FDA Looks to Enhance Data Integrity Detection Tools
In response to increasing data integrity citations in Warning Letters and inspections, FDA has signed an agreement with CluePoints to develop a data driven software tool to detect data anomalies indicative of fraud, misconduct or sloppiness. Earlier this year, the agency released a draft guidance, Data Integrity and Compliance with CGMP, to clarify the role of data integrity in current good manufacturing practice for drugs. The new agreement with CluePoints will lead to a more focused approach in detecting questionable study or manufacturing sites to inspect, according to the company.
CluePoints describes its software as a “central statistical monitoring solution designed and perfected over the last 10 years. It employs unique statistical algorithms to determine the quality, accuracy, and integrity of clinical trial data both during and after study conduct. Aligned with guidance from the FDA and EMA, CluePoints is deployed to support traditional on-site monitoring and to drive a risk-based monitoring strategy.”
Under the agreement, FDA and CluePoints will develop and test 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; explore ‘moderators of treatment effect’, i.e. factors such as center, region, or country that have a statistically significant impact on the magnitude of treatment effect; add statistical tests and models to those already in the existing software; refine the scoring system used to identify outlying centers; add an exploratory tool to identify moderators of treatment effect; test and implement the software in a high performance computing environment; and develop a user-friendly interface for use by medical reviewers and other interested parties at FDA,” the company says.
The benefits of such an enhanced data integrity 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,” CluePoints says. “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.”
Meanwhile, industry stakeholders have asked FDA to clarify portions of the draft guidance on data integrity and compliance with CGMPs (see story). The Generic Pharmaceutical Association asked the agency to clarify if the guidance applies to all laboratories, including research and development where there is no good practice impact, particularly during pre-development. It also said it would be helpful to have a section providing some guidance in case of limitations for software and vendors. Pharmaceutical Research and Manufacturers of America (PhRMA) said it supports the draft guidance and its use of a question-and-answer format that “will more easily facilitate future necessary revisions as FDA continues to clarify and reinforce its position in regard to data integrity compliance.” PhRMA provided recommendations and asked for clarifications on terms and definitions related to CGMP records; electronic versus paper records; validation of computerized systems and computers systems access; definition, review, and protection of audit trails; use of CGMP data in/for decision-making; CGMP data documentation and storage; data integrity compliance programs; and reporting of data integrity issues and personnel training requirements.