Monthly Archives

March 2017

ICH E6 Rev 2 – Ask the Experts

Last week, we hosted our second webinar of 2017, Implementing Risk-Based Monitoring – What Does the ICH E6 Rev 2 Mean for My Company? There were many great questions from the attendees. In fact, we had so many questions that we couldn’t get through them all! So as promised, we’ve documented the most common questions, along with our answers. Enjoy!

QRisk-Based Monitoring sounds like the FDA encouraging Sponsors to begin looking at Data from Sites earlier on in the Study timelines. So why are the Sites beginning to feel their “hair is now on fire” for faxing and copying HIPPA sensitive data over email and fax. This message/ perception needs to be looked at.  And know that R2 is an FDA to SPONSOR revision and should affect sites on a day to day basis

A:  Indeed Risk-Based Monitoring methodology does encourage pro-active monitoring of relevant data and information from across all participating sites in a clinical trial – with emphasis being placed on centralized monitoring using intelligent/statistical methods that help to identify sites that are outside of an expected range across various quality (or performance) measures.  This allows teams to direct their attention more effectively to clinics that may need some support to overcome particular challenges (training needs, etc.).  However, the practice of asking sites to fax or scan various patient source documents for remote review is not called for by RBM guidance/methodology.  This practice is being employed by some sponsors (for good or ill), and unfortunately, sites are being told that this is a part of “RBM”.  In our view – and based on the FDA and ICH guidance already provided – this is NOT part of RBM.

Q:  How does ICH E6 R2 impact Computer System Validation, if any?

A:  There are indeed several paragraphs added to the new R2 update that address aspects of Systems Validation.  We suggest you review those additions directly in the current final version (publicly available).

QRemind us when patient profiles will be rolled out in CluePoints

A:  Patient Profiles are available with our April release – in two weeks!

Q: ICH E6 R2 indicates the need for monitoring reports for central monitoring.  We recognize central monitoring may be conducted by various roles (dedicated resources, plus physicians, scientists, quality, data managers, etc.) and is done on an ongoing manner.  Any insights on how to best document central monitoring activities in a ‘report’ without overburdening the organization?

A: What documentation is created is dependent on where and how the monitoring activities are occurring. The most important element is defining, up front, the process, audit trail (if there is one) and criteria for assessment/outcome determination and action/escalation.  There are 2 primary ways to capture central monitoring activities in a report format: 1. A simple event-driven report typically created by the user completing the assessment listing/describing data reviewed/outcomes/actions. Or 2.  An end of study or scheduled summary report of activities that lists the activities/outcomes undertaken in a specific timeframe or throughout the study (e.g. in an RBM platform, like CluePoints). The objective of capturing the evidence of your central monitoring activities is to demonstrate that you are adhering to your monitoring plan and addressing the risk appropriately.

Q: Will you please address with ICH E6 R2 takes effect in US and EU?  In other words, when are sponsors expected to make sure their studies comply with the new guideline. 

A: ICH E6 R2 is expected to be effective in Europe, per the EMA, as of 14 June, 2017, and the FDA has not set an effective date as of today.

QHow do one can detect fraud in RBM studies?

A:  There are a number of statistical tests that can be very helpful in detecting fraud in clinical research, and we recommend using a combination of these to be most effective.  A few to consider:

– Variability testing:  looking for unusual lack of variability in patient measurements for a single patient (e.g., across visits) or across patients within one site.

– Mean values:  identifying patients whose mean measurements are consistently in a different range than other patients within the study.

– Timing of Events:  As in the ePRO fraud case that we discussed, looking at an unusual distribution of patient event dates or times can be helpful as well.

Q:  Do you have any recommendation of document that we can study for identifying KRI?

A:  We suggest visiting the TransCelerate RBM website, which posts publicly available RBM guidance materials including a suggested library of KRIs to consider.  The Metrics Champion Consortium (MCC) has also developed a list of KRI definitions – with more detailed guidance on KRI algorithms and thresholds.  Access to the MCC materials requires membership first.  CluePoints also has deep expertise in KRI methods and best practices and offers consulting in this area (and RBM methodology in general) if you are interested.

QDo you know what type of data errors were typically caught by SDV? e.g. unreported AEs? 

A:  Indeed the analysis we performed revealed that SDV had a relatively bigger impact identification of unreported AE’s (7% to 12% of total AEs) than on finding data entry errors (1% of data).  Our conclusion was not that you should do 100% SDV of AE’s, but that relatively more SDV focus should be put on AE reporting than on other data.

Q:  Do you have any examples of effective rationale documentation for the chosen monitoring strategy

A:  An appropriate rationale will associate the identified and assessed risks related to the study’s critical data to the specific mechanism of review and evaluation specified in the plan. In other words, the monitoring strategy has to show that you have control and oversight in place for data points that impact safety and study outcome.

Webinar Recording: What Does ICH E6 R2 Mean for Me and My Company?

This week, CluePoints hosted a webinar with Paragon Solutions, which was geared towards preparing attendees on how to take advantage of the ICH E6 revisions to ensure appropriate consideration of risk in study design and management. Attendees learned about the key ICH E6 updates related to Risk-Based Monitoring and their purpose, how Central Statistical Monitoring and Key Risk Indicators will work for them, and how to use the E6 R2 to support their organization’s transition to Risk-Based Monitoring.

If you missed the webinar, you can access the on-demand recording here. Please feel free to share the URL with your colleagues.

We hope to see you at future CluePoints webinars!

CluePoints Launches Patient Profiles as Latest Addition to its Risk-Based Monitoring and Data Quality Oversight Solution

13 March 2017

Cambridge, MA – CluePoints, a leading provider of Risk-Based Monitoring (RBM) and Data Quality Oversight solutions for clinical trials, has introduced Patient Profiles to its rapidly expanding platform. The powerful combination of Patient Profile reports, guided by CluePoints’ advanced central statistical monitoring, offers a new way for clinical teams to prioritize the investigation of atypical patients in clinical trials.

Patient Profiles provides detailed insight into patient experiences and offers a more targeted approach by identifying anomalies in data and ranking patients by their relative degree of atypicality.  The highly configurable Patient Profiles solution presents a rich set of customizable visualization options, including the ability to visually assess a chronological view of a patient’s visit, investigational product exposure, adverse events and concomitant medications – along with any additional relevant patient information. The solution will help to enhance overall quality management, guiding study teams to quickly and effectively characterize risk signals and enable centralized medical and safety reviews within the CluePoints platform.

“The addition of Patient Profiles to CluePoints’ portfolio aligns with our vision of expanding data exploration capabilities at both the patient and site level,” commented Steve Young, chief operations officer at CluePoints. “Reinforced by the voice of our customers, the solution will revolutionize the patient profiles review process by prioritizing and illuminating ‘at risk’ patients.

“Our agile product methodology is enabling us to rapidly evolve our solutions and exceed the expectations of our customers, delivering tangible value to them. This latest addition will significantly improve the efficiency of patient data review processes because customers can target their efforts on the patients and data that matter most.”

For further information on CluePoints’ solutions, please visit

About CluePoints

CluePoints® is a Risk-Based Monitoring and Central Statistical Monitoring solution that has been 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. The value of using CluePoints® lies in its powerful and timely ability to identify anomalous data and site errors allowing improvement in clinical data quality, optimization of on-site monitoring and a significant reduction in overall regulatory submission risk.

Media contact

Patrick Hughes – Chief Commercial Officer, CluePoints
+44 (0) 7703 532 749

CluePoints COO, Steve Young, to Present on Statistical Probability Analysis at MCC’s Central Monitoring Workgroup

The Central Monitoring Workgroup will feature speakers from several solution providers who will each present and discuss the types of analytic methods that are relevant for centralized monitoring and data quality oversight.  The first speaker will be Steve Young, COO at CluePoints (and the Metrics Champion Consortium’s Central Monitoring Workgroup leader), who will talk about Statistical Probability Analysis including the specific types of operational issues that it can uncover.

The goal with this series is to help the MCC community to better understand the types of analytics available and how each of them can help to drive effective centralized monitoring.

Webinar Date & Time

Wednesday, 15 March 2017, at 10:00am -11:00am EST

Registration for this webinar is now closed!