Mark Maietta, President

YPrime’s Expert Community is a forum for education, ideation and collaboration. Our (plus clients and partners) point of view, best practices, lessons learned, and other advice are expressed through many formats. These include webinars, white papers, ebooks, and most recently, live events. Last week, YPrime hosted its first Expert Community event at the Science History Institute to an engaged audience of clinical operations, data systems, clinical outcomes, clinical supplies, data management, patient technologies and eCOA/IRT implementation professionals.

The second of two blog posts on the event focuses on the afternoon session and IRT breakout discussions.

Marie Mc Carthy, Sr. Director of Product Innovation at ICON presented considerations for the evaluation and implementation of wearables and sensors in clinical trials. Central to her conclusions was the benefit of linking wearables with ePRO data for new signals and higher sensitivity for new endpoints or screening criteria. She charted the history of regulatory actions with similar technology, and offered these considerations to those interested in mHealth exploration:

  • Think about the data upfront. Start with a clinical hypothesis vs. allowing technology to drive objectives. Additional questions to consider: What type of data will be collected? What decisions will be made? Will it be blinded?
  • Types of data range from endpoint, compliance, real-world evidence, screening, patient engagement and more. statistical analysis and data management plans must be capable of handling massive amounts of data. Data management will be cumbersome, especially edit checks and cleaning from wearable sensors.
  • What is a valid data set? How do you deal with data loss? Data governance considerations are important.
  • What burden to the patient will the device introduce? Is it fit-for-purpose? What are the age ranges of the patients? How long do they wear it? How often does it have be changed? Is it waterproof? What technical support is available?
  • How will you ensure that the technology conforms to local privacy regulations?

Dan Hilby of Takeda and Justin Jaeschke of YPrime offered insights from their experience within sponsor/provider governance. This topic elicited a range of responses from the audience, with preferences ranging from less formal to tightly defined structures. There was consensus on the benefits of a range of approaches and the need for flexibility, with emphasis on:

  • Upfront work on communication cadence and escalation pathways
  • The need to demonstrate oversight to regulatory authorities
  • Multi-disciplinary involvement
  • Differences between transactional and strategic relationships
  • The importance of ongoing relationship management. It takes multiple projects to learn how to work together before formalizing work agreements. Collaboration guides work best as “living documents.”
  • Metrics, KPIs and continuous improvement that aligns with partnership goals

Eric Valentine, Vice President of Clinical Supplies Services for Catalent, opened the IRT session with a BREXIT Update and the impact on clinical trial supplies. He focused on key areas of concern, offering hard and soft BREXIT scenarios, solutions and potential consequences involving:

  • Qualified Persons and Regulatory. One solution includes the addition of UK QPs to an EU licence, allowing for potential remote QP release of materials into the EU, in lieu of adding a new QP into the supply chain
  • Trade and Distribution concerns included significant UK customs delays, the financial impact of VAT and the possibility of free trade zones. Solutions involved the use of third-party importer of record and VAT reclamation services, AEO accreditation for European sites and the establishment enhanced customs processes
  • Comparator Sourcing. Sourcing teams should align with their regulatory teams to establish flexibility on comparators named in CTA’s to align efficient execution strategy in all Brexit outcomes
  • EU-FMD Compliance. The recent EU directive discourages counterfeiting by requiring certain medicinal products to include unique identifies and anti-tampering devices. Harmonized systems and processes will facilitate a seamless transition of comparator products in compliance with EU-FMD.

Craig Mooney, Director, Interactive Response Technology at Bristol-Myers Squibb followed with recommendations for regulatory inspection readiness. Against a backdrop of increased regulatory scrutiny, Craig contrasted traditional regulatory approaches with new priorities. Central to regulatory expectations are sponsor proactivity, comprehensive documentation (“unfettered access”) and a culture of preparedness. He also urged the audience to consider these regulatory imperatives:

  • Audit trail reviews in support of data integrity are more important than ever, especially for data changes. Plan your audit trail reports early.
  • Delivery of investigator specific data at study end. Final documentation is not enough. Regulators want to see draft versions for the ability to take the raw data and arrive at the same conclusion.
  • An auditing process is not good enough for vendor management. Vendors require hands-on oversight during design, development and deployment vs. the traditional approach of bi-annual re-qualification audits
  • Quality needs to be engaged at every stage, vs. milestone intervals.
  • Treatment assignment on unblinding confirmations is important, as unblinding processes are receiving more scrutiny. Regulators want proof that sites follow the blinding plan.
  • Document the of impact of protocol amendment on all systems. Does it require additional programming?
  • Document risk-based regression testing in UAT. Identity potential risks and test them vs. “happy path” scenarios.

Presenting “Clinical Supply Best Practices: How to Leverage a Highly Configurable IRT System,” Bryan Clayton and Korinne D’Orsi of YPrime discussed optimizing the balance between shipment and packaging costs through the use of an IRT system.

  • While both shipment and packaging costs can be unplanned for and play a significant part on a study budget, effective use of an IRT can reduce some costs.
  • Reducing clinical supplies overage is a difficult process to plan, but worth the effort by considering all aspects of the trial design, packaging and distribution strategies.  Lowering the quantity of clinical supplies produced can save hundreds of thousands of dollars if planned correctly.  Often distribution costs can be escalated by unseen global shipments including duties and taxes.
  • If you do not have storage or temperature concerns, why not send clinical supplies shipments less frequently with more stock?  This can drastically reduce costs and risks.
  • Another best practice involves ongoing study review throughout the process to ensure that the resupply strategy you started with don’t need to be adjusted.

Bryan Clayton moderated a panel discussion on the IRT Configuration vs. Customization debate. Panelists included Carol Lee of Regeneron, Dan Hilby of Takeda and Steve Lotfi of YPrime. Discussion homed in on:

  • The lack of industry standards and consensus on configurability
  • Widespread confusion on the line between configuration and customization. Some simple functionality is not universally configurable, while other ostensibly complex functionality is

The panel concluded that while no system can be 100% configurable and some level of customization is always needed, IRT systems should be as flexible as possible to accommodate unanticipated needs and protocol amendments.

Sarosh Anjum of Astellas Pharma hosted a group discussion on the State of IRT that focused on frequent sources of pain for IRT and eClinical systems professionals, including audit trails, drug accountability, ICFs/re-consent and system complexity. The audit trail discussion reinforced Craig’s earlier recommendations that audit trail data are more important than ever, and regulators want the whole story vs. data snapshots. Comments on drug accountability revealed that more sponsors use IRT systems to centralize the process of accountability and for the added benefit of precision. Sarosh wrapped up discussion by reiterating practices made earlier from Dawn Sorenson and Aubrey Llanes. Given the expanded visibility and importance of IRT, it’s critical that IRT design are aligned with a study protocol. Sarosh urged the audience not to wait until the UAT stage for a first look at the system. The takeaway? Get involved early and stay engaged throughout the process! This advice applies to IRT leads, clinical supplies and quality personnel.

The success of YPrime’s Expert Community debut was driven by influential voices and engaged audience who provided thought-provoking conversation and thoughtful ideas. We look to continuing the discussion at future events.