Joint BES/BBS Seminar Patient Preference Studies – Introduction Conny Berlin Global Head Quantitative Safety & Epidemiology, Novartis IMI PREFER Project Leader Basel, 22 November 2018

Disclaimer The views and opinions expressed in this presentation are those of the presenter and do not necessarily reflect the official policy or position of Novartis or any of its officers.

Patient Preference Studies Background & current environment What are patient preferences? What are patient preference sensitive decisions? What patient preference methods do exist? What are open questions and how do we get answers? Contacts & references

Background & current environment FDA to release 4 guidelines on patient-focused drug development between (2018-2022) EMA includes patient involvement (and patient preference studies) in CHMP work plan 2017/2018 New EFPIA guideline on working with patient groups IMI «PREFER» (2016-2021) IMI «PARADIGM» (2018-2021) ICH guideline includes advice on how patient input can contribute to Clinical Overview benefit-risk assessment ... Driving for more patient engagement ... Specifically FDA: Incorporation of Patient’s Voice in Drug Development and Decision-Making; systematic collection and analysis of patient experience data (from anecdotes to systematic, reproducible, generalizable…. Information) “Roadmap” for Patient Engagement in R&D has been defined and published Additional “Roadmap” areas, e.g. Patient Access, are currently being developed First ever book of its kind published Why, what, how and when of Patient Engagement in HTA decision making

New Checklist utilized by FDA to evaluate submitted Patient Experience data EXAMPLE FDA has begun documenting what patient experience data have been submitted with an application through a new "Patient Experience Data" section in clinical review documentation We might expect FDA to use this approach consistently and data may be included in the label, i.e. be promotable Source: www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761083Orig1s000MultidisciplineR.pdf

New Checklist utilized by FDA to evaluate submitted Patient Experience data EXAMPLE FDA has begun documenting what patient experience data have been submitted with an application through a new "Patient Experience Data" section in clinical review documentation We might expect FDA to use this approach consistently and data may be included in the label, i.e. be promotable Source: www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761083Orig1s000MultidisciplineR.pdf

What are patient preferences*? Measures of the relative importance of benefits, harms and other characteristics of treatments Patient preference are the basis of how patients choose a particular treatment over other available options. *Definition per Medical Device Innovation Consortium (MDIC) Patient-Centered Benefit-Risk www.mdic.org

Three types of patient preferences What it Measures Attributes What Matters Relative Importance How much it matters Tradeoffs What tradeoffs patients are willing to make between benefits, harms, and other aspects It covers the use of patient preferences for benefit-risk and reimbursement decisions but also the use of preferences to inform development programs or to show that there is an unmet need; e.g. what are relevant endpoints for patients which should be measured in clnical trials? The objetcive / purpose of a preference study should always be part of the discussion and clearly described Today’s case study presentations will show how preferences have either been used or are intended to be used. Adapted from RTI-HS

Which treatment is best? Reduction in days hospitalized (benefit) Probability of infection (risk) Ideal D Device C is superior on both benefit and risk Preference information is not needed to determine the best treatment Source: MDIC Patient Centered Benefit-Risk Framework Report Public Release, May 13,2015 http://mdic.org/pcbr-framework-report-release/

Now which treatment is best? Preference information is needed to choose between devices A and C B E C D A Reduction in days hospitalized (benefit) Probability of infection (risk) Ideal Source: MDIC Patient Centered Benefit-Risk Framework Report Public Release, May 13,2015 http://mdic.org/pcbr-framework-report-release/

Patient preference sensitive decisions .. related to treatment options: 1. multiple treatment options exist and there is no option that is clearly superior for all patients 2. when the evidence supporting one option over others is considerably uncertain or variable and/or 3. patients’ views about the most important benefits and acceptable risks of a treatment vary considerably within a population, or differ from those of healthcare professionals. https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM446680.pdf

Patient preference methods Type What it Measures Methods Attributes What Matters Qualitative or simple quantitative methods What: Can often be obtained using qualitative methods; Simple quantitative methods can be used to separate those attributes that matter to patients from those attributes that do not Adapted from RTI-HS; Brett Hauber, ICPE 2018, Prague

Patient preference methods Type What it Measures Methods Attributes What Matters Qualitative or simple quantitative methods Relative Importance How much it matters Quantitative methods What: Can often be obtained using qualitative methods; Simple quantitative methods can be used to separate those attributes that matter to patients from those attributes that do not Relative importance: Requires using quantitative methods that provide a weight for each attribute Adapted from RTI-HS; Brett Hauber, ICPE 2018, Prague

Patient preference methods Type What it Measures Methods Attributes What Matters Qualitative or simple quantitative methods Relative Importance How much it matters Quantitative methods Tradeoffs What tradeoffs patients are willing to make between benefits, harms, and other aspects Simple choices by patient, approximate or accurate quantitative methods What: Can often be obtained using qualitative methods; Simple quantitative methods can be used to separate those attributes that matter to patients from those attributes that do not Relative importance: Requires using quantitative methods that provide a weight for each attribute Tradeoffs: 1. Patients are willing to make to obtain or avoid a given attribute. 2. Can be approximated by comparing the weights that patients assign to each attribute 3. Obtaining accurate trade-off information may require quantitative methods designed explicitly for this purpose Adapted from RTI-HS; Brett Hauber, ICPE 2018, Prague

Patient preference methods Type What it Measures Methods Attributes What Matters Qualitative or simple quantitative methods Relative Importance How much it matters Quantitative methods Tradeoffs What tradeoffs patients are willing to make between benefits, harms, and other aspects Simple choices by patient, approximate or accurate quantitative methods Complexity What: Can often be obtained using qualitative methods; Simple quantitative methods can be used to separate those attributes that matter to patients from those attributes that do not Relative importance: Requires using quantitative methods that provide a weight for each attribute Tradeoffs: 1. Patients are willing to make to obtain or avoid a given attribute. 2. Can be approximated by comparing the weights that patients assign to each attribute 3. Obtaining accurate trade-off information may require quantitative methods designed explicitly for this purpose Adapted from RTI-HS; Brett Hauber, ICPE 2018, Prague

Patient preference methods Most recent categorization by IMI PREFER

Open questions in patient preference studies Whose preferences? Cognitive requirements? Which methods? How relate to trial endpoints? Validity? Which patients? How communicate? When should we do it? Roles in ED? Expertise needed? Sample size? Can patients do these studies? Roles in FD? Payer requirements? Many open questions which need answers to make sure that preference studies are done in a scientific rigor way and provide valid and reliable information for decision makers in industry, HAs and HTA bodies. Some of the questions will be touched in today’s presentations. Many of the questions are currently under consideration in IMI PREFER. Regulatory requirements? Roles in reimbursement? Cost? Preference-based subgroups? Industry / regulatory /payer collaboration? Time? Stability? Do we really need it? Source: Bennett Levitan (Johnson&Johnson)

Goal of the IMI PREFER Project By developing expert and evidence-based recommendations, PREFER aims to guide industry, regulatory authorities and HTA bodies and reimbursement agencies on how patient preferences can be assessed and used to inform medical product decision making. Medical product decision making DEV: BR Patient access / HEOR: HTA PP studies which might impact both decisions Axel M: HTA as specific example 5 year project: 2016 - 2021

33 PREFER partners

Who you can contact in your companies (in Basel) Novartis: Conny Berlin (conny.berlin@novartis.com) Sheila Dickinson (sheila.dickinson@novartis.com) Roche: Marloes van Bruggen (marloes.van_bruggen@roche.com) Actelion: Monika Brand (mbrand6@its.jnj.com)

(a few) References http://www.imi-prefer.eu/publications/ MDIC Patient Centered Benefit-Risk Framework Report Public Release, May 13,2015 http://mdic.org/pcbr-framework-report-release/ PREFER webinar: Eliciting Patients’ Preferences for Parkinson’s Devices: https://www.youtube.com/watch?v=wSRXMxgUOeM