Effective application of Risk Management techniques to Drug Safety: a pragmatic approach Dr Mark Perrott WCI Consulting ltd 19th October 2009 1 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners. 2
I have worked with pvnet to develop this view of Risk Management in Drug Safety I have worked with the pvnet group of companies to look at the current state of Safety Risk Management (SRM) across industry and to identify key considerations in implementing these approaches pvnet was founded in 2001 In 2009 its membership comprises ~15 of the top 20 pharmaceutical companies with objectives to: Describe & compare performance of global drug safety operations Share best practices, debate common challenges and challenge the status quo Provide a focus for developing future solutions for effective drug safety 3 Risk Management has been a formal process in a number of industries for many years Risk Management is commonly used across aerospace, nuclear and financial (e.g. insurance) industries to identify, prioritize and manage risks Several widely-used models have been developed of which one of the most well known is the Failure Mode Effects and Criticality Analysis (FMECA) Internal and external drivers have recently resulted in the adoption of Risk Management practices in drug safety 4
Drug Safety teams need to ensure patient safety in a rapidly changing environment Evolving regulations and initiatives (e.g., Volume 9A, Report of the EU Commission on PV, IOM Report on the US Drug Safety System, FDAAA, Sentinel initiative) Safety risk management from development to end of lifecycle Proactive Data mining, Signal detection and management + response to authority signals from external databases Post authorization safety studies QPPV oversight of safety and risk management systems 5 Regulatory authorities have formalised requirements for Safety Risk Management EU Vol 9a: The EMEA has clear expectations for European Risk Management Plans (EU-RMPs) which must be provided as a core element of almost all submissions in the EU. US FDA AA: A Risk Evaluation and Mitigation Strategy (REMS) will be required if the FDA finds that one is necessary to ensure that the benefits of the drug or biological product outweigh the risks of the product. The FDA currently may require a REMS, and has required them only for a small number of pharmaceutical products. In each case, where an RMP or REMS is required, the risk management actions are considered to be commitments upon which any product approval is conditional In addition, both the EMEA and FDA have formal powers of enforcement from significant fines through to product license withdrawal for non-compliance 6
Key questions that Pharma companies must successfully address How can Pharma companies ensure that they identify and manage safety risks during a product s life to ensure effective Safety Risk Management How should Safety Risk Management be incorporated into business models to meet current and future expectations? What approaches are proving to be the most effective way to deliver effective Safety Risk Management? What does this change in the relationships with interfacing functions? What are the key considerations in implementing safety Risk Management Plans in the real world? 7 This Good Risk Management Practice model meets pharmaceutical industry needs 0. Establish the governance and team structures 1. Identify risks from all relevant sources 2. Characterise safety risks 3. Assess the severity and likelihood of safety risks, develop mitigation actions 4. Manage the implementation of mitigation actions 5. Monitor the effectiveness of the mitigation actions 8
There are 5 key principles to effective lifecycle Safety Risk Management 1. Build and support a proactive safety culture in development by including Safety Risk Management milestones in the Development process 2. Implement the CIOMS VI Safety Management Team concept into current project management approaches 3. Integrate Safety Risk Management with key Safety processes (e.g. lifecycle signal detection and management) 4. Build clarity into the accountabilities and relationships of the SMT with other teams and functions 5. Ensure SRM actions and commitments are carried out and effective 9 1.Build a proactive safety culture by including Safety Risk Management milestones in the Development process Pre-Phase I Phase I Phase II Phase III: Submit / Launch Lifecycle Management First safety spec. First development RMP Submission RMP Update and expand Manage implementation Develop go / no-go safety criteria and documentation expectations for each development decision point Build safety knowledge from pre-clinical through to market to enable continuity of safety risk management Ensure that all necessary skills and knowledge are brought together at key points 10
2. Implement the CIOMS VI Safety Management Team concept into project management approaches Pre-Phase I Phase I Phase II Phase III: Submit / Launch Lifecycle Management Safety input to Project decision points comes from the right skills at the right time SMT Pre-Clinical & Clinical The bar thickness is an example only of the relative contribution of functions, this will vary by SMT PV (lead) Medical Affairs SMT: Holistic view of product safety risk comes from the contribution of pre-clinical, clinical, epidemiology and others, led by safety One SMT per Clinical Development project and per enhanced PV - marketed product Functional input to key safety decisions depends on lifecycle phase 11 3. Integrate Safety Risk Management with key Safety processes Start with aligned safety event management across Clinical and Safety Agreed safety-based study entry and stopping criteria SAE processing Routine safety reviews (e.g. SMT, toxicity boards) Sentinel events Integration with signal detection governance across the lifecycle, don t just focus on post-marketing New skills required: Safety managers must become leaders in the SMT A combination of clinical statistical interpretation (aggregate data) and pharmacovigilance analysis (case, or detail-oriented) 12
4. Build clarity into the accountabilities and relationships of the SMT with other teams A formalised safety culture in Development is a new concept for many companies Roles and responsibilities for safety monitoring and governance must be established in particular for the independent role of Safety, with clear accountability for benefit : risk established across the teams Establish the relationship between Clinical and Safety roles as peer to peer, with equal weight and access to independent escalation Clear and simple governance for risk, enabling rapid escalation of issues to senior decision-makers 13 5. Ensure Safety Risk Management actions are carried out and effective Many post-approval safety risk management commitments will require the full co-operation of commercial functions or external partners Ensure all stakeholders clearly understand the nature of the risks, commitments made and consequences of failure May need very senior management endorsement to assure compliance Jointly define measures of implementation and effectiveness (with safety oversight) Clarify roles and responsibilities for each type of risk management action to ensure clarity across the organisation Maintain accountability in Safety for monitoring effectiveness to provide single point control, clear governance and the opportunity for intervention 14
It is critical that all steps are included and the loop is closed Having identified, characterised and prioritised safety risks: The actions required to manage risk may be difficult to define, design and implement completely as they are often owned by commercial functions Governance of R&D and commercial typically do not meet until board level When implementing safety risk management, it is imperative to put the mechanisms in place to manage the required actions before establishing where the greatest risks exist in the business 15 Effective Development Safety Risk Management brings internal benefits Establishes stronger safety culture within the organization Earlier Safety involvement in development can lead to earlier discontinuation of unsuccessful projects; lower costs, company protection Early, high quality, risk mitigation Strengthened life cycle Safety Surveillance approach Safety involvement facilitates sharing lessons learned across projects 16
which may have valuable commercial implications Pharma company focus Sales: Lost sales due to suboptimal pharmacovigilance Future? Traditionally Pharma already spends millions of dollars protecting patents Max sales potential $m Sales Revenue: Strategies to hasten speed to market can increase sales potential and longevity Sales impacted by poor pharmacovigilance Cost Time Costs: Front loading pharmacovigilance can minimize total cost, and reduce risk of exposure to future costs Source: Datamonitor Healthcare March 12 2009, London, UK 17 and which impact positively on the external facing safety profile of a company. Better, earlier characterization of the benefit / risk profile Better Risk Management Plans No surprises pre-approval / post-marketing Getting answers earlier leads to better risk management And may reduce commitments required post-approval Good labelling, reduced downstream changes Gain Regulatory confidence 18
Contact information Dr. Mark Perrott Managing Consultant E-mail: mark.perrott@wcigroup.com Tel: +44 (0) 7900 051959 19