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2
What Is Comparative
Effectiveness Research?
abstract: Comparative effectiveness research (CER) provides an oppor-
tunity to improve the quality and outcomes of health care by providing
more and better information to support decisions by the public, patients,
caregivers, clinicians, purchasers, and policy makers. Several organiza-
tions have developed definitions of CER; for purposes of this study, the
Institute of Medicine committee has defined CER as “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.”
CER’s distinguishing characteristics include informing a specific clinical
or policy decision, comparing at least two approaches or interventions,
describing results at the subgroup level, measuring benefits in real-world
populations, and applying appropriate methods and data sources. Several
federal agencies and many other organizations are involved in important
CER activities, which are summarized in this chapter. However, the exist-
ing incentives for developing CER evidence are uneven, the infrastructure
for supporting the development of such evidence has gaps, and better
coordination of research and translation of evidence into clinical practice
and health policy is needed.
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0 INITIAL NATIONAL PRIORITIES FOR CER
THE NEED FOR More AND better EvIDENCE
OF WHAT WORKS IN HEALTH CARE
While the U.S. health care system continues to make progress in im-
proving health, there is wide agreement that large gaps remain in the qual-
ity and outcomes of health services delivered to many Americans (IOM,
2001; Orszag, 2007). Moreover, the need for better value in the health care
system becomes apparent when overall health care spending and outcomes
are considered. Health care expenditures were $2.4 trillion in 2008 and
are projected to grow by an average of 6.2 percent per year for the next 10
years, more than triple the projected rate of overall gross domestic product
(GDP) growth (Sisko et al., 2009). The Congressional Budget Office (CBO)
projects that under current law, health care will consume more than 30
percent of GDP by 2035 (CBO, 2008).
Regional variations in treatment patterns and cost growth provide
deeper insight into the need for more informed medical decision making.
Researchers at the Dartmouth Institute for Health Policy and Clinical Prac-
tice have shown that patients in the highest-spending regions of the country
receive 60 percent more health services than those in the lowest-spending
regions, yet this additional care is not associated with improved outcomes
(Fisher et al., 2003). The Dartmouth research suggests that physicians in
higher-spending areas are more likely than physicians in other regions to
recommend costly interventions that have not been definitively shown to be
effective (Fisher et al., 2009). Nationwide, the Institute of Medicine (IOM)
has estimated that less than half of all treatments delivered today are sup-
ported by evidence (IOM, 2007). Even the most thoughtfully conceived and
sophisticated practice guidelines have inadequacies in their evidence base,
whereas many guidelines that are evidence-based and well-supported are
often not translated into clinical practice. A recent review of practice guide-
lines developed by the American College of Cardiology and the American
Heart Association found that relatively few recommendations were based
on high-quality evidence—randomized controlled trials, for instance—and
many were based solely on expert opinion, individual case studies, or
standard of care (Tricoci et al., 2009). A similar study revealed that more
than two-thirds of recommendations contained in 51 guidelines for treating
lung cancer were not evidence-based (Harpole et al., 2003). Researchers as-
sessing recommendations for preventing and treating breast and colorectal
cancers concluded that the overall quality of available guidelines for these
cancers was “modest” (Vigna-Taglianti et al., 2006). Thus, providers need
better information to provide the appropriate care for their patients.
Providers, hospitals, and clinics are not the only groups with a stake in
the evidence base for health care decisions. A growing movement of educa-
tion and empowerment for consumers, as well as the public and patients
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
taking a more active role in making decisions about their own health care,
has emerged together with health insurance plans shifting a greater share
of expenses to patients. New models of shared decision making promise to
bring greater emphasis to informed patient choice for “preference-sensitive”
care (Wennberg et al., 2007). Indeed, new and better research could im-
prove the quality, safety, and effectiveness of health care by providing
both patients and their health care providers with the evidence to assist in
informed decision making. To accomplish this, however, patient-focused
research is needed to identify not only the population-level effects of health
interventions, but also the patient-level predictors of both positive and
negative outcomes and the role of patient preferences in making choices
(CBO, 2008).
Beyond consumers and health care providers, those that bear substan-
tial financial responsibility for the health care needs of populations need
better evidence; they include employers, federal programs such as Medicare
and Medicaid, and private insurers. These organizations must allocate re-
sources across a panoply of medical services, procedures, and technologies
in an attempt to maximize health benefits while keeping coverage afford-
able. Moreover, these organizations must function within a growing array
of models for the delivery and financing of health care, many of which are
not yet supported with robust evidence of effectiveness.
Optimizing Evidence
Study Populations Representative of Clinical Practice
Many studies of the effects of medical interventions on health address
efficacy rather than effectiveness. Efficacy reflects the degree to which an
intervention produces the expected result under carefully controlled condi-
tions chosen to maximize the likelihood of observing an effect if it exists.
Many randomized controlled trials—generally considered to be the gold
standard—are efficacy studies, particularly those conducted to win regula-
tory approval. The study population and setting of efficacy studies may
differ in important ways from those settings in which the interventions are
likely to be used. By contrast, effectiveness research intends to measure
the benefits and harms of an intervention in ordinary settings and broader
populations, and therefore can often be more relevant to policy evaluation
and the health care decisions of providers and patients. Care needs to be
taken, however, in effectiveness research such as observational, database,
registry, and other studies to recognize that without randomization, uniden-
tified bias and confounders may weaken the level of evidence, and that ef-
ficacy studies may be strengthened by broadening eligibility of populations
or settings for trials and other attempts to increase generalizability. Issues
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INITIAL NATIONAL PRIORITIES FOR CER
regarding efficacy and effectiveness, and other aspects of CER studies are
further examined below.
Focus on the Individual Rather Than the Average Patient
With the growing knowledge of disease mechanisms, systems biology,
genomics, and other sciences that create the potential for more targeted
therapies, patients and providers are increasingly seeking evidence not
only from representative populations, but also from relevant subgroups.
Increasing emphasis on patient-level attributes that may modify the balance
of benefits or harms can lead to more personalized medicine, reducing the
pressure to try alternatives found to be ineffective in similar subgroups.
Study Two or More Interventions in Direct Comparison
Randomized, placebo-controlled studies demonstrating safety and ef-
ficacy for the purpose of gaining approval from the Food and Drug Admin-
istration (FDA) frequently serve as the basis for informing clinical decisions.
Although the FDA does require “active comparators” in some clinical cir-
cumstances, there is a paucity of head-to-head studies, and the public needs
more studies that compare evidence-based alternatives (including usual
care), particularly in subgroups that preapproval studies often omit.
Beyond specific medical interventions and technologies, there is a
need for evidence evaluating the clinical and resource effects of innova-
tions in health care delivery models, including new benefit designs, cost-
sharing techniques, integrated organizational models, public health and
population-level strategies, and interventions to improve the quality of
care. Approaches to the organization, delivery, and payment for health
care services are seldom evaluated for their impact on patient outcomes
and overall value, yet they need to be studied directly using the same prin-
ciples described previously. Because these interventions are often imple-
mented at provider or regional levels, the methods required to evaluate
them—such as cluster randomized trials—may differ from those used to
evaluate patient-level interventions.
Finally, merely generating better evidence is not enough to meet the
decision-making needs of consumers, patients, health care providers, and
purchasers. To maximize its impact on the quality and value of health care,
these parties must use evidence when making clinical and policy decisions.
Disseminating evidence into clinical practice must be accompanied by on-
going evaluation and feedback to decision makers, the key characteristic
of a true learning health care system. However, this is not happening con-
sistently. In a review of adherence to 439 indicators of health care quality
for 30 acute and chronic conditions as well as preventive care, McGlynn
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
and colleagues concluded that American adults received only 55 percent of
recommended care (McGlynn et al., 2003). Similarly, another study found
that children and youth received only 46.5 percent of recommended care
(Mangione-Smith et al., 2007). Even proven screening tests and other pre-
ventive services—such as influenza vaccines and mammograms in adults—
are utilized by only 75 percent of Medicare beneficiaries (GAO, 2002).
Furthermore, only 77 percent of U.S. children aged 19-35 months received
all of the recommended doses of six childhood vaccines in 2006 (CDC,
2007). This gap between evidence and execution underscores the need to
identify more effective tools to help patients, providers, and policy makers
to use the available evidence.
Indeed, as the number of elective treatments and procedures has grown,
so has the need for patient-centered research that compares their effective-
ness. The promise of comparative effectiveness research (CER) is that it
provides evidence that is better focused on the decisions of daily medical
practice than existing evidence and therefore helps patients, caregivers,
providers, payers, and policy makers make informed decisions about health
care.
DEFINING COMPARATIvE EFFECTIvENESS RESEARCH
CER can be very broad in scope depending on what is “compared,”
how one defines “effectiveness,” and what constitutes “research.” Virtually
any applied biomedical inquiry is fundamentally about improving health,
avoiding unnecessary costs, or both. In the current public policy environ-
ment, defining and describing CER is important: the 111th Congress made
a $1.1 billion investment in CER and has created a Federal Coordinating
Council to coordinate CER within the Department of Health and Human
Services (HHS).1 According to the American Recovery and Reinvestment
Act (ARRA) of 2009 (P.L. 111-5), this Council must provide Congress
and the Secretary of HHS with an annual report describing its activities
and specific recommendations for infrastructure and coordination of CER
activities within relevant federal departments and agencies.
Debate continues among stakeholders seeking to shape what will be
studied, how it will be studied, and how the results will be applied—a
debate reflected in the extensive response to the present study’s efforts to
encourage stakeholder input to its assigned task of setting research priori-
ties (as described in Chapter 3).
New and expanded CER efforts will build on a solid base that is gaining
wider recognition for its importance and applicability to clinical decision
1 American Recovery and Reinvestment Act of 00, P.L. 111-5, 111th Congress, 1st ses-
sion (February 17, 2009).
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INITIAL NATIONAL PRIORITIES FOR CER
making. As expectations for CER rise, more and more gaps in both knowl-
edge and research infrastructure appear. These gaps must be filled if CER
is to fulfill its promise of more informed decisions and better outcomes. In
this chapter, the committee takes inventory of different authoritative defini-
tions of CER, derives from these the discipline’s defining characteristics, and
briefly describes the range of ongoing activities that offer a foundation for
new investments in this rapidly evolving field.
Existing Definitions
Although research comparing the effectiveness of health care strategies
and interventions has been conducted for more than a century,2 the term
“comparative effectiveness research” has taken on new meaning in recent
years. Table 2-1 displays several definitions, all of which were developed by
leading public and private-sector authorities in the United States.
These definitions all emphasize CER’s role in helping to inform health
care decisions. All denote the evaluation of at least two alternatives, each
with the potential to represent best practice. Most CER definitions suggest
that the objective is to learn what works best in actual practice for a defined
population. CER includes both systematic reviews of existing data and the
collection and analysis of primary data.
A contested issue in defining CER is whether costs or cost-effectiveness
are appropriate outcomes of interest. The main justification for including
economic considerations is that the overall value of a strategy can be under-
stood best by considering costs and benefits together. Another view is that
CER in general, and the use of cost-effectiveness analysis in particular, will
inevitably discourage the use of expensive forms of care and lead to denial
of needed care. While CER may identify ways to obtain better outcomes for
the same or lower spending, cost-effectiveness analysis and CER may also
lead to the conclusion that the more expensive approach offers better value
than lower-cost approaches. For example, in the setting of breast cancer,
magnetic resonance imaging (MRI) screening was found to be cost-effective
relative to mammography in carriers of the BRCA1/2 mutation (Plevritis et
al., 2006). Similarly, adjuvant trastuzumab was found to be cost-effective
compared to conventional chemotherapy without trastuzumab in early
stage HER2/neu-positive breast cancer (Kurian et al., 2007). When CER
examines differences in costs as well as outcomes, its aim is to identify the
approach that offers the better value; it does not necessarily promote or
favor low-cost care.
2 Ernest Amory Codman, M.D. (1869–1940), was a Boston surgeon and pioneer in the study
of quality and safety outcomes. According to one biographer, he never stopped in his effort to
link care, errors, and end results and to measure, report, and improve.
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
TAbLE 2-1 Definitions of CER
Organization Definition
Congressional Budget A rigorous evaluation of the impact of different options that are
Office available for treating a given medical condition for a particular
set of patients. Such a study may compare similar treatments,
such as competing drugs, or it may analyze very different
approaches, such as surgery and drug therapy. The analysis may
focus only on the relative medical benefits and risks of each
option, or it may also weigh both the costs and the benefits of
those options. In some cases, a given treatment may prove to
be more effective clinically or more cost-effective for a broad
range of patients, but frequently a key issue is determining which
specific types of patients would benefit most from it. Related
terms include cost-benefit analysis, technology assessment, and
evidence-based medicine, although the latter concepts do not
ordinarily take costs into account.
IOM Roundtable The comparison of one diagnostic or treatment option to one or
on Evidence-Based more others. In this respect, primary comparative effectiveness
Medicine research involves the direct generation of clinical information on
the relative merits or outcomes of one intervention in comparison
to one or more others, and secondary comparative effectiveness
research involves the synthesis of primary studies to allow
conclusions to be drawn. Secondary comparisons of the relative
merits of different diagnostic or treatment interventions can be
done through collective analysis of the results of multiple head-
to-head studies, or indirectly, in which the treatment options have
not been directly compared to each other in a clinical evaluation,
and inferences must be drawn based on the relative effect of each
intervention to a specific comparison, often a placebo.
American College of Comparative effectiveness analysis evaluates the relative (clinical)
Physicians effectiveness, safety, and cost of two or more medical services,
drugs, devices, therapies, or procedures used to treat the same
condition. Although the use of the term comparative effectiveness
broadly refers to the evaluation of both the relative clinical and
cost differences among different medical interventions, it is notable
that most comparative effectiveness research engaged in and used
by stakeholders in this country focuses solely on evaluating relative
clinical differences to the exclusion of cost factors.
IOM Committee on Comparison of . . . the impacts of different options for caring for
Reviewing Evidence a medical condition for a defined set of patients. The comparison
to Identify Highly may be between similar treatments, such as competing
Effective Clinical prescription medications, or for very different treatment
Services approaches, such as surgery or radiation therapy. Or, the
comparison may be between using a specific intervention and its
nonuse (sometimes called watchful waiting). This report uses the
terms “effectiveness,” “clinical effectiveness,” and “comparative
effectiveness” interchangeably.
continued
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INITIAL NATIONAL PRIORITIES FOR CER
TAbLE 2-1 Continued
Organization Definition
Medicare Payment Comparative-effectiveness analysis evaluates the relative value of
Advisory Commission drugs, devices, diagnostic and surgical procedures, diagnostic tests,
and medical services. By value, we mean the clinical effectiveness of
a service compared with its alternatives. Comparative-effectiveness
information has the potential to promote care of higher value and
quality in the public and private sectors.
Agency for Healthcare A type of health care research that compares the results of
Research and Quality one approach for managing a disease to the results of other
approaches. Comparative effectiveness usually compares two or
more types of treatment, such as different drugs, for the same
disease. Comparative effectiveness also can compare types of
surgery or other kinds of medical procedures and tests. The
results often are summarized in a systematic review.
The direct comparison of existing health care interventions to
determine which work best for which patients and which pose the
greatest benefits and harms . . . the core question of comparative
effectiveness research (is) which treatment works best, for whom,
and under what circumstances.
SOURCES: AHRQ (2009a); American College of Physicians (2008); IOM (2007, 2008); Medi-
care Payment Advisory Commission (2008); Orszag (2007); Slutsky and Clancy (2009).
Ultimately, CER aims to provide data that can influence clinical deci-
sions for the better. If CER results are integrated into health care delivery
and facilitate improved decision making, health care outcomes can be
expected to improve. The concept has been formalized as the value of
information, or the difference between the value of the outcome given the
decision one would make in the absence of additional information and the
value of the outcome of the decision that would be made as additional in-
formation became available as a result of the research (Garber and Meltzer,
2009). In such a circumstance, value may be judged from the perspective of
the patient, provider, or payer.
The Spine Patient Outcomes Research Trial (SPORT) provides several
examples of the potential utility of CER. The investigators demonstrate
the value of spinal stenosis surgery in subjects without degenerative spon-
dylolisthesis compared to nonsurgical interventions, as well as to subjects
with degenerative spondylolisthesis (Tosteson et al., 2008; Weinstein et al.,
2008). The Veterans Administration instituted a variety of interventions
based upon their initial observations following performance scores obtained
from an external peer review program in the mid-1990s, demonstrating re-
markable improvement in 12 of 13 quality indicators over a 5-year period
(Jha et al., 2003).
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
CHARACTERISTICS OF CER
Six defining characteristics of CER may be drawn from these definitions
and the committee’s deliberations over national priorities:
1. CER has the objective of directly informing a specific clinical deci-
sion from the patient perspective or a health policy decision from
the population perspective. The range of potential objectives for
CER studies gives the field a broad scope. Clinical questions re-
fer to the health care of individual patients, including preventive,
screening, diagnostic, therapeutic, monitoring, or rehabilitative in-
terventions. Policy questions refer to the health and health care of
populations through knowledge synthesis and transfer strategies,
public health programs, or initiatives involving the organization,
delivery, or payment for health services. This characteristic has a
major implication; because CER contributes to such important de-
cisions, all relevant stakeholders (including patients and the public)
and decision makers would reasonably be included throughout the
CER process, including priority setting, study design, and imple-
mentation of results (Tunis et al., 2003). Consumer involvement
in trials began in earnest in the AIDS era (Epstein, 1996). Early
efforts in CER embraced involvement of patients, caregivers, clini-
cians, and other decision makers in setting research boundaries and
in defining populations, settings, comparisons, and outcomes that
should be addressed in the research (Helfand, 2005; Santaguida et
al., 2005; Whitlock et al., 2009).
2. CER compares at least two alternative interventions, each with the
potential to be “best practice.” Compared clinical strategies may
be very similar (drug vs. drug) or very different (drug vs. surgery).
For many clinical decisions, “optimal usual care” reflecting current
standards is an appropriate potential comparator. CER studies
may also include the alternative of “watchful waiting” when it is
considered to be a reasonable strategy in the clinical context. CER
highlights research that compares a test intervention with viable
alternatives. Interventions are implemented in accord with usual
practice, which includes co-interventions and practice preferences.
For policy decisions, a comparator may be the status quo.
3. CER describes results at the population and subgroup levels. The
primary outcome of a clinical trial is a measure of the “average
effect” of an intervention, usually as estimated in the population
assigned to the intervention in the trial. Even when selecting from
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INITIAL NATIONAL PRIORITIES FOR CER
“proven” strategies, clinicians must judge whether a particular pa-
tient is sufficiently similar to the trial population or if technological
or scientific advancement has outdated the empirical results. By its
focus on subgroup results and clinical prediction rules to identify
patients likely to benefit from an intervention, CER assists providers
and patients in individualizing decisions—going beyond the average
effects to the effect in subjects with common clinical characteristics.
This focus of CER reflects the growing potential for individualized
and predictive medicine—based on advances in genomics, sys-
tems biology, and other biomedical sciences—through the analysis
of subgroups with demographic, ethnic, physiologic, and genetic
characteristics that could be useful factors in clinical decisions.
4. CER measures outcomes—both benefits and harms—that are im-
portant to patients. The committee is using the term “effective-
ness” in reference to the extent to which a specific intervention,
procedure, regimen, or service does what it is intended to do when
used under real-world circumstances. This can be contrasted with
“efficacy,” which is the extent to which an intervention produces
a beneficial result under controlled conditions (Cochrane, 1971;
Higgins and Green, 2008). This implies an important distinction
between much clinical research and CER, in that CER places
high value on external validity, or the ability to generalize results
to real-world decision making. Harms or risks of unintended
consequences are also outcomes of interest, because they influ-
ence the net benefits3 of an intervention. Including and giving
weight to patient-reported outcomes is particularly important for
CER studies in which patient ratings of effectiveness or adverse
events may differ from clinical measures. Finally, resource utiliza -
tion may be highly relevant to net benefits when comparing the
full clinical course of interventions over time. Cost-effectiveness
analysis is a useful tool of CER, allowing evaluation of the full
range of treatment outcomes in relationship to the difference in
costs. Robust evidence of comparative clinical effectiveness is a
building block necessary for resource allocation decisions. More-
over, just as clinical effects may vary in different settings, costs
vary as well, so a given set of cost-effectiveness results is often
not generalizable.
5. CER employs methods and data sources appropriate for the deci-
sion of interest. CER includes at least three broad categories of
3 The net benefit of a particular intervention is the balance of the harms and benefits.
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
research methods. Where evidence is lacking, CER may generate
it either in nonexperimental studies (observational settings) or in
experiments (randomized and cluster randomized, as well as non-
randomized, controlled trials). For decisions that have been the
topic of substantial previous research, synthesis of existing studies
(systematic reviews and meta-analysis, technology assessments and
decision analysis) may be appropriate. Box 2-1 describes these
methods in greater detail. Data sources for CER may thus include
published studies, existing data from the delivery of care (admin-
istrative claims, medical charts, electronic health records), clinical
registries, and information collected by clinical investigators, either
retrospectively or prospectively. To ensure the wide availability
and use of these data sources will require new CER infrastruc-
ture to support a highly robust national CER program, including
methods, workforce, and data networks. For example, multisite
data networks, analyzed simultaneously via a distributed protocol
(distributed network analysis), are needed. Considerations in the
selection of methods and data sources for CER include the quality
and relevance of previously published evidence, the availability and
potential for confounding in observational data sources, and the
time and resources available for primary data collection.
6. CER is conducted in settings that are similar to those in which
the intervention will be used in practice. Consistent with the
definition of effectiveness, the settings of CER studies are a defin-
ing characteristic. Studying interventions in a realistic practice
setting has implications for both CER trials and observational
studies. For experimental studies, investigators should deliver the
intervention in settings that are as close to actual practice as pos-
sible, which is a strength of observational studies of actual clinical
practice.
The call for CER should not be interpreted to mean that all research
must have these characteristics. Early studies of an intervention are likely
to compare it to a placebo, standard care, or no intervention. In fact,
during early development of a new intervention, it is critical to determine
safety and efficacy under a defined set of circumstances. For example, the
Ischemic Optic Neuropathy Decompression Trial was a landmark examina-
tion of an innovative surgical technique used by ophthalmologists (Ischemic
Optic Neuropathy Decompression Trial Research Group, 1995). It found
no beneficial effect and possible harm compared to no therapy. Once an
intervention has been shown to be effective against a placebo, head-to-head
trials address the critical question “What works best for whom?”
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0 INITIAL NATIONAL PRIORITIES FOR CER
Foundation, authorized under the FDAAA but not yet funded, is to sup-
port public-private collaborations on applied research questions relevant
to CER, such as the Sentinel Program, which endeavors to link very large
numbers of medical records and claims data to facilitate post-marketing
surveillance for unusual complications of new therapies.5
Centers for Medicare & Medicaid Services
The mission of CMS is to “ensure effective, up-to-date health care
coverage and to promote quality care for its beneficiaries” (CMS, 2009a).
CMS is a key stakeholder in the health care system in general—its ben-
eficiaries generate about one-third of national health expenditures (CMS,
2009b)—and in CER in particular. Although Medicare does not explicitly
base coverage decisions on CER evidence, it uses such evidence in its cov-
erage reviews. Medicare’s predominance in the U.S. health care market
provides product developers with a strong incentive to tailor the evidence
they produce to the needs of CMS reviewers. The Medicare Evidence De-
velopment and Coverage Advisory Committee, a large group of clinical
experts, researchers, industry representatives, and consumer advocates,
provides CMS with guidance on specific—usually controversial—national
coverage decisions.
When CMS determines that the available evidence is insufficient to
support a definitive coverage decision, it can employ a relatively new policy
option, “Coverage with Evidence Development,” which authorizes CMS
to cover items or services only if the patient participates in a registry or
a clinical trial. This mechanism serves to expand coverage to unapproved
interventions, giving them an opportunity to prove themselves while simul-
taneously enlarging the evidence base (Tunis and Pearson, 2006).
Department of Veterans Affairs
The Veterans Healthcare System at the VA is suited to both produce and
apply evidence on treatment effectiveness because it cares for a very large
patient population, has a sophisticated electronic health records system
that supports clinical research, and provides an array of medical services.
Through its Cooperative Studies Program (CSP), the VA provides support
to its own investigators conducting multi-center, collaborative clinical trials.
The program’s research infrastructure includes five Coordinating Centers
that provide data management and analysis support, a Clinical Research
Pharmacy, four epidemiological Research and Information Centers, and a
5 Food and Drug Administration Act of 2007, P.L. 110-85, 110th Congress, 2nd session
(September 27, 2007) 121.
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
Health Economics Resource Center (Holve et al., 2008; Veteran’s Health
Administration, 2009). CSP trials study a range of conditions, from schizo-
phrenia to stroke (Veteran’s Health Administration, 2009), and have pro-
duced notable results—for instance, a large RCT with 38,546 participants
demonstrated the effectiveness of a Herpes zoster vaccine (Oxman et al.,
2005), and a very recent RCT of 1,791 diabetic military veterans showed
that intensive control of blood glucose was not superior to usual care in
preventing cardiovascular complications (Duckworth et al., 2009).
The VA conducts comparative effectiveness reviews and guides for
policy makers through its Evidence-based Synthesis Program, which works
directly with top clinical managers and the Office of Quality and Per-
formance to select priorities (VA, 2009). The VA is well-suited for CER
activities because it has broad clinical and research capacity and feeds
patient data recorded in the VA electronic health record system into a data
warehouse that contains health records on the entire VA population. These
data capabilities are a major national resource and a model for other data
research networks. As a result of the application of the above techniques,
the VA system has modified practices to markedly improve both the process
of health care delivery and its outcomes (Jha et al., 2003).
Nongovernmental CER Activities
The private sector contains the life sciences industry, a number of orga-
nizations with the capacity to conduct CER reviews, and some organizations
focused on evidence development. However, not all of the work of these
organizations meets the IOM definition of CER, and some of the work is pro-
prietary, and available by contract or purchase, if at all. Representative non-
governmental organizations involved in CER are described briefly below.
Life Sciences Industry
Manufacturers of drugs, devices, and other medical products have
made large investments in research on their products, motivated in part by
regulatory requirements set by the FDA. While most studies submitted to
the FDA compare the new drug to a placebo, manufacturers also submit
to the FDA studies comparing the new treatment to previously approved
products with increasing frequency. Head-to-head studies may be necessary
when comparison to a placebo is unethical, or to understand how the new
treatment compares to an existing standard of care. The latter may be used
to influence the content of the package insert and subsequent marketing
of the product. Consequently, the FDA has been developing the standards
and methods for comparative studies, and using the results to support the
regulation of medical products.
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INITIAL NATIONAL PRIORITIES FOR CER
The second major motivation for manufacturers to conduct CER is to
increase the likelihood that health systems will list their products in their
formularies, and that payers will reimburse them. Determination of safety
and efficacy does allow entry into the market, but it does not ensure that a
third-party payer will cover a product, or that safety and efficacy will be the
sole basis for determining payment levels. Health care payers asked to pay a
higher price for a new product increasingly require evidence that the higher
price buys additional clinical benefit. For example, drugs with similar risk-
benefit profiles may end up on different formulary tiers, depending on their
price.6 Consequently, reimbursement pressures may encourage manufactur-
ers to support CER to demonstrate that their products provide benefit at
the margin relative to existing products. Although these incentives may be
important motivators to do CER related to particular products, they are less
effective motivators to study medical practices and processes, products that
are not “on patent,” novel uses of approved products, or “class effects” or
combinations of products.
Blue Cross and Blue Shield Association Technology Evaluation Center
The Blue Cross and Blue Shield Association Technology Evaluation
Center (TEC) was established in 1985. Its mission is to provide health care
decision makers with scientifically rigorous assessments that synthesize the
available evidence on the prevention, diagnosis, treatment, and manage-
ment of disease. Its assessments review the evidence that specific medical
procedures, devices, and drugs improve health outcomes such as length of
life, quality of life, and functional ability (Blue Cross and Blue Shield As-
sociation, 2009). TEC produces 20 to 25 assessments per year for clients
including CMS, Kaiser Permanente, and other private health plans. Its re-
ports are publicly available. TEC is an EPC of the AHRQ Effective Health
Care Program.
Cochrane Collaboration
Established in 1993, the Cochrane Collaboration is an independent,
multinational nonprofit organization that creates and distributes systematic
reviews of health care interventions. These reviews are prepared by 52 Co-
chrane Review Groups. Quality standards, which are published regularly
in a handbook, are maintained by editorial teams that oversee the prepara-
tion and maintenance of the reviews. Cochrane review abstracts and plain-
6 When a payer places a drug on a high tier in the payer’s formulary, the patient is charged
a higher out-of-pocket co-payment when purchasing the drug and the drug is less likely to
be prescribed.
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
language summaries are free and publicly available online, and complete
reviews are available with a subscription (Cochrane Collaboration, 2001).
As of April 2009, The Cochrane Database of Systematic Reviews contained
a total of 5,785 systematic reviews of medical interventions, methodological
studies, and diagnostic test accuracy (Cochrane Collaboration, 2009).
A number of smaller nonprofit and for-profit enterprises are actively
involved in a variety of CER activities. A sampling of organizations includes
The ECRI Institute and Hayes, Inc., which provide exclusive proprietary in-
formation and do not make their reports publicly available (ECRI Institute,
2009; Hayes Inc., 2009). The Drug Effectiveness Review Project (DERP)
is a collaboration of public entities: the Center for Evidence-based Policy
and the EPC at Oregon Health and Science University. These organizations
produce systematic reviews of the comparative effectiveness and safety of
drugs (Oregon Health and Science University, 2009), which served as a
significant source for “Consumer Reports Best Buy Drugs” (Findlay, 2006).
The Institute for Clinical and Economic Review produces publicly available
assessments of new medical interventions to support value-based insurance
benefit designs, coverage and reimbursement policy, and patient-clinician
decision support tools (Institute for Clinical and Economic Review, 2009).
The Center for Medical Technology Policy (CMTP) provides a forum for
the collaborative design and implementation of CER, including pragmatic
trials, adaptive designs, and clinical registries (CMTP, 2009).
Lessons from Ongoing CER Activities
This account of CER initiatives supports several conclusions. First,
considerable CER is under way, often as a result of regulatory and reim-
bursement incentives, with the support of a variety of programs in the
public and private sectors. Although these programs vary in scope, goals,
and activities, all seek to provide timely and useful evidence to health care
decision makers on questions of patient care and policy significance. In its
report, the committee acknowledges that this is not an exhaustive descrip-
tion of the activities of U.S. organizations involved in CER. The Federal
Coordinating Council’s June 30, 2009, report to the Secretary of HHS will
also describe the CER activities of federal agencies. Even limiting itself to
its description of federal CER activities and the study of systematic reviews
in Knowing What Works in Health Care, the committee found consider-
able duplicated effort, which is one reason to propose a mechanism to
coordinate CER activities throughout the nation. New public investments
in CER should complement these ongoing initiatives. Federal coordination
would allow for systematic identification and rapid dissemination of best
practices, improved prioritization of research topics for future funding,
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INITIAL NATIONAL PRIORITIES FOR CER
reduction of duplication, encouragement of collaboration, improvement
and standardization of methodology, and generally leverage of private-sec-
tor initiatives with the goal of more rapidly and efficiently generating results
on priority topics.
Second, leaders of CER must evaluate the present CER workforce in
light of the requirements of an expanded, sustained program equal to the
task of undertaking the priority research described in Chapter 5. Expansion
of CER, as envisioned by ARRA, requires assessment of current capacity
and planning to support a national CER program. For example, the size
of the qualified CER workforce is not known and the workforce needed to
perform CER must be defined, assessed, and trained. NIH, FDA, AHRQ’s
DEcIDE Research Network, CERTs, CMS, VA, and CMTP are among
the organizations focused on the development of new evidence from well-
designed comparative clinical trials and observational studies. Priorities for
new CER must address the research infrastructure required to generate new
data to answer questions of interest to patients and policy makers and must
recommend investment in new capacity where needed.
Third, the United States lacks a large-scale national infrastructure for
learning from the delivery of health care through observational research
using existing clinical and administrative data sources. Moreover, a meth-
odological framework is needed to guide the translation of clinical and
policy relevant questions into answerable CER questions and to match CER
questions to appropriate CER methods.
Finally, the value of high-quality CER depends on successfully dissemi-
nating and incorporating the results into routine practice. The means to the
latter end include evidence-based guidelines, clinician and patient decision
support tools, models of shared, informed decision making, reimbursement
policy, and benefit design. Current law provides direct support for the syn-
thesis and dissemination of CER (through the AHRQ-sponsored EPCs) to
inform clinical and policy decision making—providing the building blocks
for evidence-based policy.
CONCLuSION
Greater investment in CER has the potential to help improve the qual-
ity, outcomes, and value of health care in America. But what exactly is
CER? The committee has derived from several existing definitions six
characteristics of CER studies, as well as a new working definition to guide
priority setting. CER is defined by the pragmatic aim of informing a specific
health care or health policy decision, and the explicit comparison of clini-
cally credible, alternative interventions in a representative study population.
CER studies seek to inform population-level and subgroup-level decisions
alike, using outcomes, methods, and data sources appropriate to answer
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WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
the specific question within the limitations of the study design. CER en-
compasses the collection of new experimental and observational data, the
analysis of existing observational data, studies that synthesize completed
research, and the translation and dissemination of research findings into
clinical practice.
Past clinical effectiveness studies have sought to answer questions about
the effectiveness of medical interventions and strategies, but not all clini-
cal effectiveness studies are comparative effectiveness studies. CER studies
compare the intervention under study against its best or most commonly
used alternatives in practice or in development, rather than against a pla-
cebo. Furthermore, the studies address effectiveness (i.e., how the interven-
tion performs with real-world patients) rather than assessing efficacy (i.e.,
how it performs in highly selected patient groups who receive study-related
care in parallel with usual care).
CER techniques are varied. Although RCTs, prospective cohort studies,
and patient registries are among its most important tools, CER also uses
other forms of information, such as systematic reviews, electronic health
records, patient registries, and other observational datasets.
Prospective studies based on new trials or primary analyses of patient-
level data are a very important aspect of CER. However, CER also includes
secondary analyses—such as meta-analyses, or formal pooled analyses of
multiple studies. Pooled analyses are often critically important because they
can be used to draw conclusions that could not be inferred from individual
studies.
Besides helping health care providers and patients make better clinical
decisions, CER information can improve care in other ways. For example,
hospitals and health systems might organize their facilities and personnel
to better support care that is revealed by CER to be superior. Professional
societies are likely to be both sources of CER and users of the informa-
tion, incorporating CER into the development of clinical guidelines (IOM,
2008).
A common misapprehension is that CER will lead to uniform, “one-
size-fits-all” care that ignores the ways that patients differ. In fact, CER
done well should give providers the means to tailor the choice of treatment
to the individual patient’s characteristics and preferences. Better compara-
tive effectiveness studies will make it possible to measure the implications
of individual differences in disease severity and the presence of comor-
bidities, to identify predictors of response to treatment, and to incorporate
other aspects of a person’s health and preferences. For example, CER
might assess the added value of using genomic information in addition to
traditional clinical predictors to determine the best treatment for a cancer
in a particular patient. It might suggest formal assessment of patient pref-
erences in those situations in which patient and caregiver desires might
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INITIAL NATIONAL PRIORITIES FOR CER
alter the decision to proceed with one or another treatment strategy. These
techniques might allow physicians to tailor therapy to reflect the goals and
desires of each patient. Better information can only help physicians do a
better job of matching their care to an individual patient’s needs. Indeed,
improvements in CER methods to support the use of targeted therapies are
urgently needed.
CER has been under way in a number of venues in the United States
and has received notable support from the private and public sectors. The
committee’s review of these initiatives indicates that there is considerable
capacity for evidence synthesis. However, the incentives for doing primary
CER are uneven, the infrastructure for supporting the development of new
evidence is in an early stage of development, and a wide gap exists between
CER results and their translation into consistent clinical practice and health
policy. New federal investments in CER must address these infrastructure
and translational priorities in addition to the information needs on specific
clinical topics.
REFERENCES
AHRQ (Agency for Healthcare Research and Quality). 2009a. AHRQ Effective Health Care
glossary http://effectivehealthcare.ahrq.gov/tools.cfm?tooltype=glossary&TermID=118
(accessed April 4, 2009).
———. 2009b. Centers for Education & Research on Therapeutics (CERTs) http://www.certs.
hhs.gov/ (accessed April 9, 2009).
American College of Physicians. 2008. Improved availability of comparative effectiveness
information: An essential feature for a high-quality and efficient United States health
care system. Philadelphia, PA.
Avorn, J. 2009. Debate about funding comparative-effectiveness research. New England Jour-
nal of Medicine 360(19):1927-1929.
Birkmeyer, N. J. O., J. N. Weinstein, A. N. A. Tosteson, T. D. Tosteson, J. S. Skinner, J. D.
Lurie, R. Deyo, and J. E. Wennberg. 2002. Design of the spine patient outcomes research
trial (SPORT). Spine 27(12):1361-1372.
Blue Cross and Blue Shield Association. 2009. Technology Evaluation Center criteria http://
www.bcbs.com/blueresources/tec/tec-criteria.html (accessed May 1, 2009).
Bravata, D. M., A. L. Gienger, K. M. McDonald, V. Sundaram, M. V. Perez, R. Varghese,
J. R. Kapoor, R. Ardehali, D. K. Owens, and M. A. Hlatky. 2007. Systematic review: The
comparative effectiveness of percutaneous coronary interventions and coronary artery
bypass graft surgery. Annals of Internal Medicine 147(10):703-716.
CBO (Congressional Budget Office). 2008. Technological change and the growth of health
care spending. In CBO paper. Place Published: United States Congressional Budget Of-
fice. http://www.cbo.gov/ftpdocs/89xx/doc8947/01-31-TechHealth.pdf (accessed April
30, 2008).
CDC (Centers for Disease Control and Prevention). 2007. Morbidity and mortality weekly
report. 56:880-888.
Chou, R., R. Fu, S. Carson, S. Saha, and M. Helfand. 2007. Methodological shortcomings
predicted lower harm estimates in one of two sets of studies of clinical interventions.
Journal of Clinical epidemiology 60(1):18-28.
OCR for page 57
WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
CMS (Centers for Medicare & Medicaid Services). 2009a. Mission, vision and goals overview
http://www.cms.hhs.gov/MissionVisionGoals/ (accessed May 22, 2009).
———. 2009b. National health expenditures aggregate, per capita amounts, percent distribu-
tion, and average annual percent growth, by source of funds: Selected calendar years
0-00 http://www.cms.hhs.gov/NationalHealthExpendData/downloads/tables.pdf
(accessed May 1, 2009).
CMTP (Center for Medical Technology Policy). 2009. Welcome to the Center for Medical
Technology Policy http://www.cmtpnet.org/ (accessed April 9, 2009).
Cochrane, A. L. 1971. Effectiveness and efficiency: Random reflections on health services.
London: Nuffield Provincial Hospitals Trust.
Cochrane Collaboration. 2001. Cochrane Collaboration consumer network http://www.
cochraneconsumer.com/ (accessed April 28, 2009).
———. 2005. Glossary of terms in the Cochrane Collaboration. Version ... www.cochrane.
org (accessed November 27, 2006).
———. 2009. Product descriptions-record counts http://www.interscience.wiley.com/egibin/
mrwhome/106568753/ProductDescriptions.html (accessed April 24, 2009).
Duckworth, W., C. Abraira, T. Moritz, D. Reda, N. Emanuele, P. D. Reaven, F. J. Zieve, J.
Marks, S. N. Davis, R. Hayward, S. R. Warren, S. Goldman, M. McCarren, M. E. Vitek,
W. G. Henderson, and G. D. Huang. 2009. Glucose control and vascular complications
in veterans with type 2 diabetes. New England Journal of Medicine 360(2):129-139.
ECRI Institute. 2009. Pioneering applied scientific research in healthcare https://www.ecri.
org/about/pages/default.aspx (accessed April 24, 2009).
Epstein, S. 1996. Impure science: AIDS, activism, and the politics of knowledge. In Medicine
and society. Place Published: University of California Press. http://www.loc.gov/catdir/
bios/ucal051/96016805.html (accessed April 21, 2009).
Findlay, S. D. 2006. Bringing the DERP to consumers: ‘Consumer Reports Best Buy drugs’.
Health Affairs 25(4):w283-w286.
Fisher, E. S., D. E. Wennberg, T. A. Stukel, D. J. Gottlieb, F. L. Lucas, and E. L. Pinder. 2003.
The implications of regional variations in Medicare spending. Part 2: Health outcomes
and satisfaction with care. Annals of Internal Medicine 138(4):288-298.
Fisher, E. S., J. P. Bynum, and J. S. Skinner. 2009. Slowing the growth of health care costs—
Lessons from regional variation. New England Journal of Medicine 360(9):849-852.
GAO (Government Accountability Office). 2002. Medicare: Beneficiary use of clinical preven-
tive services. Report to the Chairman, Subcommittee on Oversight and Investigations,
Committee on Energy and Commerce, House of Representatives. Washington, DC.
Garber, A. M., and D. O. Meltzer. 2009. Setting priorities for comparative effectiveness re-
search. Paper presented at Implementing Comparative Effectiveness Research: Priorities,
Methods, and Impact, Engleberg Center for Health Care Reform at Brookings: Wash-
ington, DC.
Garber, A. M., and S. R. Tunis. 2009. Does comparative-effectiveness research threaten per-
sonalized medicine? New England Journal of Medicine 360(19):1925-1927.
Glickman, S. W., F. S. Ou, E. R. DeLong, M. T. Roe, B. L. Lytle, J. Mulgund, J. S. Rumsfeld,
W. B. Gibler, E. M. Ohman, K. A. Schulman, and E. D. Peterson. 2007. Pay for
performance, quality of care, and outcomes in acute myocardial infarction. JAMA
297(21):2373-2380.
Gottlieb, S. 2009. Congress wants to restrict drug access: A bill in the House could tie your
doctor’s hands. Wall Street Journal, January 20, 2009.
Harpole, L. H., M. J. Kelley, G. Schreiber, E. M. Toloza, J. Kolimaga, and D. C. McCrory.
2003. Assessment of the scope and quality of clinical practice guidelines in lung cancer.
Chest 123(1 SUPPL.):7S-20S.
OCR for page 58
INITIAL NATIONAL PRIORITIES FOR CER
Hayes Inc. 2009. Hayes: Transforming healthcare with evidence http://www.hayesinc.com/
hayes/ (accessed May 8, 2009).
Haynes, R. B., D. L. Sackett, G. H. Guyatt, and P. Tugwell. 2006. Clinical epidemiology:
How to do clinical practice research. 3rd ed. Philadelphia, PA: Lipincott Williams &
Wilkins.
Helfand, M. 2005. Using evidence reports: Progress and challenges in evidence-based decision
making. Health Affairs 24(1):123-127.
Higgins, J., and S. Green. 2008. Cochrane handbook for systematic reviews of interventions:
Version .0. Place Published: The Cochrane Collaboration, 2008. http://www.cochrane.
org/resources/handbook/index.htm (accessed April 2, 2009).
Hlatky, M. A., D. B. Boothroyd, D. M. Bravata, E. Boersma, J. Booth, M. M. Brooks, D.
Carrié, T. C. Clayton, N. Danchin, M. Flather, C. W. Hamm, W. A. Hueb, J. Kähler, S. F.
Kelsey, S. B. King, A. S. Kosinski, N. Lopes, K. M. McDonald, A. Rodriguez, P. Serruys,
U. Sigwart, R. H. Stables, D. K. Owens, and S. J. Pocock. 2009. Coronary artery bypass
surgery compared with percutaneous coronary interventions for multivessel disease: A
collaborative analysis of individual patient data from ten randomised trials. The Lancet
373(9670):1190-1197.
Holve, E., S. Mercer, J. Kupersmith, and S. Phurrough. 2008. Exploring comparative effec-
tiveness: Activities of CDC, VA and CMS to advance evidenced-based health. National
Health Policy Forum The George Washington University, http://www.nhpf.org/library/
details.cfm/2646 (accessed October 3, 2008).
Hueb, W., N. H. Lopes, B. J. Gersh, P. Soares, L. A. C. Machado, F. B. Jatene, S. A. Oliveira,
and J. A. F. Ramires. 2007. Five-year follow-up of the medicine, angioplasty, or surgery
study (MASS II): A randomized controlled clinical trial of 3 therapeutic strategies for
multivessel coronary artery disease. Circulation 115(9):1082-1089.
Institute for Clinical and Economic Review. 2009. Mission. http://www.icer-review.org/index.
php/about.html (accessed April 9, 2009).
IOM (Institute of Medicine). 2001. Crossing the quality chasm: A new health system for
the 21st century, Edited by J. M. Corrigan. Washington, DC: National Academy Press.
http://www.nap.edu/catalog/10027.html (accessed April 20, 2009).
———. 2007. Learning what works best: The nation’s need for evidence on comparative
effectiveness in health care. http://www.iom.edu/ebm-effectiveness (accessed April 15,
2009).
———. 2008. Knowing what works in health care: A roadmap for the nation. Edited by J.
Eden, B. Wheatley, B. J. McNeil and H. Sox. Washington, DC: The National Academies
Press.
Ischemic Optic Neuropathy Decompression Trial Research Group. 1995. Optic nerve decom-
pression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not
effective and may be harmful. JAMA 273(8):625-632.
Jha, A. K., J. B. Perlin, K. W. Kizer, and R. A. Dudley. 2003. Effect of the transformation of
the Veterans Affairs health care system on the quality of care. New England Journal of
Medicine 348(22):2218-2227.
Johnston, S. C., and S. L. Hauser. 2009. Comparative effectiveness research in the neurosci-
ences. Annals of Neurology 65(2):A6-A8.
Kurian, A. W., R. N. Thompson, A. F. Gaw, S. Arai, R. Ortiz, and A. M. Garber. 2007. A
cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive
breast cancer. Journal of Clinical Oncology 25(6):634-641.
Last, J. M. 2001. A dictionary of epidemiology. New York: Oxford University Press.
Lauer, M. S. 2009. Comparative effectiveness research: The view from the NHLBI. Journal of
the American College of Cardiology 53(12):1084-1086.
OCR for page 59
WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH?
Lohr, K. N. 2007. Emerging methods in comparative effectiveness and safety: Symposium
overview and summary. Medical Care 45(10 SUPPL. 2):S5-S8.
Mangione-Smith, R., A. H. DeCristofaro, C. M. Setodji, J. Keesey, D. J. Klein, J. L. Adams,
M. A. Schuster, and E. A. McGlynn. 2007. The quality of ambulatory care delivered to
children in the United States. New England Journal of Medicine 357(15):1515-1523.
McGlynn, E. A., S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr.
2003. The quality of health care delivered to adults in the United States. New England
Journal of Medicine 348(26):2635-2645.
Medicare Payment Advisory Commission. 2008. Report to the Congress: Reforming the de-
livery system. Washington, DC.
NCI (National Cancer Institute). 2006. NCI’s clinical trials cooperative group program
http://cancertrials.nci.nih.gov/cancertopics/factsheet/nci/clinical-trials-cooperative-group
(accessed June 15, 2009).
NIH PGRN (National Institutes of Health Pharmacogenetics Research Network). 2009.
PGRN mission statement http://www.pharmgkb.org/network/pgrn_mission_statement.
jsp (accessed June 12, 2009).
Oregon Health and Science University. 2009. Drug Effectiveness Review Project http://www.
ohsu.edu/drugeffectiveness/ (accessed April 8, 2009).
Orszag, P. R. 2007. Research on the comparative effectiveness of medical treatments: Op-
tions for an expanded federal role: CBO testimony before the Subcommittee on Health,
Committee on Ways and Means, U.S. House of Representatives. U.S. Congressional
Budget Office. http://www.cbo.gov/ftpdocs/82xx/doc8209/Comparative%5FTestimony.
pdf (accessed April 28, 2009).
Oxman, M. N., M. J. Levin, G. R. Johnson, K. E. Schmader, S. E. Straus, L. D. Gelb, R. D.
Arbeit, M. S. Simberkoff, A. A. Gershon, L. E. Davis, A. Weinberg, K. D. Boardman,
H. M. Williams, J. H. Zhang, P. N. Peduzzi, C. E. Beisel, V. A. Morrison, J. C. Guatelli,
P. A. Brooks, C. A. Kauffman, C. T. Pachucki, K. M. Neuzil, R. F. Betts, P. F. Wright,
M. R. Griffin, P. Brunell, N. E. Soto, A. R. Marques, S. K. Keay, R. P. Goodman, D. J.
Cotton, J. W. Gnann Jr, J. Loutit, M. Holodniy, W. A. Keitel, G. E. Crawford, S. S. Yeh,
Z. Lobo, J. F. Toney, R. N. Greenberg, P. M. Keller, R. Harbecke, A. R. Hayward, M. R.
Irwin, T. C. Kyriakides, C. Y. Chan, I. S. F. Chan, W. W. B. Wang, P. W. Annunziato, and
J. L. Silber. 2005. A vaccine to prevent herpes zoster and postherpetic neuralgia in older
adults. New England Journal of Medicine 352(22):2271-2284+2365.
Plevritis, S. K., A. W. Kurian, B. M. Sigal, B. L. Daniel, D. M. Ikeda, F. E. Stockdale, and A.
M. Garber. 2006. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast
magnetic resonance imaging. JAMA 295(20):2374-2384.
Santaguida, P. L., M. Helfand, and P. Raina. 2005. Challenges in systematic reviews that evaluate
drug efficacy or effectiveness. Annals of Internal Medicine 142(12_Part_2):1066-1072.
Sisko, A., C. Truffer, S. Smith, S. Keehan, J. Cylus, J. A. Poisal, M. K. Clemens, and J. Lizonitz.
2009. Health spending projections through 2018: Recession effects add uncertainty to
the outlook. Health Affairs 28(2):w346-357.
Slutsky, J. R., and C. M. Clancy. 2009. AHRQ’s Effective Health Care Program: Why com-
parative effectiveness matters. American Journal of Medical Quality 24(1):67-70.
Sparano, J. A., M. Wang, S. Martino, V. Jones, E. A. Perez, T. Saphner, A. C. Wolff, G. W.
Sledge, Jr., W. C. Wood, and N. E. Davidson. 2008. Weekly paclitaxel in the adjuvant
treatment of breast cancer. New England Journal of Medicine 358(16):1663-1671.
Tosteson, A. N. A., J. D. Lurie, T. D. Tosteson, J. S. Skinner, H. Herkowitz, T. Albert, S. D.
Boden, K. Bridwell, M. Longley, G. B. Andersson, E. A. Blood, M. R. Grove, and J. N.
Weinstein for the SPORT Investigators. 2008. Surgical treatment of spinal stenosis with
and without degenerative spondylolisthesis: Cost-effectiveness after 2 years. Annals of
Internal Medicine 149(12):845-853.
OCR for page 60
0 INITIAL NATIONAL PRIORITIES FOR CER
Tricoci, P., J. M. Allen, J. M. Kramer, R. M. Califf, and S. C. Smith, Jr. 2009. Scientific evi-
dence underlying the ACC/AHA clinical practice guidelines. JAMA 301(8):831-841.
Tunis, S. R., and S. D. Pearson. 2006. Coverage options for promising technologies: Medicare’s
‘coverage with evidence development.’ Health Affairs 25(5):1218-1230.
Tunis, S. R., D. B. Stryer, and C. M. Clancy. 2003. Practical clinical trials: Increasing the
value of clinical research for decision making in clinical and health policy. JAMA
290(12):1624-1632.
VA (Veterans Affairs). 2009. Evidenced-based synthesis program http://www.hsrd.research.
va.gov/publications/esp/ (accessed May 22, 2009).
Veteran’s Health Administration. 2009. Cooperative studies program (CSP) http://www.
research.va.gov/programs/csrd/csp.cfm (accessed May 1, 2009).
Vigna-Taglianti, F., P. Vineis, A. Liberati, and F. Faggiano. 2006. Quality of systematic reviews
used in guidelines for oncology practice. Annals of Oncology 17(4):691-701.
Weinstein, J. N., T. D. Tosteson, J. D. Lurie, A. N. A. Tosteson, E. Blood, B. Hanscom, H.
Herkowitz, F. Cammisa, T. Albert, S. D. Boden, A. Hilibrand, H. Goldberg, S. Berven, H.
An, and the SPORT Investigators. 2008. Surgical versus nonsurgical therapy for lumbar
spinal stenosis. New England Journal of Medicine 358(8):794-810.
Wennberg, J. E., A. M. O’Connor, E. D. Collins, and J. N. Weinstein. 2007. Extending The
P4P agenda, part 1: How Medicare can improve patient decision making and reduce
unnecessary care. Health Affairs 26(6):1564-1574.
West, S., V. King, T. Carey, K. Lohr, N. McCoy, S. Sutton, and L. Lux. 2002. Systems to rate
the strength of scientific evidence. Evidence Report/Technology Assessment No. . (Pre-
pared by the Research Triangle Institute-University of North Carolina Evidence-based
Practice Center under Contract No. 290-97-0011). AHRQ Publication No. 02-E016.
Rockville, MD: Agency for Healthcare Research and Quality.
Whitlock, E. P., S. A. Lopez, S. Chang, M. Helfand, M. Eder, and N. Floyd. 2009. Identi-
fying, selecting, and refining topics for comparative effectiveness systematic reviews:
AHRQ and the effective health care program. http://effectivehealthcare.ahrq.gov/repFiles/
20090427IdenttifyingTopics.pdf (accessed June 5, 2009).
