FDA Extends CRADA with CluePoints to Further Explore a Data-Driven Approach to Quality Oversight in Clinical Trials

FDA and its stakeholders have an interest in assuring the integrity of clinical trial data and the protection of participants during the conduct of clinical research. Misconduct in clinical research, including, but not limited to the falsification or omission of data in reporting research results, places all subjects in that trial at possible safety risk. Fraud jeopardizes the reliability of data submitted to FDA, and undermines the Agency’s mission to protect and promote public health. FDA and other regulators rely on whistle blowers and site inspections to detect signs of possible misconduct.

Due to the volume of product submissions, FDA can only inspect a small proportion of clinical trial sites. The determination of which sites to inspect can involve recommendations by clinical and statistical reviewers, CDER’s Risk-Based site selection tool and FDA inspectors’ judgment and experiences.

The initial Cooperative Research and Development Agreement (CRADA) between FDA and CluePoints began exploration of a data driven approach to selecting sites which exhibit data anomalies indicative of fraud, misconduct or sloppiness. Under this CRADA, FDA and CluePoints, Inc. have developed and tested enhancements to CluePoints’ existing software to produce an ordered list of “anomalous sites”, i.e. sites whose data are highly inconsistent with data from other sites; added statistical tests and models to those already in the existing software; refined the scoring system used to identify outlying centers; tested and implemented the software in a high performance computing environment; and will continue to develop a user-friendly interface for use by medical reviewers and other interested parties at FDA.

The CRADA has been extended to October 2021 to include additional research focused on “moderators of treatment effect” and real-world evidence. Additional analyses based on these moderators of treatment effect will include geographic region, country and supervising Contract Research Organizations (CROs).

FDA also plans to conduct statistical tests provided by CluePoints such as Key Risk Indicators (KRIs) that will supplement the existing data-driven approach to selecting sites for inspection using a risk-based approach.

Benefits to the FDA of the CRADA’s data driven approach include the detection of anomalous sites which may have escaped detection previously, rapid turnaround of results, the ability to determine the nature and extent of data anomalies, and the ability to explore the interaction of various factors with data quality. These benefits are expected to not only accrue to the site inspection process and improve data quality for all reviewers, but may also inform the efforts of clinical and statistical reviewers to conduct sensitivity analyses, subgroup analyses and site by treatment effect explorations.