All clinical studies require staff to create and maintain extensive procedure documentation, covering virtually every aspect of the investigation—from study execution and results to patient care and safety—to ensure data integrity, adherence to best practices, and demonstration of compliance. This collection of essential documents is referred to as the regulatory binder and contains very specific content that the Food and Drug Administration (FDA) and Institutional Review Boards (IRBs) are looking for when performing regulatory inspections.
Effectively managing essential documentation is critical to a study’s success; but, too often, sites find it an unwieldy, complex process, resulting in costly overheads and information gaps.
Procedure document requirements
Traditionally, study documents are paper-based and maintained at each site—a common practice, even in today’s automated world. Study documentation has its own set of acronyms, primarily:
- Essential Documents (ED) are documents that: “individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced.” (sometimes referred to as the regulatory binder)
- Trial master file content (TMF) is the trial’s collective EDs
- The ICH Guideline for Good Clinical Practices (ICH GCP) is considered the global reference for managing the collection of ED
The FDA (or any regulatory authority) can review the TMF content at any time but does not formally require its creation. The FDA, however, expects the TMF to comply with the ICH GCP, and can evaluate it to determine whether the study adhered to best clinical practices. This means that sponsors should prepare for their TMF to undergo regulatory inspection.
What are the effects of decentralized procedure documents?
If you don’t provide your sites with official procedure documents, then, chances are, each one could be using different, non-controlled versions. These documents could be spread and stored throughout the study site, and accessed and edited by multiple members of the site staff. This throws up a multitude of issues:
- Inconsistencies: sites store documents in varied forms, including paper, shared drives, flash drives, and CDs, meaning that staff lack a common, easy, and rapid system for accessing important information
- Noncompliance: researchers are not able to easily locate official or usable protocol documents, and might even resort to devising their own cheat sheets
- Regulatory gaps: site documents that do not comply with GCP guidelines remain in circulation, with no built-in checks or monitoring
- Accessibility: staff finds it difficult to locate, obtain, and verify documents - wasting time, causing frustration, and introducing errors
- Disorganization: poor documentation control and access adds chaos to site operation and mandatory training cycles, in an already highly dynamic, fast-paced environment
- Archival risks: spread out multi-format documentation impedes mandatory archiving. Sponsors may only budget for five years of archival, but regulations may require longer retention periods for clinical trial documents in approved marketing applications – it is particularly worth noting the December 2018 guidance from the European Medicines Agency (EMA) and FDA guidance on this topic.
Importance of a central document repository
To stay competitive and on budget, the modern clinical trial requires centralization and streamlining, replacing inconsistent processes with security, ease-of-use, and built-in checks. This can mean moving your regulatory binders online and moving away from paper. This is a significant effort, but many have found benefits in doing so.
Specifically, clinical trials benefit from a single integrated technology platform, which stores key study documents in one place. This should provide version control to confirm up-to-date information; workflows to view communication history; and audit trail functionality to ensure effortless data-tracking for inspections. These core features are key to being able to comply with EMA and FDA requirements for electronic trial documents, or electronic Trial Master Files (eTMFs).
With a centralized document repository, your site staff can rapidly disseminate, control, and verify information, supporting every aspect of your study, from day one to archiving. This includes:
- Smooth initiation: at the start of a study, you can rapidly and consistently deliver study conduct related information to all sites
- Accurate interpretation and verification: with open, streamlined, and transparent site communication, site staff can easily monitor compliancy issues, including training and data reviews
- Save time: site staff can immediately access documents and confirm their communication has been received/read
- Improve site experience: site staff can access web-based information related to protocol, training, and more, 24 hours a day, via automated tools
- Easily set up new sites: studies can jump start new sites with immediate access to shared information and protocol resources, with no need to replicate data or transfer bulky binders
- Better patient experience: patients can gain easy access to their own records depending on the Health Insurance Portability and Accountability Act of 1996 (HIPAA) rules for the study
- Archiving solution: documents in the same format and centralized location can be easily stored to meet the required retention period.
To find the best solution, identify a centralized study-hub with a document repository that can bring your site staff, patients, and study together as a cohesive unit —one platform, one team—via an integrated eClinical solution, providing essential document management and workflow features.