By Maxine Bookbinder

November 10, 2016 |  Last month CluePoints and FDA signed a CRADA, Cooperative Research and Development Agreement, to enhance data integrity in clinical trial submissions to the FDA using CluePoints software.

Sponsors worldwide have employed CluePoints, a provider of risk-based monitoring and data quality oversight Software, since 2012 to run comprehensive, statistically based analyses on clinical trial data, ensuring data integrity, increasing quality and patient safety, and reducing submission risks.

In October, the FDA signed an agreement with CluePoints to use its Central Statistical Monitoring Platform to find inaccurate and incomplete data in clinical trial submissions. The framework is a standardized and objective engine based on algorithms that, in just hours, find specific anomalies in patient data submissions and site discrepancies through an independent analysis of the data. Harvard-trained biostatistician and CluePoints founder Marc Buyse began developing the program in the 1990s to find statistical patterns of fraud. The approach was later validated and extended to the detection of any data anomalies, whether due to fraud, sloppiness, non-calibrated equipment, or other sources of errors.

“Key Risk Indicators (KRIs), one of our key products, are obviously important, but the FDA and EMA guidance documents also point out that you can use a more comprehensive statistical approach to interrogate the data, and this is exactly what CluePoints’ unique SMART statistical engine is doing,” says Buyse. “Even non-critical data may be indicative of data problems and, therefore, a statistical approach that looks at the totality of the data is crucial in addition to KRIs.”

CluePoints began working commercially with sponsors in 2012; the FDA approached the organization in 2014. “The agency had similar ideas and a common vision,” says Patrick Hughes, CluePoints Chief Commercial Officer. “We had already put in the hard yards in developing a scientifically-validated platform in an objective way. The FDA recognized the amount of expertise and time needed to achieve such a powerful approach.” Although the details of developing further joint intellectual property need to be defined, Hughes says that “this is a healthy collaboration with many exciting ideas in play.”

The FDA is the first government agency to collaborate with CluePoints. “Using the CluePoints engine, the FDA can run data through the engine in just a matter of hours to determine a ranking of sites that are at risk,” says Hughes. “The platform is available to sponsors as a cloud-based solution with zero installation required. The FDA, however, will install the solution behind its firewall and take advantage of its High Performance Computing environment to get the best out of data interrogation.”

The platform will enable the FDA to use an objective, data-driven and time-efficient tool to identify intentional and unintended misconduct and develop a user-friendly interface for medical reviewers. Because of its quick turn-around time, it can be used on all submissions. While it can determine the nature and extent of data anomalies, sponsors will likely complete data interpretation and determine possible consequences.

Hughes adds that while “this can’t cure all the ills of the world,” it can highlight risks and issues that need attention. “The industry is changing with an emphasis on more unsupervised data collection directly from patients using wearables and other connected devices. This approach ensures that data collected everywhere, whether it be at a clinical site or by a patient reported outcome, is accurate and compliant.”

For example, in a clinical trial occurring in different regions of the world, some sites erroneously under-reported “adverse events” but correctly reported “serious adverse events.” The CluePoints platform found this discrepancy and reported it to the sponsor, who conducted re-training to ensure conformity among all sites. 

Hughes notes other commercial uses of the platform. If a company outsources the majority of its study contact work to third parties, it can use CluePoints to review data centrally and independently and stay in control of its trials. Also, a company considering an acquisition can run independent data consistency checks on its target’s trial data to uncover possible hidden issues that wouldn’t be evident using traditional due diligence techniques.

CluePoints is in communication with various regulatory bodies worldwide but not yet in a formal, collaborative way as with the FDA. Meanwhile, Hughes is excited by the potential of the CRADA and Risk-Based Monitoring. “The journey we are going on together is to see what makes pragmatic sense,” says Hughes. “The industry is changing with an emphasis on data and its decentralized collection. Right now, we are just scratching the surface. We have a huge amount of ground to cover in terms of adoption of Risk-Based Monitoring, which is a catalyst for disruptive change but, as we’ve seen with most technological advancements over the years, change is difficult in a highly-regulated industry. The rewards are huge operational cost-savings and improved data quality and patient safety.”