Alice K. Jacobs, M.D. Boston Medical Center Boston University School of Medicine

1. Practice Guideline Requirement for New Technology Alice K. Jacobs, M.D. Boston Medical Center Boston University School of Medicine ISCTR Consensus Summit September 2018

2. Disclosure Statement of Financial Interest I, Alice Jacobs, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. ACC/AHA Clinical Practice Guidelines • Overall goal to develop evidence-based recommendations for selection of diagnostic tests, procedures and treatments to improve the quality of care and outcomes for patients with cardiovascular disease

4. Revised (2015) COR/LOE Schema

5. Standards Assessing Individual Studies • Critical appraisal of each study • 3 domains: • Risk of bias • Relevance • Fidelity of implementation

6. Quality Assessment Cochrane Risk of Bias Assessment for RCTs* Domains: • Sequence generation • Allocation concealment • Blinding of participants and outcomes assessors • Incomplete outcome data • Selective outcome reporting • Other sources of bias *Low, Unclear, High Risk

7. Quality Assessment Newcastle-Ottawa Scale for Observational Studies Case vs controls, exposed and non-exposed cohort • Selection: Case/cohort definition, selection and definition of controls,representativeness • Comparability:Comparability of cases or cohorts and controls on the basis of the design or analysis • Exposure: (Case Control) method of ascertainment, same ascertainment and response rate for case vs controls • Outcome:(Cohort) method of assessment (blinded, record linkage), study long enough to occur, adequacy of follow-up

9. Cost Assessment Level of Value Considerations: • Important goal for current and future healthcare economy • Cost of therapy, available technology, practice patterns highly dynamic • Costs associated with unintended harm or complications • Evaluation of burden of cost based on varied perspectives (individual, third party, stakeholder, societal)

10. Cost Assessment Level of Value • High Value (H): better outcomes at lower cost or ICER <$50,000 per QALY gained • Intermediate Value (I): $50,000 to <$150,000 per QALY gained • Low Value (L): ≥$150,000 per QALY gained • Uncertain Value (U): data insufficient • Not assessed (NA): value not assess by writing committee Anderson JA. JACC 2014:63:2304-2322.

11. Cost and Value of ICDs ACC/AHA VA/SCD Guideline 2017.

12. Cost/Value Analysis-> Upcoming Guidelines 2018 Cholesterol Guideline: Cost/value analysis on PCSK9 inhibitors

13. FINDING WHAT WORKS IN HEALTH CARE IOM Report 2011 CLINICAL PRACTICE GUIDELINES WE CAN TRUST STANDARDS FOR SYSTEMATIC REVIEWS

15. Challenges and Opportunities Clinical Practice Guidelines • Perform Systematic Evidence Reviews • Include patient/patient representative point of view • Address Conflict of Interest (COI) • Create “living” documents that lead rather than lag behind clinical practice

16. Challenges and Opportunities Clinical Practice Guidelines • Perform Systematic Evidence Reviews • Include patient/patient representative point of view • Address Conflict of Interest (COI) • Create “living” documents that lead rather than lag behind clinical practice

17. Systematic Review Using Standardized Protocols • Evidence Review Committee • PICO(TS): population, intervention, comparator, outcomes, timing, setting • Formal peer and public assessment of the PICO(TS) question • Simultaneous publication of systematic evidence review (SR) and guideline

18. Risk of Bias*, Relevance, and Fidelity of Included RCTs of DAPT Evidence Review Committee Members. Circulation. 2016;134:e156-e178.

19. DAPT Focused Update 2016

20. Challenges and Opportunities Clinical Practice Guidelines • Perform Systematic Evidence Reviews • Include patient/patient representative point of view • Address Conflict of Interest (COI) • Create “living” documents that lead rather than lag behind clinical practice

21. Inclusion of Patients • Task Force will invite patient representatives (defined as patients and former patients, patient advocates, or patient/consumer organization representatives) to participate (as a member of the Task Force and a GWC). • Methods to identify, select, train, and manage RWI and intellectual perspectives of patient representatives proposed • Patient representatives will participate in topic selection, patient choices, values, preferences, and shared decision making

22. Patient Point of View “Adherence to recommendations can be enhanced by shared decision making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.” ACC/AHA Guidelines Preamble.

23. Shared Decision Making ACC/AHA VA/SCD Guideline 2017.

24. Challenges and Opportunities Clinical Practice Guidelines • Perform Systematic Evidence Reviews • Include patient/patient representative point of view • Address Conflict of Interest (COI) • Create “living” documents that lead rather than lag behind clinical practice

25. Concerns About Practice Guidelines Rowman & Littlefield 2007 Oxford Univ Press 2005

26. Hidden Conflicts? Science Magazine. 2018;361:17-21

27. Writing committee member with RWI >> Bias Writing committee member without RWI >> No Bias Concept: Relationship with Industry (RWI)

28. Number and Type of COI in ACC/AHA Guidelines 17 CPGs through 2008, n=498, 56% Mendelson TB. Arch Intern Med. 2011;171:577-584.

29. Scientific Evidence Underlying ACC/AHA Clinical Practice Guidelines Level of Evidence C Tricoci. JAMA. 2009;301:831-841.

30. RWI: The Questions • What constitutes a RWI ? • Can you be biased without RWI ? • Does RWI = COI? • Does RWI lead to bias in recommendations? • What is the quantitative impact of RWI ? • What is the impact of excluding all RWI?

31. ACC/AHA believes… • including experts with RWI on GWCs, when transparent and properly managed, strengthens the writing effort and results in improved documents by assuring the availability of necessary expertise. • absence of experts (perhaps with relevant RWI) on the GWC would undermine the credibility of the review and CPG as much or more than the presence of committee members with RWI.

32. Define - relevance - scope - amount/level Disclose - in advance - ongoing - publish RWI: General Principles

34. Voting Recusal

35. Define - relevance - scope - amount/level Disclose - in advance - ongoing - publish Manage RWI: General Principles

36. Manage: RWI Policy • >50% GWC no relevant RWI including Chair • Balance race, ethnicity, sex, geography • Balance intellectual stance - referring to prior published opinion or research • Balance scope of clinical practice - applying when an individual’s income derived from reimbursement for performing specific tests or procedures • Intellectual perspectiveand clinical practice perspective (rather than bias) denote intellectual and practice-related opinions and expertise based on knowledge or experience.

37. Challenges and Opportunities Clinical Practice Guidelines • Perform Systematic Evidence Reviews • Include patient/patient representative point of view • Address Conflict of Interest (COI) • Create “living” documents that lead rather than lag behind clinical practice

38. Modular Chunk Formatting • Retrofitted • VA/SCD • Hypertension • ACHD • Afib focused update • De Novo • Cholesterol • Chest pain Synopsis References Rec specific text

39. Table of Recs Modular Chunk Formatting Guideline Focused Update Synopsis Rec-Specific Supportive Text--> References

40. Practice Guideline Requirement for New Technology: Summary • FDA Approval • COR->Risk/benefit ratio • LOE->Study design consistent with quality assessment metrics • Consider cost and value • Include patient point of view • Manage RWI • Translate evidence-based recommendations into clinical practice Commitment to Process and Methods: