Clinical Trial Modernization Raises FDA Compliance Issues

The shift toward greater use of remote data collection methods and innovative clinical trial designs has focused the attention of FDA officials on related challenges for ensuring the quality and accuracy of research reports and appropriate protection of research participants. In outlining a range of compliance issues important to drug development and oversight, Don Ashley, director of the Office of Compliance (OC) in the Center for Drug Evaluation and Research (CDER), recently addressed how an increasingly complex clinical research system raises issues for ensuring the reliability of research results and patient safety.

For many clinical trials, Ashley observed in a compliance policy presentation at the PDA/FDA joint regulatory conference Sept. 13, the COVID-19 pandemic encouraged the adoption of modern study approaches, creating new challenges in the process. These developments and the overall modernization of clinical trial design, operational approaches, and data sources have helped increase the speed and efficiency in developing medical products to treat serious diseases and conditions, Ashley acknowledged. He noted a shift to more pragmatic study designs, increased used of real world-data (RWD) and real-world evidence (RWE), and decentralized and point-of-care trial operations—developments that also generate concerns among regulatory officials for ensuring that clinical data can be relied on in making regulatory decisions.

Advancing quality

One approach for addressing the reliability of innovative research is for sponsors to adopt quality-by-design methods for clinical research operations, as is now widespread for drug manufacturing, Ashley proposed. This involves ensuring that trial design is adequate to answer the scientific question so that results are credible and resulting data is sufficiently accurate and reliable—fit for purpose—to support decision-making. When using digital technology to obtain study data, sponsors also should consider how to ensure that the rights, safety, and welfare of trial participants are adequately protected.

Ashley discussed these concerns about clinical trial data quality and reliability as part of a broader presentation at the PDA conference on how his office works to protect patients from poor-quality, unsafe, and ineffective drugs. Much of his presentation involved ongoing OC efforts to establish a modern drug supply chain security system based on enhanced methods for identifying and tracing drugs through national distribution operations. This initiative involves new licensing standards for distributors, changes in the National Drug Code, and implementation of an enhanced product verification system for 2023. Ashley further emphasized the importance of top corporate leadership in maintaining a robust state of control and a strong corporate quality culture to assure sustainable compliance and consistent production of high-quality drugs at a given facility in another presentation on Sustainable Compliance at the PDA/FDA conference.

These issues, including efforts to enhance clinical trial oversight to protect trial participants, are described in the OC annual report for 2021.¹ The report highlights continuing FDA efforts to expand oversight of drug compounding and to bring criminal charges against manufacturers that fail to correct ongoing product contamination problems. It also describes compliance actions to ensure that clinical trial sponsors submit required results information to the ClinicalTrials.gov data bank and collaborations with other CDER offices to challenge misconduct and violations by research organizations. And it notes that OC’s Office of Scientific Investigations (OSI) helped address challenges raised by expanded use of new research technologies in contributing to an FDA draft guidance published in January 2022 on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations.²

References

1. https://www.fda.gov/media/157954/download
2. https://www.fda.gov/media/155022/download