What is CluePoints and How Does it Work?

Closely aligned with guidance from the FDA, EMA and ICH E6 R2, CluePoints® is used by sponsors and CROs as the engine to drive risk-based monitoring and study execution (what we are now calling RBx) and to provide broader risk mitigation and patient safety through overall Data Quality Oversight. The value of using CluePoints® lies in its powerful and timely ability to identify anomalous patient data and site discrepancies allowing improvement in clinical data quality, optimization of on-site monitoring and a significant reduction in overall regulatory submission risk.

Since the early 2000s, a dedicated team of statistical experts has been developing, validating and enhancing a powerful engine known as SMART™, a patent-protected software engine based on the industry-recognised concept of Central Statistical Monitoring (CSM). The solution allows users to assess the quality and integrity of clinical trial data in an independent and objective manner. Further our development team has added new product enhancements such as modules for Patient Profiles and Site Inspection Readiness and underlying technology to harness Machine Learning and Predictive Analytics. The product will continue to evolve to improve cost and resource efficiencies in clinical trials and ensure compliance with the regulatory requirements.

The brainchild of Harvard-trained biostatistician Marc Buyse, CluePoints® has evolved from an academic research interest to a full commercial entity. Buyse is cited a number of times in the FDA’s Risk-Based Monitoring Guidance for his work in detecting fraud in clinical trials using statistical modelling techniques.

In contrast to traditional methods, CSM is a completely technology-agnostic approach that is based on the actual clinical data and key operational variables. The concept is that all the hundreds of patient-related variables and endpoints in a study and many operational data are deemed to be indicative of quality, from lab data, CRF data, and baseline data to treatment outcomes and time to resolve queries, everything is assessed. The assessment techniques use complex and proven algorithms to drill down into individual patient and site data to better manage risk and determine variations between sites, regions, countries and even patients in order to identify statistical outliers. This enables aspects that are at risk or demonstrate errant results to be identified and resources deployed as required, significantly enhancing overall quality, reducing risk and improving patient safety.

How do I Determine the Value of CluePoints?

Based on the experience of analysing dozens of trials using the CSM approach advocated by the regulators, CluePoints has found that the use of as single approach to data interrogation is insufficient to ensure data quality and patient safety:

“Key Risk Indicators (KRIs) are obviously important, but the guidance also points out that you can use a more comprehensive statistical approach to interrogate the data, and this is exactly what CluePoints is doing. In fact, if you look at the FDA guidance, it explicitly states that you can target on-site monitoring by identifying higher risk clinical sites with findings that may or may not be related to critical data. So, that means that 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.” Marc Buyse.

RBM strategies have historically relied on KRIs that are pre-defined by the study team and potentially reveal deviations in study conduct while identifying poor performance in investigative sites. Predefined metrics are computed for each site, and risk is controlled by closely analyzing data to identify issues. Targeted monitoring frequency can then be adapted based on site performance. Although KRIs are effective to a certain degree, their implementation is far from straightforward. They need to be pre-defined, programmed, tested, and validated, and they only use part of the massive volumes of data collected in clinical trials. Unlike Key Risk Indicators (KRIs), which use subjective signals to suggest where problems might lie, Intelligent Statistical Monitoring approach determines issues based on an objective and accurate process.

In response to the widespread issues that the industry is facing, an innovative Central Statistical Monitoring (CSM) approach has been introduced that takes a more neutral view of data and offers a complementary layer to traditional KRI and data management techniques. Based on advanced statistical methods and data mining tools aimed at detecting sites with abnormal patterns in data, this approach is helping to focus monitoring activities on centers where it is most necessary and on data that matters most.

How Can I Test CluePoints?

CluePoints® has been developed since the early 2000s using hundreds of clinical trial data sets, but the real way to assess the value is to have your clinical trial data analyzed by CluePoints® and see the results for yourself.

The elegance of this solution lies in its simple and pragmatic approach to enhancing efficiency in the monitoring process:

  • Select a data set from an ongoing or completed trial.
  • We will upload the data into the CluePoints SMART™ engine which will automatically determine the most appropriate statistical techniques to use based on our proprietary set of highly-tuned algorithms, to provide a comprehensive analysis on all of the clinical data.
  • We will also consult with you to agree on a limited number of operational variables to analyse using a statistically-based KRI approach.
  • We will then assist you to evaluate the resulting output and determine the signals that highlight anomalous and inconsistent data and why they occurred.
  • We will work together to determine how to best supplement ongoing monitoring activity and Source Data Verification based on these results.
  • You will enhance patient safety, cleanse and improve site results throughout your trial and, ultimately, reduce regulatory submission risk by providing the best quality data set based on an objective interpretation of all relevant information.

We are confident that you will see the benefit and would welcome the opportunity to prove the power of this unique approach. Contact us for more information