Comparative Effectiveness Research

What is it? Why do it? What’s Happening Now?

American Health Lawyers AssociationInstitute for Medicare and Medicaid Payment Issues

Baltimore, MDMarch 29, 2012

Donna A. Messner, PhD Research Director Center for Medical Technology Policy

CER In Essence Simplest definition (AHRQ)

◦ Core question for CER is: which treatment works best, for whom, and under what circumstances?

CER “Hypothesis”◦ Goal of CER is to inform decision-makers

(patients, healthcare consumers, clinicians, payers, policy makers). Therefore, these stakeholders should have greater influence in guiding the activities of the clinical research enterprise.

Why do it? The Great Divide

ResearchersDecision makers

3

Basis for medical and health policy decisions…

SR Tunis, DB Stryer, Carolyn M Clancy, JAMA 2003; 290(12): 1624-1632

“…widespread gaps in evidence-based

knowledge suggest that systematic flaws exist in the production of scientific evidence . .

.”

Decision makers “interested in using high-quality evidence to

support clinical and health policy choices . . . [but] the quality of available scientific evidence is often found to be inadequate.

Types of Evidence Gaps Although RCTs

provide “essential,

high-quality evidence about the

benefits and harms of medical

interventions, many such trials have

limited relevance to

clinical practice.”

Types of evidence and relevance to clinical practice Operative question

Will intervention work under

narrowly prescribed,

experimental conditions?

Design PurposeMaximize chance

of seeing treatment effect in some group of

patients

Design ChoiceStrict limits on

population studied,

treatment setting, follow-up, etc.

Uses of Output FDA Marketing

Clearance, Phase IV, efficacy for

additional indications

Efficacy

Operative question

Will intervention work under real-

world, clinical conditions?

Design PurposeInform specific clinical decision

Design ChoiceUse

representative population,

typical treatment

setting and follow-up, etc.

Uses of Output Clinician,

Patient, Payer, Policy decision-

making

Effectiveness

Need larger study populations to offset more liberal design criteria…Very efficient design

Uses of Efficacy Output

FDA Marketing Clearance, Phase IV,

efficacy for additional indications

Uses of Effectiveness

Output Clinician,

Patient, Payer, Policy

decision-making

Who is likely to pay for each type of research?

Increased data availability from Payers

2003 2009 2010 2013

Medicare Modernization Act

(AHRQ Effective Health Care

Program)

ARRA (FCC-CER; IOM Prioritization)

BCBS TEC (1985)

CMS Coverage withEvidence

Development(2006)

Veterans Affairs, NIH conduct of CER

PCORI

ECRIHayes

CMTPICER

(2008)

Increasing Academic

Private Centers for

CER

Implementation

DERP (2001)

Others?

Publ

ic In

vest

men

tPr

ivat

e In

vest

men

tEfforts to Design Better Research

Adapted from The Lewin Group

CER Funding Growth

*ARRA= $1.1 Billion ($400M NIH; $400M HHS; $300 ARHQ) **PCORI Trust Fund = $1/Covered Life in 2013; $2/Covered Life 2014 with enhancement adjusted for inflation

Definitions of CER by…

Congressional Budget OfficeIOM Roundtable on EBMAmerican College of PhysiciansIOM Committee on Reviewing Evidence to Identify Highly Effective Clinical Services

Medicare Payment Advisory CommissionAgency for Healthcare Research and Quality (AHRQ)American Recovery and Reinvestment Act (ARRA)Patient Protection and Affordable Care Act (ACA)

Defining CER

1. CER has the objective of informing a specific clinical decision from the patient perspective or a health policy decision from the population perspective

2. CER compares at least two alternative interventions, each with the potential to be “best practice”

3. CER describes results at the population and subgroup levels

Common Characteristics of CER Across Definitions*

*IOM (Institute of Medicine). 2009. Initial National Priorities for Comparative Effectiveness Research. Washington, DC: The National Academies Press.

4. CER measures outcomes – both benefits and harms – that are important to patients

5. CER employs methods and data sources appropriate for the decision of interest

6. CER is conducted in settings that are similar to those in which the intervention will be used in practice

Common Characteristics of CER Across Definitions (cont’d)*

*IOM (Institute of Medicine). 2009. Initial National Priorities for Comparative Effectiveness Research. Washington, DC: The National Academies Press.

A synthesis…IOM National Priorities Committee Definition: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.

2009 ARRA

•Establishes Federal Coordinating Council for Comparative Effectiveness Research•Describes CER as “research that compares the clinical outcomes, effectiveness, and appropriateness of items, services, and procedures that are used to prevent, diagnose, or treat diseases, disorders, and other health conditions”

2010 ACA

• Abolishes Federal Coordinating Council• Establishes non-profit Patient-Centered Outcomes Research Institute

(PCORI)• Shift in language, but CER still defined as research “comparing health

outcomes and the clinical effectiveness, risks, and benefits of 2 or more medical treatments, services, and items…”

2011•PCORI defines “patient-centered outcomes research” (PCOR)

What’s in a name? CER to PCOR?

Research to answer patient questions: “Given my personal characteristics, conditions

and preferences, what should I expect will happen to me?”

“What are my options and what are the benefits and harms of those options?”

“What can I do to improve the outcomes that are most important to me?”

“How can the health care system improve my chances of achieving the outcomes I prefer?”

What is PCOR?

http://www.pcori.org/patient-centered-outcomes-research/

Assesses the benefits and harms of preventive, diagnostic, therapeutic, or health delivery system interventions to inform decision making, highlighting comparisons and outcomes that matter to people;

Is inclusive of an individual’s preferences, autonomy and needs, focusing on outcomes that people notice and care about such as survival, function, symptoms, and health-related quality of life; ◦ Incorporates a wide variety of settings and diversity of participants

to address individual differences and barriers to implementation and dissemination; and

Investigates (or may investigate) optimizing outcomes while addressing burden to individuals, resources, and other stakeholder perspectives.

To answer questions, PCOR:

http://www.pcori.org/patient-centered-outcomes-research/

CER PCORInform specific clinical decision from patient or policy perspective

“to inform decision-making”

Compare two interventions “…highlighting comparisons…”Describe outcomes for populations and subgroups

“address individual differences”

Measure benefits and harms important to patients

“assess benefits and harms . . . that matter to people”

Appropriate methods and data sources

[Not in def…but PCORI addresses in other ways]

Use real-world settings Incorporate a “wide variety of settings”

CER “hypothesis” Integrates stakeholder perspective

Shift in emphasis…language more individualistic and patient-focused

Does CER = PCOR?

Should it be?◦ Often stated fear: cost pressures will result in healthcare

“rationing” and stifling of innovation Some considerations:

◦ Innovative process is incremental, not revolutionary Most devices cleared under 510(k)

◦ “New” is not necessarily better. ◦ Even technically revolutionary products may offer only modest

benefits to patients. ◦ When cost is factored in CER, goal is not lower cost but better

value – higher cost is justified with superior patient outcomes.◦ Rationing: should we base on benefit to patient or ability to

pay?

Cost effectiveness NOT in CER definition

Prioritization/selection of research questions

Picking the best comparator◦ Typically want to use “standard of care”

or “current best practice”◦ What if many approaches used, no

consensus on best practice? Balancing benefits and harms

◦ As much methodological as a social judgment

Other methodological challenges

Some Challenges for CER

Stakeholder preferences inform many of these issues

What’s happening now?

Est. 2010 Patient Protection and Affordable Care Act “Independent, non-profit organization created to conduct

research to provide information about the best available evidence to help patients and their health care providers make more informed decisions”

Pilot grants: About 40 two-year projects, $20 million; funding to be announced in May 2012◦ Identifying evidence gaps; priority setting◦ Stakeholder engagement methods◦ New measurement tools for patient-centered outcomes◦ Other basic methods and tools for PCOR

Internally, methodology committee developing “translation framework” for doing CER/PCOR ◦ Outcome/NPC/CMTP parallel effort

PCORI

Source: PCORI Draft National Priorities for Research and Research Agenda, v.1, p. 14

Funded through Agency for Healthcare Research and Quality (AHRQ) grants since 2000

Networks of primary care clinicians and practices working to answer community-based health care questions and translate research findings into practice

Recruit typical patients from real-world practice settings receiving routine standards of care

“Learning health care system” Presents challenges for informed consent, IRB

review, data management◦ CMTP and U of Alabama CERT informed consent project

Practice-Based Research Networks

http://pbrn.ahrq.gov

Over 130 PBRNs funded through four major competitive AHRQ grant programs since 2000

Recent Funding Opportunity Announcements (FOAs) for PCT demos and “collaboratory” projects

Collaboratory program: ◦ Aim: “enable the participation of many health care systems in clinical

research” because this type of research is “essential to strengthen the relevance of research results to ‘real world’ health practice.”

Demonstration projects:◦ pragmatic trials “primarily designed to determine the effects of an

intervention under the usual conditions in which it will be applied”◦ Projects should provide innovative approaches to overcoming barriers

to doing pragmatic clinical trials in networks of health care systems◦ List of example “high-impact” study topics include many of the IOM

top priorities for CER

NIH

Partnership in Applied Comparative Effectiveness Science Advance PCOR by leveraging heretofore unused stores of

FDA data Buccaneer, Lewin Group, Johns Hopkins University, and

CMTP collaborating with FDA◦ set research priorities and gather stakeholder input◦ create secure platforms for FDA data usage◦ work to standardize FDA data sets for analysis◦ develop statistical methods for subgroup analysis

Will allow FDA to understand which interventions are most effective for patients under specific circumstances

FDA - PACES

Increasing recognition that CER will become a necessary part of development programs ◦ FDA approval no longer the end game

CMTP partnered with the Office of Health Economics (UK) on response to RFI to:◦ assess the future CER landscape◦ anticipate CER requirements pharma companies are

likely to have to meet◦ describe at what point in the product development

process pharma should design for CER◦ publish findings on behalf of consortium of

participating companies

Big Pharma

In Conclusion… From CER to PCOR Original focus was on improving information for

patients, clinicians, payers and policy makers◦ Better decisions in context of anticipated payment and

delivery system reforms Emphasis now shifted to primary emphasis on

information needs of patients, especially “patient-centered outcomes”

But health policy forces behind original interest in CER and creation of PCORI have not vanished:◦ Innovation with real impact; reliable evidence for

informed, independent decision-making; enhance care and reduce harms; use resources more effectively

Thank you