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RBM and eCOA/ePRO: Pearls from recent conference

By Penelope Manasco M.D. - November 12, 2018

I was asked to speak at a recent ePRO/eCOA conference on the topic of Identifying and Monitoring Risks with ePRO/eCOA implementation.  Much of the conference focused on “Big Pharma’s” implementation issues, which are usually not relevant to small companies.  I did, however, learn a few interesting “pearls” relevant to all companies and listed them below.

Jonathan Helfgott, a tremendous speaker as usual, is the former Associate Director for Risk Science at the FDA (now at Hopkins and Stage 2 Innovations).  He played an instrumental role in drafting the eSource and Risk Based Monitoring Guidance documents (among his many contributions). 

Here were some of his talking points:
  • Clearly articulate endpoints: never lose sight about what is important: people and processes are important.  Penelope’s pearls: That is why trial oversight needs to include an analysis of processes, not just analysis of the data for submission.
  • Provide agency with a data flow diagram;  always be transparent.  
  • QC all primary endpoint and safety data that has been changed.  That is a red flag for the agency.  Penelope’s pearls: That is why process review, including audit trail review is an important component of trial oversight. Note audit trail requirements are not recommendations, but actual requirements as stated in 21CFR Part 11.
  • The Chain of Custody of data is important.  Auditing who has access for critical data and when staff who leave the study have access to technology systems removed is critical to assure data integrity.
  • eSource is not just a FDA recommendation; the FDA promotes it.  Penelope’s pearls: in a recent survey I conducted to determine the Barriers to RBM adoption, 25% fewer organizations had adopted eSource compared to RBM adoption, yet eSource significantly enhances Risk-Based Monitoring.
  • Pitfalls to avoid in trial conduct and oversight:
    • Treating all data equally; Focus should be on critical data and processes, which should be specified up front.
    • Quality data is defined as the absence of errors that matter, according to Janet Woodcock, M.D. (Director of CDER/FDA) .  Mr. Helfgott used this to emphasize the importance of focusing on the critical data and processes.
    • Not appreciating the nature of data errors.  It is important  to recognize problems that affect multiple sites (i.e., systematic errors) and fix them in real time.
    • Ineffective methods for detecting trends 
    • Avoid using equipment and instruments prone to malfunction
    • Poorly written protocols (with poorly defined endpoints) and eCRFs
Finally, I asked Mr. Helfgott how Sponsors and CROs using Risk Based Monitoring can better prepare for audits.  He worked on the algorithm used for auditing sites and he provided these recommendations concerning preparing for audits. 
  • Share your oversight plans with the FDA; even if they don’t respond, you can document you provided the info to the FDA.  If findings are identified as part of an FDA audit and you have submitted the monitoring approach that you follow, the agency is unlikely to issue a warning letter based on audit findings.  

Our Risk Based Monitoring Method (MANA Method) is focused completely on identifying and correcting errors that matter.  We also identify and correct systematic errors.  You can’t expect to find these important errors without specifically designing your oversight approach to do so.  Every Sponsor should be asking:  “Tell me specifically what the errors that matter you are looking for and how will you find them using your current monitoring approach”.  If you are using SDV as your oversight approach, you cannot identify the errors that matter.

If you don’t like the answer you get or are using SDV as your oversight for a critical trial, don’t hesitate to contact MANA RBM.  We offer two approaches to executive oversight to identify errors that matter.