Approaches to Patient Input for BR-PV and Risk Minimization Stephen Heaton

Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to 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. All other trademarks are the property of their respective owners.

Regulatory Authorities Have begun to appraise the value of patient perspectives and preferences for benefit-risk management US FDA is working on several programs to ensure patient perspectives have an effect on determining which products are developed and approved FDA has launched the Patient Preference Initiative EMA also is working to implement more structured medicine benefit-risk methods in evaluations that take patients’ values and their willingness to accept risks into account

CIOMS IX CIOMS Working Group IX stated, “In the context of risk minimisation planning, input from patients regarding the relevance, acceptability, and feasibility of a proposed initiative is critical in order to optimize the design of the risk minimization plan, broaden support and gain cooperation for implementation.” Incorporating patient perspective and preference information into benefit-risk acceptability, assuming risk can be minimized to offset its negative impact on the benefit-risk balance

PV Patient Engagement Roadmap Goals: PV as a key stakeholder in patient engagement initiatives from early development through launch and lifecycle Achieve broad internal recognition that PV has a unique opportunity to generate patient insights worldwide through the ability to interact directly with patients through the AE reporting and follow-up process, under safe harbor Achieve broad internal recognition that PV provides unique expertise in patient focused communications on risk as well as benefit risk balance

PV Patient Engagement Roadmap Why PV as a key stakeholder? Primary focus on patient – safety and benefit-risk Unique opportunity for two-way communication under safe harbor Patient AE self-reporting and follow-up activities Unique opportunities for non-brand/product focused collaborations Academia, Regulatory Agency consultants, other (eg PSCAP) Patient advocacy groups External environment expectations Regulatory agencies (eg RM communication tools, PIL, REMS) Lay public Corporate Brand expectations and reputation

PV Patient Engagement Roadmap Opportunities for Increase Patient Insights Development & BU Pharmacovigilance Discovery and Development Advocacy groups Study subject insights Focus Groups Preference studies Market insights Regulatory Agency Insights Development Risk management tools Risk minimization tools F/U Questionnaires Patient Preference Studies (BR) Patient Insights Medical Affairs & BU Launch / Lifecycle Management Advocacy groups Patient Insights Focus Groups Preference Studies Medical Information Queries Social Media PSP-PSDMP Regulatory Agency Patient Insights Post-Marketing Surveillance AE self-report F-U Questionnaires PSP-PSDMP Social media monitoring AE Reporting Other

PV Patient Engagement Roadmap Opportunities for Enhance Patient Communication Development & BU Pharmacovigilance Development Risk management tools ) Risk minimization tools Other Discovery and Development Recruitment tools Informed consent document Retention tools Other Enhance Patient Communication Medical Affairs & BU Launch / Lifecycle Management Education and Counseling materials Advocacy groups Medical Information Queries PSP-PSDMP External communications programs Post-Marketing Surveillance Additional RMin materials PIL Other

What patient input can we consider? Patient perspectives1 : wide range of information including anecdotal comments in correspondence to e.g., FDA or testimony at Advisory Committee Panel meetings, patient opinions expressed publicly including social media, patient responses to qualitative ad hoc surveys, quantitative measurements of PROs, and more This can be applied when patient views, experiences, or feelings on some topics are examined. Patient preference1 information is defined as qualitative or quantitative assessments of relative desirability or acceptability of attributes that differ among alternative diagnostic or therapeutic strategies. This can be applied: - when multiple options exist without an option clearly superior - when evidence supporting one over others is more uncertain; - when pts’ views about the most important benefits / acceptable risks of a product vary considerably within a population or differ considerably from those of HCPs. Patient-reported outcome (PRO)2 measure that reports status of patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.  PRO instruments fall under a broader caption of perspective /engagement;do not really fall under preference methodology. 1. FDA draft guidance on patient preference information (May 2015) 2. FDA Guidance on patient-reported outcome measures: use in medical product development to support labeling claims (Dec 2009)

Patient Preference Patient preference and perspective methodologies can be applied during benefit risk assessment and risk minimization tool design Helps ensure that patients use them in least burdensome and most effective manner RMin tools need to be designed with more specific patient input from given target population who will use the medication Patient input during tool selection may help determine feasibility as well as potential effectiveness Potentially can save substantial time and cost, especially if performed during development Providing results of patient input to regulatory authorities also may increase benefit-risk acceptability

Patients and additional risk minimization tools Patients are medication end users Patients and caregivers who live with and endure a disease on a daily basis for which they receive medical treatments may have developed their own insights regarding perspectives and preferences on their medical treatments’ benefits and risks As such, patients can contribute in managing risks

Termination of Market Supply How can PPP risk minimization information be applied in the product lifecycle? …… A PoC Phase B C D E … Start Phase I PoC Start Phase II b Start Phase III Release for Submission Launch Variation/Change Termination of Market Supply

Process

Conclusion Patient insights for BR-PV requires a cross functional partnership Focus is on BRM, RM - including risk minimization Applied methodology overall that appears to fit the requirements for these activities is patient preference Regulators are not yet aligned and at speed as to the right approach

Thank you