MDICx webinar series From Stories to Evidence: Quantitative - PowerPoint PPT Presentation

MDICx webinar series From Stories to Evidence: Quantitative patient-preference information to inform product- development and regulatory reviews Shelby Reed Professor, Duke School of Medicine F. Reed Johnson Professor, Duke School of Medicine February 15, 2018 Juan Marcos Gonzalez Assistant Professor, Duke School of Medicine 1

From Stories to Evidence: Quantitative patient-preference information to inform product-development and regulatory reviews MDIC Webinar February 15, 2018 Shelby Reed Professor, Duke School of Medicine F. Reed Johnson Professor, Duke School of Medicine Juan Marcos Gonzalez Assistant Professor, Duke School of Medicine Preference Evaluation Research Group (PrefER) This is presentatio tion refle lects ts th the v vie iews o of t the a auth thors a and should ld n not t be c construed to to r represent th the p polic licie ies o of t the U U.S. FDA.

Patient-centered healthcare movement 3

Who is qualified to make relative-importance value judgments? • Clinicians • Politicians • Patients – Informed consent – Individualistic ethic: Individuals are the best judge of their own welfare “Patient preferences are critical in determining when a product’s benefits outweigh its risks… .” -- R obert M. Califf (JAMA 2017) 4

Increasing Support from FDA FDA’s guidance on benefit-risk determinations for device approvals describes patient tolerance for risk and perspective on benefit as an explicit factor the agency may consider in approval decisions. 4

Dr. Rob Califf, FDA Deputy, Former FDA Commissioner You don’t know people’s preferences unless you ask them. How do people look at these differences? And I fell in love with the discrete- choice experiments, which I had heard about from the Business School, but had not seen in action and I think that provides major advantages. So this is a great day for me. It’s you know been a long time. Who would have thought it would come from the device world? … I think it’s a major triumph for the device world that we’re here today, not just talking about it, but with the FDA very involved. To the extent that FDA takes preferences seriously, I think it’s a great day. Release Event for the MDIC Framework for Integrating Patient Perspective into Medical Device Benefit-Risk Assessments and the FDA Center for Devices and Radiological Health Draft Guidance, May 13, 2015 6

History of CDRH interest in PPI Based on Levitan, NIH HCS Collaboratory and PCORnet Grand Rounds, 2016 7

Preference-Sensitive Regulatory Decisions Risks ? Lower risks Diet & Exercise Weight Less weight loss Loss Patient Engagement Advisory Board (2015) Bennett Levitan 8 Available at: https://www.noexperiencenecessarybook.com/wwzgN/powerpoint-presentation.html

Regulatory Impact of the Study • EnteroMedics’s Maestro Rechargeable System for weight loss • Device failed to meet its original trial endpoints • Device was approved in January 2015 – First new obesity device approved by FDA since 2007 – First approval to result from CDRH's patient preference initiative http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430223.htm 9

Center for Devices and Radiological Health “FDA understands that patients and care-partners who live with a disease or condition on a daily basis and utilize devices in their care may have developed their own insights into and perspectives on the benefits and risks of devices reviewed...” --August 2016 Guidance 10

What are “preferences”? Evidence Stories from representative Often obtained individuals of a group from surveys “Qualitative or quantitative statements of the Characteristics relative desirability or acceptability of attributes or features that differ among alternative interventions.” or Defined by what • health states people are willing to • care processes give up • convenience features • other Medical Device Innovation Consortium (PCBR Framework Report 2015)

Approaches • Qualitative methods (focus groups, public meetings) – Identify areas of concern – Provide context for product-development and regulatory decisions • Simple quantitative methods (ranking, threshold) – Prioritization – Tradeoffs involving only two outcomes • More advanced quantitative methods (choice experiments, best-worst scaling) – Tradeoffs involving more than two outcomes – Statistical preference measures (risk tolerance, minimum acceptable benefit, time equivalents) – Publishable regulatory-quality evidence • Today’s focus: discrete-choice experiments 12

Discrete-Choice Experiments to Quantify Patient Preferences • Developed, tested, and validated over past 40 years in – market research – transportation planning – environmental economics – health • Daniel McFadden received the Nobel Prize in Economics in 2000 for conceptual and statistical foundations • Increased interest and regulatory support because of commitment to patient-centered healthcare 10

Example Choice Task: Cystic Fibrosis Mohamed, Johnson, Balp, Calado, The Patient 2016 14

Choice-Experiment Features • Also known as choice-based conjoint analysis • Alternatives consist of combinations of features • Preferences among alternatives depend on the relative importance of features • Respondents indicate choices among hypothetical alternatives • Statistical analysis of pattern of choices indicates relative importance of features 12

Steps in a Choice-Experiment Study Choice Tasks Definitions Endpoints Survey Development Pretest Interviews Preference Weights Experimental Design Data Collection & Analysis Level B1 Level B1 Level B2 Level B2 Level R1 Level R1   Level R2 Level R2   Prefer X Prefer Y   Prefer Y Prefer X Prefer X Prefer Y 16

Applications over product life cycles CLINICAL REGULATORY ACCESS GUIDANCE USE DEVELOPMENT REVIEW Weighted Benefit- Value Evidence Personalized endpoints risk frameworks reviews medicine Study Cost Outcome 1 1 2 3 Health outcomes Outcome 2 Tx A Outcome 3 + - ++ R Side effects Quality SAE 1 Tx B SAE 2 SAE 3 100 50 300 Convenience N - + + EndptA Alternatives + + - EndptB Disease severity 17

Applications over product life cycles CLINICAL REGULATORY ACCESS GUIDANCE USE DEVELOPMENT REVIEW Weighted Benefit- Value Evidence Personalized endpoints risk frameworks reviews medicine Study Cost Outcome 1 1 2 3 Health outcomes Outcome 2 Tx A Outcome 3 + - ++ R Side effects Quality SAE 1 Tx B SAE 2 SAE 3 100 50 300 Convenience N - + + EndptA Alternatives + + - EndptB Disease severity EXAMPLE Weighted PRO endpoints 18

European Organisation for Research and Treatment of Cancer Patient-Reported Outcome Quality of Life Questionnaire Preference Weights Mohamed AF, Hauber AB, Johnson FR, Coon CD. Patient preferences and linear 16 scoring rules for patient reported outcomes. Patient. 2010;3(4):217-27.

Applications over product life cycles CLINICAL REGULATORY ACCESS GUIDANCE USE DEVELOPMENT REVIEW Weighted Benefit- Value Evidence Personalized endpoints risk frameworks reviews medicine Study Cost Outcome 1 1 2 3 Health outcomes Outcome 2 Tx A Outcome 3 + - ++ R Side effects Quality SAE 1 Tx B SAE 2 100 50 300 SAE 3 Convenience N - + + EndptA Alternatives + + - EndptB Disease severity EXAMPLE Weight- Loss Devices 21

Preferences and Regulatory Decisions Regulators’ Benefit- Risk o Disapprove Risk o o Threshold o o Patients’ o + + Benefit-Risk Threshold o o + + o + o o + + + o + + + Approve Benefit 22

Preference-Sensitive Regulatory Decisions Risks ? Lower risks Diet & Exercise Weight Less weight loss Loss Patient Engagement Advisory Board (2015) Bennett Levitan 23 Available at: https://www.noexperiencenecessarybook.com/wwzgN/powerpoint-presentation.html

FDA Obesity Study 24 Ho, Gonzalez, Lerner, et al., Surgical Endoscopy . 2015

FDA Obesity Study Ho, Gonzalez, Lerner, et al., Surgical Endoscopy . 2015 25

FDA Obesity Study 30% weight loss ≈ 1.2% mortality risk Ho et al. Surgical Endoscopy (2015) Ho, Gonzalez, Lerner, et al., Surgical Endoscopy . 2015 26

Weight-Loss Device Decision Tool 27

Applications over product life cycles CLINICAL REGULATORY ACCESS GUIDANCE USE DEVELOPMENT REVIEW Weighted Benefit- Value Evidence Personalized endpoints risk reviews medicine Study Cost Outcome 1 1 2 3 Health outcomes Outcome 2 Tx A Outcome 3 + - ++ R Side effects Quality SAE 1 Tx B SAE 2 100 50 300 SAE 3 Convenience N - + + EndptA Alternatives + + - EndptB Disease severity EXAMPLE Value Frameworks 28

Value Frameworks 2014 2015 2016 2017 29

Traditional Value Assessment − C C = ExpTrx StdCare ICER − QALYs QALYs ExpTrx StdCare To compare cost-effectiveness for treatments across conditions, outcomes must be measured using the same units.

Other Elements of Value Option value Cost Dosing Value of regimen knowing Other Value Elements of Value Impact on Equity Clinical others benefits Value of hope Adapted from Garrison L, 2016 and Neumann PJ, 2016. 31