Comparative effectiveness research may shape treatment, coverage decisions

Key Points

The economic stimulus package approved by Congress in February provides more than $1 billion to support research on competing medical treatments. Although a fairly minor piece of the larger $789 billion American Recovery and Reinvestment Act of 2009 (ARRA), the provision set off widespread reaction to the possibility that comparative study results may be used to limit coverage of more expensive medicines.

While conservatives raised the specter of "government rationing" and "cookbook medicine," supporters of comparative effectiveness research (CER), including Obama administration officials, countered that more and better information about which medical products and procedures are most effective could potentially improve healthcare and decrease unnecessary spending. But a white paper released last year by the Congressional Budget Office (CBO) suggested that CER could "provide a basis for applying costly new technologies only when they are likely to confer added benefits."

The final ARRA legislative report compromised, stating that Congress does not intend CER to be used to "mandate coverage, reimbursement or other policies for any public or private payer." Some observers noted, however, that once CER results are available to the public, health plans, payers, and formulary committees can use the data as they see fit.

In any case, the government-funded CER program opens the door for the federal government to play a larger role in selecting and shaping comparative assessments. Instead of establishing a new, independent entity to carry out CER, as some advocated, the stimulus package divides $1.1 billion among three arms of the Department of Health and Human Services (HHS). The Agency for Healthcare Research and Quality (AHRQ) gains $300 million to bolster its relatively small outcomes and effectiveness research program. The National Institutes of Health (NIH) gets $400 million to fund CER conducted by its various institutes. The remaining $400 million goes to the HHS secretary to support standards development, establish registry and data systems, and carry out other activities.

How these agencies dole out the money will be shaped by a June 30 report from the Institute of Medicine (IOM) recommending priorities for CER. The importance of the committee's deliberations is clear, as dozens of interested parties presented their opinions at a March public meeting on how CER should be conducted and which topics should be studied. In recommending study areas, the IOM panel will consider the needs of populations served by federal programs, such as the elderly, children, the disabled, and patient subpopulations, including women and minorities.

A new Federal Coordinating Council for CER will monitor how well HHS meets the IOM priorities in awarding CER grants. The 15-member council includes top officials from HHS, NIH, AHRQ, FDA, and others. In the spirit of transparency, HHS will publish information on grants and contracts awarded under this program, will disseminate the research findings that result, and will report annually on the program to Congress.

One benefit of a broader CER program would be improved methods for conducting comparative studies. Some research experts see a need-and an opportunity-to use part of the federal funding to develop innovative trial designs for real-world assessment of medical treatments. At the IOM meeting, Bryan Luce, senior vice president of United Biosource Corporation (UBC), urged "true transformational thinking" in designing CER studies; otherwise, he said, we will "waste vast amounts of money answering the wrong questions, or the right questions too late."

NOTHING NEW

The federal CER initiative builds on years of activity in this area. The Medicare Modernization Act of 2003 provided limited funding to AHRQ for research to determine the clinical effectiveness and appropriateness of various health services, including prescription drugs. In the private sector, the Blue Cross and Blue Shield Association's Technology Evaluation Center has been reviewing clinical evidence since 1985 to assess the effectiveness of certain medical procedures, drugs, and medical devices. The Drug Effectiveness Review Project (DERP) at the Oregon Health & Science University provides state Medicaid agencies and large insurers with comparative information on the efficacy and safety of expensive new medications and on drugs that are frequently used off-label.

A number of foreign CER programs have spurred interest in the United States. Most prominent is the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom, which provides Britain's National Health Service with recommendations on the coverage of new drugs and diagnostics and on clinical best practices. NICE sets a clear cost-effectiveness threshold that has led to controversial no-coverage decisions on a number of costly new therapies.

Pharmaceutical companies also are underwriting more comparative studies to meet regulatory and reimbursement requests. Payers and formulary committees want data on superior efficacy and safety of new drugs compared to available treatments. More postapproval safety studies are comparing new drugs to existing therapies. Even FDA, which generally requests placebo-controlled studies, finds comparative clinical information useful in documenting advantages for new drugs in crowded therapeutic classes or when serious safety issues arise.

Johnson & Johnson's Centocor, for example, sponsored a large phase 3 comparator trial to assess whether its investigational psoriasis drug, ustekinumab, is more effective than etanercept (Enbrel, Amgen). Eli Lilly has compared its anticlotting drug prasugrel to field leader clopidogrel (Plavix) to better assess efficacy and reports of internal bleeding. GlaxoSmithKline is testing albiglutide (Syncria), its investigational long-acting type 2 diabetes treatment, against multiple active comparators, such as metformin and insulin, in a multiarm, 4,000-patient study.

Such large comparative studies are usually funded by NIH, which has the resources and research networks necessary to carry out long-term, multisite assessments. Several of these high-profile trials have concluded that newer, more costly drugs may not perform any better than older, less expensive medications, a finding likely to dismay the pharmaceutical companies with interests at stake. A controversial comparative study now in the works seeks to compare the safety, efficacy, and cost of treating age-related macular degeneration with ranibizumab (Lucentis) or bevacizumab (Avastin). Both drugs are produced by Genentech and are derived from the same monoclonal antibody, but treatment with bevacizumab is less than one-tenth the cost of ranibizumab therapy.

FUTURE DIRECTIONS

Instead of such drug-drug comparisons, pharmaceutical companies want CER to weigh medications against surgery or other invasive treatments and to compare care processes, such as disease management, care coordination, and various benefit designs. But the demand on many sides for more information on the value and quality of drugs and medical products means that pharmaceuticals will be a visible focus of the new CER initiative. Drugs are ready targets, moreover, because there is much more information on FDA-regulated products from clinical trials, outcomes studies, and adverse event reports. NIH proposes to use some of its ARRA funds to address pharmaceutical efficacy and costs, such as risks and benefits of commonly used cancer treatments and the factors involved in treating fibromyalgia, depression in children, and autoimmune rheumatic and skin diseases.

One concern about linking CER to coverage limitations has to do with the possibility that broad comparative-research studies could stymie development of more targeted therapies integral to advancing personalized medicine. Comparative studies basically aim to identify drugs and establish treatment standards that are most beneficial for the largest numbers of patients. Personalized medicine, conversely, involves treatment of small patient populations in ways that often differ from practice guidelines.

The challenge for policy-makers and study sponsors is to develop research methods and systems that can support more informed standards of care, along with flexibility to address individual patient needs. Some policy-makers have insisted that CER will not lead to coverage denials, but will steer providers to treatments that offer greater benefits for particular patients. The important questions, comments health-policy expert Gail Wilensky, are whether CER data have credibility, whether research practices are open and transparent, and whether studies are objective and not politically motivated.

Ms Wechsler is a Washington-based reporter specializing in federal and state healthcare issues.