On June 6, 2023, the U.S. Food and Drug Administration (“FDA”) released draft guidance (“Draft Guidance”) updating Good Clinical Practices (“GCPs”) recommendations for interventional clinical trials involving human subjects. The Draft Guidance, which is aimed at enabling the incorporation of rapidly evolving technological and methodological innovations into clinical trials, is adapted from the International Council for Harmonisation’s (“ICH”) recently updated E6(R3) draft guideline (“ICH GCP Guideline”). The updated ICH GCP Guideline modernizes clinical trial design and conduct by allowing more flexibility without compromising data integrity or human subject protections. The objective of the ICH GCP Guideline is to provide a unified standard to facilitate the acceptance of clinical trial data for all ICH member countries and regions by applicable regulatory authorities. While it is important for entities that engage in human subject research to review and understand the Draft Guidance adopted by the FDA given that it reflects the FDA’s current thinking on this topic, such entities should remember that guidance documents do not establish any rights and are not binding on the FDA or the public. Accordingly, alternative approaches may be used if they satisfy the requirements of applicable statutes and regulations.
Background and Scope
GCPs are international guidelines developed by the ICH that establish ethical, scientific and quality standards for the development and conduct of trials that involve human participants. They seek to create a uniform standard that safeguards the rights, safety, and well-being of trial participants by incorporating principles drawn from the Declaration of Helsinki, while also ensuring the reliability of clinical trial results. Given that the FDA is a Founding Regulatory Member of ICH, it plays a critical role in the development of each of the ICH guidelines, which the FDA subsequently adopts and issues as guidance to the industry. The last version of GCP guidance, known as E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1), became effective in March 2018.
The current updates to the ICH GCP Guideline and corresponding Draft Guidance apply to clinical trials that are interventional in nature, meaning they are intended to test investigational products (e.g., drugs and devices) that will be submitted to regulatory authorities for review. However, as permitted by local requirements, the ICH GCP Guideline may also apply to other interventional clinical trials of investigational products that are not intended to support a marketing authorization.
Greater Flexibility in Trial Design and Execution
The key changes proposed by the Draft Guidance are intended to provide additional flexibility to clinical trial sponsors in the design and implementation of their trials by allowing sponsors to use innovative trial designs and data analysis methods to customize their trials as new technology is adapted and perfected. For instance, the Draft Guidance includes the option to perform remote site monitoring and encourages the use of fit-for-purpose innovative digital health technologies (“DHTs”). Examples of DHTs include wearable sensors to record blood pressure or glucose levels, mobile phone applications used to track health information or physical activity, and computerized programs used to perform electronic clinical outcome assessments during clinical trials. Furthermore, the Draft Guidance provides recommendations on how sponsors can develop trial-specific oversight mechanisms to allow for broader design flexibility, such as endpoint assessment/adjudication committees to exclusively review Investigator-reported endpoints and determine whether they meet protocol-specific criteria. These endpoint committees would be separate from the more general independent data monitoring committees currently used in many clinical trials.
Data Governance
The Draft Guidance also strengthens the existing focus on data governance from both a sponsor and investigator perspective. While data governance has always been a key concern in clinical trials, the proliferation of electronic data records and electronic trial management systems necessitated an overhaul of the GCP data governance guidelines and reference language, such as renaming “essential documents” as “essential records” to indicate that trial records may be electronic in nature and not hard copy documents. In addition, the protection of confidential data is key for the success of a trial, throughout the lifecycle of that trial. The Draft Guidance includes recommendations for data capture methods, digital audit trails, and data transfer and migration safeguards.
In the context of the proliferation of modern clinical trial management systems and essential record databases, the new guidelines are intended to create flexibility by allowing sponsors and research sites to use systems that work best for their purposes. Therefore, the Draft Guidance also includes recommendations for the management of computerized systems in general. Under the Draft Guidance, both sites and sponsors should have procedures in place for training on their systems, system security and system and data integrity validation, as well as technical support and system failure contingencies.
Practical Takeaways
Historically, the clinical trial enterprise has been seen as expensive, inefficient and slow to adapt to technological and other innovations—problems that were brought into relief by the COVID-19 pandemic. The Draft Guidance is intended to address these challenges by affording greater flexibility and efficiency and by creating more room for innovation within clinical trial administration while maintaining the essential role of GCPs in ensuring human subject safety and clinical trial data integrity.
As part of the FDA’s established process, this Draft Guidance will be open for public comment until September 5, 2023. The ICH Expert Working Group, a working group of ICH members charged with developing a harmonized guideline that meets ICH objectives, will also review and consider comments on this Draft Guidance, as well as feedback from other ICH member countries, including the United States, before finalizing the ICH GCP Guideline.
Clinical trial sponsors and trial sites should consider the impact of these updated guidelines carefully. If you have any questions on how to prepare and submit a comment, please contact the following:
- Caitlin Bell-Butterfield at cbell-butterfield@hallrender.com or (919) 228-2408; or
- Your primary Hall Render contact.
Special thanks to Summer Associate, Ben Murphy, for his assistance with the preparation of this Article.
Hall Render blog posts and articles are intended for informational purposes only. For ethical reasons, Hall Render attorneys cannot give legal advice outside of an attorney-client relationship.
