Using science to improve the nation's health system: NIH's commitment to comparative effectiveness research.

SINCE BARACK OBAMA BECAME THE 44TH PRESIDENT OF the United States in January 2009, nearly all sectors of society have engaged in intense discussions about the best ways to stimulate the nation’s economy and reform the US health care system. The National Institutes of Health (NIH) has been—and will continue to be—in the middle of such conversations, emphasizing the power of biomedical research to show what health interventions yield the greatest benefits. Health reform and economic concerns may have moved comparative effectiveness research (CER) from relative obscurity into the public policy spotlight. However, CER is not a new concept to NIH, which has long recognized and supported the value of CER for providing evidence-based, wellvalidated approaches to medical care. For instance, nearly 2 decades ago, NIH-supported researchers published results of the Cardiac Arrhythmia Suppression Trial (CAST). To the surprise of many, 3 drugs that suppressed ventricular premature beats (encainide, flecainide, and moricizine) not only failed to reduce the risk of sudden cardiac death, but actually increased arrhythmic death rates. About 14 years later, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), a comparative effectiveness trial funded by NIH, demonstrated that oral administration of the antiarrhythmic drug amiodarone proved no better than standard heart failure care (such as -blockade), whereas implantation of an internal cardioverter defibrillator reduced mortality by 23%. Despite the positive results of SCD-HeFT, only a subset of patients with heart failure derives benefit from implantable defibrillators. Consequently, NIH, the Agency for Healthcare Research and Quality (AHRQ), and the American College of Cardiology have joined together to support an observational CER study of 3500 patients receiving implantable cardioverter-defibrillators. The 31⁄2-year study, launched in January 2010, should help clinicians better gauge whether a patient is likely to benefit from a defibrillator. Other major CER efforts supported by NIH have compared antipsychotic drugs for the treatment of schizophrenia, strategies for preventing deaths from prostate cancer, antihypertensive medications, treatments for bullous emphysema, and approaches to preventing diabetes. A 2007 report by the CongressionalBudgetOfficecitedNIH’scomparativeeffectiveness studies asprimeexamplesof government-sponsored research that could directly inform clinical practice and public policy. Today, the biomedical research community has an unprecedented opportunity to build on this foundation. The United States urgently needs the evidence to design a system that offers health interventions that are both beneficial and cost-effective. The American Recovery and Reinvestment Act (ARRA) of 2009 appropriated $1.1 billion for CER, with $400 million of that funding allocated to NIH and the remainder to AHRQ and the Office of the Secretary of the Department of Health and Human Services. While the ARRA-mandated report of the Federal Coordinating Council acknowledged that NIH historically has been the largest source of federal support for CER, NIH has important partners in other government agencies, particularly AHRQ. NIH generally contributes to CER by supporting primary research, including both observational studies and randomized control trials. AHRQ’s strength is in conducting secondary comprehensive meta-analyses of multiple studies, seeking to identify overarching conclusions and propose practice guidelines. By the end of September 2009, NIH had committed most of its $400 million ARRA allocation for CER through a variety of mechanisms, including Challenge grants, larger-scale Grand Opportunity grants, pay line expansions, competitive revisions, and administrative supplements. To prioritize these spending decisions, a high-level, trans-NIH committee considered a variety of criteria that met the Federal Coordinating Council’s definition of CER. These criteria included potential public health benefit, variability in practice, low probability for support by nongovernmental sectors, potential for multiplicative effect, focus on diverse populations and subgroups, engagement of communities in research, and application to the stated priorities of the Medicare Modernization Act and the Institute of Medicine (IOM). In addition to providing a much-needed funding boost for CER, ARRA-related activities helped delineate 5 important challenges facing NIH as it considers how to use science to benefit health care reform.