comparative effectiveness research

Billions of dollars are spent annually on medical research in the United States: on basic science to uncover the causes and mechanisms of disease, and on testing the safety and effectiveness of new drugs and treatments. Among the reams of reports resulting from this research, however, there is little to guide clinicians in determining which of many available treatments would be most effective for patients – and particularly, which is most cost-effective. As a result, there are wide disparities in clinical practice and cost of health care delivery across the U.S.[1]

Comparative effectiveness research (CER) can be used to develop analyses comparing the benefits of one drug or treatment to another. CER is sometimes viewed narrowly, as limited to analysis of the relative clinical effectiveness of comparable drugs or treatments; or more broadly, expanding the analysis of clinical effectiveness to add considerations of relative cost effectiveness, and analyses of alternative methods of health care delivery. Some health policy experts view CER as an effective tool to control health care costs while maintaining quality. Others worry that CER will stifle innovation in health care delivery, and hinder the ability of physicians to recommend treatments best suited to the needs of individual patients.[2] Drug and device makers have expressed concerns that CER will be used to deny access to care.[3] In addition, the role of CER has become a contentious issue between liberals and conservatives, as part of the general debate surrounding health care reform.[4]

U.S. Experience with Comparative Effectiveness Research

While the controversy over CER is new, the Agency for Healthcare Research and Quality (AHRQ) has been conducting CER for several years. The Medicare Prescription Drug, Improvement and Modernization Act of 2003 authorized AHRQ to support research with a focus on outcomes, comparative clinical effectiveness, and appropriateness of pharmaceuticals, devices and health care services. AHRQ identified ten priority conditions for CER:

  • Arthritis and nontraumatic joint disorders
  • Cancer
  • Chronic obstructive pulmonary disease and asthma
  • Dementia including Alzheimer's disease
  • Depression and other mood disorders
  • Diabetes mellitus
  • Ischemic heart disease
  • Peptic ulcer disease and dyspepsia
  • Pneumonia
  • Stroke and hypertension.[5]

AHRQ has completed several comparative effectiveness reviews, and published materials for clinicians and for consumers. One example is a review published in 2006 of the comparative effectiveness and safety of analgesics for osteoarthritis. The Clinician's Guide published on this topic[6] is a four-page summary including observations drawn from a systematic review of published research, comparing clinical effectiveness of acetaminophen, NSAIDs (including aspirin and celecoxib), glucosamine and chondroitin, and topical medications. The guide also includes a table of average wholesale prices for generic and brand name medications. The corresponding consumer's guide[7] is a 12-page pamphlet explaining the risks and benefits of treatment alternatives in laymen's terms. The pamphlet suggests that consumers first consider what kind of pain relief they need (do they want to be more active, or are they seeking to reduce swelling), then determine whether they are at risk for complications such as stomach bleeding or heart attack, and finally consider cost of treatment alternatives. Similar guides have been published analyzing the comparative effectiveness of Epoetin and Darbepoetin for managing anemia in cancer patients; off-label use of atypical antipsychotics; second generation antidepressants for treatment of adult depression; oral diabetes medication for adults with Type 2 diabetes; angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists for treating essential hypertension; and drug therapy for rheumatoid arthritis and psioratic arthritis.[8]

The Congressional Budget Office (CBO) released a study on CER in December 2007.[9] The CBO's report noted that federal spending on Medicare and Medicaid as a percentage of gross domestic product tripled over the past 30 years (rising from 1.3% in 1975 to 4% in 2007). The report commented on CER's potential to hold down health care spending:

To affect medical treatment and reduce health care spending, the results of comparative effectiveness analyses would ultimately have to change the behavior of doctors and patients. For any large-scale changes to occur, the new or expanded entity would have to generate new findings for a substantial number of medical conditions -which would take many years. To have the maximum effect on behavior, those findings would then have to be incorporated into the incentives for providers and patients, a process of adjustment that might also take time. Although some patients and providers might object to such changes, over the long term the combination of additional information and revised incentives would tend to reduce spending for health care below currently projected levels, potentially to a substantial degree.[10]

Funding for Comparative Effectiveness Research in the Stimulus Bill

The American Recovery and Reinvestment Act (the ARRA) included a total of $1.1 billion in funding for CER, divided among the AHRQ, the National Institutes of Health, and the Secretary of the Department of Health and Human Services (HHS).[11] The ARRA provides that the Secretary of HHS shall use appropriated funds

…to accelerate the development and dissemination of research assessing the comparative effectiveness of health care treatments and strategies, through efforts that: (1) conduct, support, or synthesize 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; and (2) encourage the development and use of clinical registries, clinical data networks, and other forms of electronic health data that can be used to generate or obtain outcomes data. [12]

The ARRA also establishes a Federal Coordinating Council for Comparative Effectiveness Research, all of the members of which are senior Federal officers appointed by the Secretary of HHS, and at least half of whom are required to be physicians. A 15-member council has been appointed, including the following members: from HHS, representatives of the Centers for Disease Control and Prevention; Centers for Medicare & Medicaid Services; the Substance Abuse and Mental Health Services Administration; AHRQ; the Health Resources and Services Administration; the Office of the National Coordinator for Health Information Technology; the National Institutes of Health; the Food and Drug Administration; the Office on Disability; the Office of Minority Health; legal counsel to the Secretary of HHS; and the Acting Assistant Secretary for Planning and Evaluation; and from other agencies, representatives of the Veterans Administration, Department of Defense, and Office of Management and Budget. In announcing the appointment of the Coordinating Council, HHS defined the role as helping to "coordinate research and guide investments in comparative effectiveness research funded by the Recovery Act…The Council will not recommend clinical guidelines for payment, coverage or treatment."[13]

The Coordinating Council held a public listening session on April 15, 2009, hearing presentations from thirty representatives of health care providers, consumer and patient advocacy groups, and drug and device manufacturers.[14] The panel members covered a broad range of topics, touching on fundamental questions such as:

  • What should be the priorities for comparative effectiveness research (CER)? Panelists suggested that the focus should be on medical conditions with the greatest impact for morbidity and costs (most often, chronic conditions).
  • What data sources should be used for CER? While clinical trials will be one important source, there are several disadvantages to relying on clinical trial data alone. Frequently, older patients, patients with multiple chronic illnesses, and disabled persons are underrepresented in clinical trials. An example given of how this could distort results of CER was that sometimes, a drug that is less effective for the general population may be preferred for older adults because it is less toxic and has a lower risk of drug interaction. In addition to clinical trial data, data sources could include electronic health record systems, data systems developed by regional health improvement organizations, health care claims databases, and databases of government health plans such as Medicare and the Veterans Administration.
  • How should "effectiveness" be defined? It was suggested that the Institute of Medicine's definition of evidence-based practice (which combines best research evidence, best clinical experience, and consistency with patient values) may be appropriate.
  • What areas of the health care system should be included? Panelists suggested that CER should not be limited just to comparing one product or treatment against another, but should also consider preventive care, complementary and alternative medicine, and health care delivery issues such as insurance benefit design and organization of care delivery.


There is broad (but not universal) support for expanding CER studies of clinical effectiveness. When CER goes beyond clinical effectiveness into studies of cost effectiveness, CER encounters more opposition – but it is precisely this use of CER that is most intriguing to proponents of health care cost control. The most controversial use of CER studies is for coverage determinations by federal and private health care programs. The appropriate use of comparative effectiveness research is shaping up to be one of the most important health policy debates of the coming push for health reform.

[1] Disparities in cost of health care delivery have been documented for over 20 years by the Dartmouth Atlas Project. The most recent report of the Dartmouth Atlas Project was published in the New England Journal of Medicine on Feb. 26, 2009 (NEJM, Vol. 360, pp. 849-852.

[2] An interesting discussion of the tradeoffs involved in CER is presented in a recent whitepaper (Balancing Act: Comparative Effectiveness Research and Innovation in U.S. Health Care, New England Healthcare Institute, April 2009). See also Steinbrook, Saying No Isn't NICE: The Travails of Britain's National Institute for Health and Clinical Excellence, New England Journal of Medicine, Vol. 359, pp. 1977-1981.

[3] Push to Compare Treatments Worries Drug, Device Makers, Wall Street Journal, April 14, 2008.

[4] Some interesting examples are Consumers Union, Comparative effectiveness: Common-sense research that saves money, lives, available at; Republican Study Committee, Conservative Concerns on the Comparative Effectiveness Research Provision in the American Recovery and Reinvestment Act (‘Stimulus'), available at

[5] Testimony of Carolyn Clancy, M.D., Director, Agency for Healthcare Research and Quality, before the House Subcommittee on Labor-HHS-Education Appropriations, March 5, 2008, available at

[6] Available at

[7]Choosing Pain Medication for Osteoarthritis: A Guide for Consumers, available at

[8] Links to these reports are at

[9] Research on the Comparative Effectiveness of Medical Treatments: Issues and Options for an Expanded Federal Role, U.S. Congressional Budget Office, Dec. 2007, available at

[10] Id., pp. 28-29.

[11] H.R. 1, Sec. 2, Division A, Title XVIII.

[12] Id.

[13] U.S. Dept. of Health and Human Services, announcement of appointment of Coordinating Council for Comparative Effectiveness Research, March 19, 2009, available at

[14] A summary of comments is available at

Patricia King, J.D.

About the Author

Patricia King is a health care attorney in Illinois, and principal of the web-based business Digital Age Healthcare LLC (

Topics #Agency for Healthcare Research and Quality #AHRQ #ARRA #comparative effectiveness research #CRE #NIH #stimulus package