting data points and insights regarding TMF practices.
SURVEY BACKGROUND/RESPONDENT DEMOGRAPHICS
The survey committee collected and analyzed data from 307 respondents. Most of the respondents (85%) are from a sponsor or a CRO organization located primarily in the USA and EU. Other countries represented include Asia Pacific (8%), Canada (5%), and Africa, Latin America, and the Middle East (2% combined).
TMF / eTMF INSIGHTS
At LMK, we believe the TMF is a living breathing document and the foundation of every clinical trial. To our great surprise, more than 30% of organizations view the TMF as an end state repository rather than a study project management tool. Since the last survey, the use of an eTMF system has increased by 150%. Over 41.% of study respondents are exclusively utilizing an eTMF system, and 54.5% use a combination of a paper and an eTMF system. Of the eTMF users, over 70% maintain blinded records within their TMF. Those who do not state risk and system security as the main reason for not doing so.
Surprisingly, even though the majority of companies use some form of an eTMF system, only 19.3% use their eTMF data or metrics in their Risk-Based Monitoring Program. Risk-based Monitoring (RBM) is an approach to clinical trial monitoring prompted by the current ICH E6(R2) Guideline for Good Clinical Practice. The purpose of risk-based monitoring is to help clinical research organizations predict and control uncertainty at an early stage. The advantages of implementing an RBM system are patient safety, cost efficiency, and reduced time to market.
TMF REFERENCE MODEL USE
Notably, over 90% of respondents have adopted the TMF Reference Model. The TMF is the compilation of essential documents that allows the conduct, compliance, and integrity of the clinical trial to be evaluated. In other words, it is the story of how the trial was administered and managed. Of the 94.2% of organizations that have embraced the TMF RM, 61.8% of them have modified it to meet their needs. Over 75% of respondents have more than 200 document types in their TMF index; no wonder so many trial teams struggle with filing the appropriate documents in each stage.
Over 50% of businesses have not had a remote/off-premise inspection by any regulatory agency/health authority. As a result of the COVID-19 pandemic, we anticipate remote inspections becoming more common. Following an Audit/Inspection, the most common findings are TMF Completeness, CRO Oversight, TMF Timeliness, and TMF/eTMF Quality. Over 50% of respondents have not undergone a joint inspection with a Sponsor/CRO, where both organizations were equally held accountable. Before issuing them credentials, 80.5% of organizations require inspectors to complete training.
TMF BEST PRACTICES
One of the biggest inconsistencies in the TMF has to do with how to address certified copy requirements. The majority of organizations do not have a certified copy process, while those who do either apply the process to any documents filed or only apply it when an original document is irreversibly replaced.
Overall, the TMF survey results provide very insightful information that will influence future revisions to the TMF Reference Model. Thank you to everyone who took the time to answer the survey. Continuous improvement to the RM could not be achieved without the data you all provide.