Compared to What?

The economic stimulus package approved by Congress in February set off a firestorm of speculation that comparative studies will block patient access to necessary treatment. Although the $1.1 billion allocated for research comparing medical products and procedures is just a tiny piece of the $789 billion American Recovery and Reinvestment Act of 2009 (ARRA), it has already prompted cries of "government rationing" and "cookbook medicine" from conservative legislators and commentators.

Jill Wechsler

Comparative studies aim to identify the treatments that will be most beneficial for the largest number of people, in contrast to personalized treatments for small patient populations. Comparative-effectiveness research (CER) enthusiasts insist that better information on medical products and procedures can improve care and cut unnecessary spending, but pharma companies have raised the specter of limiting coverage for targeted therapies essential to personalized medicine.

The final report on the stimulus bill sought to diffuse this controversy by asserting that Congress does not intend CER to be used to "mandate coverage, reimbursement, or other policies for any public or private payer." Senate Republicans tried to insert similar limitations in the 2010 budget resolution, but Democrats objected to specific curbs on CER use. Even if public programs are constrained from basing coverage on comparative studies, there's nothing to stop private insurers and payers from using the data as they see fit. As a Congressional Budget Office (CBO) white paper stated last year, CER can "provide a basis for applying costly new technologies only when they are likely to confer added benefits."

Setting priorities

What's clear is that the federal government will play a large role in selecting treatments and topics to be analyzed, as well as the methods for conducting comparative studies. (See "Better Methods,".) Instead of creating a new, multi-billion dollar CER operation, the stimulus package divides the $1.1 billion among three arms of the Department of Health and Human Services (HHS). The HHS secretary gets $400 million to run the program and build infrastructure for future CER, including registries and data networks. The Agency for Healthcare Research and Quality (AHRQ) adds $300 million to its $50 million outcomes and effectiveness research program. And $400 million goes to the National Institutes of Health (NIH). That's just a drop in the bucket when compared to the $10 billion ARRA funds for NIH scientific research and facilities improvement.

How these agencies dole out the money will be determined by a June 30 report from the Institute of Medicine recommending CER priorities. The IOM panel is considering the needs of populations most served by federal programs, such as the elderly and children, as well as subpopulations such as women and minorities.

A new Federal Coordinating Council for CER will weigh in on investments, monitor how well HHS grants fit the IOM priorities, and coordinate government-funded initiatives. This 15-member council includes top officials from HHS, NIH, AHRQ, FDA, and other federal agencies. HHS will publish information on grants and contracts awarded under the program, disseminate research findings, and report to Congress each year.

Considering costs

The big question is whether investment in CER will steer providers and patients to more effective care and reduce inappropriate expenditures. Instead of drug-to-drug cost assessments, pharma companies want CER to compare medicines to surgery or other treatments, and assess the value of disease management, care coordination, and benefit design. Focusing on drugs and devices "misses the point," according to Gail Wilensky of Project HOPE. "The real explosion in costs is in medical procedures."

However, pharmaceuticals are an easy CER target because so much drug data is available from clinical trials, outcomes studies, and adverse-event reports. The clamor for information on pharmaceutical value and quality ensures that more studies will be conducted in this area. AHRQ's research program began in 2005 with an emphasis on pharmaceuticals to support the then-new Medicare drug benefit, along with instructions from Congress not to use CE information in making coverage decisions. But at an AHRQ advisory meeting, Anthony Wisniewski, head of health policy for the US Chamber of Commerce, said that it is unrealistic to ignore cost-effectiveness issues in CER. Analysis of costs should not be the first priority, he noted, but "it must remain a critical component" of CER activity.

If the past is prologue, costs will indeed be a regular CER component. Several large, multi-center trials sponsored in recent years by NIH have made headlines by concluding that newer, more costly drugs for blood pressure control and schizophrenia treatment, (among others) may not perform any better than older, cheaper medicines. All eyes (pun intended) are now on the National Eye Institute's assessment of treatment for age-related macular degeneration (AMD) with Lucentis (ranibizumab) or Avastin (bevacizumab). Both drugs (produced by Genentech) derive from the same monoclonal antibody. However, Avastin is less than one-tenth the cost of Lucentis.

The Future of CER

Analysis of drug effectiveness and cost-effectiveness is nothing new for insurers and payers. Blue Cross and Blue Shield Association's Technology Evaluation Center has reviewed clinical evidence since 1985 to determine the effectiveness of drugs and medical technologies. The Drug Effectiveness Review Project (DERP) at the Oregon Health and Science University provides comparative efficacy and safety information on high-cost, heavily used medicines, as well as drugs frequently used off-label. Consumer Reports' Best Buy Drugs program uses the DERP analyses to provide advice on medical appropriateness and affordability of widely used medicines.

Foreign CER programs have spurred interest in US initiatives. 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. NICE sets a clear cost-effectiveness threshold that has led to controversial no-coverage decisions on a number of new, but costly, therapies.

Pharma companies have also been sponsoring more of their own comparative studies to meet regulatory and reimbursement requirements. Payers and formulary committees increasingly want to see data indicating superior efficacy or safety of new drugs compared to available treatments. There are more postapproval comparator studies to meet FDA requirements, and comparative clinical information is increasingly important for gaining market access, particularly in crowded therapeutic classes or for new products that raise serious safety issues. There, of course, sponsors write the protocols, select the comparators, and control the results.

The future promises more oversight of industry studies, along with more CER. Pharma is lobbying hard for such research to focus on clinical value and outcomes, as opposed to cost-effectiveness. Drug and device makers have enlisted support from patient and medical groups to form the Partnership to Improve Patient Care, which has signed up former Congressman Tony Coelho to carry the banner for ensuring that CE studies are well-designed, promote continued medical innovation, and protect patient access to "advanced treatment options." The National Pharmaceutical Council has narrowed its agenda to focus on CER issues and plans a mid-June symposium on the CER landscape in the US and abroad.

Policymakers insist that CER will not lead to coverage denials, but will steer doctors and providers to treatments offering greater benefits for patients and will support flexibility to address special needs. According to Wilensky, the important questions are whether CE data has credibility, whether research practices are open and transparent, and whether studies are objective and not politically motivated.

Better Methods

One positive result of a broader CER program is to develop standards and improve trial designs for real-world assessment of medical treatments. AHRQ plans more investment in methods for designing CER studies, particularly those involving under-represented populations, and is holding a symposium June 1-2 on the subject. NIH is offering grants to improve CER research practices, assess quality of life measures and establish patient registries. At the IOM public meeting, Bryan Luce, senior vice president of UBC, urged "true transformational thinking" in designing CE research studies; otherwise, he said, we will "waste vast amounts of money answering the wrong questions, or the right questions too late."

Now NIH is proposing a number of studies addressing pharmaceutical efficacy and costs for ARRA-funded challenge grants. Research officials would like to assess costs along with risks and benefits of commonly used cancer treatments, and compare those costs and other factors for treating autoimmune rheumatic and skin diseases. The NIH "wish list" includes comparisons of efficacy, outcomes and costs of treatments for kidney stones, for fibromyalgia and for patients newly diagnosed with type 2 diabetes.

Interest is high in the IOM committee's deliberations, as dozens lined up at a March public meeting to propose CER study methods and topics to explore. Similarly, there was standing-room-only at a meeting of AHRQ's National Advisory Council, which heard presentations on how the agency should invest its ARRA funds.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com