Monthly Archives

April 2020

Beyond COVID-19: The New Normal in Risk-Based Monitoring (RBM) and Quality Management (RBQM)

Join our next webinar to learn first-hand how the CluePoints and Parexel partnership is driving best-in-class Risk-Based Quality Management Strategies to support clinical development. This session will focus on how early risk detection can be leveraged to detect issues across your trial and ensure operational excellence. As the COVID-19 pandemic continues, actions need to be prioritized to combat the disruption to both new and in-flight trials. We believe the challenge of identifying and actioning these critical issues in a timely manner will be the catalyst in driving the adoption of central/remote monitoring for all trials from this point on. We will share best practices for rapid use today and future adoption as we enter a new normal.

KEY DISCUSSION POINTS FOR THIS WEBINAR:

  • Enhanced data quality oversight and regulatory compliance
  • Proactive risk management to protect patient safety and support site conduct
  • Driving improved quality, accuracy, and integrity of clinical trial data
  • Increasing productivity, efficiency and cost effectiveness for sponsors

WE WILL BE RUNNING TWO SESSIONS TO ACCOMMODATE DIFFERENT TIME ZOMES:

Tuesday, May 12, 2020 at 10:30 AM EDT Registration

Wednesday, May 20 at 11:00 AM IST Registration

We hope that you can join us and please feel free to send us questions that you’d like to see covered during the event via contact@cluepoints.com.

EPS Corporation Signs Groundbreaking Agreement To Drive Increased Quality And Safety Using CluePoints RBQM Solution

King of Prussia, PA  – April 14, 2020: CluePoints, the premier provider of Risk-Based Study Execution (RBx) and Data Quality Oversight Software for clinical trials, today announced that EPS have entered into an agreement with CluePoints to offer Risk Based Quality Management (RBQM) solutions to its sponsors to drive early risk detection, improve quality and enhance patient safety in a cost-effective and resource-efficient manner.

Throughout the global Clinical Research and Pharmaceutical industry, RBQM is fast becoming an essential component to drive efficiency and quality and allowing sponsors and CROs alike to adhere to the regulatory mandates within ICH E6 (R2) published in 2016. CluePoints advocates a unique approach to ensuring regulatory compliance using Central Statistical Monitoring (CSM), an unsupervised, independent and objective analysis of all clinical and operational data. CSM is rapidly being adopted throughout Europe and North American as a proven method to identify risks earlier within the study lifecycle. EPS recognizes that CSM use in Japan can benefit both local and global trials and will be offering the pioneering methodology to all its clients.

EPS will be able to add a suite of RBQM tools to complement either new or existing RBM processes through the CluePoints Central Monitoring Platform. The platform offers a range of tools includes Risk Assessment, Key Risk Indicators, Data Surveillance, Patient Profiles, Data Visualizations, Duplicate Patients and Issues and Actions Management. The combination of these modules provides EPS and its clients with a systemic approach designed to increase the efficiency and effectiveness of study conduct. With guidance from EPS, sponsors are now able to choose the modules that will best suit their needs and that of their studies for successful implementation of RBQM. This approach is also being used by FDA, via a Cooperative Research and Development Agreement (CRADA), to select sites for regulatory inspection and to test treatment effect in different study populations.

Recent announcements by worldwide regulatory agencies such as FDA, EMA, PMDA and MHRA are quick to advocate the adoption of central and remote monitoring techniques in the wake of the COVID-19 pandemic. EPS recognizes that enhancing its own central monitoring capabilities using elements of the CluePoints Central Monitoring Platform will give their sponsors peace of mind that no stone is being left unturned in ensuring that issues are detected as early as possible and managed remotely. This is crucial for business and trial continuity within both new and ongoing studies and will include the use of COVID-19 specific Risk Assessment and Key Risk Indicators for risk planning and mitigation.

Patrick Hughes, CluePoints Co-Founder and CCO commented, “We are delighted to enter into this agreement with EPS as it demonstrates the pioneering approach to increasing the efficiency in conducting trials within Japan. The partnership comes at a time when remote monitoring of studies is the only option and we are keen to demonstrate to EPS and its sponsors how RBQM will improve the conduct of studies, not just at this critical time but for all time”.

Register to access to COVID-19 Risk Assessment package and a CluePoints expert will be in touch. For further information on CluePoints’ solutions, please visit www.cluepoints.com

[About EPS]
EPS continues to contribute to the development of the medical and healthcare industries by constantly transforming and evolving itself, as the name of the company, “Every Progressing System”, shows.
Website: http://www.eps.co.jp

[About CluePoints]
CluePoints is the premier provider of Risk-Based Study Execution (RBx) and Data Quality Oversight Software. Its products utilize comprehensive 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, EMA, and ICH E6 (R2), CluePoints® is deployed to support central and on-site monitoring, medical review, quality risk management and to drive a holistic Risk-Based Quality Management (RBQM) strategy in all trials. Coupled with thought leadership and consulting expertise to aid pre-study risk assessment, identification of risk controls and solution implementation you now have everything you need to adhere with global regulatory guidance. The result is increased operational efficiency, lower costs and reduced regulatory submission risk as part of the industry paradigm shift to RBx.
Website: https://cluepoints.com/

Early Risk Detection During the COVID-19 Crisis – Your Questions Answered

On Tuesday, March 31, 2020, CluePoints delivered a webinar centred around the critical importance of early risk detection. Our presenter also shared insights on how to navigate risk management and risk assessment during the COVID-19 crisis. If you missed the webinar, you can watch it on-demand. Watching the webinar before digesting the answers shared in this document will provide context to the questions being answered.

Also, please take a look at our complimentary COVID-19 Risk Management package which includes free access to the CluePoints Risk Assessment and Categorization Tool which includes a template to guide you through COVID-19 specific risks that are likely to be relevant to your study.

Below, you will find the questions asked along with answers from our Chief Scientific officer, Steve Young.

At what Time Points/Frequency would you Recommend Running a Study through CluePoints?

It depends on the study, and in particular the expected rate of accumulation of patients and patient data across the study.  CluePoints has a “Review Planner” tool that we share with our clients to help them define a schedule for DQA and KRI/QTL reviews, which uses a handful of study planning parameters to recommend the frequency/timing of reviews.

Could you Please Talk a Little bit About Access to Data Needed for the Risk Assessment? e.g. How Does CluePoints have Access to the Audit Data of the ePRO Device? What is Involved in Accessing the Data?

We have found that ePRO/eCOA vendors are easily able to provide the audit trail data as part of their extracts, and as it forms part of the sponsor-owned data, it is readily available once requested by the sponsor or by CluePoints. We have an sFTP facility for receiving data extracts securely.  And if needed, we and/or our clients can directly upload files in any number of formats (e.g., SAS, SDTM, csv, etc.).

Does CluePoints Make Recommendations on how to Define QTLs - not what QTLs to Implement, but Rather how to Best Define those that the Study Team will Implement to Ensure the Sensitivity is Optimal?

CluePoints does indeed provide guidance to our clients on optimal design of QTLs, as illustrated during the webinar on how to consider normalization of the QTL parameter.

How Did you get Access to Audit Data for the ePROs you Discussed?

We have found that ePRO/eCOA vendors are easily able to provide the audit trail data as part of their extracts, and as it forms part of the sponsor-owned data, it is readily available once requested by the sponsor or by CluePoints

How Does your System Link to an EDC system, and if we use a CROs EDC, do you Need Some Kind of Data Transfer Agreement in place?

We have connectors already built for commonly used EDC systems:  Medidata Rave, Oracle Inform, OmniComm TrialMaster.  We don’t need transfer agreements in place with each vendor – instead authorization comes from the sponsor/CRO partner that we are working with. We can easily build connectors to other EDC, eCOA and IRT systems when working in partnership with Sponsors and CROs Besides the connectors, we have an sFTP facility for receiving data extracts securely.  And if needed, we and/or our clients can directly upload files in any number of formats (e.g., SAS, SDTM, csv, etc.).

What Information is Needed to Estimate QTL? Like Source Data/SDTM/?

For deriving the QTL metric/parameter, it really depends on the specific QTL.  For example, a QTL for patient early termination rate will require source data regarding patient status which is typically captured in EDC.

What is the Percentage of Trials used RBM in Phase 2 Studies?

We don’t have current industry level metrics on % of studies by phase using RBM.  However, we are generally observing that organizations implementing RBM are applying it to all study phases including Phase 2.  This includes centralized monitoring, which can be applied effectively to detect risk for smaller studies as well as large studies.

What would be your Suggestions for COVID-19 for Studies that are being Paused for Screening and Enrolment?

Generally speaking, we recommend continuing to use central monitoring for risk detection even if enrolment has been paused – assuming that existing patients are continuing to participate in the study.  If a study has been put on hold completely, then of course there will be no new activity to monitor until/unless the study is restarted.

Could you Please Discuss Early Phase (Phase 1 or 2) Applications of CluePoints?

The CluePoints RBQM platform is being used increasingly for smaller studies, both phase 1 and 2.  And we have developed best practice guidance for our clients for leveraging CluePoints on small studies.  We would be happy to share that with you, just contact us.

What are the KPIs you would Suggest for Central Vendor Provided Data? For Example, Imaging data and Biopsy data?

Central data should generally be included in DQA statistical analyses along with site-generated data, and sometimes included in KRIs depending on study-specific risk assessment.  Site-level and/or systemic

In one of the case studies presented in the webinar, there were a lot of Errors in Site 105. How About Other Outstanding Sites Such as Site 101, 102?

Yes, there were other sites that showed high degrees of atypical data as you saw in the bubble plot. On that particular trial those additional sites had their own problems, but they were problems that were managed by the study team at the time and didn’t escalate into anything nearly as problematic as the site we focused on. It’s just not possible to change some of the data that’s collected, or the metadata around it like when it was collected. In this respect the data you have will always tell a story which is why understanding what those stories are before submission is so important, as regulators like the FDA (who use CluePoints to help identify Sites for audit) can analyse the data and see the same trends and results independently. It’s a great to have found all such patterns in the data and have justifications and corrective actions at hand, be they good or bad, before the data is submitted as it avoids delay in the submission process responding to the regulators. I recently heard that a different customer had seen a site be flagged by the system because of a significantly higher number of adverse events reported. During the subsequent investigation, where data was being reviewed and checks done to make sure that medical histories weren’t being mistakenly reported as AEs etc, it turned out that the site was actually an oncology site. It wasn’t an oncology trial, but there was nothing precluding oncology patients participating in the trial and it just so happened that one site was an oncology site. The system rightly detected that the site was different, but the subsequent investigation work concluded that it was understandably different and not a concern. That’s all good information to have documented prior to submission and it can also be referenced in the CSR so that the regulator knows all about it if they notice the same pattern in the data when they review it.

What will be your Recommendation if Key Data Cannot be Remotely SDVed (e.g. ICFs, Medical Records) - in EU it is not Permitted for Example?

The good news around SDV is that many of the problems that could be detected by having eyes on the source at site can also be detected remotely, other than the check to see if the data has been transcribed properly. The addition of statistical monitoring will test all the data that you can receive electronically to destruction and identify atypical patterns that show procedural issues at the site or data tampering/fabrication (it’s very hard to cheat well – as we’ve proven many times). It’s detecting these other issues via the process of SDV that I think still drives trials to have a lot of SDV implemented, when these higher value problems in the data can still be detected by other means. When I sat through the DIA webinar last week, presented by local research professionals in China, they certainly called out statistical monitoring as being a valuable tool to taking up the strain of losing the on-site activity, but what wasn’t clear was whether it had been an existing quality control technique already in use that then became increasingly important, or whether study teams have implemented statistical monitoring as a new technique in response to losing their eyes on-site. As well as statistical monitoring, remote patient data review can also be valuable, especially if it’s through visualization techniques such as Patient Profiles, where it’s easy to see patient specific data from multiple datasets on a single Gantt chart view. We’re having conversations with a number of existing customers that hadn’t chosen the Patient Profile component of our platform originally, but now want to implement that onto their existing trials to facilitate better remote patient review. The regulators seem to all be saying it’s fine to leverage appropriate and proportionate alternatives, be they centralised and or remote as you feel necessary, and have those changes documented.

Are the % Progress Milestones Based on Clendar Dates (i.e. from Study Start-Up Date to Study Closeout Date), or Based on Data Availability within the Clinical Database (i.e. 5%, 10%, 20%, etc. of Data Available in Database)?

Each progress milestone represented the date by which that particular % of patient visits had been conducted at the key problem site.

What do CROs think About your Tools? Against their Business? In Favour?

The CRO dilemma has been an interesting one over the years. At the advent of RBM, CROs were uncertain about replacing any on-site monitoring efforts in favour of this sort of remote monitoring technology. However, as time has gone on, CROs realise that the paradigm is changing, and the astute players have tried to get out in front of the change to ensure that they are the innovators in the field. We are now enjoying some excellent partnerships with CRO partners and the adoption is growing rapidly within the CRO community. RBQM isn’t going to go away and the COVID-19 crisis is making it a priority. Any CRO who is still in the dark ages is going to have to get their act together pretty quickly now, I think. And of course, sponsors can (and do!) insist on the use of Central Statistical Monitoring by their CROs to ensure their trials are better, faster and cheaper.

CluePoints Launches Complimentary COVID-19 Risk Management Package for Clinical Studies

Risk Planning Guidance Addresses FDA, EMA, PMDA and MHRA Coronavirus Advice

King of Prussia, PA  – April 06, 2020: CluePoints, the premier provider of Risk-Based Study Execution (RBx) and Data Quality Oversight Software for clinical trials, today announced that it has launched a complimentary COVID-19 risk management package available to all at no cost. With the FDA, EMA, PMDA and MHRA issuing specific guidelines as a result of the coronavirus, the CluePoints package will help meet these new recommendations and address additional study risks. The platform includes a widely used online Risk Assessment and Control solution that can be leveraged for performing risk planning and mitigation activities addressing inherent risks during this crisis. Register here for the COVID-19 risk management package.

Many clinical trials are facing key challenges, including an increase in missed patient visits, missed assessments, missed study treatments and increased dropouts. Studies are encountering IP supply chain disruptions, recruitment issues and slower site responsiveness. There are gaps in reporting adverse events, less frequent interactions with patients and reduced on-site monitoring visits. The relative scope and impact of these common risks will vary by study, as will the proposed mitigations.

Additional study-specific risks need to be addressed and the regulatory bodies recommend that a fresh risk assessment is performed for each study to identify and mitigate risks pertinent to the COVID-19 crisis. The CluePoints COVID-19 package incorporates a special coronavirus-specific Risk Assessment template that includes a set of relevant risk categories and associated considerations gleaned from the regulatory guidance documents issued by FDA, EMA, PMDA and MHRA. The increased threat of Coronavirus infection may pose a particularly high risk for certain patient populations and/or study treatments (e.g., studies testing immunosuppressant therapies). Further, CluePoints provides recommendations regarding risk controls in the form of specific COVID-19 Key Risk Indicators (KRIs) and will assess each study position before offering advice.

Commenting on the current situation, Patrick Hughes, Co-Founder and Chief Commercial Officer of CluePoints said,“In the wake of COVID-19, we are hearing that many Sponsors and CROs are struggling to keep up with the need to assess and control risk on new and ongoing studies , with documentation and audit trail even more important in this highly dynamic environment. We currently have over 50 requests from sponsors and CROs to help them implement COVID-19 specific risk management ASAP and over 400 have wanted to hear more about the free offer. At this unprecedented time, we are delighted to play our part by helping all operational teams to manage their studies remotely by doing what we do best, interrogating clinical and operational data in a completely unsupervised fashion.”

The complimentary risk assessment package includes:

  • Free access to the CluePoints Risk Assessment Categorization Tool (RACT) for the duration of the crisis
  • Complimentary guidance supporting users to focus on the new COVID-19 specific risks that are likely evident in most studies and how to control them
  • Access to simple online eLearning (30 mins) to allow rapid setup
  • Support via CluePoints Subject Matter Experts (SMEs) to facilitate onboarding

Hughes continued, “As pioneers in the field of RBM we are able to help, which is why we are offering this package free of charge. We are committed to our clients, and will do all we can to ensure sponsors, CROs and Clinical Technology Partners benefit from constant innovation and transparency.”

Register to access to COVID-19 Risk Assessment package and a CluePoints expert will be in touch. For further information on CluePoints’ solutions, please visit www.cluepoints.com

About CluePoints

CluePoints is the premier provider of Risk-Based Study Execution (RBx) and Data Quality Oversight Software. Our products utilize comprehensive 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, EMA, and ICH E6 (R2), CluePoints® is deployed to support central and on-site monitoring, medical review, quality risk management and to drive a holistic Risk-Based strategy in all trials. Coupled with thought leadership and consulting expertise to aid pre-study risk assessment, identification of risk controls and solution implementation you now have everything you need to adhere with global regulatory guidance. The result is increased operational efficiency, lower costs and reduced regulatory submission risk as part of the industry paradigm shift to RBx.

# # #

Media Contacts:

CluePoints Contacts:

Patrick Hughes – Co-Founder and Chief Commercial Officer, CluePoints

Patrick.Hughes@CluePoints.com

+44 (0) 7703 532 749

Webinar Recording: The Critical Importance of Early Risk Detection with a Special Feature Addressing COVID-19

We’re delighted to announce that the recording for our COVID-19 webinar has been posted!

About the Webinar

The clinical research industry is in the midst of adopting Risk-Based Quality Management (RBQM) as a primary method for managing quality. RBQM encourages less reliance on traditional on-site monitoring including 100% source data verification/review (SDV/SDR), and greater reliance on centralized monitoring including the use of statistical methods to identify quality-related risks (e.g., unusual or unexpected data patterns).

CluePoints and our clients are accumulating an impressive body of evidence supporting the power of Centralized Statistical Monitoring in effectively detecting emerging issues not only effectively but proactively as well.  Early detection is critical to success, to ensure that corrective actions can be taken in time to prevent significant damage to patient safety, trial outcomes, and related costs.  CluePoints recently conducted “Data Quality Challenge” projects designed to demonstrate the ability of the CluePoints CSM solution to effectively and proactively identify sites with important known quality issues on previously completed clinical studies.  The participating sponsor organizations provided completed clinical study databases to the CluePoints team with the following challenges:

  • Can you identify the problem site(s) that the sponsor team discovered late in the execution phase of the study? The CluePoints team remained blinded to the scope and nature of the known issues, until after the initial analysis was executed on the completed study database and findings presented to the sponsor team
  • How early in the conduct of the study would the CluePoints solution have identified the problem site(s)?

In this webinar, we presented and discussed the results of these data quality challenges, and also provided some key considerations and best practices for ensuring early detection of operational risks and issues and:

  • The added importance of centralized monitoring as a quality monitoring tool in light of the challenges being imposed on site activities and site monitoring by the coronavirus (COVID-19) pandemic.
  • Designing Key Risk Indicators (KRIs) and Quality Tolerance Limits (QTLs) for earliest possible risk detection.
Watch the Webinar Recording

Please feel free to share the recording with your colleagues and don’t hesitate to contact us if you need any support, advice and recommendations – contact@cluepoints.com