Data Integrity in Global Clinical Trials: Discussions From Joint US Food and Drug Administration and UK Medicines and Healthcare Products Regulatory Agency Good Clinical Practice Workshop

Abstract

Recently, regulatory bodies have published guidance related to this topic. 2-7 A common thread among these various documents is an emphasis on risk-based approach to data management, specifically targeting data and study procedures that are critical and have the greatest impact on maintaining subject safety and determining product efficacy. For example, the Medicines and Healthcare products Regulatory Agency (MHRA) Good Practices (GXP) Data Integrity Guidance and Definitions document discusses the data lifecycle, data governance, and other organizational culture features to be considered in a risk-based approach. 2 An open reporting culture in organizations should be encouraged as fundamental to data integrity promotion throughout the data lifecycle, including processes from generation or recording of data to destruction, if needed, and the intervening processes (Figure 1).

Clinical Quality Considerations when Using Next-Generation Sequencing (NGS) in Clinical Drug Development

“…Data controllers, processors and accountabilities should be traceable through a combination of contractual agreements, and data integrity controls (procedural and technical) throughout the data lifecycle (see also Sect. 4) [12,15]. Documentation should objectively demonstrate the integrity of the data was maintained to support patient care and treatment, efficacy and/or other analysis decisions [9,12,13,15].…”

“…4) [12,15]. Documentation should objectively demonstrate the integrity of the data was maintained to support patient care and treatment, efficacy and/or other analysis decisions [9,12,13,15].…”

“…In clinical drug development, all GxP computerised systems (e.g., laboratory instruments, laboratory information management systems (LIMS), sample management systems, IT development tools) must be qualified or validated for their intended use [9,12,15]. This includes risk-based validation or qualification of the software, components and infrastructure that comprises the system or is used in the post sequencing analysis bioinformatics pipeline.…”

“…In clinical trials, NGS service providers can perform various levels of GxP type activities under different types of relationships such as a standard service provider relationship, co-development relationship or collaborative model relationship. Irrespective of the relationship type the pharmaceutical sponsors must ensure clear oversight of the GxP service provider (and their third parties) including assurance they are fulfilling contractual obligations and regulatory requirements to ensure end-to-end sequencing data integrity and data credibility [9,15,18].…”

“…Data quality considerations -Computerised system validation and/or qualification policies, processes, controls and monitoring in place to ensure systems are fit for their intended use[9,12,15,18] -Audit trails implemented (as required) and assessed as fit for purpose and regularly reviewed[9,12,15] -A data workflow, including data processing and analysis procedures clearly documented and followed.…”