The recent release of the final guidance document detailing the FDA’s stance on the “Oversight of Clinical Investigations” is welcome news for the biopharmaceutical and medical device industry. The guidance clearly describes how central monitoring methodologies should be used, where appropriate, to oversee studies and effectively monitor clinical investigations to protect subjects and enhance the quality of research. The FDA also states that the previously preferred approach for regular on-site monitoring with 100% Source Data Verification (SDV) is no longer called for in the modern era, particularly due to technological advances that make it possible to monitor data quality more efficiently.
Central Statistical Monitoring (CSM)
The guidance advocates the use of central monitoring to ensure the quality of clinical trial data. The agency cites two papers written by the architects of CluePoints’ intelligent statistical algorithms that describe how these techniques can be used to effectively detect anomalies and “help improve the effectiveness of on-site monitoring by prioritizing site visits using central statistical data checks” (Buyse et al., Statistics in Medicine 1999 and Venet et al., Clinical Trials 2012).
Beyond Risk-Based Monitoring
Not only do the Central Statistical Monitoring techniques offered by CluePoints play a crucial role in Risk-Based Monitoring but they are used even more generally as part of a sponsor’s risk-mitigation strategy as they are extremely efficient at identifying data anomalies and consequently enhancing the quality of the final submission. Larger pharma sponsors are taking the clinical oversight advantage a stage further and are using CluePoints to ensure that their strategic outsourcing programs are not just getting them to database lock on-time and on budget, they are also safe in the knowledge that the quality and integrity of their clinical data is beyond reproach. They are running regular analyses of the clinical data throughout the study and charging their partners with taking corrective actions as discrepancies are identified.
Proven and Validated
The resulting efficiencies from undertaking Central Statistical Monitoring to target the sites identified ‘at risk’ are now being successfully harnessed by many sponsors and CROs alike. The savings that sponsors will enjoy from a comprehensive Central Monitoring approach will no doubt be quite significant in the medium-term, but even today sponsors can experience tangible cost benefits by reducing on-site monitoring efforts through targeting those sites that are deemed to be outliers using advanced statistical techniques to analyze the clinical trial data.
Marc Buyse, Founder of CluePoints commented, “This is a major step forward for our industry and one that all sponsors should embrace. The opportunity to improve data quality and integrity whilst mitigating risk is the outcome that everyone wants and the agency is encouraging an approach that not only does this but offers companies the opportunity to increase efficiencies and, ultimately, save a lot of money. CluePoints is delighted to be at the forefront of this initiative and is available to consult with anyone who is interested in the practical application of these techniques based on proven and validated experience to date”.
Francois Torche, CEO, CluePoints recognizes that the guidance reflects the passionate commitment of his colleagues, “The agency’s guidance is recognition of an approach that the CluePoints team has been working towards for a number of years. We have a talented and enthusiastic group of experts that have been assisting sponsors to implement various approaches to Risk-Based Monitoring and the final guidance is a very close match to our overall vision. Subjective Key Risk Indicators based on operational metrics are of value but there is no doubt that an objective assessment of data quality is crucial to managing regulatory risk and ultimately reducing costs”.
For copies of the papers on Central Statistical Monitoring that are referenced in the FDA Guidance for Industry “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring” please email [email protected] and visit www.cluepoints.com for the guidance itself. Also, you can register for CluePoints upcoming Webinar “Risk-Based Monitoring Improves Data Quality – It’s A Fact!” with speakers Marc Buyse of CluePoints and Kostia Franklin, Senior Manager, Clinical Data Management of Cubist Pharmaceuticals here.