Clinical Trials: Mitigating Inspection and TMF Efficiency Delays

In the world of clinical product development, the challenges of navigating the interplay between innovation and regulation are continually evolving. This interplay is complicated by variables such as global events (COVID-19, for example), site management, patient safety, patient recruitment and inclusivity, and more. While trying to navigate these variables, sponsors must comply with strict regulations with precision, a responsibility that is even further complicated when a study is operating across countries and their respective regulatory personnel. These variables, and the processes meant to account for them, amount to a significant amount of risk for sponsors to mitigate. In this complex and ever-evolving landscape, preparedness and compliance play pivotal roles in achieving successful clinical trial outcomes.

The Trial Master File (TMF) represents a significant source of risk for clinical sponsors. According to drug-dev a staggering 85% of studies experience delays due to inspection findings, emphasizing the importance of proactive risk assessment. To create an effective inspection-readiness strategy, it is important for sponsors to conduct a self-analysis to identify areas of risk and, in turn, create recommendations for improvement to resolve these points of vulnerability.  In response to the need for risk-based strategies, the team at Trial Interactive developed a tool to help sponsors get a quick snapshot of their overall TMF risk within minutes. Pragmatically named the risk score survey, this risk calculator gives sponsors a sense of how likely they are to encounter inspection findings with their current TMF strategy, highlights the risk areas, and makes recommendations to resolve these points of vulnerability.

Before delving into the details of inspection findings and where the risk lies, it is crucial to grasp the concept of TMF health. A well-maintained TMF is characterized by three main areas–quality, completeness, and timeliness.

Maintaining TMF Health: Quality

The documents within the TMF must adhere to quality standards. This commitment ensures the creation of precise and comprehensive records of the trial, thorough observance of regulatory guidelines, and documentation of informed consent.

Managing a TMF is no small act, and when it comes to maintaining quality in clinical trials, there are several key risks to be aware of. Clinical trials, by their very nature, are complex endeavors and involve many partners, making TMF management challenging. When outsourcing support for the TMF, it’s crucial to streamline, centralize, and minimize the impact of working with different parties on inspection readiness. Failure to do so can bring risk which, in turn, could lead to missing documents from the sponsor eTMF.

A centralized structure, combined with a robust TMF process and SOP, is an effective strategy for streamlining outsourcing and ensuring regulators’ expectations are met for quality standards across systems and processes.

Maintaining TMF Health: Completeness

The TMF should be a comprehensive record of all essential documents, reflecting the entirety of the trial's conduct. This means that the TMF should not only contain all required documents but also ensure that each document is the most recent and accurate version. Maintaining the latest version of a document in the TMF is essential. A document's latest version ensures it captures the most up-to-date information. Additionally, ensuring the presence of newer versions is vital as some eTMF documents expire over the course of a study.

Maintaining TMF Health: Timeliness

For a TMF to be considered contemporaneous, it should contain documents that are created and updated in real-time, reflecting the ongoing status and activities of the trial. This ensures that the TMF provides a current and accurate picture of the trial's progression. Having immediate insight and visibility into every aspect of the TMF, such as monitoring visits, ensures that the documentation is current and accurately represents the trial's status.

By prioritizing the quality, completeness, and timeliness of the TMF, life sciences sponsors can mitigate these risks and maintain the momentum of their studies. It is crucial for companies to take proactive steps, invest in training, and regularly conduct self-assessments to ensure TMF Health. Only then can we hope to reduce the 85% of clinical trials encountering delays, and continue to advance medical science for the benefit of patients worldwide.

If you want to quickly assess your TMF risk, take the TMF Risk Score survey and get a quick assessment to help you identify potential vulnerabilities and close the gaps in your risk-based TMF strategy.