Inspection & Audit Preparation in Decentralized Trials
April 7, 2021
Decentralized clinical trials (DCTs) are expanding the potential sources for collection of clinical trial data. To ensure successful end-to-end execution of a DCT, steps to ensure audit readiness must be taken. While DCTs have changed the data collection landscape, the core elements of an inspection have stayed the same and Sponsors must ensure these new data capture technologies are fit-for-purpose. Below are several areas for consideration to ensure audit readiness from start-up through submission.
- End-to-End Data Flow: Data flow from collection through delivery of statistical analyses should be detailed. This includes data transfers, transformations, and derivations. Some key documents used to describe the clinical data flow are data transfer agreements, SDTM and ADaM submission packages, and display programs. These documents and programs will outline how data flow from the point of collection through analysis. If sites prepare data (e.g. mapping MRN to subject ID) prior to sending to the Sponsor or CRO this should be clearly outlined in a data flow also.
- Vendor Qualification: Applications being used for data collection must be assessed to ensure they are fit-for-purpose with respect to validation of the platform along with appropriate data protection and security.
- Audit Trail: An audit trail should exist and be readily accessible for all applications where data are directly entered by a participant. This ensures any questionable data can be investigated. The Sponsor or CRO should have a clear risk-based approach for review of the audit trail during the course of the study.
- System Access: Documentation of who has access to each system, when access was granted and removed, along with their level of access should be readily available. Additionally, an inspector may request access to the system. The Sponsor or CRO should ensure the availability for read-only roles within the system and the ability to grant access at both a site and study level.
- System Decommissioning: There is an increasing need for inspectors to access data and audit trails within the data collection application. This means a thoughtful approach needs to be implemented for decommissioning of systems that takes into account the timing of possible inspections. For example, a pivotal Phase III study may need to keep applications available until regulatory approval to support any inspections.
- Archival of Site Data: Upon decommission of the data capture system patient data and audit trails will need to be archived. An archival plan should be discussed early on to ensure what media will be used for storage. Additionally, considerations should be given to whether audit trails can be saved in a searchable format. With increasing data sizes audit trails saved in PDF format are sufficient to quickly identify specific points of data.
- Complete eTMF: With additional applications and systems being utilized, qualified, and validated it is essential that documents are stored in the eTMF in real time. Regular reviews of the eTMF are recommended to ensure documents are up to date and well organized. This will ensure inspection readiness activities will be less labor intensive.
Early consideration and implementation of these key elements will ensure audit readiness with respect to the technological applications utilized to support data capture in a DCT.
Heather Kopetskie, Director of Biostatistics, has over 16 years of experience in statistical planning, analysis, and reporting. She brings an extensive background of statistical and project leadership experience working on NIH and industry funded clinical trials in all phases of clinical development. Ms. Kopetskie has contributed to the publication of peer reviewed manuscripts and industry publications.