Red Pill or Blue Pill? Comparative Effectiveness and Patient-Centered Outcomes Research

1. Red Pill or Blue Pill?Comparative Effectiveness and Patient-Centered Outcomes Research Glen T. Schumock, PharmD, MBA, PhD Professor and Director Center for Pharmacoeconomic Research University of Illinois at Chicago November 15, 2012 NN/LM Greater Midwest Region

2. Red Pill or Blue Pill "You take the blue pill – the story ends, you wake up in your bed and believe whatever you want to believe. You take the red pill – you stay in Wonderland and I show you how deep the rabbit-hole goes." –Morpheus From 1999 film The Matrix

3. Premise • We have a lot of choices in health care. • If we knew the most effective option among the choices available then we could obtain best outcomes at lowest cost. • In many cases there is not sufficient evidence to determine the best option, which results in poor decisions, worse outcomes, and higher cost.

4. What is the Problem? • The US continues to spend more on health care than other countries. • Outcomes of the health care system are not better in the US compared to other developed countries. • There is much variation in the provision and cost of care between regions of the US. • Clinicians often do not have necessary evidence on which to base decisions.

5. Health Expenditure per Capita Source: Organisation for Economic Co-operation and Development (2010), "OECD Health Data", OECD Health Statistics (database).doi: 10.1787/data-00350-en(Accessed on 14 February 2011). Notes: Data from Australia and Japan are 2007 data. Figures for Belgium, Canada, Netherlands, Norway and Switzerland, are OECD estimates. Numbers are PPP adjusted.

6. Spending per capita & as percentof GDP

7. Total Health Expenditure per Capita and GDP per Capita, US and Selected Countries, 2008 Source: Organisation for Economic Co-operation and Development (2010), "OECD Health Data", OECD Health Statistics (database).doi: 10.1787/data-00350-en(Accessed on 14 February 2011). Notes: Data from Australia and Japan are 2007 data. Figures for Belgium, Canada, Netherlands, Norway and Switzerland, are OECD estimates.

8. We spend more on health care in the United States. What do we get for it?

9. Life Expectancy

10. Amenable Mortality

11. Health Care Spending and Life Expectancy

12. Per Capita Medicare Spending

13. The Information Gap • Insufficient evidence to support rational decisions about one alternative versus another for the same indication. • Not studied in same patient population. • Not compared to true therapeutic alternatives. • Not studied in actual practice. • Outcomes of interest not measured. • Illustrated by drug approval process in the US which does not require manufacturers to produce evidence necessary for clinicians or policymakers to choose between drugs for the same indication.

14. Drug Approval Process Safety: Side effects acceptable? Efficacy: Can it work? (under optimal conditions) Effectiveness: Does it work? (under average or usual conditions) Efficiency: Is there sufficient value?

15. Knowns “ [T]here are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know. ”—Former US Secretary of State, Donald Rumsfeld

16. Definition of Comparative Effectiveness Research Comparative effectiveness research is the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings. From Federal Coordinating Council 2009

17. Purpose of CER • 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. From Institute of Medicine 2009

18. Essential Elements • Comparison of two or more drugs, devices, surgeries, diagnostic tools, care management strategies, or other approaches to care that are considered true therapeutic alternatives. • Examines effects/outcomes in actual practice (i.e., effectiveness).

19. Comparison to Traditional RCTs

20. Differences Between Efficacyand Effectiveness Drug Studies From: Schumock. AJHP 2009

21. Types of CER • Primary comparative effectiveness. • Prospective observational studies (aka “large simple clinical trial,” “pragmatic clinical trials”). • Cluster randomized studies. • Registry-based studies. • Retrospective observational studies (case control or cohort studies). • Secondary comparative effectiveness. • Systematic review and meta-analyses. • Modeling and decision-analysis.

22. Example: CER - Primary Prospective Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) • Patients: • Schizophrenia • Intervention: • Drug treatment (antipsychotics) • Comparators: • Olanzapine, perphenazine, quetiapine, risperidone, ziprasidone • Endpoint/outcome • Treatment failure (time to discontinue) Other Examples: ALLHAT, WHI

23. CATIE Impact • CATIE found little difference between the effectiveness of older, cheaper antipsychotics and that of more expensive “second-generation” drugs. • If reimbursement policies had been changed in response and Medicaid had stopped paying for the more costly drugs, it would have saved $1.2 billion out of the $5.5 billion that it spent on these medications in 2005. Sources: Philipson, 2011

24. Advantages and Disadvantages of Prospective CER • Allows for inclusion of outcomes that might not be available in a retrospective database. • Can be randomized. • However, it is an unrealistic expectation that we will have head-to-head randomized trials… • for every intervention and • its combinations • in every patient subgroup • that exactly mimic routine care. • Prospective studies are expensive and take time to conduct.

25. Example: CER - Primary Retrospective • Patients: • Adults with COPD • Intervention: • Drug regimens containing theophylline • Comparators: • Drug regimens not containing theophylline • Endpoint/outcome • Death • COPDexaccerbations • COPD hospitalizations

26. Advantages of Retrospective CER • Are more representative of routine care • Spectrum of disease severity • Spectrum of co-morbidities • Co-medications • Real world adherence • Have very large sample sizes, good for • Infrequent exposure, recently marketed medications • Many subgroups to study treatment effect heterogeneity • May allow Long follow-up • With hard clinical endpoints • Produce results fast, inexpensive

27. Disadvantages of Retrospective CER • Not randomized therefore subject to bias • Confounding by indication (selection bias) • Important outcomes may not be present in data • Clinical outcomes, quality of life

28. Example: CER – Secondary • Patients: • Chronic obstructive pulmonary disease (COPD) • Intervention: • Drug therapy (anticholinergics) • Comparators: • Ipratropium or tiotropium vs. control (placebo or active comparator) • Endpoint/outcome • Death • Myocardial infarction (MI) • Stroke • Many meta-analyses may not be easily characterized as “secondary CER” as are often based on clinical trials setting not actual practice

29. Patient-Centered Outcomes Research • 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. (PCORI)

30. Other Elements that Distinguish CER and PCOR • Importance of “stakeholder” input. • Inclusion of patient input (PCOR). • Prioritization of research topics. • Focus on uptake/dissemination.

31. Stakeholder Input • Purpose: To ensure that the research question, when answered, will provide evidence that can be used. • Examples of stakeholders: Anyone involved in decision-making (patients, physicians, other health care providers, pharmacists, payers, policy-makers).

32. IOM CER Priorities

33. Dissemination/Uptake • Stakeholder engagement does not end with identification of important research questions. • Also involved in study design, analysis of results, and most importantly – interpretation and dissemination. • Stakeholders expected to implement results.

34. Who Conducts CER or PCOR? • Academics/researchers • Clinicians • Pharmaceutical companies • Health provider organizations • Government

35. Who Funds CER and PCOR? • Government • AHRQ, NIH • PCORI – quasi governmental • Pharmaceutical companies • Foundations

36. AHRQ

37. DEcIDE-2 Centers • Brigham and Women's Hospital, Boston, MA • Duke University, Durham, NC • Harvard Pilgrim Health Care, Harvard Medical School, Boston, MA • Johns Hopkins University, Baltimore, MD • Rutgers University, New Brunswick, NJ • University of Illinois Chicago (Chicago-Area DEcIDE) , Chicago, IL • University of Iowa, Iowa City, IA • University of Minnesota School of Public Health, Minneapolis, MN • University of North Carolina at Chapel Hill, Chapel Hill, NC • University of Pennsylvania School of Medicine, Philadelphia, PA • Vanderbilt University Medical Center, Nashville, TN

38. EPCs • Blue Cross and Blue Shield Association, Chicago, IL • Brown University, Providence, RI • ECRI Institute – Penn Medicine EPC, Plymouth Meeting, PA • Johns Hopkins University, Baltimore, MD • Kaiser Permanente Research Affiliates – Portland, OR • Pacific Northwest EPC/OHSU – Portland, OR • RTI International/University of North Carolina – Chapel Hill, NC • Southern California Evidence-based Practice Center--RAND, Santa Monica, CA • University of Alberta, Edmonton, Alberta, Canada • Minnesota Evidence-based Practice Center, Minneapolis, MN • Vanderbilt University Medical Center, Nashville, TN

39. CERTs • Duke University Medical Center, Durham, NC • University of Alabama, Birmingham, AL • Brigham and Women's Hospital, Boston, MA • Rutgers, The State University of New Jersey, New Brunswick, NJ • Cincinnati's Children's Hospital Medical Center, Cincinnati, OH • University of Illinois at Chicago, Chicago, IL

40. pcori • Independent, nonprofit Institute with public and private sector funding . • Sets priorities and coordinates existing agencies that support CER. • Lead by a Board of Governors, and a Methodology Committee (sets research agenda). • Focus on patient-centered outcomes.

41. What are Opportunities for Medical Librarians? • Primary CER/PCOR • Identify evidence gaps in the literature • Determine research priorities • Secondary CER/PCOR • Identify relevant published literature for inclusion • Grading of literature • Synthesis • Interpretation/Dissemination

42. Conclusion • CER/PCOR data can be used to help inform: • Individual patient care decisions/recommendations (patient-level) • Population or system-level decisions (e.g., formulary decisions) • CER/PCOR data can add to body of evidence on: • Effectiveness of one drug compared to another • Safety of one drug compared to another • But does not replace efficacy studies • CER/PCOR is

43. Questions