Pushing past the placebo: Legislating for a new kind of clinical trials

In January, a study published in the Journal of the American Medical Association on the first two commercially available drug-eluting stents found no significant differences in clinical outcomes.

In August, a report in the New England Journal of Medicine concluded that patients with stable angina who underwent percutaneous coronary intervention showed slightly more improvement over those treated with medication. But that added benefit disappeared by 36 months.

Then in September, a study in the NEJM found that arthroscopic surgery for osteoarthritis of the knee provided no additional benefit over physical and drug therapy.

What these very different studies have in common is that they compare the effectiveness of one treatment option with another instead of on its own. Although more of this type of research is being conducted than ever before, physicians, insurers and consumer groups widely agree that not enough comparative-effectiveness data exist on pharmaceuticals, medical devices and procedures.

When drugs and devices go through the Food and Drug Administration approval process, they're compared with placebos. Few are tested in head-to-head trials. "They just have to be better than nothing," said David O. Barbe, MD, chair of the AMA Council on Medical Service, speaking on his own behalf.

Medical procedures often don't have clinical effectiveness data attached, noted Gail Wilensky, PhD, a former Medicare administrator and senior fellow at Project Hope, an international health advocacy organization.

But if some leading politicians and policy experts have their way, much more comparative-effectiveness research will be generated soon. In his health platform, President-elect Barack Obama calls for starting an independent institute to guide comparative-effectiveness research. In August, Senate Finance Committee Chair Max Baucus (D, Mont.) and Senate Budget Committee Chair Kent Conrad (D, N.D.) introduced a measure that would form a national entity to fund and oversee such research. The bill is expected to be at the center of congressional debate on the issue next year.

The concept of a national comparative-effectiveness body has support in the health care, insurance, consumer and public policy world. But many details, some controversial, must be worked out. How should the national entity be structured? Should it examine cost effectiveness as well? How will public and private payers use the data? How can patient-doctor decision-making be protected?

The rationale for more comparative effectiveness research is twofold: improving quality and lowering costs. Experts say providing the research results to physicians and the public will improve health care decision-making and thus boost quality. Meanwhile, giving the right treatment to the right patient would reduce spending on complications and hospitalizations. Another common belief is that many newer, costlier medical products or services would be found to offer little or no additional benefit than the older, less-expensive alternatives.

"I regard it as a strategy to help us learn how to spend smarter and treat better," Wilensky said, noting this will help slow the unsustainable health spending growth rate. The nation spent an estimated $2.2 trillion last year on health care, which is projected to nearly double by 2017, according to the Centers for Medicare & Medicaid Services.

Many doctors are interested in the benefits comparative effectiveness promises for the practice of medicine. "These are the questions that we as clinicians ask ourselves all the time -- what's the best treatment for my patient?" said Carrie Nelson, MD, program director for the Rush-Copley Family Medicine Residency Program in Aurora, Ill., and assistant professor in the Dept. of Family Medicine at Rush Medical College in Chicago.

Most of the information doctors get about medications comes from drug reps who have conflicts of interest, said Dr. Barbe, a family physician. Doctors want more independent research on the comparative effectiveness of various medical options, Drs. Barbe and Nelson said.

Data also would strengthen the doctor-patient relationship, research advocates said. "It would help patients understand their situations so they can be truly informed participants in the decision-making process," said Neil Kirschner, PhD, senior associate for regulatory and insurer affairs for the American College of Physicians.

Some resources already exist for physicians who want this type of data. In 2003, Congress authorized the Agency for Healthcare Research and Quality to support comparative effectiveness research. AHRQ makes findings public through guides for patients, clinicians and policymakers. But experts view that effort and a few private initiatives as too fragmented and too small to have enough of an impact. Plus, there is no one place physicians can go to access data easily.

These issues have helped spur the call for a national research body.

"The need for a centralized, adequately funded comparative-effectiveness research entity is apparent," states an AMA Council on Medical Services report approved at the Association's Interim Meeting in November. The report includes nearly a dozen principles that the entity should follow, including that physicians and patients have a significant oversight role and that the research it sponsors be disseminated in a timely manner. The American College of Physicians also has formal policy calling for such a body.

What about costs?

Many in the health care community agree that the entity should be independent and protected from political pressure, have adequate and stable funding, involve all stakeholders, use rigorous scientific standards and operate transparently. But disagreements exist on whether the body should focus solely on clinical comparative effectiveness or also consider treatment costs.

Wilensky opposes having the body review costs because it is controversial and could jeopardize clinical effectiveness research. Pharmaceutical Research and Manufacturers of America Senior Vice President Ken Johnson said any initiative should focus on comparing health outcomes, not cost effectiveness.

But some doctors want both efforts handled by the same body, as long as it's done with care. "Now the primary entity dealing with costs is the health plans," Dr. Barbe said. "It raises the issue of conflict of interest."

Creating separate infrastructure for cost analysis also would be wasteful, said Barbara McAneny, MD, chair-elect of the AMA Council on Medical Service, speaking on her own behalf.

If cost data came from an independent national entity, it would be trusted more, Dr. Barbe said. But findings on a procedure's clinical effectiveness should come first and be reported separately from cost-effectiveness data, he noted.

If two treatments are clinically equivalent, doctors need to know which one is less expensive, Dr. McAneny said. One of the profession's ethical obligations is to be an effective steward of the nation's limited health care resources, added the ACP's Kirschner.

More patients are seeking this information as insurers shift more costs onto them, Dr. Barbe said. "Physicians are in the best position to help them decide when it's worth it to spend more for a certain treatment."

Consumers Union, publisher of Consumer Reports, is comfortable comparing treatments' costs and clinical benefits. It does both in its Best Buy Drugs reports, noted Gail Shearer, the organization's director of health policy analysis and director of Best Buy Drugs. "People are ready to talk about value."

Limiting the entity's scope

The AMA and other physician organizations are adamant that any national entity not be involved in coverage or payment determinations, a position with which the trade group America's Health Insurance Plans agrees. But the data generated would help inform insurers' decisions, said Karen Ignagni, AHIP president and CEO. Medicare officials also are monitoring the research out of AHRQ.

Many experts predict payers will use the data to establish tiered co-pays for services, much as they do now for drugs. They also might take clinical and cost-effectiveness data into account in their payment policies.

Plans already make coverage decisions, only they're based solely on cost, Dr. Barbe said. Adding clinical-effectiveness data "will help us hold payers accountable. Right now, we don't have the information we need to say they're denying treatment they should not deny."

But the way plans might use the data raises concerns. Patients are not all the same, Dr. Barbe noted. A treatment deemed the most effective in general may not work for subgroups of patients because of factors such as age, sex, race or comorbidities.

Experts stress that treatment decisions must remain in doctors' and patients' hands and that an easily navigable exceptions or appeals process must be built into insurance coverage. That way patients who wouldn't benefit from the treatment generally accepted as most effective might be able to access an alternative without paying more.

Knowing which types of patients would benefit most from a given intervention will require more studies on subpopulations. Wilensky estimates that $4 billion to $6 billion per year should be invested in the research. Of the $2.2 trillion spent on health care annually, only 5% is dedicated to research, and less than 0.1% goes toward comparative effectiveness studies.

With the election of Obama and the interest from lawmakers, many policy experts predict that comparative-effectiveness legislation will get serious consideration in 2009, either as part of a larger health system reform bill or on its own. "It's a white-hat issue" that appeals across party lines, said Shawn Friesen, government affairs associate for the American College of Surgeons, which supports the idea of the research but has not yet adopted formal policy.

If a bill becomes law it will be years before a large enough body of evidence exists to have a major impact on medical practice and spending, notes a December 2007 Congressional Budget Office report. For research to have an effect, CBO notes, doctors and patients would need to use the data.

Physicians who do a particular procedure that is profitable might need to adapt if research finds it less effective than clinically equivalent, less-costly treatments, Kirschner said. This transition could at times be hard for them.

"People get used to doing what they do, and when they're asked to make a change that affects their livelihood, it's difficult," he said. "That's the human part of this."