The Daoist Diaries

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.

Less than 0.1% of the money spent on health research is for studies that compare the effectiveness of two products.

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.

The U.S. spent an estimated $2.2 trillion on health care services in 2007.

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.

Comparative effectiveness weighs medical treatments against each other, rather than against a placebo.

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."

A federal trial court rejected a Centers for Medicare & Medicaid Services policy allowing Medicare claims contractors to limit payment for Part B drugs administered in a physician's office to the least costly alternative.

The court in an Oct. 16 ruling found that Medicare law did not authorize CMS or the contractors to redefine payment rates that were already set in statutory formulas.

In this case, Ilene Hays' physician had prescribed the inhalation medication DuoNeb to treat her chronic obstructive pulmonary disease. In April 2008, however, four Medicare contractors changed the basis of the nebulizer's payment from the average sales price of that drug to the price of the least costly alternative -- in this case, separate doses of DuoNeb's active ingredients, albuterol sulfate and ipratropium bromide.

Dept. of Health & Human Services Secretary Michael Leavitt argued in court documents that the Medicare statute prohibits payments for services that are not "reasonable and necessary" for treatment. Cost was a factor in that payment decision, he said.

But the U.S. District Court for the District of Columbia said that once coverage was approved, as in this case, payments are set in preexisting, explicit formulas that CMS and Medicare contractors may not change as they see fit. "It does not make sense to conclude that Congress, having minutely detailed the reimbursement rates for covered items and services, intended that the secretary could ignore these formulas whenever [he or she] determined that the expense of an item or service was not reasonable or necessary," U.S. District Judge Henry H. Kennedy Jr. wrote. "There is no indication that Congress intended to confer such broad authority."

Spokesman Peter Ashkenaz said CMS was disappointed in the ruling and is pondering its next move. Hays' attorneys declined comment.

Better access to come?

Experts disagree on whether the ruling, if it stands, will invalidate other uses of the least-costly-alternative policy. But it could discourage Medicare claims contractors from using the policy as a cost-control measure in Part B drug coverage determinations, said Joseph Bailes, MD, chair of the American Society of Clinical Oncology's Government Relations Council.

That would be a welcome change for physicians who say the policy is arbitrary and hurts beneficiaries' access to needed treatments.

Medicare typically pays 106% of the average sales price for Part B drugs.

The only reference to the least-costly-alternative principle lies in CMS' instruction manual for Medicare contractors, Dr. Bailes noted. Otherwise, the policy "is not part of the statute, and the court is saying [CMS] can't pretend it is by calling it medical necessity," he said.

Most challenges to such determinations go through Medicare's administrative appeals process, though the recent court decision could prompt similar litigation, Dr. Bailes added.

Treatment decisions belong in the hands of physicians and patients, and imposing unwarranted cost restrictions "degrades that process," said Rick Rutherford, the American Urological Assn.'s director of practice management. Medicare contractors "have said that physicians and patients can choose whatever drug they want, but then they only pay the least costly amount."

Cheaper is not always better, Rutherford added. Some more expensive options for treating prostate cancer may include longer-acting drugs more amenable to patient tolerance levels. Medicare typically pays 106% of the average sales price for Part B drugs. Doctors receive a separate payment for administering the medications. While not ideal, average sales price-based payments generally cover the medication cost and physicians' overhead associated with stocking the drugs, Rutherford said. When contractors pay at lower levels, doctors in many instances cannot afford to buy the drugs because Medicare dollars will not cover the up-front cost.

Without certain cancer drugs, patients could face more invasive and unnecessary surgical procedures, Rutherford added.

The AMA continues to advocate for Medicare pay reform, including improved transparency for payment amounts for Medicare Part B. AMA policy also advocates that contractors provide clear guidelines that identify noncovered and medically unnecessary services.

Results of a large-scale study offered significant evidence that statin drugs reduced cardiovascular disease risks for patients with normal cholesterol but high levels of an inflammatory marker. As a result, physicians now face the challenge of incorporating this promising, albeit incomplete, data into everyday preventive care.

For instance, testing for the inflammatory marker, high-sensitivity C-reactive protein, hasn't been a big part of the practice of Bob Gramling, MD, DSc, a family physician in Rochester, N.Y. But he expects that to change in the very near future.

"I will be asked to do it more," said Dr. Gramling, an assistant professor in family medicine as well as community and preventive medicine at the University of Rochester. "I'm going to be thinking about it more."

This point of view is gaining momentum because results from that heavily publicized trial -- the first to use hs-CRP to guide cardiovascular prevention rather than only assess risk -- were released Nov. 9 at the American Heart Assn.'s scientific sessions in New Orleans. They also were published in the Nov. 20 New England Journal of Medicine and attracted widespread media attention.

Researchers with the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin, or JUPITER, tracked 17,802 participants for just short of two years. They found that patients with high levels of hs-CRP but otherwise healthy cholesterol profiles who took 20 mg of this drug daily dramatically reduced their risks of cardiovascular events and death when compared with those who were taking placebos. Another pair of papers presented at the AHA meeting reinforced hs-CRP's potential for cardiovascular disease risk stratification.

The CRP test is not a part of the Framingham Risk Score.

"These findings suggest that adding hs-CRP levels to traditional risk factors could identify millions more adults for whom treatment with statins appears to lower the risk of heart attack," said Elizabeth G. Nabel, MD, director of the National Heart, Lung, and Blood Institute.

Most physicians concur that JUPITER is a significant study. But a great deal of disagreement still exists about how widespread hs-CRP testing should become and how often a prescription for statins is needed.

"It's a very important study. It was well done. The people who did it are to be congratulated," said Mark Hlatky, MD, a cardiologist and professor at California's Stanford University School of Medicine. He wrote the accompanying NEJM editorial. "But how do we generalize the results?"

What will be JUPITER's impact?

Whether to test for hs-CRP and how to respond to the numbers has been controversial for years. Physicians increasingly are using this marker to determine strategies for those at intermediate risk for cardiovascular disease. Several studies have suggested that it is an effective strategy, and the Reynolds Risk Score includes it. This risk assessment tool was designed by Paul Ridker, MD, the principal investigator of JUPITER. He also is one of the patent holders for the hs-CRP assay.

This biomarker, however, is not a part of the more widely used Framingham Risk Score. AHA guidelines say its role in directing prevention strategies is unclear, and several papers comparing it with other risk factor measures have not found that it adds much to an overall assessment.

The response to this latest development varied widely. For some physicians, this trial gave them the evidence for which they were waiting.

"I think it's very important and very significant," said Lawrence K. Monahan, MD, an internist in Roanoke, Va., and clinical professor at the University of Virginia School of Medicine and the Virginia College of Osteopathic Medicine. He added that he would "without a doubt" be testing for hs-CRP more often.

Others are more hesitant. The relative risk reduction was significant, but questions remain about how clinically meaningful it would be to apply cholesterol-lowering treatment to those whose baseline risk may not be that high. "What we have not seen is what were the absolute levels of risk, and how far did they go down," said Dr. Hlatky.

Another necessary step is to identify the characteristics that make some patients benefit more than others from this statin use.

Concerns also stem from the potential long-term implications of more people taking statins at even younger ages for an even longer portion of their lives -- issues not answered by this project. The study, which was originally planned to follow patients for five years, was halted after an average of 1.9 years because the immediate benefits were so significant.

"We could find after 15 to 20 years of statin use higher rates of some other life-threatening condition. We have the potential to create a fair amount of harm," Dr. Gramling said.

Others worry about the cost associated with hs-CRP testing and treating patients who have high levels of this marker but normal cholesterol, especially if they are prescribed rosuvastatin. This drug is one of the more expensive in its class, although several physicians said they would likely opt for a generic. But it's not clear if JUPITER's results can be generalized in this manner.

"My own personal belief is that for the same degree of lipid lowering, it doesn't matter much which statin you're on," Dr. Hlatky said.

In addition, some physicians were skeptical about the possible role the study's funder may have played in the results. AstraZeneca Pharmaceuticals, the manufacturer of rosuvastatin, paid for the research.

"This immediately makes me suspicious," said Elizabeth Gabay, MD, an internist at Interfaith Community Health Center in Bellingham, Wash. "I would like to see a study not paid for by a maker of a statin. Then I would be more inclined to believe the results." The study authors noted in the published report, though, that AstraZeneca had no access to the data before the paper was submitted for publication and played no part in data analyses or drafting the paper.

The company now plans to file an application with the Food and Drug Administration for an expanded indication for this drug, according to an AstraZeneca statement. Rosuvastatin currently has FDA approval as an add-on to dietary efforts to lower cholesterol. It is marketed by AstraZeneca as Crestor.

The Framingham Risk Score, the crystal ball that helps physicians determine who is most and least in need of intervention to reduce the chance of a heart attack, is the subject of increasing debate over how to make it more accurate.

"We are humbled when patients at low risk have events, and we know that the sensitivity of the score is a problem," said James De Lemos, MD, a cardiologist and associate professor of medicine at the University of Texas Southwestern Medical Center at Dallas.

A version of the calculator, a product of six decades of research conducted as part of the Framingham Heart Study, was first proposed in several papers appearing in 1976 in the American Journal of Cardiology. The articles detailed how various factors could be used to profile an individual patient's risks. The goal was to identify those most in need of prevention and give peace of mind to those who may have one elevated factor but otherwise are healthy.

"The importance of risk stratification is that it helps you focus without needlessly alarming or falsely reassuring people," said William Kannel, MD, MPH, then the director and now a senior investigator with the project.

Subsequent versions have been published over the years. The most recent one was in the May 12, 1998, Circulation. That risk calculator iteration was then simplified and incorporated into a report by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, which was published in the May 16, 2001, Journal of the American Medical Association. The current assessment incorporates age; total and HDL cholesterol; smoking status; systolic blood pressure; and whether a patient is taking an anti-hypertensive drug. Experts believe this tool is one of the reasons heart attack death rates have decreased. Still, a great deal of talk focuses on the tool's next revision.

Most people who have heart attacks and strokes were not considered high risk.

"The risk algorithm should continually be re-examined if new evidence comes along," said Christopher O'Donnell, MD, associate director of the Framingham Heart Study. "And I think there are three areas that are going to frame the next decade of risk assessment -- blood biomarkers, vascular imaging and genetic markers."

Experts also say an update is due for reasons beyond the fact that time has passed and additional data are available. The focus of risk assessment is changing, with researchers wanting to devise one tool to determine the risk of all cardiovascular conditions, not just myocardial infarction. In addition, a great deal of work is going into attempts to design more accurate assessments of those identified as having intermediate risk.

A paper published in the Feb. 14, 2007, JAMA by a group at Brigham and Women's Hospital in Boston, and another online Jan. 22 in Circulation by Framingham researchers, outlined strategies to determine the 10-year risk of any cardiovascular event. The JAMA paper, for instance, outlined the Reynolds Risk Score for women, incorporating traditional risk factors along with family history and C-reactive protein, both of which are the most likely candidates to be included in future versions of Framingham. Approximately 40% to 50% of women at intermediate risk were reclassified as having a high or low chance of a cardiovascular event. A men's version was released at the American Heart Assn. meeting in New Orleans last month.

"The bottom line of both [Framingham and Reynolds] risk scores is getting the right drug to the right patient at the right time," said Paul Ridker, MD, lead author of the JAMA paper and director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital. "The majority of heart attacks and strokes occur in apparently healthy men and women of intermediate risk. How can we better define high and low risk within the intermediate risk group? We did it with greatly improved accuracy by adding two simple things to do a better job of getting patients stratified."

Researchers also want to create tools that don't require blood draws or multiple patient visits. The more recent Circulation document provided two means of risk assessment. One relied on the usual Framingham risk factors, and the other substituted body mass index for cholesterol numbers.

Washington -- Understanding the medical care, technology and economic wherewithal it takes to age well in the U.S. is the goal of a new survey funded by the National Institute on Aging and led by Johns Hopkins University's Bloomberg School of Public Health in Baltimore.

NIA intends to provide about $24 million over the next five years to develop and implement the survey. Still in its earliest phase, the survey aims to further understanding of how older people overcome obstacles in daily life -- whether by installing grab bars in a bathroom or by having joint replacement surgery.

The surveyors also plan to include measures related to social interactions by asking, for example, whether a person does any volunteer work.

Since nearly 40 million people in the nation are already 65 or older, and most are expected to live about 20 more years, finding ways for people to continue to function is in everyone's interest. The AMA is putting forth a major effort to guide physicians as they care for aging patients, with resources ranging from guidelines on the use of assistive technology and the safety of older drivers to dementia and assistance to caregivers.

The new survey will pick up on trends noted in the "1982-2004 National Long-Term Care Survey," which showed a major decline in disability among people 65 and older.

Nearly 40 million people in the U.S. are 65 or older.

"Our aim is to provide scientific evidence that can help in reducing disability and improving the daily lives of older people," said the project's principal investigator Judy Kasper, PhD, professor in the Dept. of Health Policy and Management at Hopkins' School of Public Health.

Data released earlier this year by the Federal Interagency Forum on Aging-Related Statistics also show that as life expectancy increased, older people were, for the most part, enjoying better health and financial security than in the past.

The new study will try to zero in on how people are achieving these gains. "We hope that this study will play a critical role in maintaining or accelerating this trend as we address the challenges of our aging population," said Richard Suzman, PhD, director of the Division of Behavioral and Social Research at NIA.

Questions on the economic consequences of aging also will be asked, said Kasper. For example: "How do people pay for services when they need them for long-term disability problems?"

Evidence from earlier reports also revealed that while disabilities have been declining, gains were not as great for blacks and Hispanics or for low-income seniors as for others.

To address these disparities, the survey population will include more people from minority and low-income groups to ensure they are well-represented, said Kasper.

Today's generation of people 65 and older is less likely to be disabled than this age group was before 1984.

The first phase of the study will sign up 12,000 Medicare enrollees who will be followed annually. The enrollees will be grouped by age. As people age into older groups, researchers will bring in younger people to replace them.

The resulting database is expected to prove valuable to researchers and policymakers, said Kasper. "In addition to design and data collection, an important piece is the dissemination of data to the research community and workshops to get people interested in using the data."

It's rare to start a new national survey of this size given the current constraints on research funding, said Kasper. "The NIA deserves a lot of credit for recognizing that our existing national surveys are not designed to address the kinds of issues this survey is designed to address."

The undertaking will include investigators from the University of Medicine and Dentistry of New Jersey; Brown University in Providence, R.I.; Columbia University in New York City; the Medical College of Wisconsin; the Urban Institute, a nonpartisan economic and social policy research group in Washington, D.C.; the University of Iowa; Syracuse University in New York; and the survey research firm, Westat in Maryland.