Comparative clinical effectiveness research has been discussed as an avenue for producing information to help health care decision makers, such as patients, providers, and public and private payers, reach informed, evidence-based decisions. Proponents maintain that such information would aid in using limited resources effectively and efficiently, becomes even more necessary as resources become more limited, variation in medical practice patterns persist, and the rate of health care spending continues to rise. A recent Institute of Medicine (IOM) report on the future of drug safety notes "what is newest is not always the best" and that decision makers need information on the comparative risks and benefits of treatments and services. Diverse governmental and non-governmental organizations have publicly expressed their support or reservations about increased comparative clinical effectiveness research. The House Ways and Means Subcommittee on Health held a hearing on June 12, 2007, that discussed the creation of a public-private body that would oversee comparative clinical effectiveness research. The director of the Congressional Budget Office (CBO) concluded at the hearing that comparative clinical effectiveness research, combined with changes in payment incentives, "offers a promising mechanism for reducing health care costs to a significant degree over the long term while maintaining or improving the health of Americans," while emphasizing that significant cost savings from such research would not been seen for many years. The executive director of the Medicare Payment Advisory Commission (MedPAC) stated that "there is not enough credible, empirically based comparative-effectiveness information available to patients, providers, and payers to make informed treatment decisions." AARP, an advocacy group for persons aged 50 and older, mentioned the need for comparative effectiveness studies for pharmaceuticals as early as 2005 in their Solutions Statement to the White House Conference on Aging. America's Health Insurance Plans (AHIP), a trade association representing health insurance plans, has urged Congress to give the Centers for Medicare and Medicaid Services (CMS) the authority to use comparative effectiveness and cost-effectiveness information in its coverage and reimbursement decisions. Jack Rowe, the former chief executive officer of Aetna, has stated that employers are "dying" to have information on the comparative effectiveness of treatments. On the other hand, some have expressed reservations about funding increased comparative clinical effectiveness research. Scott Gottlieb, a researcher at the American Enterprise Institute for Public Policy Research (AEI), articulated problems he perceived with government-sponsored prescription drug research, including poor study design, lack of access to full study results, and bias in interpreting the results. Robert Goldberg, vice president of the Center for Medicine in the Public Interest, argued that comparative clinical effectiveness research ignores individual differences and is biased towards concluding cheaper drugs are more effective. A number of bills have been introduced that support comparative clinical effectiveness research, including several in the 110 th Congress. S. 3 , the Medicare Part D price negotiation bill sponsored by Senate Finance Committee Majority Leader Max Baucus, would require the Director of Health and Human Services (HHS) to develop a prioritized list of comparative effectiveness research studies. Representatives Tom Allen (D-ME) and Jo Ann Emerson (R-MO) co-sponsored H.R. 2184 , which would establish a public-private funding mechanism for comparative clinical effectiveness research, overseen by an independent advisory board. The Act would establish a trust fund for the research that would receive $100 million in FY2008, $200 million in FY2009, and $900 million per year for FY2010-FY2012. Similarly, H.R. 3162 , the Children's Health and Medicare Protection (CHAMP) Act of 2007, would establish a public-private funding mechanism for comparative clinical effectiveness research, overseen by an independent commission, and a trust fund that would be appropriated at least $90 million in FY2008, $100 million in FY2009, $110 million in 2010, and no more than $90 million in years thereafter. CBO has stated that the information produced by the comparative effectiveness portion of the CHAMP Act would reduce total spending by public and private purchasers by $0.5 billion over 5 years and $6 billion over 10 years. Direct spending by the federal government was estimated to be reduced by $0.1 billion over 5 years and $1.3 billion over 10 years. Thus, the majority of the savings from the research would be realized by private purchasers rather than by the federal government. The net federal expenditures from the comparative effectiveness portion of the CHAMP Act were estimated to be $0.5 billion over 5 years and $1.1 billion over 10 years. CBO assumed the savings would primarily be realized through changes in physicians' practice patterns and, to a lesser extent, changes in coverage rules. The Healthy Americans Act, S. 334 and H.R. 3163 , includes tax deduction, patent extension, and market exclusivity incentives for pharmaceutical and medical device manufacturers to conduct comparative clinical effectiveness research. The Josephine Butler United States Health Service Act, H.R. 3000 , would create a National Health Board that includes a new institute—the National Institute of Evaluative Clinical Research. Among the Institute's responsibilities would be to identify the most effective methods of prevention, diagnosis, and treatment and assist the National Health Board in establishing clinical practice guidelines. More details about these bills and others in the 109 th and 110 th Congress are included in the Appendix . To help inform the discussion surrounding comparative clinical effectiveness research, this report provides an overview and discusses past and current comparative clinical effectiveness research and other forms of technology assessment in the United States. This report also briefly discusses the use of technology assessment in the U.S. and other countries, and the potential role of a new comparative effectiveness research entity. Comparative effectiveness research is a term that has been defined by people in many different ways. All agree that comparative effectiveness research compares the effectiveness of two or more health care services or treatments, and is one form of health technology assessment. It compares outcomes resulting from different treatments or services, and provides information about the relative effectiveness of treatments. Additional specifics about the research and its definition are sources of contention. In particular: Effectiveness—How should effectiveness be measured? Should the research compare only the effectiveness (the effect in routine clinical practice) or also the efficacy (the effect under optimal conditions) of treatments or services? Costs—Should costs be included in the research? Should the costs be reported separately from the effectiveness results? Or should a cost-effectiveness ratio be the ultimate goal? Measuring the benefit or effectiveness is not a straightforward matter; which factors are included and how they are counted can greatly affect the results. Quantifying benefits and effectiveness often requires assumptions about the population benefitting from the treatment. For example, to what extent will the benefits from the treatment vary across the country and in different settings? More specifically, how should the benefits observed in a clinical trial be extrapolated to the rest of the population? Researchers have debated such questions over the years, resulting in an expert consensus concerning best research methods. These suggested methods include the practice of conducting sensitivity analyses to assess how study results would change if parameters, such as effectiveness, were measured differently. A treatment's efficacy is the effect of the treatment under optimal conditions. A treatment's effectiveness is the effect of the treatment in routine clinical practice. For example, randomized clinical trials conducted for Food and Drug Administration (FDA) marketing approval typically aim to assess the relative safety and efficacy of a treatment so as to best determine the sole effect of the treatment, absent any other influential factors. Clinical trials for FDA approval also typically compare the efficacy of an investigational treatment to a placebo, rather than another treatment. Effectiveness research relaxes the strict exclusionary criteria that are typically required in such trials, in order to assess the treatment in the wide range of patients and environments in which the product is actually used. Efficacy and effectiveness research results may differ because often in clinical practice, patients may have more than one illness, doses may vary, methods of administering the treatment may vary, and patients may simultaneously take treatments for multiple illnesses. Moreover, large segments of the potential patient population are often excluded from efficacy trials in order to achieve a more uniform study population. An often cited example is that many patients with high blood pressure also have diabetes; yet, efficacy clinical trials for high blood pressure treatments may not include patients with diabetes. As a result, any interaction between blood pressure and diabetes medications may not be known until the treatment is approved by the FDA and used in clinical practice. Also, different patients may respond to treatments differently due to physiologic differences, such as different metabolic rates of drugs and safety of anesthesia in surgical options. Although conducted after FDA approval, post-marketing (also known as phase IV) studies are not necessarily effectiveness studies, and only rarely could be classified as comparative effectiveness studies. Post-marketing studies most often assess any ongoing safety concerns of one drug or device rather than the effectiveness of a product. Moreover, the few studies that compare two or more treatments often only assess the equivalence or superiority of the study sponsor's product, rather than the relative effectiveness of competing products. Costs are not always easy to define or measure. The total treatment costs may differ, sometimes dramatically, depending upon which perspective (e.g., patient, government payer, private insurer, society) is taken in the analysis, and which costs are included. As with the measurement of effectiveness, researchers have tried to resolve these issues through expert consensus of best research methods and the practice of conducting sensitivity analyses. Much of the controversy surrounding whether costs should be included in comparative effectiveness research lies in the questions: when, how, and by whom will the research results be used to make decisions? The issue is most controversial if results that include costs are used to make insurance reimbursement, pricing, or coverage decisions. The inclusion of costs in research tends to not be as controversial when the results are not directly linked to medical and health policy decision making. One reason for the controversy is that policymakers may disagree about the way costs are measured or which costs are included in a research study.