Good Clinical Practice (GCP) is a critical set of internationally recognized guidelines that govern the ethical, scientific, and quality standards for conducting clinical trials. Adherence to GCP standards is fundamental in ensuring the protection of the rights, safety, and well-being of clinical trial participants. These standards, in line with the Declaration of Helsinki, maintain the ethical rigor of clinical trials, resulting in the production of reliable and credible data. They are primarily designed to safeguard the human rights of clinical trial subjects and volunteers while instilling confidence in the safety and effectiveness of the tested compounds.
The International Council for Harmonization (ICH) E6 guideline, first published in 1996, was updated with the R2 version in 2016 with a strong emphasis on risk-based approaches and quality management concepts. The updated ICH E6(R3) GCP, released in 2023, continues to facilitate mutual recognition of clinical trial data by ICH member states and regions, streamlining regulatory authority acceptance. The R3 version of the guideline further advances concepts related to data collection, management, electronic data technologies, new trial designs, trial service providers, and the complexities of clinical supply chains.
The ICH E6 guideline focuses on interventional clinical trials involving investigational products, building upon the foundational principles outlined in the ICH E8(R1) document, titled "General Considerations for Clinical Studies." These principles center on cultivating a culture of quality, effective drug development planning, identifying critical factors for trial execution, and adopting a risk-based approach in proportion to the circumstances.
Given the multifaceted nature of clinical trials, the GCP guideline comprehensively addresses various aspects, including those related to Institutional Review Boards/Independent Ethics Committees (IRB/IEC), the roles of trial Investigators and Sponsors, and data management throughout its lifecycle, encompassing the use of computerized systems and data security.
The guideline also features several appendices that provide additional guidance on the Investigator's Brochure, the Clinical Trial Protocol, protocol amendments, and the maintenance of Essential Records for the Conduct of a Clinical Trial.
As the guideline is extensive, it is impractical to cover all of its elements in one sitting. We can focus on a specific question related to data integrity and data management.
The E6 (R3) guideline is designed to accommodate emerging technologies, including digital health technologies like wearables and sensors, with a forward-looking approach to advance the science of healthcare. It anticipates the incorporation of innovative technologies into existing healthcare infrastructures, broadening the nature of specific data sources generated in clinical trials. This guideline aims to keep future clinical trials aligned with the rapidly evolving data and technology landscape, and it is media-neutral, allowing for the use of various technologies for documentation purposes.
Projections for the use of wearable medical devices suggest continued growth and innovation in the healthcare industry, encompassing health and fitness tracking, remote patient monitoring, personalized medicine, chronic disease management, telehealth integration, drug delivery, monitoring, and elder care. These devices enable healthcare providers to remotely monitor vital signs, health metrics, and changes in chronic conditions, collect individualized health data, and generate personalized treatment plans. Wearable device-based drug delivery and monitoring ensure patient adherence to medication regimens. Integration of artificial intelligence-based data analysis is expected to provide real-time health insights and predictive analytics. The global wearable medical device market has already become a multibillion-dollar industry and is poised for further expansion.
The guideline dedicates significant attention to data governance from both the investigator and sponsor perspectives. Health authorities worldwide recognize that proper data management, ensuring data integrity, traceability, and security, is essential for accurate reporting, verification, and interpretation of clinical information. The ICH has previously issued ICH E8(R1) and ICH E9 guidelines, covering related topics. The ICH E6(R3) discussed here identifies critical processes for a comprehensive approach to the full data lifecycle, including data protection, managing computerized systems, safeguarding trial randomization and blinding, and establishing data-driven decision-making processes.
The Data and Records section of the E6(R3) guideline covers data handling, including steps to ensure data integrity and confidentiality. The guideline underscores the importance of planning data collection, methods of data acquisition and storage, ensuring a sufficient level of security, and safeguarding data. It places a significant burden on the trial sponsor while outlining the roles of the investigator, service providers, and trial participants in data capture, retention, and disposal. The use of computerized systems in data collection and handling is also discussed, emphasizing control, documentation, and quality assurance of these systems. The availability of a large volume of data necessitates the need for statistical analysis, which is also addressed in the guidance. The guideline calls for documented quality control of statistical programming, traceability of analysis, and clear procedures for blinding and unblinding. Finally, it stresses the importance of data recording, retention, and record access control in ensuring overall data quality and safeguarding.
In summary, ICH E6(R3) continues to advance standards governing conduct of clinical trials while moving in step with the quickly developing data technology.
This guest editorial article was written by Boris Gorovits, Ph.D., principal at Gorovits BioSolutions, LLC. Dr. Gorovits was part of an AAPS Scientific Advisory Committee commenting team that provided feedback for the published ICH draft guidance.