Comparative Effectiveness Research:

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• Comparative Effectiveness Research
• Focus on Pragmatism

Sean Tunis MD, MSc July 29, 2009
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Overview

• Policy context for CER
• Definition of CER
• Focus on decision makers
• Engaging stakeholders
• CER methods
• PCTs as one form of CER
• Developing CER methodological framework
• CER methods for DRR

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Billion Dollar Bet on CER

• Total 1.1B for CER
• 300 million to AHRQ
• 400 million to NIH
• 400 million to HHS Secretary
• Vigorous organizing underway
• IOM to report on national priorities for CER
• Federal Coordinating Council report
• AHRQ, NIH, AHRQ-NIH Councils
• CER in House and Senate reform bills
• Propose to create new CER Center

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High Stakes for CER

• At the core of both the stimulus bill and
  Obamas budget is Orszags belief that a
  government empowered with research on the most
  effective medical treatments can, using the
  proper incentives, persuade doctors to become
  more efficient health care providers, thus saving
  billions of dollars. Obama is in effect betting
  his Presidency on Orszags thesis.
• The New Yorker. May 4, 2009.

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http//www.cbo.gov/ftpdocs/89xx/doc8972/02-15-Geog
Health.pdf
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Quality of Evidence for Guideline
Recommendations in CV disease
Robert Califf, IOM Meeting on Evidence-based
Medicine, December 2007
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The EBM Paradox

• How to reconcile
• 18,000 RCTs are published per year
• Available evidence is limited or poor quality
• The gaps, as seen by decision makers
• Patients are highly selected
• Research settings are not typical of community
• Missing or incorrect comparators
• Physiologic or surrogate outcomes, not function
• Results are not available when decisions made

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The Paradox Explained

• Decision makers (patients, consumers, clinicians,
  payers, policy makers) have had limited ability
  to influence the clinical research enterprise

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IOM Committees 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.

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IOM Recommendation 6

• The CER Program should fully involve consumers,
  patients, and caregivers in key aspects of CER,
  including strategic planning, priority setting,
  research proposal development, peer review, and
  dissemination.

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Engaging stakeholders

• Recommendation 1 Conduct a systematic
  assessment of best practices for effective
  engagement of decision makers
• Recommendation 2 As a condition of receiving
  federal funding for any CER study, the
  investigators must form a stakeholder advisory
  committee whose function is based on findings of
  1

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CER Defining Characteristics

• Objective of directly informing clinical or
  health policy decision
• Compares at least 2 alternative, each with
  potential to be best practice
• Results at population and subgroup level
• Measures outcomes important to patients
• Methods and data sources appropriate for the
  decision of interest
• Conducted in real world settings

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Categories of CER Methods

• Systematic reviews of existing research
• Decision modeling, with or without cost
  information
• Retrospective analysis of existing clinical or
  administrative data
• Prospective non-experimental studies, including
  registries
• Experimental studies, including randomized
  clinical trials (RCTs)

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All methods have a role

• Inevitable tradeoff between internal validity and
  feasibility, generalizability, cost, time
• The nature of the research question, and the
  decision maker will influence best practices
• Experimental studies will have a crucial role in
  CER, and there is need for improving design and
  implementation
• Non-experimental methods hold great promise,
  particularly as methods are refined and data
  infrastructure is improved

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IOM Recommendation 7

• The CER Program should devote sufficient
  resources to research and innovation in the
  methods of CER, including the development of
  methodological guidance for CER study design such
  as the appropriate use of observational data and
  more informative, practical, and efficient
  clinical trials.

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Explanatory / Pragmatic Trials

• Explanatory seek to estimate maximum possible
  effect of an intervention
• And to understand how/why effect occurs
• Pragmatic seek to inform choices between
  feasible alternative
• By estimating real world outcome probabilities
• Schwartz and Lellouch, 1967
• Explanatory and pragmatic attitudes in
  therapeutic trials. J Chron Dis 196720637-48.
• Tunis, Stryer, Clancy 2003
• Increasing the value of clinical research for
  decision makers in clinical and health policy.
  JAMA 20032901624-32

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Recent PCT Papers

• CONSORT extension - BMJ (Nov 2008)
• Merrick Zwarenstein, Shaun Treweek, Joel Gagnier,
  Doug Altman, Sean Tunis et al
• PRECIS Journal Clinical Epidemiology (April
  2009)
• Kevin Thorpe, Merrick Zwarenstein, Andy Oxman,
  Shaun Treweek, Curt Furberg, Doug Altman, Sean
  Tunis et al

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The blank pragmaticexplanatory continuum
indicator summary (PRECIS) wheel.
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PRECIS Domains Illustrating the Extremes of
Explanatory and Pragmatic Approaches to Each
Domain
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PRECIS Domains Illustrating the Extremes of
Explanatory and Pragmatic Approaches to Each
Domain
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Pragmatic Pharmaceutical Trials

• Optimize design of phase III trials to be more
  informative for post-FDA decision makers
• Clarify patient, clinician, payer evidence needs
• Identify critical regulatory, methodological
  financial, operational barriers
• Develop PPCT guidance document
• Industry, FDA, CMS, NICE, PBAC, CDR, Consumers
  Union, Medco, BSBCA, others

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Effectiveness Guidance Documents

• Analogous to FDA-guidance
• Targeted to product developers, clinical
  researchers
• Recommendations for design of clinical studies to
  generate evidence that is adequate for decision
  making
• reasonable confidence of improved health
  outcomes
• Started from insights from systematic reviews
• Multi-stakeholder advisory group, iterative draft
  and comment process
• Ongoing work
• Gene expression profiling for breast cancer
• Treatments for chronic wounds
• Cardiac imaging
• Radiation oncology

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Methodological Framework for CER in Disability
and Rehabilitation Research

• Identify planning committee for CER Methods
  Summit
• Background research on existing writing on CER in
  DRR
• Convene Summit on Methods and Strategies for
  Improving Evidence in DRR
• Create Expert-Stakeholder Working Group(s)
• Begin work on Effectiveness Guidance Documents in
  major domains of DRR

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CMTP Mission

• Collaborative projects to promote generation of
  new evidence that it is more informative to
  patients, consumer clinicians, and payers
• We dont do CER studies we develop methods,
  policies, and collaborations to make CER happen

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Review

• Policy context for CER
• Definition of CER
• Focus on decision makers
• Engaging stakeholders
• CER methods
• PCTs as one form of CER
• Developing CER methodological framework
• CER methods for DRR

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Contact Info

• sean.tunis_at_cmtpnet.org
• www.cmtpnet.org
• 443-759-3116 (D)
• 410-963-8876 (M)