Stakeholder –defined research Designing Studies that reflect the perspectives of Patients, clinicians and Payers

1. Stakeholder –defined research Designing Studies that reflect the perspectives of Patients, clinicians and Payers • EPG Grand Rounds, University of Maryland • February 6, 2014 • Patricia Deverka, MD, MS

2. The Center for Medical Technology Policy (CMTP) is an independent ,non-profit 501(c) (3) organization that seeks to advance health care innovation and effectiveness by improving the quality, relevance, and efficiency of health care research. CMTP works on methods, infrastructure and policy to support the conduct of comparative effectiveness research that generates information to assist patients, clinicians, and payers in making informed clinical and health policy decisions. Center for MedicalTechnology Policy

3. Overview • Rationale for engaging stakeholders • Definitions and approach • Case examples • Generative discussion

4. The Evidence Paradox • How to reconcile: • ~18,000 RCTs are published each year* • A growing number of non-experimental studies • Many systematic reviews, health technology assessments, clinical guidelines conclude that the available evidence is limited or studies are poor quality • Up to 60% of clinical recommendations made by ACC or AHA based on expert opinion and/or low quality studies • Systematic review of off-label uses of 19 FDA-approved oncology drugs (428 pages, several thousand trials) “Because of the paucity of high quality evidence, the data available – though voluminous – may have little meaning or value for informing clinical practice” * Chalkidou, Tunis, Whicher, et al. The role for pragmatic, randomized controlled trials (pRCTs) in comparative effectiveness research. ClinicalTrials .Published online before print July 2, 2012, doi: 10.1177/1740774512450097

5. Reasons evidence produced by current clinical research enterprise not translatedinto practice • Differences between settings where research is conducted and where medicine is practiced • Patient population • Interventions, including usual care • Providers, referral patterns access to care • Failure to (be able to) report how treatment effects vary in individual patients and subgroups • Underrepresentation of children, women, elderly, ethnic & racial minorities, patients with comorbidities • Research priorities, study questions, endpoints, etc. defined by researchers and funders, not end users

6. The CER Hypothesis • Gaps in evidence will be reduced with increased guidance from payers, patients and clinicians in study design • A functional definition of CER would be research designed in light of meaningful engagement of these decision makers

7. Definitions of cer and pcor Definition of CER The generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels. Source: Institute of Medicine Definition of PCOR Patient-Centered Outcomes Research (PCOR) helps people and their caregivers communicate and make informed health care decisions, allowing their voices to be heard in assessing the value of health care options. PCOR has the following characteristics: • Actively engages patients and key stakeholders throughout the research process. • Compares important clinical management options. • Evaluates the outcomes that are most important to patients. • Addresses implementation of the research finings in clinical care environments. Source: PCORI

8. What is unique about CER? • Many CER studies will require an understanding of the trade-offs between internal validity and increased generalizability, relevance, feasibility and timeliness • The right balance is not solely a scientific issue, it’s also a social judgment about an acceptable level of uncertainty, involving multiple stakeholders • Process to achieve this with stakeholder input is evolving

9. THEORY OF STAKEHOLDER ENGAGEMENT Evidence suggests that engaging stakeholders in research increases: Relevance and Content Relevance and Content Knowledge Exchange Application of Evidence Dissemination Avenues

10. Barriers to involving stakeholders in cer Confusing terminology, lack of standard definitions Timing; restrictions on availability of stakeholders Training needs for all stakeholders to maximize participation Concerns that process will add time and costs to project plans Lack of shared conceptualization of what it means to “successfully” or “effectively” involve stakeholders in research Limited data regarding impact; systematic evaluation rare Sources: Guise, O'Haire, McPheeters, et al. A practice-based tool for engaging stakeholders in future research: a synthesis of current practices. J Clin Epidemiol. 2013 Jun;66(6):666-74. doi: 10.1016/j.jclinepi.2012.12.010. Epub 2013 Mar 13. and CMTP experience

12. Addressing the Barriers • Literature review • Biomedical • Social science • Practical experience based on projects involving stakeholders • Drafted definitions and conceptual model • Review and revision by an expert panel • Patient and Consumer Advisory Council • NICE Patient and Public Involvement Program and Citizen Council in the UK • Applied it to a complex multi-stakeholder project

13. Diverse Roots of Public Participation Activities *Community-based participatory research

14. Typology of stakeholder engagement Stakeholder engagement “light” Stakeholderengagement Source: Nass, Levine, and Yancy.Methods for Involving Patients in Topic Generation for Patient-Centered Comparative Effectiveness Research –An International Perspective

15. Stakeholders Individuals, organizations, or communities that have a direct interest in the process and outcomes of a project, organization, or policy. Deverka, Lavallee, Desai, et al. Stakeholder participation in comparative effectiveness research: defining a framework for effective engagement. J Compar Effect Res 2012; 2:181-94.

16. Target stakeholder groups for CER

17. Stakeholder Engagement A process of actively soliciting the knowledge, experience, judgment and values of individuals selected to represent a broad range of direct interests in a particular issue, for the dual purposes of: 1) Creating a shared understanding; 2) Making relevant, transparent, and effective decisions.

18. Inputs Methods Outputs Conceptual Model for Stakeholder Engagement in CER Analytic-Deliberative Model Types of evidence • Values • Research • Professional Experience • Patient and consumer knowledge and experience Methods of combining evidence Quantitative • Questionnaires • Delphi method • Multi-Criteria Mapping • Value of Information modeling Qualitative • Facilitated • workshops/meetings • Stakeholder decision analysis Decisions • Topic generation • Research priorities • Study designs • Evidentiary thresholds for clinical and health policy decision • making • Implementation strategies Outcomes

19. Deciding which stakeholder groups to involve in a project • What topic(s) does the research address? • What health care decision is the research meant to inform? • Who are the decision makers responsible for these decisions? • Who are the individuals and groups that are affected by these decisions? Concannon TW, Meissner P, Grunbaum JA, et al. A new taxonomy for stakeholder engagement in patient-centered outcomes research. JGIM 2012;27(8):985-91.

20. When to involve patients and other stakeholders in research? Topic identification and refinement Priority-setting Writing proposals (including deciding research methods) Reviewing research conduct Interpretation of findings Dissemination of information Implementation Evaluation Curtis, Slaughter-Mason, Thielke, et al. PCORI Expert Interviews Project: Final Report. Portland, OR: Center for Evidence-based Policy. Oregon Health & Sciences University.

21. STAKEHOLDER INVOLVEMENT IN GOVERNANCE • Decision-making • Data access • Data security • Data privacy • Conflicts of interest • Consent • Communication • Coordination with other committees Adapted from: Rein A, Holve E, Hamilton Lopez M, and Winkler J. A framework for patient and consumer engagement in evidence generation,” EDM Forum,Academy-Health, September 2012. *Refers to the creation/modification of the Patient Engagement Platform needed to support both clinical management and the conduct of PCOR

22. PATient-centered Involvement in Evaluating the effectiveNess of TreatmentS PATIENTS

23. Aims of PATIENTS Foster sustainable partnerships with local, regional, and national communities of diverse patients and healthcare systems Conduct and expand PCOR in partnership with patients and healthcare delivery systems Advance dissemination and implementation strategies for PCOR findings

24. Vision • The PATIENTS Program vision is that its projects will: • Further the process of UM institutional transformation for “MPowering the State” in the area of health • Eliminate health disparities within Baltimore, throughout Maryland, and across the nation • Align with the spirit of the NIH roadmap for transformative and interdisciplinary research

25. University of Maryland has broad participation • UMB professional schools • Pharmacy • Medicine • Nursing • Social Work • Dentistry • Law • UM College Park

26. PATIENTS Partners

27. Innovation in the PATIENTS Program • Conducting PCOR with continuous patient and stakeholder engagement • Translating research into practice • Continuous development through formative and impact evaluation • Bidirectional learning • Sustainability

28. The Ten-Step Process for Conducting CER • Topic Solicitation • Prioritization • Framing the Question Based on: Mullins CD, AbdulhalimAM, Lavallee DC. Continuous Patient Engagement in Comparative Effectiveness Research. JAMA 2012; 307(15): 1587-8.

29. The Ten-Step Process for Conducting CER • Selection of Comparators and Outcomes • Creation of Conceptual Framework • Analysis Plan • Data Collection Based on: Mullins CD, AbdulhalimAM, Lavallee DC. Continuous Patient Engagement in Comparative Effectiveness Research. JAMA 2012; 307(15): 1587-8.

30. The Ten-Step Process for Conducting CER • Reviewing & Interpreting Results • Translation • Dissemination Based on: Mullins CD, AbdulhalimAM, Lavallee DC. Continuous Patient Engagement in Comparative Effectiveness Research. JAMA 2012; 307(15): 1587-8.

31. Education and Training: Engaging Partners Bidirectional Learning Stakeholder Engagement Cultural Competence Using Online Platforms Research Methods Manuscript Writing Grant Writing Community Partners UM Faculty and Staff • Examples: • PatientsLikeMe: Social Media • BSBHS/Riverside Heath System: Implementation

32. Examples: Study Designs Reflecting Views of Decision Makers

33. Two Examples • Genomic Testing in Cancer (CANCERGEN) • Evidence Guidance Documents • Molecular Dx in Cancer

34. The Promise: Transform Cancer Care Molecular diagnostic (MDx) tests have the potential to transform oncology practice by helping physicians classify and manage various cancers Diagnose and stage cancers Help guide therapy selection and dosing Assess treatment response Aid in detection of residual or recurrent disease

35. CANCERGEN Structure

36. Thariani R, Wong W, Carlson JJ, et al. Prioritization in Comparative Effectiveness Research: The CANCERGEN Experience in Cancer Genomics. Medical Care 2012; 50(5):388-393

37. Ranking of Tests Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN)

38. Lessons Learned • Full participation of all stakeholders on highly technical topics is possible with adequate preparation • Multi-modal approaches are necessary • Engagement method should be matched to particular study question • Stakeholders were open to novel methods (e.g., VOI), but more work needs to be done to ensure full benefits of the approach are fully realized • Possible to engage most stakeholders for a multi-year project • Federal officials are the most difficult

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40. A Stakeholder-Driven Approach to Improving the Evidence Base • Molecular Diagnostics (MDx) In Oncology

41. Decision Makers’ Key Questions for Cancer MDx Tests • Does the MDx test provide correct information? (analytic validity) • How well does the test result correlate with clinical outcome? (clinical validity) • Does use of the MDx test lead to improved patient outcomes as compared with the alternative? (clinical utility) • Does use of the MDx test lead to greater value as compared with the alternative? (cost-effectiveness)

42. Problem • Analytic validity and clinical validity now available for an increasing number of MDx tests • Clinical utility largely unknown for most MDx tests • Uncertain clinical utility has consequences for patients and health care system • Decreases quality through inconsistent or unnecessary use of tests • Wastes health care resources

43. What’s needed • Structured data about MDx test use • Stakeholder-driven process • Clear evidentiary standards for clinical utility • Willingness to consider range of methods, outcome measures that are relevant to real-world clinical decisions

44. THE Response: Effectiveness Guidance Documents Provide specific recommendations on the design of studies intended to inform decisions by patients, clinicians and payers Developed for specific clinical conditions and categories of technologies Based on a structured, transparent, multi-stakeholder process led by CMTP Aim to balance internal validity, relevance, timeliness and feasibility provide decision-makers with a reasonable level of confidence that the intervention improves net health outcomes Analogous and complementary to FDA guidance Targeted to researchers working in industry or academic settings

45. Technical Working Group • Academic researchers 2 • Industry 3 • Payers 2 • Research funders 1 • Policy makers 1 • Patient advocate 1

46. Recommendations: 10 covering clinical validity and clinical utility • MDx test development follows phases similar to the phases of drug development • Recommendations have been organized around these phases • Biomarker discovery (Phase 0) and the assessment of population impacts (Phase 5) go beyond the scope of this EGD

47. How EGDs Might be Used • By test developers and researchers in designing studies • By payers in evaluating evidence submitted for coverage and reimbursement • By guidelines developers in judging quality of evidence and strength of recommendations • By research funding organizations in evaluating grant proposals • By patient advocacy and other groups generating guidance for patients

48. Summary • Stakeholder engagement is essential for fulfilling the objectives of CER • Research funding requests and support need to account for resources required to meaningfully implement engagement activities • The terminology and methods are being developed and tested worked for CER • Methods need to be tailored to the particular phase of research, but stakeholders should be involved throughout the process • Careful attention to communication at multiple levels is critical to ensuring true collaboration and a respectful, accountable process • There is a growing body of examples of rigorous methods of SE being applied to CER • Evaluation is critical for measuring impact and process improvement

49. Extra Slides

50. CMTP: Principles for Involving Patients in Comparative Effectiveness Research • Each CER-related project includes patient representatives.** Examples of such projects include identifying research topics, setting priorities, developing questions to be studied, designing study protocols and establishing methodological standards. • Project leaders recruit a diverse group of patients for whom the project topic is relevant. • Project leaders, patients and other stakeholders make their mutual expectations for patient involvement known to each other. • The project team, other stakeholders and patients disclose potential conflicts of interest. • Project budget includes appropriate remuneration for patients and support for their participation, including training, stipends, travel and lodging, and other resources critical for their full involvement in the project. **Includes patients, family caregivers and consumers representatives of all types